{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:21:46Z","timestamp":1791825706871,"version":"4.3.4"},"reference-count":99,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T00:00:00Z","timestamp":1625529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Secondary enucleation (SE) puts an irreversible end to eye-preserving therapies, whenever their prolongation is expected to violate the presumed state of metastatic grace. At present, it must be acknowledged that clear criteria for SE are missing, leading to empiric and subjective indications commonly related to disease progression or relapse, disease persistence masking the optic nerve head or treatment-related complications obscuring the fundus view. This absence of evidence-based consensus regarding SE is explained by the continuously moving frontiers of the conservative management as a result of diagnostic and therapeutic advances, as well as by the lack of studies sufficiently powered to accurately stratify the risk of metastasis in conservatively treated patients. In this position paper of the European Retinoblastoma Group (EURbG), we give an overview of the progressive shift in the indications for SE over the past decades and propose guidelines to assist decision-making with respect to when SE becomes imperative or recommended, with corresponding absolute and relative SE indications. Further studies and validation of biologic markers correlated with the risk of metastasis are expected to set more precisely the frontiers of conservative management and thus consensual criteria for SE in the future.<\/jats:p>","DOI":"10.3390\/cancers13143392","type":"journal-article","created":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T11:36:44Z","timestamp":1625571404000},"page":"3392","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Current Indications of Secondary Enucleation in Retinoblastoma Management: A Position Paper on Behalf of the European Retinoblastoma Group (EURbG)"],"prefix":"10.3390","volume":"13","author":[{"given":"Christina","family":"Stathopoulos","sequence":"first","affiliation":[{"name":"Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, University of Lausanne, 1003 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"Lumbroso-Le Rouic","sequence":"additional","affiliation":[{"name":"Department of Ocular Oncology, Institut Curie, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette C.","family":"Moll","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoj","family":"Parulekar","sequence":"additional","affiliation":[{"name":"Birmingham Children\u2019s Hospital Eye Department, Birmingham Women\u2019s and Children\u2019s NHS Foundation Trust, Birmingham B4 6NH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Maeder","sequence":"additional","affiliation":[{"name":"Department of Radiology, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9286-4831","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Doz","sequence":"additional","affiliation":[{"name":"SIREDO Centre (Care, Innovation and Research in Pediatric, Adolescent and Young Adult Oncology), Institut Curie and University of Paris, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Jenkinson","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Birmingham Women\u2019s and Children\u2019s NHS Foundation Trust, Birmingham B4 6NH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Beck Popovic","sequence":"additional","affiliation":[{"name":"Pediatric Hematology-Oncology Unit, Centre Hospitalier Universitaire Vaudois, 1010 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9375-9336","authenticated-orcid":false,"given":"Guillermo","family":"Chantada","sequence":"additional","affiliation":[{"name":"Hospital Sant Joan de Deu, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis L.","family":"Munier","sequence":"additional","affiliation":[{"name":"Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, University of Lausanne, 1003 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,6]]},"reference":[{"key":"ref_1","first-page":"16","article-title":"Treatment of retinoblastoma","volume":"114","author":"Thompson","year":"1972","journal-title":"Am. J. Roentgenol. Radium Ther. Nucl. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1001\/archopht.1978.03910060338008","article-title":"Visual results and ocular complications following radiotherapy for retinoblastoma","volume":"96","author":"Egbert","year":"1978","journal-title":"Arch. