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1. The Global Retinoblastoma Outcome Study: a prospective, cluster-based analysis of 4064 patients from 149 countries

Author

Alia, DB, Tandili, A, Paiva, L, Wime, AD, Chantada, GL, Fandino, AC, Sgroi, M, Papyan, R, Tamamyan, G, Camuglia, JE, Gole, GA, Clark, A, Lam, GC, Elder, JE, McKenzie, JD, Staffieri, SE, Jones, MM, Manudhane, R, Sia, D, Ritter-Sovinz, P, Schwab, C, Balayeva, R, Khan, Z, Nuruddin, M, Roy, SR, Rashid, R, Sultana, S, Shakoor, SA, Naumenko, L, Zhilyaeva, K, Bartoszek, P, Brichard, BG, De Potter, P, Bio, AIA, Salas, B, Coleoni Suarez, ME, Mbumba, FB, Bonanomi, MTBC, Donato Macedo, CR, Grigorovski, NDAK, Mattosinho, CCDS, Teixeira, LF, Oscar, AH, Veleva-Krasteva, NV, Bouda, GC, Kabore, RL, Philbert, R, Evina, TGA, Nkumbe, HE, Kamsang, P, Muyen, OM, Dimaras, H, Mallipatna, A, Hamel, P, Superstein, R, Paton, KE, Strahlendorf, C, Palet, JEKK, Tyau-Tyau, H, Cavieres, I, Lopez, JP, Oporto, J, Ossandon, D, Chen, W, Xiang, D, Du, Y, Li, K, Ji, X, Tang, J, Li, C, Xu, B, Qian, J, Xue, K, Sun, X, Wang, Y-Z, Zhang, Y, Wu, S-Q, Xiao, Y, Yang, H, Ye, H, Polania, RA, Berete, RC, Couitchere, L, Peric, S, Alemany-Rubio, E, Gonzalez-Rodriguez, L, Autrata, R, Kepak, T, Pochop, P, Svojgr, K, Gregersen, PA, Urbak, SF, Montero, MM, Budiongo, A, Yanga, JM, Amani, TBK, Lukamba, RM, Numbi, MN, Calle Jara, DA, Villacis Chafla, EG, Sanchez, GL, Abouelnaga, S, Afifi, MA, Elhaddad, AM, Ali, AM, Elzembely, M, Said, AMA, Ziko, OAO, Fuentes-Alabi, SL, Goenz, MA, Eerme, K, Klett, A, Hordofa, DF, Mengesha, AA, Sherief, ST, Kivela, TT, Nummi, K, Cassoux, N, Desjardins, L, Obono-Obiang, G, Kardava, T, Khotenashvili, Z, Bechrakis, NE, Biewald, EM, Schlueter, S, Ketteler, P, Amankwaa-Frempong, D, Essuman, VA, Paintsil, V, Renner, LA, Alejos, A, Giron, A, Carreras, YA, Fu, LD, Maldonado, C, Wong, ES, Yam, JC, Csoka, M, Maka, E, Aggarwal, P, Gupta, V, Bhaduri, A, Bhattacharyya, A, Das, A, Chawla, B, Das, P, Das, S, Gupta, H, Gupta, S, Verma, N, Kaliki, S, Khetan, V, Maitra, P, Mahajan, A, Menon, V, Mishra, DKC, Palanivelu, MS, Ramanjulu, R, Mudaliar, SS, Nair, AG, Natarajan, S, Seth, R, Singh, U, Bhat, S, Dudeja, G, Tripathy, D, Akib, IMNR, Pagarra, H, Amiruddin, PO, Kuntorini, MW, Armytasari, I, Supriyadi, E, Sutyawan, IWE, Yuliawati, P, Lutfi, D, Soebagjo, HD, Rahman, A, Sitorus, RS, Victor, AA, Tehuteru, ES, Widiarti, W, Nency, YM, Faranoush, M, Mehrvar, A, Tashvighi, M, Sedaghat, A, Ghassemi, F, Khodabande, A, Abdulqader, RA, Al-Shaheen, AASM, Al Ani, MH, Haydar, H, Al-Badri, SAF, Al-Jadiry, MF, Sabhan, AH, Al-Jumaily, U, Al-Mafrachi, AARM, Al-Shammary, EH, Al-Janabi, ANH, Qadir, AO, Capra, M, Blum, S, Gomel, N, Fabian, ID, Goldberg, H, Kapelushnik, N, Madgar, S, Vishnevskia-Dai, V, Frenkel, S, Pe'er, J, Gorfine, M, Refaeli, D, Steinberg, DM, Lavy, Y, Toledano, H, Caspi, S, De Francesco, S, Hadjistilianou, T, Ida, R, Valente, P, Midena, E, Parrozzani, R, Cowan-Lyn, KE, Vaughan, LO, Suzuki, S, Mohammad, MT, Yousef, YA, Manzhuova, L, Atsiaya, R, Matende, IO, Begimkulova, AS, Makimbetov, EK, Keomisy, J, Sayalith, P, Valeina, S, Viksnins, M, Al-Haddad, CE, Saab, RH, Alsawidi, KM, Elbahi, AM, Krivaitiene, D, Tateshi, B, Randrianarisoa, HL, Raobela, L, Msukwa, G, Nyirenda, C, Hamzah, N, Teh, KH, Sylla, F, Traore, F, Cheikh, SS, Zein, E, Perez, GG, Sanchez Orozco, AJ, Ortega-Hernandez, M, Ramirez-Ortiz, MA, Chuluunbat, T, Abdallah, E, Benmiloud, S, El Kettani, A, Hessissen, L, Almeida, AA, Limbu, B, Rajkarnikar, P, Saiju, R, Moll, AC, Wijsard, MVH, Cockcroft, RL, Ng, Y, Dodgshun, AJ, Calderon-Sotelo, P, Abdullahi, SU, Hassan, S, Umar, AB, Abdulrahaman, AA, Wali, AH, Ademola-Popoola, DS, Adio, A, Aghaji, AE, Ezegwui, IR, Akinsete, A, Musa, KO, Fasina, O, Ibanga, A, Nkanga, ED, Mustapha, T, Ribadu, D, Hummelen, M, Ahmad, A, Mushtaq, A, Qayyum, S, Chaudhry, S, Fadoo, Z, Jeeva, I, Masud, S, Hamid, SA, Zia, N, Siddiqui, SN, Janjua, T, Yaqub, MA, Khaqan, HA, Quintero D, K, Yee, R, Jairaj, V, Cano, MR, Fernandez, DDPG, Diaz Coronado, RY, Zapata Lopez, AM, Garcia, JL, Ponce, J, Garcia Pacheco, HN, Pascual Morales, CR, Vasquez Anchaya, JK, Tarrillo Leiva, FF, Alcasabas, APA, Mercado, GJ, Cieslik, K, Hautz, W, Rogowska, A, Castela, G, Silva, S, Jo, DH, Kim, JH, Comsa, C, Dragomir, MD, Neroev, V, Saakyan, S, Polyakov, V, Ushakova, TL, Yarovaya, VA, Yarovoy, AA, Theophile, T, Al Mesfer, S, Maktabi, A, Al-Dahmash, SA, Alkatan, HM, Moreira, C, Roth, PAN, Ilic, VR, Nikitovic, M, Latinovic, S, Quah, B, Tan, D, Hederova, S, Husakova, K, Groznik, AL, Pompe, MT, Davidson, A, Du Bruyn, M, Du Plessis, J, Stones, DK, Geel, JA, Myezo, KH, Kruger, M, Mayet, I, Naidu, G, Naidu, N, Mustak, H, Reynders, D, Wetter, J, Alarcon Portabella, S, Martin-Begue, N, Wolley Dod, C, Balaguer, J, Barranco, H, Catala-Mora, J, Correa Llano, MG, Fernandez-Teijeiro, A, Garcia Aldana, D, Peralta Calvo, J, San Roman Pacheco, S, Gunasekera, DS, Elhassan, MMA, Mohamedani, AA, All-Eriksson, C, Bartuma, K, Popovic, MB, Munier, FL, Liu, C-H, Chiwanga, FS, Kyara, A, Mndeme, FG, Msina, MS, Scanlan, TA, Atchaneeyasakul, L-O, Buaboonnam, J, Dangboon, W, Singha, P, Hongeng, S, Kulvichit, K, Rojanaporn, D, Surukrattanaskul, S, Wangtiraumnuay, N, Wiwatwongwana, A, Wiwatwongwana, D, Wongwai, P, Sharma, MK, Guedenon, KM, Bouguila, H, Atalay, HT, Hasanreisoglu, M, Ataseven, E, Kantar, M, Gunduz, AK, Kebudi, R, Kiratli, H, Koc, I, Tuncer, S, Unal, E, Kalinaki, A, Matua, M, Waddell, K, Musika, AA, Ssali, G, Al Harby, L, Reddy, MA, Astbury, NJ, Bascaran, C, Bowman, R, Burton, MJ, Foster, A, Zondervan, M, Sagoo, MS, Bobrova, N, Sorochynska, T, Lysytsia, L, Castillo, L, Afshar, AR, Berry, JL, Kim, JW, Randhawa, JK, Binkley, E, Boldt, HC, Larson, SA, Brennan, RC, Chandramohan, A, Stacey, AW, Corson, TW, Plager, DA, Davanzo, JM, Singh, AD, Demirci, H, Ericksen, C, Magrath, GN, Gold, AS, Murray, TG, Gonzalez, E, Shah, AS, Hansen, ED, Hartnett, ME, Harbour, JW, Hubbard, GB, Uner, OE, Laurenti, KD, Mets, MB, Leverant, AA, Ramasubramanian, A, Luna-Fineman, S, Miller, A, Skalet, AH, Mruthyunjaya, P, Hassan, M, Oliver, SC, Shields, CL, Yaghy, A, Stahl, ED, Wilson, MW, Villegas, VM, Islamov, Z, Usmanov, RH, Graells, J, Romero, L, Pham, CTM, Trang, DL, Al-Hussaini, HH, Thawaba, ADM, Muma, KIM, Nyaywa, M, Alia, DB, Tandili, A, Paiva, L, Wime, AD, Chantada, GL, Fandino, AC, Sgroi, M, Papyan, R, Tamamyan, G, Camuglia, JE, Gole, GA, Clark, A, Lam, GC, Elder, JE, McKenzie, JD, Staffieri, SE, Jones, MM, Manudhane, R, Sia, D, Ritter-Sovinz, P, Schwab, C, Balayeva, R, Khan, Z, Nuruddin, M, Roy, SR, Rashid, R, Sultana, S, Shakoor, SA, Naumenko, L, Zhilyaeva, K, Bartoszek, P, Brichard, BG, De