Global Retinoblastoma Presentation and Analysis by National Income Level
Authors: Ido Didi Fabian, Elhassan Abdallah, Shehu U. Abdullahi, Rula A. Abdulqader, Sahadatou Adamou Boubacar, Dupe S. Ademola-Popoola, Adedayo Adio, Armin R. Afshar, Priyanka Aggarwal, Ada E. Aghaji, Alia Ahmad, Marliyanti N. R. Akib, Lamis Al Harby, Mouroge H. Al Ani, Aygun Alakbarova, Silvia Alarcón Portabella, Safaa A. F. Al-Badri, Ana Patricia A. Alcasabas, Saad A. Al-Dahmash, Amanda Alejos, Ernesto Alemany-Rubio, Amadou I. Alfa Bio, Yvania Alfonso Carreras, Christiane Al-Haddad, Hamoud H. Y. Al-Hussaini, Amany M. Ali, Donjeta B. Alia, Mazin F. Al-Jadiry, Usama Al-Jumaily, Hind M. Alkatan, Charlotta All-Eriksson, Ali A. R. M. Al-Mafrachi, Argentino A. Almeida, Khalifa M. Alsawidi, Athar A. S. M. Al-Shaheen, Entissar H. Al-Shammary, Primawita O. Amiruddin, Romanzo Antonino, Nicholas J. Astbury, Hatice T. Atalay, La-ongsri Atchaneeyasakul, Rose Atsiaya, Taweevat Attaseth, Than H. Aung, Silvia Ayala, Baglan Baizakova, Julia Balaguer, Ruhengiz Balayeva, Walentyna Balwierz, Honorio Barranco, Covadonga Bascaran, Maja Beck Popovic, Raquel Benavides, Sarra Benmiloud, Nissrine Bennani Guebessi, Rokia C. Berete, Jesse L. Berry, Anirban Bhaduri, Sunil Bhat, Shelley J. Biddulph, Eva M. Biewald, Nadia Bobrova, Marianna Boehme, H.C. Boldt, Maria Teresa B. C. Bonanomi, Norbert Bornfeld, Gabrielle C. Bouda, Hédi Bouguila, Amaria Boumedane, Rachel C. Brennan, Bénédicte G. Brichard, Jassada Buaboonnam, Patricia Calderón-Sotelo, Doris A. Calle Jara, Jayne E. Camuglia, Miriam R. Cano, Michael Capra, Nathalie Cassoux, Guilherme Castela, Luis Castillo, Jaume Català-Mora, Guillermo L. Chantada, Shabana Chaudhry, Sonal S. Chaugule, Argudit Chauhan, Bhavna Chawla, Violeta S. Chernodrinska, Faraja S. Chiwanga, Tsengelmaa Chuluunbat, Krzysztof Cieslik, Ruellyn L. Cockcroft, Codruta Comsa, Zelia M. Correa, Maria G. Correa Llano, Timothy W. Corson, Kristin E. Cowan-Lyn, Monika Csóka, Xuehao Cui, Isac V. Da Gama, Wantanee Dangboon, Anirban Das, Sima Das, Jacquelyn M. Davanzo, Alan Davidson, Patrick De Potter, Karina Q. Delgado, Hakan Demirci, Laurence Desjardins, Rosdali Y. Diaz Coronado, Helen Dimaras, Andrew J. Dodgshun, Craig Donaldson, Carla R. Donato Macedo, Monica D. Dragomir, Yi Du, Magritha Du Bruyn, Kemala S. Edison, I. Wayan Eka Sutyawan, Asmaa El Kettani, Amal M. Elbahi, James E. Elder, Dina Elgalaly, Alaa M. Elhaddad, Moawia M. Ali Elhassan, Mahmoud M. Elzembely, Vera A. Essuman, Ted Grimbert A. Evina, Zehra Fadoo, Adriana C. Fandiño, Mohammad Faranoush, Oluyemi Fasina, Delia D. P. G. Fernández, Ana Fernández-Teijeiro, Allen Foster, Shahar Frenkel, Ligia D. Fu, Soad L. Fuentes-Alabi, Brenda L. Gallie, Moira Gandiwa, Juan L. Garcia, David García Aldana, Pascale Y. Gassant, Jennifer A. Geel, Fariba Ghassemi, Ana V. Girón, Zelalem Gizachew, Marco A. Goenz, Aaron S. Gold, Maya Goldberg-Lavid, Glen