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/0360-3016(89)90502-6","article-title":"External beam irradiation for retinoblastoma: Patterns of failure and dose-response analysis","volume":"16","author":"Foote","year":"1989","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1136\/bjo.79.2.112","article-title":"External beam radiotherapy for retinoblastoma: II. Lens sparing technique","volume":"79","author":"Toma","year":"1995","journal-title":"Br. J. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0360-3016(96)85020-6","article-title":"External beam radiation for retinoblastoma: Results, patterns of failure, and a proposal for treatment guidelines","volume":"35","author":"Hernandez","year":"1996","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S0360-3016(96)85010-3","article-title":"External beam radiation therapy and retinoblastoma: Long-term results in the comparison of two techniques","volume":"35","author":"Blach","year":"1996","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1097\/00043426-200205000-00005","article-title":"Ocular preservation after 36 Gy external beam radiation therapy for retinoblastoma","volume":"24","author":"Merchant","year":"2002","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1046\/j.1440-1673.2003.01167.x","article-title":"Retinoblastoma: Review of 30 years\u2019 experience with external beam radiotherapy","volume":"47","author":"Phillips","year":"2003","journal-title":"Australas. Radiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1001\/archopht.122.9.1316","article-title":"Outcome following initial external beam radiotherapy in patients with Reese-Ellsworth group Vb retinoblastoma","volume":"122","author":"Abramson","year":"2004","journal-title":"Arch. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"546","DOI":"10.3346\/jkms.2010.25.4.546","article-title":"Long term follow-up results of external beam radiotherapy as primary treatment for retinoblastoma","volume":"25","author":"Choi","year":"2010","journal-title":"J. Korean Med. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.4103\/ijo.IJO_634_19","article-title":"Outcomes of neonatal retinoblastoma in pre-chemotherapy and chemotherapy eras","volume":"67","author":"Camp","year":"2019","journal-title":"Indian J. Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2881","DOI":"10.1200\/JCO.2000.18.15.2881","article-title":"First-line chemotherapy with local treatment can prevent external-beam irradiation and enucleation in low-stage intraocular retinoblastoma","volume":"18","author":"Beck","year":"2000","journal-title":"J. Clin. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1200\/JCO.2003.09.103","article-title":"Treatment of intraocular retinoblastoma with vincristine and carboplatin","volume":"21","author":"Wilson","year":"2003","journal-title":"J. Clin. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1016\/j.ophtha.2004.04.016","article-title":"Causes of chemoreduction failure in retinoblastoma and analysis of associated factors leading to eventual treatment with external beam radiotherapy and enucleation","volume":"111","author":"Gunduz","year":"2004","journal-title":"Ophthalmology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1097\/01.mph.0000149238.60772.7f","article-title":"Conservative therapy in intraocular retinoblastoma: Response\/recurrence rate","volume":"27","author":"Schiavetti","year":"2005","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1002\/pbc.21067","article-title":"Risk factors for extraocular relapse following enucleation after failure of chemoreduction in retinoblastoma","volume":"49","author":"Chantada","year":"2007","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1016\/j.ophtha.2007.11.009","article-title":"Conservative treatments of intraocular retinoblastoma","volume":"115","author":"Aerts","year":"2008","journal-title":"Ophthalmology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"219","DOI":"10.3341\/kjo.2010.24.4.219","article-title":"Eye-preserving therapy in retinoblastoma: Prolonged primary chemotherapy alone or combined with local therapy","volume":"24","author":"Shin","year":"2010","journal-title":"Korean J. Ophthalmol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1200\/JCO.2010.32.5332","article-title":"Pre-enucleation chemotherapy for eyes severely affected by retinoblastoma masks risk of tumor extension and increases death from metastasis","volume":"29","author":"Zhao","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1111\/aos.12282","article-title":"A 10-year experience of outcome in chemotherapy-treated hereditary retinoblastoma","volume":"92","author":"Bartuma","year":"2014","journal-title":"Acta Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1136\/bjophthalmol-2014-306364","article-title":"Comparison of high-risk histopathological features in eyes with primary or secondary enucleation for retinoblastoma","volume":"99","author":"Brennan","year":"2015","journal-title":"Br. J. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e26270","DOI":"10.1002\/pbc.26270","article-title":"Risk of metastasis and orbital recurrence in advanced retinoblastoma eyes treated with systemic chemoreduction versus primary enucleation","volume":"64","author":"Berry","year":"2017","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1136\/bjophthalmol-2016-309298","article-title":"First-line intra-arterial versus intravenous chemotherapy in unilateral sporadic group D retinoblastoma: Evidence of better visual outcomes, ocular survival and shorter time to success with intra-arterial delivery from retrospective review of 20 years of treatment","volume":"101","author":"Munier","year":"2017","journal-title":"Br. J. Ophthalmol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/j.ophtha.2017.01.048","article-title":"High-Risk Histopathology Features in Primary and Secondary Enucleated International Intraocular Retinoblastoma Classification Group D Eyes","volume":"124","author":"Fabian","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_25","first-page":"1548","article-title":"Long-term (20-year) real-world outcomes of intravenous chemotherapy (chemoreduction) for retinoblastoma in 964 eyes of 554 patients at a single centre","volume":"104","author":"Shields","year":"2020","journal-title":"Br. J. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1038\/s41433-020-0898-9","article-title":"A 20-year audit of retinoblastoma treatment outcomes","volume":"34","author":"Gunduz","year":"2020","journal-title":"Eye"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1007\/s10792-020-01472-8","article-title":"High-risk features in primary versus secondary enucleated globes with advanced retinoblastoma: A retrospective histopathological study","volume":"40","author":"Alkatan","year":"2020","journal-title":"Int. Ophthalmol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Abramson, D.H., Marr, B.P., Brodie, S.E., Dunkel, I., Palioura, S., and Gobin, Y.P. (2012). Ophthalmic artery chemosurgery for less advanced intraocular retinoblastoma: Five year review. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034120"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1002\/pbc.24170","article-title":"Ophthalmic artery chemosurgery for the management of retinoblastoma in eyes with extensive (>50%) retinal detachment","volume":"59","author":"Palioura","year":"2012","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"981","DOI":"10.2147\/OPTH.S43398","article-title":"Superselective intra-arterial melphalan therapy for newly diagnosed and refractory retinoblastoma: Results from a single institution","volume":"7","author":"Thampi","year":"2013","journal-title":"Clin. Ophthalmol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1097\/IAE.0b013e318295f783","article-title":"Management of advanced retinoblastoma with intravenous chemotherapy then intra-arterial chemotherapy as alternative to enucleation","volume":"33","author":"Shields","year":"2013","journal-title":"Retina"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1111\/j.1755-3768.2011.02296.x","article-title":"Superselective ophthalmic artery infusion of melphalan for intraocular retinoblastoma: Preliminary results from 140 treatments","volume":"91","author":"Venturi","year":"2013","journal-title":"Acta Ophthalmol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1136\/bjophthalmol-2013-303267","article-title":"Intra-arterial chemotherapy with melphalan for intraocular retinoblastoma","volume":"97","author":"Bracco","year":"2013","journal-title":"Br. J. Ophthalmol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/j.ophtha.2014.01.026","article-title":"Intra-arterial chemotherapy for retinoblastoma in 70 eyes: Outcomes based on the international classification of retinoblastoma","volume":"121","author":"Shields","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s10384-014-0356-y","article-title":"Selective ophthalmic arterial injection of melphalan for intraocular retinoblastoma: A 4-year review","volume":"59","author":"Ong","year":"2015","journal-title":"Jpn. J. Ophthalmol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1001\/jamaophthalmol.2015.2243","article-title":"Enucleation