Potter, P, Bio, AIA, Salas, B, Coleoni Suarez, ME, Mbumba, FB, Bonanomi, MTBC, Donato Macedo, CR, Grigorovski, NDAK, Mattosinho, CCDS, Teixeira, LF, Oscar, AH, Veleva-Krasteva, NV, Bouda, GC, Kabore, RL, Philbert, R, Evina, TGA, Nkumbe, HE, Kamsang, P, Muyen, OM, Dimaras, H, Mallipatna, A, Hamel, P, Superstein, R, Paton, KE, Strahlendorf, C, Palet, JEKK, Tyau-Tyau, H, Cavieres, I, Lopez, JP, Oporto, J, Ossandon, D, Chen, W, Xiang, D, Du, Y, Li, K, Ji, X, Tang, J, Li, C, Xu, B, Qian, J, Xue, K, Sun, X, Wang, Y-Z, Zhang, Y, Wu, S-Q, Xiao, Y, Yang, H, Ye, H, Polania, RA, Berete, RC, Couitchere, L, Peric, S, Alemany-Rubio, E, Gonzalez-Rodriguez, L, Autrata, R, Kepak, T, Pochop, P, Svojgr, K, Gregersen, PA, Urbak, SF, Montero, MM, Budiongo, A, Yanga, JM, Amani, TBK, Lukamba, RM, Numbi, MN, Calle Jara, DA, Villacis Chafla, EG, Sanchez, GL, Abouelnaga, S, Afifi, MA, Elhaddad, AM, Ali, AM, Elzembely, M, Said, AMA, Ziko, OAO, Fuentes-Alabi, SL, Goenz, MA, Eerme, K, Klett, A, Hordofa, DF, Mengesha, AA, Sherief, ST, Kivela, TT, Nummi, K, Cassoux, N, Desjardins, L, Obono-Obiang, G, Kardava, T, Khotenashvili, Z, Bechrakis, NE, Biewald, EM, Schlueter, S, Ketteler, P, Amankwaa-Frempong, D, Essuman, VA, Paintsil, V, Renner, LA, Alejos, A, Giron, A, Carreras, YA, Fu, LD, Maldonado, C, Wong, ES, Yam, JC, Csoka, M, Maka, E, Aggarwal, P, Gupta, V, Bhaduri, A, Bhattacharyya, A, Das, A, Chawla, B, Das, P, Das, S, Gupta, H, Gupta, S, Verma, N, Kaliki, S, Khetan, V, Maitra, P, Mahajan, A, Menon, V, Mishra, DKC, Palanivelu, MS, Ramanjulu, R, Mudaliar, SS, Nair, AG, Natarajan, S, Seth, R, Singh, U, Bhat, S, Dudeja, G, Tripathy, D, Akib, IMNR, Pagarra, H, Amiruddin, PO, Kuntorini, MW, Armytasari, I, Supriyadi, E, Sutyawan, IWE, Yuliawati, P, Lutfi, D, Soebagjo, HD, Rahman, A, Sitorus, RS, Victor, AA, Tehuteru, ES, Widiarti, W, Nency, YM, Faranoush, M, Mehrvar, A, Tashvighi, M, Sedaghat, A, Ghassemi, F, Khodabande, A, Abdulqader, RA, Al-Shaheen, AASM, Al Ani, MH, Haydar, H, Al-Badri, SAF, Al-Jadiry, MF, Sabhan, AH, Al-Jumaily, U, Al-Mafrachi, AARM, Al-Shammary, EH, Al-Janabi, ANH, Qadir, AO, Capra, M, Blum, S, Gomel, N, Fabian, ID, Goldberg, H, Kapelushnik, N, Madgar, S, Vishnevskia-Dai, V, Frenkel, S, Pe'er, J, Gorfine, M, Refaeli, D, Steinberg, DM, Lavy, Y, Toledano, H, Caspi, S, De Francesco, S, Hadjistilianou, T, Ida, R, Valente, P, Midena, E, Parrozzani, R, Cowan-Lyn, KE, Vaughan, LO, Suzuki, S, Mohammad, MT, Yousef, YA, Manzhuova, L, Atsiaya, R, Matende, IO, Begimkulova, AS, Makimbetov, EK, Keomisy, J, Sayalith, P, Valeina, S, Viksnins, M, Al-Haddad, CE, Saab, RH, Alsawidi, KM, Elbahi, AM, Krivaitiene, D, Tateshi, B, Randrianarisoa, HL, Raobela, L, Msukwa, G, Nyirenda, C, Hamzah, N, Teh, KH, Sylla, F, Traore, F, Cheikh, SS, Zein, E, Perez, GG, Sanchez Orozco, AJ, Ortega-Hernandez, M, Ramirez-Ortiz, MA, Chuluunbat, T, Abdallah, E, Benmiloud, S, El Kettani, A, Hessissen, L, Almeida, AA, Limbu, B, Rajkarnikar, P, Saiju, R, Moll, AC, Wijsard, MVH, Cockcroft, RL, Ng, Y, Dodgshun, AJ, Calderon-Sotelo, P, Abdullahi, SU, Hassan, S, Umar, AB, Abdulrahaman, AA, Wali, AH, Ademola-Popoola, DS, Adio, A, Aghaji, AE, Ezegwui, IR, Akinsete, A, Musa, KO, Fasina, O, Ibanga, A, Nkanga, ED, Mustapha, T, Ribadu, D, Hummelen, M, Ahmad, A, Mushtaq, A, Qayyum, S, Chaudhry, S, Fadoo, Z, Jeeva, I, Masud, S, Hamid, SA, Zia, N, Siddiqui, SN, Janjua, T, Yaqub, MA, Khaqan, HA, Quintero D, K, Yee, R, Jairaj, V, Cano, MR, Fernandez, DDPG, Diaz Coronado, RY, Zapata Lopez, AM, Garcia, JL, Ponce, J, Garcia Pacheco, HN, Pascual Morales, CR, Vasquez Anchaya, JK, Tarrillo Leiva, FF, Alcasabas, APA, Mercado, GJ, Cieslik, K, Hautz, W, Rogowska, A, Castela, G, Silva, S, Jo, DH, Kim, JH, Comsa, C, Dragomir, MD, Neroev, V, Saakyan, S, Polyakov, V, Ushakova, TL, Yarovaya, VA, Yarovoy, AA, Theophile, T, Al Mesfer, S, Maktabi, A, Al-Dahmash, SA, Alkatan, HM, Moreira, C, Roth, PAN, Ilic, VR, Nikitovic, M, Latinovic, S, Quah, B, Tan, D, Hederova, S, Husakova, K, Groznik, AL, Pompe, MT, Davidson, A, Du Bruyn, M, Du Plessis, J, Stones, DK, Geel, JA, Myezo, KH, Kruger, M, Mayet, I, Naidu, G, Naidu, N, Mustak, H, Reynders, D, Wetter, J, Alarcon Portabella, S, Martin-Begue, N, Wolley Dod, C, Balaguer, J, Barranco, H, Catala-Mora, J, Correa Llano, MG, Fernandez-Teijeiro, A, Garcia Aldana, D, Peralta Calvo, J, San Roman Pacheco, S, Gunasekera, DS, Elhassan, MMA, Mohamedani, AA, All-Eriksson, C, Bartuma, K, Popovic, MB, Munier, FL, Liu, C-H, Chiwanga, FS, Kyara, A, Mndeme, FG, Msina, MS, Scanlan, TA, Atchaneeyasakul, L-O, Buaboonnam, J, Dangboon, W, Singha, P, Hongeng, S, Kulvichit, K, Rojanaporn, D, Surukrattanaskul, S, Wangtiraumnuay, N, Wiwatwongwana, A, Wiwatwongwana, D, Wongwai, P, Sharma, MK, Guedenon, KM, Bouguila, H, Atalay, HT, Hasanreisoglu, M, Ataseven, E, Kantar, M, Gunduz, AK, Kebudi, R, Kiratli, H, Koc, I, Tuncer, S, Unal, E, Kalinaki, A, Matua, M, Waddell, K, Musika, AA, Ssali, G, Al Harby, L, Reddy, MA, Astbury, NJ, Bascaran, C, Bowman, R, Burton, MJ, Foster, A, Zondervan, M, Sagoo, MS, Bobrova, N, Sorochynska, T, Lysytsia, L, Castillo, L, Afshar, AR, Berry, JL, Kim, JW, Randhawa, JK, Binkley, E, Boldt, HC, Larson, SA, Brennan, RC, Chandramohan, A, Stacey, AW, Corson, TW, Plager, DA, Davanzo, JM, Singh, AD, Demirci, H, Ericksen, C, Magrath, GN, Gold, AS, Murray, TG, Gonzalez, E, Shah, AS, Hansen, ED, Hartnett, ME, Harbour, JW, Hubbard, GB, Uner, OE, Laurenti, KD, Mets, MB, Leverant, AA, Ramasubramanian, A, Luna-Fineman, S, Miller, A, Skalet, AH, Mruthyunjaya, P, Hassan, M, Oliver, SC, Shields, CL, Yaghy, A, Stahl, ED, Wilson, MW, Villegas, VM, Islamov, Z, Usmanov, RH, Graells, J, Romero, L, Pham, CTM, Trang, DL, Al-Hussaini, HH, Thawaba, ADM, Muma, KIM, and Nyaywa, M

