Ophthalmology Science (Mar 2025)

Retinoblastoma with and without Extraocular Tumor Extension

  • Swathi Kaliki, MD,
  • Vijitha S. Vempuluru, MD,
  • Ido Didi Fabian, MD,
  • Ido Didi Fabian, MD,
  • Elhassan Abdallah, MD,
  • Shehu U. Abdullahi, MD,
  • Rula A. Abdulqader, MD,
  • Aminatu A. Abdulrahaman, MD,
  • Sherif Abouelnaga, MD,
  • Dupe S. Ademola-Popoola, FMCOph, FWACS,
  • Adedayo Adio, FWACS,
  • Mahmoud A. Afifi, MD,
  • Armin R. Afshar, MD,
  • Priyanka Aggarwal, MD,
  • Ada E. Aghaji, FMCOph MSc,
  • Alia Ahmad, MRCPCH UK,
  • Marliyanti N.R. Akib, MD,
  • Adeseye M. Akinsete, MBBS,
  • Lamis Al Harby, MD,
  • Saleh A. Al Mesfer, MD,
  • Mouroge H. Al Ani, MD,
  • Silvia Alarcón Portabella, MD,
  • Safaa A.F. Al-Badri, MD,
  • Ana Patricia A. Alcasabas, MD,
  • Saad A. Al-Dahmash, MD,
  • Amanda Alejos, MD,
  • Ernesto Alemany-Rubio, MD,
  • Amadou I. Alfa Bio, MD,
  • Yvania Alfonso Carreras, MD,
  • Christiane E. Al-Haddad, MD,
  • Hamoud H.Y. Al-Hussaini, MD, MSc,
  • Amany M. Ali, MD,
  • Donjeta B. Alia, MD,
  • Mazin F. Al-Jadiry, MD,
  • Usama Al-Jumaly, MD,
  • Hind M. Alkatan, MD,
  • Charlotta All-Eriksson, MD, PhD,
  • Ali A.R.M. Al-Mafrachi, FIBMS,
  • Argentino A. Almeida, MD,
  • Khalifa M. Alsawidi, MD,
  • Athar A.S.M. Al-Shaheen, MD,
  • Entissar H. Al-Shammary, MD,
  • Doreen Amankwaa-Frempong, MBChB,
  • Primawita O. Amiruddin, MD,
  • Inggar Armytasari, MD,
  • Nicholas J. Astbury, FRCS, FRCOphth,
  • Hatice T. Atalay, MD,
  • Eda Ataseven, MD,
  • La-ongsri Atchaneeyasakul, MD,
  • Rose Atsiaya, OCO,
  • Rudolf Autrata, MD, PhD,
  • Julia Balaguer, MD, PhD,
  • Ruhengiz Balayeva, PhD,
  • Honorio Barranco, MD, PhD,
  • Paulina Bartoszek, MD,
  • Katarina Bartuma, MD, PhD,
  • Covadonga Bascaran, MD, MSc,
  • Nikolaos E. Bechrakis, MD,
  • Maja Beck Popovic, MD,
  • Ainura S. Begimkulova, MD,
  • Sarra Benmiloud, MD,
  • Rokia C. Berete, MD, PhD,
  • Jesse L. Berry, MD,
  • Anirban Bhaduri, MD,
  • Sunil Bhat, MBBS, MD,
  • Arpita Bhattacharyya, MD,
  • Eva M. Biewald, MD,
  • Elaine Binkley, MD,
  • Sharon Blum, MD,
  • Nadia Bobrova, MD,
  • H. Culver Boldt, MD,
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  • Gabrielle C. Bouda, MD,
  • Hédi Bouguila, MD, PhD,
  • Rachel C. Brennan, MD,
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  • Aléine Budiongo, MD,
  • Matthew Burton, FRCOphth,
  • Patricia Calderón-Sotelo, MD,
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  • Miriam R. Cano, MD, MSc,
  • Michael Capra, FRCPI,
  • Shani Caspi, MD,
  • Nathalie Cassoux, MD, PhD,
  • Guilherme Castela, MD,
  • Luis Castillo, MD,
  • Jaume Català-Mora, MD, PhD,
  • Isabel Caviedes, MD,
  • Arthika Chandramohan, MD,
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  • Shabana Chaudhry, MD,
  • Bhavna Chawla, MD,
  • Wensi Chen, MD,
  • Faraja S. Chiwanga, MSc,
  • Tsengelmaa Chuluunbat, MD, PhD,
  • Krzysztof Cieslik, MD,
  • Antony Clark, FRANZCO,