vs. Ophthalmic Artery Chemosurgery for Advanced Intraocular Retinoblastoma: A Retrospective Analysis","volume":"133","author":"Yannuzzi","year":"2015","journal-title":"JAMA Ophthalmol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1159\/000439357","article-title":"Intra-Arterial Chemotherapy for Retinoblastoma: A Single-Center Experience","volume":"234","author":"Akyuz","year":"2015","journal-title":"Ophthalmologica"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Abramson, D.H., Daniels, A.B., Marr, B.P., Francis, J.H., Brodie, S.E., Dunkel, I.J., and Gobin, Y.P. (2016). Intra-Arterial Chemotherapy (Ophthalmic Artery Chemosurgery) for Group D Retinoblastoma. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0146582"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Abramson, D.H., Marr, B.P., Francis, J.H., Dunkel, I.J., Fabius, A.W., Brodie, S.E., Mondesire-Crump, I., and Gobin, Y.P. (2016). Simultaneous Bilateral Ophthalmic Artery Chemosurgery for Bilateral Retinoblastoma (Tandem Therapy). PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0156806"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"275","DOI":"10.3928\/01913913-20160719-04","article-title":"Retinoblastoma Control with Primary Intra-arterial Chemotherapy: Outcomes Before and During the Intravitreal Chemotherapy Era","volume":"53","author":"Shields","year":"2016","journal-title":"J. Pediatr. Ophthalmol. Strabismus"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1111\/aos.13333","article-title":"Outcome of intra-arterial chemotherapy for retinoblastoma and its influencing factors: A retrospective study","volume":"95","author":"Chen","year":"2017","journal-title":"Acta Ophthalmol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e27086","DOI":"10.1002\/pbc.27086","article-title":"Feasibility and results of an intraarterial chemotherapy program for the conservative treatment of retinoblastoma in Argentina","volume":"65","author":"Funes","year":"2018","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1001\/jamaophthalmol.2014.414","article-title":"Combined intravitreal melphalan and topotecan for refractory or recurrent vitreous seeding from retinoblastoma","volume":"132","author":"Ghassemi","year":"2014","journal-title":"JAMA Ophthalmol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Abramson, D.H., Fabius, A.W., Issa, R., Francis, J.H., Marr, B.P., Dunkel, I.J., and Gobin, Y.P. (2015). Advanced Unilateral Retinoblastoma: The Impact of Ophthalmic Artery Chemosurgery on Enucleation Rate and Patient Survival at MSKCC. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0145436"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.jaapos.2016.05.009","article-title":"Secondary and tertiary intra-arterial chemotherapy for massive persistent or recurrent subretinal retinoblastoma seeds following previous chemotherapy exposure: Long-term tumor control and globe salvage in 30 eyes","volume":"20","author":"Say","year":"2016","journal-title":"J. AAPOS"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2276","DOI":"10.1016\/j.ophtha.2006.06.018","article-title":"The International Classification of Retinoblastoma predicts chemoreduction success","volume":"113","author":"Shields","year":"2006","journal-title":"Ophthalmology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1002\/pbc.24303","article-title":"Long-term outcomes of Group D eyes in bilateral retinoblastoma patients treated with chemoreduction and low-dose IMRT salvage","volume":"60","author":"Berry","year":"2013","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e26696","DOI":"10.1002\/pbc.26696","article-title":"Long-term outcomes of Group D retinoblastoma eyes during the intravitreal melphalan era","volume":"64","author":"Berry","year":"2017","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e644","DOI":"10.1111\/aos.13077","article-title":"Superselective intra-arterial chemotherapy in the primary management of advanced intra-ocular retinoblastoma: First 4-year experience from a single institution in Turkey","volume":"94","author":"Tuncer","year":"2016","journal-title":"Acta Ophthalmol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1001\/archophthalmol.2011.150","article-title":"Intra-arterial chemotherapy for retinoblastoma: Report No. 1, control of retinal tumors, subretinal seeds, and vitreous seeds","volume":"129","author":"Shields","year":"2011","journal-title":"Arch. Ophthalmol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.ohc.2004.11.003","article-title":"Intraocular retinoblastoma: The case for a new group classification","volume":"18","year":"2005","journal-title":"Ophthalmol. Clin. N. Am."