Abstract

BACKGROUND: Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS: We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS: The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0-36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8-100·0) for children from high-income countries, 91·2% (89·5-93·0) for children from upper-middle-income countries, 80·3% (78·3-82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76-50·00), cT4 advanced tumour compared to

Published
2022

2. Global Retinoblastoma Presentation and Analysis by National Income Level

Author

Fabian, ID, Abdallah, E, Abdullahi, SU, Abdulqader, RA, Boubacar, SA, Ademola-Popoola, DS, Adio, A, Afshar, AR, Aggarwal, P, Aghaji, AE, Ahmad, A, Akib, MNR, Al Harby, L, Al Ani, MH, Alakbarova, A, Portabella, SA, Al-Badri, SAF, Alcasabas, APA, Al-Dahmash, SA, Alejos, A, Alemany-Rubio, E, Bio, AIA, Carreras, YA, Al-Haddad, C, Al-Hussaini, HHY, Ali, AM, Alia, DB, Al-Jadiry, MF, Al-Jumaly, U, Alkatan, HM, All-Eriksson, C, Al-Mafrachi, AARM, Almeida, AA, Alsawidi, KM, Al-Shaheen, AASM, Al-Shammary, EH, Amiruddin, PO, Antonino, R, Astbury, NJ, Atalay, HT, Atchaneeyasakul, L-O, Atsiaya, R, Attaseth, T, Aung, TH, Ayala, S, Baizakova, B, Balaguer, J, Balayeva, R, Balwierz, W, Barranco, H, Bascaran, C, Popovic, MB, Benavides, R, Benmiloud, S, Guebessi, NB, Berete, RC, Berry, JL, Bhaduri, A, Bhat, S, Biddulph, SJ, Biewald, EM, Bobrova, N, Boehme, M, Boldt, HC, Bonanomi, MTBC, Bornfeld, N, Bouda, GC, Bouguila, H, Boumedane, A, Brennan, RC, Brichard, BG, Buaboonnam, J, Calderon-Sotelo, P, Calle Jara, DA, Camuglia, JE, Cano, MR, Capra, M, Cassoux, N, Castela, G, Castillo, L, Catala-Mora, J, Chantada, GL, Chaudhry, S, Chaugule, SS, Chauhan, A, Chawla, B, Chernodrinska, VS, Chiwanga, FS, Chuluunbat, T, Cieslik, K, Cockcroft, RL, Comsa, C, Correa, ZM, Correa Llano, MG, Corson, TW, Cowan-Lyn, KE, Csoka, M, Cui, X, Da Gama, I, Dangboon, W, Das, A, Das, S, Davanzo, JM, Davidson, A, De Potter, P, Delgado, KQ, Demirci, H, Desjardins, L, Diaz Coronado, RY, Dimaras, H, Dodgshun, AJ, Donaldson, C, Donato Macedo, CR, Dragomir, MD, Du, Y, Du Bruyn, M, Edison, KS, Sutyawan, IWE, El Kettani, A, Elbahi, AM, Elder, JE, Elgalaly, D, Elhaddad, AM, Elhassan, MMA, Elzembely, MM, Essuman, VA, Evina, TGA, Fadoo, Z, Fandino, AC, Faranoush, M, Fasina, O, Fernandez, DDPG, Fernandez-Teijeiro, A, Foster, A, Frenkel, S, Fu, LD, Fuentes-Alabi, SL, Gallie, BL, Gandiwa, M, Garcia, JL, Garcia Aldana, D, Gassant, PY, Geel, JA, Ghassemi, F, Giron, A, Gizachew, Z, Goenz, MA, Gold, AS, Goldberg-Lavid, M, Gole, GA, Gomel, N, Gonzalez, E, Gonzalez Perez, G, Gonzalez-Rodriguez, L, Garcia Pacheco, HN, Graells, J, Green, L, Gregersen, PA, Grigorovski, NDAK, Guedenon, KM, Gunasekera, DS, Gunduz, AK, Gupta, H, Gupta, S, Hadjistilianou, T, Hamel, P, Hamid, SA, Hamzah, N, Hansen, ED, Harbour, JW, Hartnett, ME, Hasanreisoglu, M, Hassan, S, Hederova, S, Hernandez, J, Carcamo Hernandez, LM, Hessissen, L, Hordofa, DF, Huang, LC, Hubbard, GB, Hummlen, M, Husakova, K, Al-Janabi, ANH, Ida, R, Ilic, VR, Jairaj, V, Jeeva, I, Jenkinson, H, Ji, X, Jo, DH, Johnson, KP, Johnson, WJ, Jones, MM, Kabesha, TBA, Kabore, RL, Kaliki, S, Kalinaki, A, Kantar, M, Kao, L-Y, Kardava, T, Kebudi, R, Kepak, T, Keren-Froim, N, Khan, ZJ, Khaqan, HA, Khauv, P, Kheir, WJ, Khetan, V, Khodabande, A, Khotenashvili, Z, Kim, JW, Kim, JH, Kiratli, H, Kivela, TT, Klett, A, Palet, JEKK, Krivaitiene, D, Kruger, M, Kulvichit, K, Kuntorini, MW, Kyara, A, Lachmann, ES, Lam, CPS, Lam, GC, Larson, SA, Latinovic, S, Laurenti, KD, Le, BHA, Lecuona, K, Leverant, AA, Li, C, Limbu, B, Quah, BL, Lopez, JP, Lukamba, RM, Lumbroso, L, Luna-Fineman, S, Lutfi, D, Lysytsia, L, Magrath, GN, Mahajan, A, Majeed, AR, Maka, E, Makan, M, Makimbetov, EK, Manda, C, Martin Begue, N, Mason, L, Mason, JO, Matende, IO, Materin, M, Mattosinho, CCDS, Matua, M, Mayet, I, Mbumba, FB, McKenzie, JD, Medina-Sanson, A, Mehrvar, A, Mengesha, AA, Menon, V, Mercado, GJVD, Mets, MB, Midena, E, Mishra, DKC, Mndeme, FG, Mohamedani, AA, Mohammad, MT, Moll, AC, Montero, MM, Morales, RA, Moreira, C, Mruthyunjaya, P, Msina, MS, Msukwa, G, Mudaliar, SS, Muma, K, Munier, FL, Murgoi, G, Murray, TG, Musa, KO, Mushtaq, A, Mustak, H, Muyen, OM, Naidu, G, Nair, AG, Naumenko, L, Roth, PAN, Nency, YM, Neroev, V, Ngo, H, Nieves, RM, Nikitovic, M, Nkanga, ED, Nkumbe, H, Nuruddin, M, Nyaywa, M, Obono-Obiang, G, Oguego, NC, Olechowski, A, Oliver, SCN, Osei-Bonsu, P, Ossandon, D, Paez-Escamilla, MA, Pagarra, H, Painter, SL, Paintsil, V, Paiva, L, Pal, BP, Palanivelu, MS, Papyan, R, Parrozzani, R, Parulekar, M, Morales, CRP, Paton, KE, Pawinska-Wasikowska, K, Pe'er, J, Pena, A, Peric, S, Pham, CTM, Philbert, R, Plager, DA, Pochop, P, Polania, RA, Polyakov, VG, Pompe, MT, Pons, JJ, Prat, D, Prom, V, Purwanto, I, Qadir, AO, Qayyum, S, Qian, J, Rahman, A, Rahman, S, Rahmat, J, Rajkarnikar, P, Ramanjulu, R, Ramasubramanian, A, Ramirez-Ortiz, MA, Raobela, L, Rashid, R, Reddy, MA, Reich, E, Renner, LA, Reynders, D, Ribadu, D, Riheia, MM, Ritter-Sovinz, P, Rojanaporn, D, Romero, L, Roy, SR, Saab, RH, Saakyan, S, Sabhan, AH, Sagoo, MS, Said, AMA, Saiju, R, Salas, B, San Roman Pacheco, S, Sanchez, GL, Sayalith, P, Scanlan, TA, Schefler, AC, Schoeman, J, Sedaghat, A, Seregard, S, Seth, R, Shah, AS, Shakoor, SA, Sharma, MK, Sherief, ST, Shetye, NG, Shields, CL, Siddiqui, SN, Cheikh, SS, Silva, S, Singh, AD, Singh, N, Singh, U, Singha, P, Sitorus, RS, Skalet, AH, Soebagjo, HD, Sorochynska, T, Ssali, G, Stacey, AW, Staffieri, SE, Stahl, ED, Stathopoulos, C, Kranjc, BS, Stones, DK, Strahlendorf, C, Suarez, MEC, Sultana, S, Sun, X, Sundy, M, Superstein, R, Supriyadi, E, Surukrattanaskul, S, Suzuki, S, Svojgr, K, Sylla, F, Tamamyan, G, Tan, D, Tandili, A, Tarrillo Leiva, FF, Tashvighi, M, Tateshi, B, Tehuteru, ES, Teixeira, LF, Teh, KH, Theophile, T, Toledano, H, Trang, DL, Traore, F, Trichaiyaporn, S, Tuncer, S, Tyau-Tyau, H, Umar, AB, Unal, E, Uner, OE, Urbak, SF, Ushakova, TL, Usmanov, RH, Valeina, S, Wijsard, MVH, Varadisai, A, Vasquez, L, Vaughan, LO, Veleva-Krasteva, NV, Verma, N, Victor, AA, Viksnins, M, Villacos