  • Ruellyn L. Cockcroft, MB ChB , M Med Paed,
  • Codruta Comsa, MD,
  • Maria G. Correa Llano, MD,
  • Timothy W. Corson, PhD,
  • Line Couitchere, MD,
  • Kristin E. Cowan-Lyn, MD, MBBS,
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  • Wantanee Dangboon, MD,
  • Anirban Das, MD,
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  • Jacquelyn M. Davanzo, BSN, BSPH,
  • Alan Davidson, MBChB, MPhil,
  • Sonia De Francesco, MD,
  • Patrick De Potter, MD, PhD,
  • Karina Q. Delgado, MD, PhD,
  • Hakan Demirci, MD,
  • Laurence Desjardins, MD,
  • Rosdali Y. Diaz Coronado, MD,
  • Helen Dimaras, PhD,
  • Andrew J. Dodgshun, M Phil,
  • Carla R. Donato Macedo, MD,
  • Monica D. Dragomir, MD, PhD,
  • Yi Du, MD,
  • Magritha Du Bruyn, MD,
  • Johannes P. Du Plessis, MMed (Paed),
  • Gagan Dudeja, MBBS, MS,
  • Katrin Eerme, MD,
  • I Wayan Eka Sutyawan, MD,
  • Asmaa El Kettani, MD,
  • Amal M. Elbahi, MD,
  • James E. Elder, MBBS,
  • Alaa M. Elhaddad, MD, PhD,
  • Moawia M.A. Elhassan, MD,
  • Mahmoud M. Elzembely, MD,
  • Connor Ericksen, MD,
  • Vera A. Essuman, FWACS,
  • Ted Grimbert A. Evina, MD,
  • Ifeoma R. Ezegwui, FMCOph, FWACS, FAEH,
  • Zehra Fadoo, MBBS,
  • Adriana C. Fandiño, MD,
  • Mohammad Faranoush, MD,
  • Oluyemi Fasina, FWACS,
  • Delia D.P.G. Fernández, MSc,
  • Ana Fernández-Teijeiro, MD, PhD,
  • Allen Foster, FRCOphth,
  • Shahar Frenkel, MD, PhD,
  • Ligia D. Fu, MD,
  • Soad L. Fuentes-Alabi, MD, MPH,
  • Juan L. Garcia, MSc,
  • David García Aldana, MD,
  • Henry N. Garcia Pacheco, MD,
  • Jennifer A. Geel, MBChB, MMed,
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  • Aaron S. Gold, OD,
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  • Glen A. Gole, MD, FRANZCO,
  • Nir Gomel, MD,
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  • Graciela Gonzalez Perez, MD,
  • Liudmira González-Rodríguez, MD,
  • Malka Gorfine, PhD,
  • Jaime Graells, MD,
  • Pernille A. Gregersen, MD,
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  • Koffi M. Guedenon, MD,
  • D Sanjeeva Gunasekera, MD,
  • Ahmet K. Gündüz, MD,
  • Himika Gupta, MD,
  • Sanjiv Gupta, MS,
  • Vineeta Gupta, MD,
  • Theodora Hadjistilianou, MD,
  • Patrick Hamel, MD,
  • Syed A. Hamid, FCPS,
  • Norhafizah Hamzah, MSc,
  • Eric D. Hansen, MD,
  • J William Harbour, MD,
  • M. Elizabeth Hartnett, MD,
  • Murat Hasanreisoglu, MD,
  • Sadiq Hassan, MD, FWACS,
  • Shadab Hassan, FRCS, FCPS,
  • Wojciech Hautz, MD,
  • Huda A. Haydar, CHD,
  • Stanislava Hederova, MD,
  • Laila Hessissen, MD,
  • Hoby Lalaina, MD,
  • Suradej Hongeng, MD,
  • Diriba F. Hordofa, MD,
  • G. Baker Hubbard, MD,
  • Marlies Hummlen, MD,
  • Kristina Husakova, MD,
  • Allawi N. Hussein Al-Janabi, MD,
  • Affiong A. Ibanga, MB.BCh, FMCOph,
  • Russo Ida, MD,
  • Vesna R. Ilic, MD,
  • Ziyavuddin Islamov, MD,
  • Vivekaraj Jairaj, DNB,
  • Teyyeb A. Janjua, MD, FCPS, FRCSEd,
  • Irfan Jeeva, FRCOphth,
  • Xunda Ji, MD,