A. Gole, Nir Gomel, Efren Gonzalez, Graciela Gonzalez Perez, Liudmira González-Rodríguez, Henry N. Garcia Pacheco, Jaime Graells, Liz Green, Pernille A. Gregersen, Nathalia D. A. K. Grigorovski, Koffi M. Guedenon, D. Sanjeeva Gunasekera, Ahmet K. Gündüz, Himika Gupta, Sanjiv Gupta, Theodora Hadjistilianou, Patrick Hamel, Syed A. Hamid, Norhafizah Hamzah, Eric D. Hansen, J. William Harbour, M. Elizabeth Hartnett, Murat Hasanreisoglu, Sadiq Hassan, Shadab Hassan, Stanislava Hederova, Jose Hernandez, Lorelay Marie Carcamo Hernandez, Laila Hessissen, Diriba F. Hordofa, Laura C. Huang, G. B. Hubbard, Marlies Hummlen, Kristina Husakova, Allawi N. Hussein Al-Janabi, Russo Ida, Vesna R. Ilic, Vivekaraj Jairaj, Irfan Jeeva, Helen Jenkinson, Xunda Ji, Dong Hyun Jo, Kenneth P. Johnson, William J. Johnson, Michael M. Jones, Theophile B. Amani Kabesha, Rolande L. Kabore, Swathi Kaliki, Abubakar Kalinaki, Mehmet Kantar, Ling-Yuh Kao, Tamar Kardava, Rejin Kebudi, Tomas Kepak, Naama Keren-Froim, Zohora J. Khan, Hussain A. Khaqan, Phara Khauv, Wajiha J. Kheir, Vikas Khetan, Alireza Khodabande, Zaza Khotenashvili, Jonathan W. Kim, Jeong Hun Kim, Hayyam Kiratli, Tero T. Kivelä, Artur Klett, Jess Elio Kosh Komba Palet, Dalia Krivaitiene, Mariana Kruger, Kittisak Kulvichit, Mayasari W. Kuntorini, Alice Kyara, Eva S. Lachmann, Carol P. S. Lam, Geoffrey C. Lam, Scott A. Larson, Slobodanka Latinovic, Kelly D. Laurenti, Bao Han A. Le, Karin Lecuona, Amy A. Leverant, Cairui Li, Ben Limbu, Quah Boon Long, Juan P. López, Robert M. Lukamba, Livia Lumbroso, Sandra Luna-Fineman, Delfitri Lutfi, Lesia Lysytsia, George N. Magrath, Amita Mahajan, Abdul Rahim Majeed, Erika Maka, Mayuri Makan, Emil K. Makimbetov, Chatonda Manda, Nieves Martín Begue, Lauren Mason, John O. Mason, Ibrahim O. Matende, Miguel Materin, Clarissa C. D. S. Mattosinho, Marchelo Matua, Ismail Mayet, Freddy B. Mbumba, John D. McKenzie, Aurora Medina-Sanson, Azim Mehrvar, Aemero A. Mengesha, Vikas Menon, Gary John V. D. Mercado, Marilyn B. Mets, Edoardo Midena, Divyansh K. C. Mishra, Furahini G. Mndeme, Ahmed A. Mohamedani, Mona T. Mohammad, Annette C. Moll, Margarita M. Montero, Rosa A. Morales, Claude Moreira, Prithvi Mruthyunjaya, Mchikirwa S. Msina, Gerald Msukwa, Sangeeta S. Mudaliar, Kangwa I. Muma, Francis L. Munier, Gabriela Murgoi, Timothy G. Murray, Kareem O. Musa, Asma Mushtaq, Hamzah Mustak, Okwen M. Muyen, Gita Naidu, Akshay Gopinathan Nair, Larisa Naumenko, Paule Aïda Ndoye Roth, Yetty M. Nency, Vladimir Neroev, Hang Ngo, Rosa M. Nieves, Marina Nikitovic, Elizabeth D. Nkanga, Henry Nkumbe, Murtuza Nuruddin, Mutale Nyaywa, Ghislaine Obono-Obiang, Ngozi C. Oguego, Andrzej Olechowski, Scott C. N. Oliver, Peter Osei-Bonsu, Diego Ossandon, Manuel A. Paez-Escamilla, Halimah Pagarra, Sally L Painter, Vivian Paintsil, Luisa Paiva, Bikramjit P. Pal, Mahesh Shanmugam Palanivelu, Ruzanna Papyan, Raffaele