Chafla, EG, Vishnevskia-Dai, V, Vora, T, Wachtel, AE, Wackernagel, W, Waddell, K, Wade, PD, Wali, AH, Wang, Y-Z, Weiss, A, Wilson, MW, Wime, ADC, Wiwatwongwana, A, Wiwatwongwana, D, Dod, CW, Wongwai, P, Xiang, D, Xiao, Y, Yam, JC, Yang, H, Yanga, JM, Yaqub, MA, Yarovaya, VA, Yarovoy, AA, Ye, H, Yousef, YA, Yuliawati, P, Zapata Lopez, AM, Zein, E, Zhang, C, Zhang, Y, Zhao, J, Zheng, X, Zhilyaeva, K, Zia, N, Ziko, OAO, Zondervan, M, Bowman, R, Fabian, ID, Abdallah, E, Abdullahi, SU, Abdulqader, RA, Boubacar, SA, Ademola-Popoola, DS, Adio, A, Afshar, AR, Aggarwal, P, Aghaji, AE, Ahmad, A, Akib, MNR, Al Harby, L, Al Ani, MH, Alakbarova, A, Portabella, SA, Al-Badri, SAF, Alcasabas, APA, Al-Dahmash, SA, Alejos, A, Alemany-Rubio, E, Bio, AIA, Carreras, YA, Al-Haddad, C, Al-Hussaini, HHY, Ali, AM, Alia, DB, Al-Jadiry, MF, Al-Jumaly, U, Alkatan, HM, All-Eriksson, C, Al-Mafrachi, AARM, Almeida, AA, Alsawidi, KM, Al-Shaheen, AASM, Al-Shammary, EH, Amiruddin, PO, Antonino, R, Astbury, NJ, Atalay, HT, Atchaneeyasakul, L-O, Atsiaya, R, Attaseth, T, Aung, TH, Ayala, S, Baizakova, B, Balaguer, J, Balayeva, R, Balwierz, W, Barranco, H, Bascaran, C, Popovic, MB, Benavides, R, Benmiloud, S, Guebessi, NB, Berete, RC, Berry, JL, Bhaduri, A, Bhat, S, Biddulph, SJ, Biewald, EM, Bobrova, N, Boehme, M, Boldt, HC, Bonanomi, MTBC, Bornfeld, N, Bouda, GC, Bouguila, H, Boumedane, A, Brennan, RC, Brichard, BG, Buaboonnam, J, Calderon-Sotelo, P, Calle Jara, DA, Camuglia, JE, Cano, MR, Capra, M, Cassoux, N, Castela, G, Castillo, L, Catala-Mora, J, Chantada, GL, Chaudhry, S, Chaugule, SS, Chauhan, A, Chawla, B, Chernodrinska, VS, Chiwanga, FS, Chuluunbat, T, Cieslik, K, Cockcroft, RL, Comsa, C, Correa, ZM, Correa Llano, MG, Corson, TW, Cowan-Lyn, KE, Csoka, M, Cui, X, Da Gama, I, Dangboon, W, Das, A, Das, S, Davanzo, JM, Davidson, A, De Potter, P, Delgado, KQ, Demirci, H, Desjardins, L, Diaz Coronado, RY, Dimaras, H, Dodgshun, AJ, Donaldson, C, Donato Macedo, CR, Dragomir, MD, Du, Y, Du Bruyn, M, Edison, KS, Sutyawan, IWE, El Kettani, A, Elbahi, AM, Elder, JE, Elgalaly, D, Elhaddad, AM, Elhassan, MMA, Elzembely, MM, Essuman, VA, Evina, TGA, Fadoo, Z, Fandino, AC, Faranoush, M, Fasina, O, Fernandez, DDPG, Fernandez-Teijeiro, A, Foster, A, Frenkel, S, Fu, LD, Fuentes-Alabi, SL, Gallie, BL, Gandiwa, M, Garcia, JL, Garcia Aldana, D, Gassant, PY, Geel, JA, Ghassemi, F, Giron, A, Gizachew, Z, Goenz, MA, Gold, AS, Goldberg-Lavid, M, Gole, GA, Gomel, N, Gonzalez, E, Gonzalez Perez, G, Gonzalez-Rodriguez, L, Garcia Pacheco, HN, Graells, J, Green, L, Gregersen, PA, Grigorovski, NDAK, Guedenon, KM, Gunasekera, DS, Gunduz, AK, Gupta, H, Gupta, S, Hadjistilianou, T, Hamel, P, Hamid, SA, Hamzah, N, Hansen, ED, Harbour, JW, Hartnett, ME, Hasanreisoglu, M, Hassan, S, Hederova, S, Hernandez, J, Carcamo Hernandez, LM, Hessissen, L, Hordofa, DF, Huang, LC, Hubbard, GB, Hummlen, M, Husakova, K, Al-Janabi, ANH, Ida, R, Ilic, VR, Jairaj, V, Jeeva, I, Jenkinson, H, Ji, X, Jo, DH, Johnson, KP, Johnson, WJ, Jones, MM, Kabesha, TBA, Kabore, RL, Kaliki, S, Kalinaki, A, Kantar, M, Kao, L-Y, Kardava, T, Kebudi, R, Kepak, T, Keren-Froim, N, Khan, ZJ, Khaqan, HA, Khauv, P, Kheir, WJ, Khetan, V, Khodabande, A, Khotenashvili, Z, Kim, JW, Kim, JH, Kiratli, H, Kivela, TT, Klett, A, Palet, JEKK, Krivaitiene, D, Kruger, M, Kulvichit, K, Kuntorini, MW, Kyara, A, Lachmann, ES, Lam, CPS, Lam, GC, Larson, SA, Latinovic, S, Laurenti, KD, Le, BHA, Lecuona, K, Leverant, AA, Li, C, Limbu, B, Quah, BL, Lopez, JP, Lukamba, RM, Lumbroso, L, Luna-Fineman, S, Lutfi, D, Lysytsia, L, Magrath, GN, Mahajan, A, Majeed, AR, Maka, E, Makan, M, Makimbetov, EK, Manda, C, Martin Begue, N, Mason, L, Mason, JO, Matende, IO, Materin, M, Mattosinho, CCDS, Matua, M, Mayet, I, Mbumba, FB, McKenzie, JD, Medina-Sanson, A, Mehrvar, A, Mengesha, AA, Menon, V, Mercado, GJVD, Mets, MB, Midena, E, Mishra, DKC, Mndeme, FG, Mohamedani, AA, Mohammad, MT, Moll, AC, Montero, MM, Morales, RA, Moreira, C, Mruthyunjaya, P, Msina, MS, Msukwa, G, Mudaliar, SS, Muma, K, Munier, FL, Murgoi, G, Murray, TG, Musa, KO, Mushtaq, A, Mustak, H, Muyen, OM, Naidu, G, Nair, AG, Naumenko, L, Roth, PAN, Nency, YM, Neroev, V, Ngo, H, Nieves, RM, Nikitovic, M, Nkanga, ED, Nkumbe, H, Nuruddin, M, Nyaywa, M, Obono-Obiang, G, Oguego, NC, Olechowski, A, Oliver, SCN, Osei-Bonsu, P, Ossandon, D, Paez-Escamilla, MA, Pagarra, H, Painter, SL, Paintsil, V, Paiva, L, Pal, BP, Palanivelu, MS, Papyan, R, Parrozzani, R, Parulekar, M, Morales, CRP, Paton, KE, Pawinska-Wasikowska, K, Pe'er, J, Pena, A, Peric, S, Pham, CTM, Philbert, R, Plager, DA, Pochop, P, Polania, RA, Polyakov, VG, Pompe, MT, Pons, JJ, Prat, D, Prom, V, Purwanto, I, Qadir, AO, Qayyum, S, Qian, J, Rahman, A, Rahman, S, Rahmat, J, Rajkarnikar, P, Ramanjulu, R, Ramasubramanian, A, Ramirez-Ortiz, MA, Raobela, L, Rashid, R, Reddy, MA, Reich, E, Renner, LA, Reynders, D, Ribadu, D, Riheia, MM, Ritter-Sovinz, P, Rojanaporn, D, Romero, L, Roy, SR, Saab, RH, Saakyan, S, Sabhan, AH, Sagoo, MS, Said, AMA, Saiju, R, Salas, B, San Roman Pacheco, S, Sanchez, GL, Sayalith, P, Scanlan, TA, Schefler, AC, Schoeman, J, Sedaghat, A, Seregard, S, Seth, R, Shah, AS, Shakoor, SA, Sharma, MK, Sherief, ST, Shetye, NG, Shields, CL, Siddiqui, SN, Cheikh, SS, Silva, S, Singh, AD, Singh, N, Singh, U, Singha, P, Sitorus, RS, Skalet, AH, Soebagjo, HD, Sorochynska, T, Ssali, G, Stacey, AW, Staffieri, SE, Stahl, ED, Stathopoulos, C, Kranjc, BS, Stones, DK, Strahlendorf, C, Suarez, MEC, Sultana, S, Sun, X, Sundy, M, Superstein, R, Supriyadi, E, Surukrattanaskul, S, Suzuki, S, Svojgr, K, Sylla, F, Tamamyan, G, Tan, D, Tandili, A, Tarrillo Leiva, FF, Tashvighi, M, Tateshi, B, Tehuteru, ES, Teixeira, LF, Teh, KH, Theophile, T, Toledano, H, Trang, DL, Traore, F, Trichaiyaporn, S, Tuncer, S, Tyau-Tyau, H, Umar, AB, Unal, E, Uner, OE, Urbak, SF, Ushakova, TL, Usmanov, RH, Valeina, S, Wijsard, MVH, Varadisai, A, Vasquez, L, Vaughan, LO, Veleva-Krasteva, NV, Verma, N, Victor, AA, Viksnins, M, Villacos Chafla, EG, Vishnevskia-Dai, V, Vora, T, Wachtel, AE, Wackernagel, W, Waddell, K, Wade, PD, Wali, AH, Wang, Y-Z, Weiss, A, Wilson, MW, Wime, ADC, Wiwatwongwana, A, Wiwatwongwana, D, Dod, CW, Wongwai, P, Xiang, D, Xiao, Y, Yam, JC, Yang, H, Yanga, JM, Yaqub, MA, Yarovaya, VA, Yarovoy, AA, Ye, H, Yousef, YA, Yuliawati, P, Zapata Lopez, AM, Zein, E, Zhang, C, Zhang, Y, Zhao, J, Zheng, X, Zhilyaeva, K, Zia, N, Ziko, OAO, Zondervan, M, and Bowman, R