  • Dong Hyun Jo, MD, PhD,
  • Michael M. Jones, MD, PhD, FRANZCO,
  • Theophile B. Amani Kabesha, MD, PhD,
  • Rolande L. Kabore, MD,
  • Swathi Kaliki, MD,
  • Abubakar Kalinaki, MD,
  • Pius Kamsang, MD,
  • Mehmet Kantar, MD,
  • Noa Kapelushnik, MD,
  • Tamar Kardava, PhD,
  • Rejin Kebudi, MD,
  • Jonny Keomisy, MD,
  • Tomas Kepak, MD,
  • Petra Ketteler, MD,
  • Zohora J. Khan, MD,
  • Hussain A. Khaqan, MD,
  • Vikas Khetan, FRCS, FACS,
  • Alireza Khodabande, MD,
  • Zaza Khotenashvili, MD,
  • Jonathan W. Kim, MD,
  • Jeong Hun Kim, MD, PhD,
  • Hayyam Kiratli, MD,
  • Tero T. Kivelä, MD,
  • Artur Klett, MD, PhD,
  • Irem Koç, MD,
  • Jess Elio Kosh Komba Palet, MD,
  • Dalia Krivaitiene, MD, PhD,
  • Mariana Kruger, Mmed Paed, PhD,
  • Kittisak Kulvichit, MD,
  • Mayasari W. Kuntorini, MD,
  • Alice Kyara, BA,
  • Geoffrey C. Lam, FRANZCO,
  • Scott A. Larson, MD,
  • Slobodanka Latinović, MD, PhD,
  • Kelly D. Laurenti, MD,
  • Yotam Lavi, MD, PhD,
  • Alenka Lavric Groznik, MD,
  • Amy A. Leverant, MD,
  • Cairui Li, MD,
  • Kaijun Li, MD,
  • Ben Limbu, MD,
  • Chun-Hsiu Liu, MD,
  • Quah Boon Long, FRCS (Ed), MMed ( Ophth), FAMS,
  • Juan P. López, MD,
  • Robert M. Lukamba, MD,
  • Sandra Luna-Fineman, MD,
  • Delfitri Lutfi, MD,
  • Lesia Lysytsia, MD,
  • Shiran Madgar, MD,
  • George N. Magrath, MD,
  • Amita Mahajan, MD,
  • Puja Maitra, MD,
  • Erika Maka, MD,
  • Emil K. Makimbetov, MD,
  • Azza M.Y. Maktabi, MD,
  • Carlos Maldonado, MD,
  • Ashwin Mallipatna, MD,
  • Rebecca Manudhane, MD,
  • Lyazat Manzhuova, MD,
  • Nieves Martín Begue, MD, PhD,
  • Sidra Masud, MBBS,
  • Ibrahim O. Matende, MD, M. Med (Oph),
  • Clarissa C.D.S. Mattosinho, MD,
  • Marchelo Matua, BAPH,
  • Ismail Mayet, MD,
  • Freddy B. Mbumba, MD, MMed Paed,
  • John D. McKenzie, MD,
  • Azim Mehrvar, MD,
  • Aemero A. Mengesha, MD,
  • Vikas Menon, MD,
  • Gary John V.D.D. Mercado, MD,
  • Marilyn B. Mets, MD,
  • Edoardo Midena, MD, PhD,
  • Audra Miller, MD,
  • Divyansh K.C. Mishra, DNB,
  • Furahini G. Mndeme, MD,
  • Ahmed A. Mohamedani, FRCPath,
  • Mona T. Mohammad, MD, FRCS,
  • Annette C. Moll, MD, PhD,
  • Margarita M. Montero, MD,
  • Claude Moreira, MD, PhD,
  • Prithvi Mruthyunjaya, MD, MHS,
  • Mchikirwa S. Msina, MMed Ophth,
  • Gerald Msukwa, MMed Ophth,
  • Sangeeta S. Mudaliar, DNB Pediatric,
  • Hassan Muhammad, MD,
  • Kangwa I. Muma, MMed Ophth, FCOphth,
  • Francis L. Munier, MD,
  • Timothy G. Murray, MD, MBA,
  • Kareem O. Musa, FWACS, FMCOphth, FICO,
  • Asma Mushtaq, MD,
  • Anne A. Musika, MD,
  • Hamzah Mustak, MD,
  • Tajudeen Mustapha, MBBS, FWACS,
  • Okwen M. Muyen, MD,
  • Khumo H. Myezo, Msc,
  • Gita Naidu, MMed Paed, PhD,
  • Natasha Naidu, MBCHB, FCS Ophthalmol,
  • Akshay Gopinathan Nair, MD,
  • Sundaram Natarajan, FRCS,
  • Larisa Naumenko, MD, PhD,
  • Paule Aïda Ndoye Roth, MD PhD,
  • Yetty M. Nency, MD,
  • Vladimir Neroev, MD, PhD,
  • Yvonne Ng, MBChB ( Auckland) , FRANZCO,