},{"key":"ref_52","unstructured":"(2021, May 01). European Retinoblastoma Group. Available online: https:\/\/www.eurbg.org."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1001\/archopht.1983.01040020364004","article-title":"Retinoblastoma treated in infants in the first six months of life","volume":"101","author":"Abramson","year":"1983","journal-title":"Arch. Ophthalmol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1001\/archopht.1996.01100140548005","article-title":"Chemotherapy plus local treatment in the management of intraocular retinoblastoma","volume":"114","author":"Murphree","year":"1996","journal-title":"Arch. Ophthalmol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e26908","DOI":"10.1002\/pbc.26908","article-title":"Loss of fundus view as an indication for secondary enucleation in retinoblastoma","volume":"65","author":"Berry","year":"2018","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1136\/bjo.55.1.19","article-title":"Retinoblastoma. A study of 139 cases","volume":"55","author":"Bedford","year":"1971","journal-title":"Br. J. Ophthalmol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"100764","DOI":"10.1016\/j.preteyeres.2019.05.005","article-title":"Conservative management of retinoblastoma: Challenging orthodoxy without compromising the state of metastatic grace. \u201cAlive, with good vision and no comorbidity\u201d","volume":"73","author":"Munier","year":"2019","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1016\/j.ophtha.2007.12.014","article-title":"A phase I\/II study of direct intraarterial (ophthalmic artery) chemotherapy with melphalan for intraocular retinoblastoma initial results","volume":"115","author":"Abramson","year":"2008","journal-title":"Ophthalmology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1097\/APO.0000000000000172","article-title":"Unilateral retinoblastoma managed with intravenous chemotherapy versus intra-arterial chemotherapy. Outcomes based on the International Classification of retinoblastoma","volume":"5","author":"Shields","year":"2016","journal-title":"Asia Pac. J. Ophthalmol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1080\/13816810.2017.1393826","article-title":"Successful conservative treatment of massive choroidal relapse in 2 retinoblastoma patients monitored by ultrasound biomicroscopy and\/or spectral domain optic coherence tomography","volume":"39","author":"Stathopoulos","year":"2018","journal-title":"Ophthalmic Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.oret.2017.08.022","article-title":"Choroidal Invasion in Retinoblastoma Treated with Intrarterial Chemotherapy","volume":"2","author":"Abramson","year":"2018","journal-title":"Ophthalmol. Retin."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.ophtha.2017.11.010","article-title":"Intracameral Chemotherapy for Globe Salvage in Retinoblastoma with Secondary Anterior Chamber Invasion","volume":"125","author":"Munier","year":"2018","journal-title":"Ophthalmology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"190","DOI":"10.3109\/13816810.2010.499888","article-title":"(106)Ruthenium brachytherapy for ciliary recurrence with supraciliary effusion in retinoblastoma","volume":"31","author":"Chhablani","year":"2010","journal-title":"Ophthalmic Genet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e509","DOI":"10.1097\/MPH.0000000000000167","article-title":"Anterior segment invasion in retinoblastoma: Is it a risk factor for extraocular relapse?","volume":"36","author":"Baroni","year":"2014","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1002\/cncr.11952","article-title":"Results of a prospective study for the treatment of retinoblastoma","volume":"100","author":"Chantada","year":"2004","journal-title":"Cancer"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1001\/jamaophthalmol.2018.1501","article-title":"Treatment of Nonmetastatic Unilateral Retinoblastoma in Children","volume":"136","author":"Perez","year":"2018","journal-title":"JAMA Ophthalmol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1136\/bjophthalmol-2011-301016","article-title":"Profiling safety of intravitreal injections for retinoblastoma using an anti-reflux procedure and sterilisation of the needle track","volume":"96","author":"Munier","year":"2012","journal-title":"Br. J. Ophthalmol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1136\/bjophthalmol-2017-310641","article-title":"Intravitreal