Abstract

IMPORTANCE: 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. OBJECTIVES: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. MAIN OUTCOMES AND MEASURES: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. RESULTS: 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

Published
2020

3. Differences in Childhood Growth Parameters Between Patients With Somatic and Heritable Retinoblastoma.

Author

Hicks RM, Ji X, Zou Y, Sultana S, Rashid R, Sherief ST, Cassoux N, Garcia Leon JL, Diaz Coronado RY, López AMZ, Ushakova TL, Polyakov VG, Roy SR, Ahmad A, Reddy MA, Sagoo MS, Al Harby L, Berry JL, Polski A, Astbury NJ, Bascaran C, Blum S, Bowman R, Burton MJ, Gomel N, Keren-Froim N, Madgar S, Zondervan M, Kaliki S, Fabian ID, and Stacey AW

Subjects
Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Male, Body Height genetics, Body Weight, Child Development physiology, Germ-Line Mutation, Longitudinal Studies, Retrospective Studies, Birth Weight, Retinal Neoplasms genetics, Retinoblastoma genetics
Abstract

Purpose: Little is known regarding differences in childhood growth between somatic and heritable retinoblastoma (Rb) populations. We aimed to compare childhood growth parameters between somatic and heritable Rb cohorts at birth and at time of diagnosis with Rb., Methods: A multinational, longitudinal cohort study was conducted with patients from 11 centers in 10 countries who presented with treatment naïve Rb from January to December 2019. Variables of interest included age, sex, and size characteristics at birth and at time of presentation, as well as germline mutation status. After Bonferroni correction, results were statistically significant if the P value was less than 0.005., Results: We enrolled 696 patients, with 253 analyzed after exclusion criteria applied. Between somatic (n = 39) and heritable (n = 214) Rb cohorts, with males and females analyzed separately, there was no significant difference in birth weight percentile, weight percentile at time of diagnosis, length percentile at time of diagnosis, weight-for-length percentile at time of diagnosis, or change of weight percentile from birth to time of diagnosis. Patients with heritable Rb had a smaller mean weight percentile at birth and smaller mean weight and length percentiles at time of diagnosis with Rb, although this difference was not statistically significant. All cohorts experienced a slight negative change of weight percentile from birth to time of diagnosis. No cohort mean percentiles met criteria for failure to thrive, defined as less than the 5th percentile., Conclusions: Children with Rb seem to have normal birth and childhood growth patterns. There is no definitive evidence that somatic or heritable Rb has a biological or environmental impact on childhood growth parameters.

Published
2024
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4. Survival and prognostic factors in pediatric patients with medulloblastoma treated at a national pediatric hospital in Peru: a retrospective cohort.