  • Marina Nikitovic, MD, PhD,
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  • Henry E. Nkumbe, MD,
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  • Kalle Nummi, MD,
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Journal volume & issue
Vol. 5, no. 2
p. 100637

Abstract

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Purpose: To study the treatment and outcomes of children with retinoblastoma (RB) with extraocular tumor extension (RB-EOE) and compare them with RB without extraocular tumor extension (RB-w/o-EOE). Design: Multicenter intercontinental collaborative prospective study from 2017 to 2020. RB-EOE cases included those with overt orbital tumor extension in treatment-naive patients. Cases with microscopic orbital extension detected postenucleation were excluded from the study. Participants: A total of 319 children with RB-EOE and 3116 children with RB-w/o-EOE. Intervention: Chemotherapy, enucleation, exenteration, radiotherapy. Main Outcome Measures: Systemic metastasis and death. Results: Of the 3435 RB patients included in this study, 309 (9%) were from low-income countries (LIC), 1448 (42%) from lower-middle income, 1012 (29%) from upper-middle income, and 666 (19%) patients from high-income countries. There was an inverse relationship between the percentage of RB-EOE and national income level, with 96 (31%) patients from LIC, 197 (6%) lower-middle income, 20 (2%) upper-middle income, and 6 (1%) patients from high-income countries (P = 0.0001). The outcomes were statistically significant for RB-EOE compared with RB-w/o-EOE: systemic metastasis (32% vs. 4% respectively; P = 0.0001) and metastasis-related death (63% vs. 6% respectively; P = 0.0001). Multimodal treatment was the most common form of treatment (n = 177; 54%) for RB-EOE, with most cases undergoing a combination of intravenous chemotherapy and enucleation (n = 97; 30%). Adjuvant external beam radiotherapy (EBRT) after surgery (enucleation/orbital exenteration) was given in only 68 (21%) cases. Kaplan–Meier analysis for systemic metastasis and metastasis-related death in RB-EOE was 28% and 57% at 1 year, 29% and 60% at 2 years, and 29% and 61% at 3 years, respectively. Cox regression analysis revealed that the risk of death from RB-EOE was greater in patients aged >4 years than <2 years (hazard ratio, 2.912; P < 0.001) and for unimodal (surgery or intravenous chemotherapy) and bimodal (surgery and intravenous chemotherapy) treatment than trimodal treatment (surgery, intravenous chemotherapy, and EBRT) (hazard ratio, 2.023; P = 0.004 and hazard ratio, 1.819; P = 0.027, respectively). Conclusions: Retinoblastoma with extraocular tumor extension is associated with a higher risk of metastasis and death. Patients with RB-EOE are likely to benefit from trimodal treatment (intravenous chemotherapy, surgery, and EBRT) rather than treatment protocols excluding EBRT. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Keywords