Parrozzani, Manoj Parulekar, Claudia R. Pascual Morales, Katherine E. Paton, Katarzyna Pawinska-Wasikowska, Jacob Pe'er, Armando Peña, Sanja Peric, Chau T. M. Pham, Remezo Philbert, David A. Plager, Pavel Pochop, Rodrigo A. Polania, Vladimir G. Polyakov, Manca T. Pompe, Jonathan J. Pons, Daphna Prat, Vireak Prom, Ignatius Purwanto, Ali O. Qadir, Seema Qayyum, Jiang Qian, Ardizal Rahman, Salman Rahman, Jamalia Rahmat, Purnima Rajkarnikar, Rajesh Ramanjulu, Aparna Ramasubramanian, Marco A. Ramirez-Ortiz, Léa Raobela, Riffat Rashid, M. Ashwin Reddy, Ehud Reich, Lorna A. Renner, David Reynders, Dahiru Ribadu, Mussagy M. Riheia, Petra Ritter-Sovinz, Duangnate Rojanaporn, Livia Romero, Soma R. Roy, Raya H. Saab, Svetlana Saakyan, Ahmed H Sabhan, Mandeep S. Sagoo, Azza M. A. Said, Rohit Saiju, Beatriz Salas, Sonsoles San Román Pacheco, Gissela L. Sánchez, Phayvanh Sayalith, Trish A. Scanlan, Amy C. Schefler, Judy Schoeman, Ahad Sedaghat, Stefan Seregard, Rachna Seth, Ankoor S. Shah, Shawkat A. Shakoor, Manoj K. Sharma, Sadik T. Sherief, Nandan G. Shetye, Carol L. Shields, Sorath Noorani Siddiqui, Sidi Sidi Cheikh, Sónia Silva, Arun D. Singh, Niharika Singh, Usha Singh, Penny Singha, Rita S. Sitorus, Alison H. Skalet, Hendrian D. Soebagjo, Tetyana Sorochynska, Grace Ssali, Andrew W. Stacey, Sandra E. Staffieri, Erin D. Stahl, Christina Stathopoulos, Branka Stirn Kranjc, David K. Stones, Caron Strahlendorf, Maria Estela Coleoni Suarez, Sadia Sultana, Xiantao Sun, Meryl Sundy, Rosanne Superstein, Eddy Supriyadi, Supawan Surukrattanaskul, Shigenobu Suzuki, Karel Svojgr, Fatoumata Sylla, Gevorg Tamamyan, Deborah Tan, Alketa Tandili, Fanny F. Tarrillo Leiva, Maryam Tashvighi, Bekim Tateshi, Edi S. Tehuteru, Luiz F. Teixeira, Kok Hoi Teh, Tuyisabe Theophile, Helen Toledano, Doan L. Trang, Fousseyni Traoré, Sumalin Trichaiyaporn, Samuray Tuncer, Harba Tyau-Tyau, Ali B. Umar, Emel Unal, Ogul E. Uner, Steen F. Urbak, Tatiana L. Ushakova, Rustam H. Usmanov, Sandra Valeina, Milo van Hoefen Wijsard, Adisai Varadisai, Liliana Vasquez, Leon O. Vaughan, Nevyana V. Veleva-Krasteva, Nishant Verma, Andi A. Victor, Maris Viksnins, Edwin G. Villacís Chafla, Vicktoria Vishnevskia-Dai, Tushar Vora, Antonio E. Wachtel, Werner Wackernagel, Keith Waddell, Patricia D. Wade, Amina H. Wali, Yi-Zhuo Wang, Avery Weiss, Matthew W. Wilson, Amelia D. C. Wime, Atchareeya Wiwatwongwana, Damrong Wiwatwongwana, Charlotte Wolley Dod, Phanthipha Wongwai, Daoman Xiang, Yishuang Xiao, Jason C. Yam, Huasheng Yang, Jenny M. Yanga, Muhammad A Yaqub, Vera A. Yarovaya, Andrey A. Yarovoy, Huijing Ye, Yacoub A. Yousef, Putu Yuliawati, Arturo M. Zapata López, Ekhtelbenina Zein, Chengyue Zhang, Yi Zhang, Junyang Zhao, Xiaoyu Zheng, Katsiaryna Zhilyaeva, Nida Zia, Othman A. O. Ziko, Marcia Zondervan, Richard Bowman
Journal: JAMA Oncology (2020)

Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.