topotecan in the management of refractory and recurrent vitreous seeds in retinoblastoma","volume":"102","author":"Rao","year":"2018","journal-title":"Br. J. Ophthalmol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1016\/j.ophtha.2014.03.028","article-title":"Local and systemic toxicity of intravitreal melphalan for vitreous seeding in retinoblastoma: A preclinical and clinical study","volume":"121","author":"Francis","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1016\/j.ophtha.2017.05.034","article-title":"Not All Seeds Are Created Equal: Seed Classification Is Predictive of Outcomes in Retinoblastoma","volume":"124","author":"Berry","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1136\/bjophthalmol-2011-301450","article-title":"Intravitreal chemotherapy for vitreous disease in retinoblastoma revisited: From prohibition to conditional indications","volume":"96","author":"Munier","year":"2012","journal-title":"Br. J. Ophthalmol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1097\/IAE.0000000000000903","article-title":"Intravitreous Chemotherapy for Active Vitreous Seeding from Retinoblastoma: Outcomes after 192 Consecutive Injections. The 2015 Howard Naquin Lecture","volume":"36","author":"Shields","year":"2016","journal-title":"Retina"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1136\/bjophthalmol-2011-300498","article-title":"Intra-arterial chemotherapy for retinoblastoma in eyes with vitreous and\/or subretinal seeding: 2-year results","volume":"96","author":"Abramson","year":"2012","journal-title":"Br. J. Ophthalmol."},{"key":"ref_74","first-page":"179","article-title":"Intravitreal chemotherapy","volume":"6","author":"Stathopoulos","year":"2019","journal-title":"Clinical Ophthalmic Oncology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/j.ophtha.2014.11.029","article-title":"Efficacy and toxicity of second-course ophthalmic artery chemosurgery for retinoblastoma","volume":"122","author":"Francis","year":"2015","journal-title":"Ophthalmology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.jfo.2015.03.004","article-title":"Rescue intra-arterial chemotherapy following retinoblastoma recurrence after initial intra-arterial chemotherapy","volume":"38","author":"Shields","year":"2015","journal-title":"J. Fran\u00e7ais Ophtalmol."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Stathopoulos, C., Sergenti, J., Gaillard, M.C., Munier, F.L., and Daruich, A. (2020). Pars plana vitrectomy under melphalan irrigation for recurrent retinal detachment in eyes treated for retinoblastoma: A case report. BMC Ophthalmol., 20.","DOI":"10.1186\/s12886-020-1315-7"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e17","DOI":"10.5301\/ejo.5000683","article-title":"Intraocular surgery with melphalan irrigation for vitreous hemorrhage in an only eye with retinoblastoma","volume":"26","author":"Yarovoy","year":"2015","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"349","DOI":"10.3928\/01913913-20091218-03","article-title":"Rhegmatogenous retinal detachment following treatment for retinoblastoma","volume":"47","author":"Gopal","year":"2010","journal-title":"J. Pediatr. Ophthalmol. Strabismus"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1097\/IAE.0000000000002339","article-title":"Intravitreal Anti-Vascular Endothelial Growth Factor for the Management of Neovascularization in Retinoblastoma after Intravenous and\/or Intraarterial Chemotherapy: Long-Term Outcomes in a Series of 35 Eyes","volume":"39","author":"Stathopoulos","year":"2019","journal-title":"Retina"},{"key":"ref_81","first-page":"1663","article-title":"Aqueous seeding: Fall of the ultimate intraocular retinoblastoma sanctuary by a new in situ chemotherapy technique","volume":"56","author":"Munier","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1159\/000453617","article-title":"Intracameral Chemotherapy (Melphalan) for Aqueous Seeding in Retinoblastoma: Bicameral Injection Technique and Related Toxicity in a Pilot Case Study","volume":"3","author":"Munier","year":"2017","journal-title":"Ocul. Oncol. Pathol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1159\/000452305","article-title":"Eye Salvage with Combination of Intravitreal and Intracameral Melphalan Injection for Recurrent Retinoblastoma with Anterior Chamber Involvement: Report of a Case","volume":"3","author":"Cassoux","year":"2017","journal-title":"Ocul. Oncol. Pathol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1001\/jamaophthalmol.2017.4603","article-title":"Intracameral