Author

Flores-Sanchez JD, Perez-Chadid DA, Diaz-Coronado RY, Hernandez-Broncano E, Ugas-Charcape CF, Ramirez A, Racchumí-Vela AE, Boop FA, and Preguntegui I

Abstract

Objective: The objectives of this study were to determine the overall survival (OS) and event-free survival (EFS) rates of patients with medulloblastoma treated in a national pediatric hospital in Peru, as well as to identify demographic, clinical, imaging, postoperative, and histopathological characteristics and prognostic factors associated with OS and EFS., Methods: The authors conducted a retrospective study analyzing information from the medical records of children with a diagnosis of medulloblastoma who underwent surgical treatment at the Instituto Nacional de Salud del Niño-San Borja, a public hospital in Lima, Peru, from 2015 to 2020. Clinical-epidemiological variables, degree of disease extension, risk stratification, extent of resection, postoperative complications, status of oncological treatment received, histological subtype, and neurological sequelae were taken into account. The Kaplan-Meier method and Cox regression analysis were used to estimate OS, EFS, and prognostic factors., Results: Of the 57 children evaluated with complete medical records, only 22 children (38.6%) underwent complete oncological treatment. OS was 37% (95% CI 0.25-0.55) at 48 months. EFS was 44% (95% CI 0.31-0.61) at 23 months. High-risk stratification-meaning patients with ≥ 1.5 cm2 of residual postoperative tumor, those younger than 3 years, those with disseminated disease (HR 9.69, 95% CI 1.40-67.0, p = 0.02), and those who underwent subtotal resection (HR 3.78, 95% CI 1.09-13.2, p = 0.04)-was negatively associated with OS. Failure to receive complete oncological treatment was negatively associated with OS (HR 20.0, 95% CI 4.84-82.6, p < 0.001) and EFS (HR 7.82, 95% CI 2.47-24.7, p < 0.001)., Conclusions: OS and EFS of patients with medulloblastoma in the author's milieu are below those reported in developed countries. Incomplete treatment and treatment abandonment in the authors' cohort were also high compared with high-income country statistics. Failure to complete oncological treatment was the most important factor associated with poor prognosis, both in terms of OS and EFS. High-risk patients and subtotal resection were negatively associated with OS. Interventions are needed to promote the completion of adjuvant oncological therapy for medulloblastoma in the disadvantaged Peruvian population.

Published
2023
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5. The role of maternal age & birth order on the development of unilateral and bilateral retinoblastoma: a multicentre study.

Author

Lloyd P, Westcott M, Kaliki S, Ji X, Zou Y, Rashid R, Sultana S, Sherief ST, Cassoux N, Diaz Coronado RY, Garcia Leon JL, López AMZ, Polyakov VG, Ushakova TL, Roy SR, Ahmad A, Harby LA, Berry JL, Kim J, Polski A, Astbury NJ, Bascaran C, Blum S, Bowman R, Burton MJ, Foster A, Gomel N, Keren-Froim N, Madgar S, Stacey AW, Mohamed A, Zondervan M, Sagoo MS, Fabian ID, and Reddy MA

Subjects
Child, Humans, Birth Order, Cohort Studies, Maternal Age, Retrospective Studies, Risk Factors, Female, Retinal Neoplasms epidemiology, Retinal Neoplasms genetics, Retinal Neoplasms pathology, Retinoblastoma epidemiology, Retinoblastoma genetics, Retinoblastoma pathology
Abstract

Background/objectives: Retinoblastoma is a common childhood intraocular malignancy, the bilateral form of which most commonly results from a de novo germline pathogenic variant in the RB1 gene. Both advanced maternal age and decreasing birth order are known to increase the risk of de novo germline pathogenic variants, while the influence of national wealth is understudied. This cohort study aimed to retrospectively observe whether these factors influence the ratio of bilateral retinoblastoma cases compared to unilateral retinoblastoma, thereby inferring an influence on the development of de novo germline pathogenic variants in RB1., Subjects/methods: Data from 688 patients from 11 centres in 10 countries were analysed using a series of statistical methods., Results: No associations were found between advanced maternal age, birth order or GDP per capita and the ratio of bilateral to unilateral retinoblastoma cases (p values = 0.534, 0.201, 0.067, respectively), indicating that these factors do not contribute to the development of a de novo pathogenic variant., Conclusions: Despite a lack of a definitive control group and genetic testing, this study demonstrates that advanced maternal age, birth order or GDP per capita do not influence the risk of developing a bilateral retinoblastoma., (© 2022. The Author(s).)

Published
2023
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6. Factors influencing outcomes of older children with medulloblastoma over 15 years in Peru, a resource-limited setting.

Author

Diaz-Coronado RY, Reinecke JB, Stanek JR, Finlay JL, Hernández Broncano E, Chávez Paredes S, Tunque YM, Heredia Zelaya A, Casavilca Zambrano S, García-Corrochano Medina P, Ojeda Medina L, Orrego Puelles E, Torres Malca E, Sernaque Quintana R, Quispe Valverde W, García León JL, and Osorio DS

Subjects
Adolescent, Child, Child, Preschool, Disease-Free Survival, Humans, Peru epidemiology, Prognosis, Risk Factors, Brain Neoplasms, Cerebellar Neoplasms pathology, Medulloblastoma pathology
Abstract

Background: Medulloblastoma is the most common malignant brain tumor in children. While survival has improved in high-income countries (HIC), the outcomes for patients in low-to-middle-income countries (LMIC) are unclear. Therefore, we sought to determine the survival of children with medulloblastoma at the Instituto Nacional de Enfermedades Neoplasicas (INEN) between 1997 and 2013 in Peru., Methods: Between 1997 and 2013, data from 103 children older than 3 years with medulloblastoma were analyzed. Fourteen patients were excluded. The patients were split into two distinct cohorts, 1997-2008 and 2009-2013, corresponding with chemotherapy regimen changes. Event-free (EFS) and overall survival (OS) were calculated using the Kaplan-Meier method, whereas prognostic factors were determined by univariate analysis (log-rank test)., Results: Eighty-nine patients were included; median age was 8.1 years (range: 3-13.9 years). The 5-year OS was 62% (95% CI: 53%-74%), while EFS was 57% (95% CI: 48%-69%). The variables adversely affecting survival were anaplastic histology (compared to desmoplastic; OS: HR = 3.4, p = .03), metastasis (OS: HR = 3.5, p = .01; EFS: HR = 4.3, p = .004), delay in radiation therapy of 31-60 days (compared to ≤30 days; EFS: HR = 2.1, p = .04), and treatment 2009-2013 cohort (OS: HR = 2.2, p = .02; EFS: HR = 2.0, p = .03)., Conclusions: Outcomes for medulloblastoma at INEN were low compared with HIC. Anaplastic subtype, metastasis at diagnosis, delay in radiation therapy, and treatment in the period 2009-2013 negatively affected the outcomes in our study. Multidisciplinary teamwork, timely delivery of treatment, and partnerships with loco-regional groups and colleagues in HIC is likely beneficial., (© 2022 Wiley Periodicals LLC.)

Published
2022
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7. An international study evaluating the epidemiology of intracranial germ cell tumors in the native versus immigrant Japanese populations: the need for an international registry.

Author

Plant-Fox AS, Suzuki T, Diaz Coronado RY, Epelman S, Sakamoto L, Cheng S, Yanagisawa T, Rosner B, Chi SN, and Kieran MW

Subjects
Adolescent, Adult, Child, Child, Preschool, Humans, Incidence, Infant, Infant, Newborn, Japan epidemiology, Registries, Young Adult, Brain Neoplasms epidemiology, Brain Neoplasms pathology, Cerebellar Neoplasms, Emigrants and Immigrants, Medulloblastoma, Neoplasms, Germ Cell and Embryonal epidemiology
Abstract

Background: Pediatric intra-cranial germ cell tumors (iGCTs) occur at an incidence of 0.6-1.2 cases/million/year in Western countries. The incidence is reported up to 5 times higher in Japan. It is unknown whether this increased incidence is due to genetic predisposition or environment., Methods: The incidence of iGCTs in children ages 0-19 years was evaluated from December 1st, 1996-December 1st, 2016 in stable Japanese immigrant populations living abroad and compared to current native Japanese registry data. The incidence of medullobblastoma was used as a control to account for assumptions in the data. Sites were identified based on historical and population data of known large scale emigration from Japan during a period of industrialization from 1868-1912 which resulted in large, stable Japanese immigrant populations abroad. These three representative sites included Lima, Peru, San Paolo, Brazil, and Vancouver, Canada. Data was collected from registry and hospital-based resources within each region., Results: A review of the Brain Tumor Registry of Japan from 1984-2004 revealed an incidence of 2.5 cases/million/year, lower than previously reported, and a lower incidence of medulloblastoma at 1.2 cases/million/year. Data from Vancouver, Canada, Lima, Peru, and San Paolo, Brazil included a total population of 731,174 Japanese persons. The ratio of all medulloblastoma to iGCT cases in Japan was identified as 1:2 while the ratio was 2:1, 6.5:1, and 5:1, respectively, in the other three locations. The data suggests increased incidence in native Japan may not translate to higher incidence in immigrant Japanese populations abroad and a clear genetic component was not found in our data set., Conclusions: A more precise and comprehensive study is needed to determine the cause of this difference in incidence. This study also emphasizes the importance of national and state registries and is a call to collaborate on state and country level epidemiology studies., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Published
2022
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8. Primary central nervous system sarcoma with DICER1 mutation-treatment results of a novel molecular entity in pediatric Peruvian patients.

Author

Diaz Coronado RY, Mynarek M, Koelsche C, Mora Alferez P, Casavilca Zambrano S, Wachtel Aptowitzer A, Sahm F, von Deimling A, Schüller U, Spohn M, Sturm D, Pfister SM, Morales La Madrid A, Sernaque Quintana R, Sarria Bardales G, Negreiros Chinchihuara T, Ojeda Medina L, Garcia-Corrochano Medina P, Campos Sanchez DA, Ponce Farfan J, Rutkowski S, and Garcia Leon JL

Subjects
Adolescent, Central Nervous System pathology, Child, Child, Preschool, DEAD-box RNA Helicases genetics, Humans, Mutation, Peru epidemiology, Ribonuclease III genetics, Central Nervous System Neoplasms drug therapy, Central Nervous System Neoplasms genetics, Sarcoma drug therapy, Sarcoma genetics
Abstract

Background: A high frequency of primary central nervous system (CNS) sarcomas was observed in Peru. This article describes the clinical characteristics, biological characteristics, and outcome of 70 pediatric patients., Methods: Data from 70 pediatric patients with primary CNS sarcomas diagnosed between January 2005 and June 2018 were analyzed. DNA methylation profiling from 28 tumors and gene panel sequencing from 27 tumors were available., Results: The median age of the patients was 6 years (range, 2-17.5 years), and 66 of 70 patients had supratentorial tumors. DNA methylation profiling classified 28 of 28 tumors as primary CNS sarcoma, DICER1 mutant. DICER1 mutations were found in 26 of 27 cases, TP53 mutations were found in 22 of 27 cases, and RAS-pathway gene mutations (NF1, KRAS, and NRAS) were found in 19 of 27 tumors, all of which were somatic (germline control available in 19 cases). The estimated incidence in Peru was 0.19 cases per 100,000 children (<18 years old) per year, which is significantly higher than the estimated incidence in Germany (0.007 cases per 100,000 children [<18 years] per year; P < .001). Patients with nonmetastatic disease (n = 46) that were treated with a combination therapy had a 2-year progression-free survival (PFS) rate of 58% (95% CI, 44%-76%) and a 2-year overall survival rate of 71% (95% CI, 57%-87%). PFS was the highest in patients treated with chemotherapy with ifosfamide, carboplatin, and etoposide (ICE) after upfront surgery followed by radiotherapy and ICE (2-year PFS, 79% [59%-100%], n = 18)., Conclusions: Primary CNS sarcoma with DICER1 mutation has an aggressive clinical course. A combination of surgery, chemotherapy, and radiotherapy seems beneficial. An underlying cancer predisposition syndrome explaining the increased incidence in Peruvian patients has not been identified so far., Lay Summary: A high incidence of primary pediatric central nervous system sarcomas in the Peruvian population is described. Using sequencing technologies and DNA methylation profiling, it is confirmed that these tumors molecularly belong to the recently proposed entity "primary central nervous system sarcomas, DICER1 mutant." Unexpectedly, DICER1 mutations as well as all other defining tumor mutations (TP53 mutations and RAS-pathway mutations) were not inherited in all 19 patients where analyzation was possible. These tumors have an aggressive clinical course. Multimodal combination therapy based on surgery, ifosfamide, carboplatin, and etoposide chemotherapy, and local radiotherapy leads to superior outcomes., (© 2021 American Cancer Society.)

Published
2022
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9. Global Retinoblastoma Presentation and Analysis by National Income Level.