Topotecan Hydrochloride for Anterior Chamber Seeding of Retinoblastoma","volume":"135","author":"Bagheri","year":"2017","journal-title":"JAMA Ophthalmol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1136\/bjophthalmol-2013-303188","article-title":"Evaluating the risk of extraocular tumour spread following intravitreal injection therapy for retinoblastoma: A systematic review","volume":"97","author":"Smith","year":"2013","journal-title":"Br. J. Ophthalmol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1007\/s00247-016-3554-6","article-title":"A review of the literature for intra-arterial chemotherapy used to treat retinoblastoma","volume":"46","author":"Wyse","year":"2016","journal-title":"Pediatr. Radiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1001\/jamaophthalmol.2016.0244","article-title":"Intra-arterial Chemotherapy for Retinoblastoma: A Systematic Review","volume":"134","author":"Yousef","year":"2016","journal-title":"JAMA Ophthalmol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1001\/archophthalmol.2011.304","article-title":"Intra-arterial chemotherapy for advanced retinoblastoma: Is the time right for a prospective clinical trial?","volume":"129","author":"Levin","year":"2011","journal-title":"Arch. Ophthalmol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s40942-017-0093-8","article-title":"Metastatic deaths in retinoblastoma patients treated with intraarterial chemotherapy (ophthalmic artery chemosurgery) worldwide","volume":"3","author":"Abramson","year":"2017","journal-title":"Int. J. Retin. Vitr."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1136\/bjophthalmol-2016-309899","article-title":"Diagnosis and management of secondary epipapillary retinoblastoma","volume":"101","author":"Fabian","year":"2017","journal-title":"Br. J. Ophthalmol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.ophtha.2021.01.014","article-title":"OCT imaging of Schlemm\u2019s canal invasion in a retinoblastoma patient","volume":"128","author":"Stathopoulos","year":"2021","journal-title":"Ophthalmology"},{"key":"ref_92","first-page":"98","article-title":"Fluorescein angiography of retinoblastoma","volume":"80","author":"Shields","year":"1982","journal-title":"Trans. Am. Ophthalmol. Soc."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1002\/jmri.26961","article-title":"Diagnosis of Postlaminar Optic Nerve Invasion in Retinoblastoma with MRI Features","volume":"51","author":"Li","year":"2020","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s00234-020-02538-1","article-title":"Diagnostic performance of MRI of post-laminar optic nerve invasion detection in retinoblastoma: A systematic review and meta-analysis","volume":"63","author":"Cho","year":"2021","journal-title":"Neuroradiology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e28963","DOI":"10.1002\/pbc.28963","article-title":"Adjuvant therapy of histopathological risk factors of retinoblastoma in Europe: A survey by the European Retinoblastoma Group (EURbG)","volume":"68","author":"Reschke","year":"2021","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"4654","DOI":"10.1167\/iovs.17-22111","article-title":"Anterior Chamber Invasion in Retinoblastoma: Not an Indication for Adjuvant Chemotherapy","volume":"58","author":"Sreelakshmi","year":"2017","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.5858\/2010-0311-OAR2","article-title":"A study of pathologic risk factors in postchemoreduced, enucleated specimens of advanced retinoblastomas in a developing country","volume":"135","author":"Suryawanshi","year":"2011","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e28964","DOI":"10.1002\/pbc.28964","article-title":"Response criteria for intraocular retinoblastoma: RB-RECIST","volume":"68","author":"Berry","year":"2021","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1001\/jamaophthalmol.2017.4097","article-title":"Potential of Aqueous Humor as a Surrogate Tumor Biopsy for Retinoblastoma","volume":"135","author":"Berry","year":"2017","journal-title":"JAMA Ophthalmol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/14\/3392\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:26:46Z","timestamp":1760164006000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/14\/3392"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,6]]},"references-count":99,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["cancers13143392"],"URL":"https:\/\/doi.org\/10.3390\/cancers13143392","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,6]]}}}