Author

Fabian ID, Abdallah E, Abdullahi SU, Abdulqader RA, Adamou Boubacar S, Ademola-Popoola DS, Adio A, Afshar AR, Aggarwal P, Aghaji AE, Ahmad A, Akib MNR, Al Harby L, Al Ani MH, Alakbarova A, Portabella SA, Al-Badri SAF, Alcasabas APA, Al-Dahmash SA, Alejos A, Alemany-Rubio E, Alfa Bio AI, Alfonso Carreras Y, Al-Haddad C, Al-Hussaini HHY, Ali AM, Alia DB, Al-Jadiry MF, Al-Jumaily U, Alkatan HM, All-Eriksson C, Al-Mafrachi AARM, Almeida AA, Alsawidi KM, Al-Shaheen AASM, Al-Shammary EH, Amiruddin PO, Antonino R, Astbury NJ, Atalay HT, Atchaneeyasakul LO, Atsiaya R, Attaseth T, Aung TH, Ayala S, Baizakova B, Balaguer J, Balayeva R, Balwierz W, Barranco H, Bascaran C, Beck Popovic M, Benavides R, Benmiloud S, Bennani Guebessi N, Berete RC, Berry JL, Bhaduri A, Bhat S, Biddulph SJ, Biewald EM, Bobrova N, Boehme M, Boldt HC, Bonanomi MTBC, Bornfeld N, Bouda GC, Bouguila H, Boumedane A, Brennan RC, Brichard BG, Buaboonnam J, Calderón-Sotelo P, Calle Jara DA, Camuglia JE, Cano MR, Capra M, Cassoux N, Castela G, Castillo L, Català-Mora J, Chantada GL, Chaudhry S, Chaugule SS, Chauhan A, Chawla B, Chernodrinska VS, Chiwanga FS, Chuluunbat T, Cieslik K, Cockcroft RL, Comsa C, Correa ZM, Correa Llano MG, Corson TW, Cowan-Lyn KE, Csóka M, Cui X, Da Gama IV, Dangboon W, Das A, Das S, Davanzo JM, Davidson A, De Potter P, Delgado KQ, Demirci H, Desjardins L, Diaz Coronado RY, Dimaras H, Dodgshun AJ, Donaldson C, Donato Macedo CR, Dragomir MD, Du Y, Du Bruyn M, Edison KS, Eka Sutyawan IW, El Kettani A, Elbahi AM, Elder JE, Elgalaly D, Elhaddad AM, Elhassan MMA, Elzembely MM, Essuman VA, Evina TGA, Fadoo Z, Fandiño AC, Faranoush M, Fasina O, Fernández DDPG, Fernández-Teijeiro A, Foster A, Frenkel S, Fu LD, Fuentes-Alabi SL, Gallie BL, Gandiwa M, Garcia JL, García Aldana D, Gassant PY, Geel JA, Ghassemi F, Girón AV, Gizachew Z, Goenz MA, Gold AS, Goldberg-Lavid M, Gole GA, Gomel N, Gonzalez E, Gonzalez Perez G, González-Rodríguez L, Garcia Pacheco HN, Graells J, Green L, Gregersen PA, Grigorovski NDAK, Guedenon KM, Gunasekera DS, Gündüz AK, Gupta H, Gupta S, Hadjistilianou T, Hamel P, Hamid SA, Hamzah N, Hansen ED, Harbour JW, Hartnett ME, Hasanreisoglu M, Hassan S, Hassan S, Hederova S, Hernandez J, Hernandez LMC, Hessissen L, Hordofa DF, Huang LC, Hubbard GB, Hummlen M, Husakova K, Hussein Al-Janabi AN, Ida R, Ilic VR, Jairaj V, Jeeva I, Jenkinson H, Ji X, Jo DH, Johnson KP, Johnson WJ, Jones MM, Kabesha TBA, Kabore RL, Kaliki S, Kalinaki A, Kantar M, Kao LY, Kardava T, Kebudi R, Kepak T, Keren-Froim N, Khan ZJ, Khaqan HA, Khauv P, Kheir WJ, Khetan V, Khodabande A, Khotenashvili Z, Kim JW, Kim JH, Kiratli H, Kivelä TT, Klett A, Komba Palet JEK, Krivaitiene D, Kruger M, Kulvichit K, Kuntorini MW, Kyara A, Lachmann ES, Lam CPS, Lam GC, Larson SA, Latinovic S, Laurenti KD, Le BHA, Lecuona K, Leverant AA, Li C, Limbu B, Long QB, López JP, Lukamba RM, Lumbroso L, Luna-Fineman S, Lutfi D, Lysytsia L, Magrath GN, Mahajan A, Majeed AR, Maka E, Makan M, Makimbetov EK, Manda C, Martín Begue N, Mason L, Mason JO 3rd, Matende IO, Materin M, Mattosinho CCDS, Matua M, Mayet I, Mbumba FB, McKenzie JD, Medina-Sanson A, Mehrvar A, Mengesha AA, Menon V, Mercado GJVD, Mets MB, Midena E, Mishra DKC, Mndeme FG, Mohamedani AA, Mohammad MT, Moll AC, Montero MM, Morales RA, Moreira C, Mruthyunjaya P, Msina MS, Msukwa G, Mudaliar SS, Muma KI, Munier FL, Murgoi G, Murray TG, Musa KO, Mushtaq A, Mustak H, Muyen OM, Naidu G, Nair AG, Naumenko L, Ndoye Roth PA, Nency YM, Neroev V, Ngo H, Nieves RM, Nikitovic M, Nkanga ED, Nkumbe H, Nuruddin M, Nyaywa M, Obono-Obiang G, Oguego NC, Olechowski A, Oliver SCN, Osei-Bonsu P, Ossandon D, Paez-Escamilla MA, Pagarra H, Painter SL, Paintsil V, Paiva L, Pal BP, Palanivelu MS, Papyan R, Parrozzani R, Parulekar M, Pascual Morales CR, Paton KE, Pawinska-Wasikowska K, Pe'er J, Peña A, Peric S, Pham CTM, Philbert R, Plager DA, Pochop P, Polania RA, Polyakov VG, Pompe MT, Pons JJ, Prat D, Prom V, Purwanto I, Qadir AO, Qayyum S, Qian J, Rahman A, Rahman S, Rahmat J, Rajkarnikar P, Ramanjulu R, Ramasubramanian A, Ramirez-Ortiz MA, Raobela L, Rashid R, Reddy MA, Reich E, Renner LA, Reynders D, Ribadu D, Riheia MM, Ritter-Sovinz P, Rojanaporn D, Romero L, Roy SR, Saab RH, Saakyan S, Sabhan AH, Sagoo MS, Said AMA, Saiju R, Salas B, San Román Pacheco S, Sánchez GL, Sayalith P, Scanlan TA, Schefler AC, Schoeman J, Sedaghat A, Seregard S, Seth R, Shah AS, Shakoor SA, Sharma MK, Sherief ST, Shetye NG, Shields CL, Siddiqui SN, Sidi Cheikh S, Silva S, Singh AD, Singh N, Singh U, Singha P, Sitorus RS, Skalet AH, Soebagjo HD, Sorochynska T, Ssali G, Stacey AW, Staffieri SE, Stahl ED, Stathopoulos C, Stirn Kranjc B, Stones DK, Strahlendorf C, Suarez MEC, Sultana S, Sun X, Sundy M, Superstein R, Supriyadi E, Surukrattanaskul S, Suzuki S, Svojgr K, Sylla F, Tamamyan G, Tan D, Tandili A, Tarrillo Leiva FF, Tashvighi M, Tateshi B, Tehuteru ES, Teixeira LF, Teh KH, Theophile T, Toledano H, Trang DL, Traoré F, Trichaiyaporn S, Tuncer S, Tyau-Tyau H, Umar AB, Unal E, Uner OE, Urbak SF, Ushakova TL, Usmanov RH, Valeina S, van Hoefen Wijsard M, Varadisai A, Vasquez L, Vaughan LO, Veleva-Krasteva NV, Verma N, Victor AA, Viksnins M, Villacís Chafla EG, Vishnevskia-Dai V, Vora T, Wachtel AE, Wackernagel W, Waddell K, Wade PD, Wali AH, Wang YZ, Weiss A, Wilson MW, Wime ADC, Wiwatwongwana A, Wiwatwongwana D, Wolley Dod C, Wongwai P, Xiang D, Xiao Y, Yam JC, Yang H, Yanga JM, Yaqub MA, Yarovaya VA, Yarovoy AA, Ye H, Yousef YA, Yuliawati P, Zapata López AM, Zein E, Zhang C, Zhang Y, Zhao J, Zheng X, Zhilyaeva K, Zia N, Ziko OAO, Zondervan M, and Bowman R

Subjects
Child, Preschool, Female, Humans, Infant, Male, Retinoblastoma economics, Retinoblastoma epidemiology
Abstract

Importance: 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., Objectives: 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., Design, Setting, and Participants: 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., Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis., Results: 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])., Conclusions and Relevance: 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.

Published
2020
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10. Bridging the Gap in Access to Care for Children With CNS Tumors Worldwide.

Author

Moreira DC, Rajagopal R, Navarro-Martin Del Campo RM, Polanco AC, Alcasabas AP, Arredondo-Navarro LA, Campos D, Casavilca-Zambrano S, Diaz Coronado RY, Faizal N, Ganesan D, Hamid SA, Khan R, Khu K, Loh J, Lukban M, Negreiros T, Pineda E, Yaqoob N, Zia N, Gajjar A, Rodriguez-Galindo C, and Qaddoumi I

Subjects
Child, Humans, Central Nervous System Neoplasms therapy, Health Services Accessibility
Published
2020
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11. Primary intracranial spindle cell sarcoma with rhabdomyosarcoma-like features share a highly distinct methylation profile and DICER1 mutations.

Author

Koelsche C, Mynarek M, Schrimpf D, Bertero L, Serrano J, Sahm F, Reuss DE, Hou Y, Baumhoer D, Vokuhl C, Flucke U, Petersen I, Brück W, Rutkowski S, Zambrano SC, Garcia Leon JL, Diaz Coronado RY, Gessler M, Tirado OM, Mora J, Alonso J, Garcia Del Muro X, Esteller M, Sturm D, Ecker J, Milde T, Pfister SM, Korshunov A, Snuderl M, Mechtersheimer G, Schüller U, Jones DTW, and von Deimling A

Subjects
DNA Methylation genetics, Female, Germ-Line Mutation, Humans, Male, Retrospective Studies, Rhabdomyosarcoma, Embryonal pathology, Sarcoma pathology, DEAD-box RNA Helicases genetics, Genetic Predisposition to Disease genetics, Mutation genetics, Rhabdomyosarcoma, Embryonal genetics, Ribonuclease III genetics, Sarcoma genetics
Abstract

Patients with DICER1 predisposition syndrome have an increased risk to develop pleuropulmonary blastoma, cystic nephroma, embryonal rhabdomyosarcoma, and several other rare tumor entities. In this study, we identified 22 primary intracranial sarcomas, including 18 in pediatric patients, with a distinct methylation signature detected by array-based DNA-methylation profiling. In addition, two uterine rhabdomyosarcomas sharing identical features were identified. Gene panel sequencing of the 22 intracranial sarcomas revealed the almost unifying feature of DICER1 hotspot mutations (21/22; 95%) and a high frequency of co-occurring TP53 mutations (12/22; 55%). In addition, 17/22 (77%) sarcomas exhibited alterations in the mitogen-activated protein kinase pathway, most frequently affecting the mutational hotspots of KRAS (8/22; 36%) and mutations or deletions of NF1 (7/22; 32%), followed by mutations of FGFR4 (2/22; 9%), NRAS (2/22; 9%), and amplification of EGFR (1/22; 5%). A germline DICER1 mutation was detected in two of five cases with constitutional DNA available. Notably, none of the patients showed evidence of a cancer-related syndrome at the time of diagnosis. In contrast to the genetic findings, the morphological features of these tumors were less distinctive, although rhabdomyoblasts or rhabdomyoblast-like cells could retrospectively be detected in all cases. The identified combination of genetic events indicates a relationship between the intracranial tumors analyzed and DICER1 predisposition syndrome-associated sarcomas such as embryonal rhabdomyosarcoma or the recently described group of anaplastic sarcomas of the kidney. However, the intracranial tumors in our series were initially interpreted to represent various tumor types, but rhabdomyosarcoma was not among the typical differential diagnoses considered. Given the rarity of intracranial sarcomas, this molecularly clearly defined group comprises a considerable fraction thereof. We therefore propose the designation "spindle cell sarcoma with rhabdomyosarcoma-like features, DICER1 mutant" for this intriguing group.

Published
2018
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