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5. 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

6. Real-Time Signal Processing for Mitigating SiPM Dark Noise Effects in a Scintillating Neutron Detector

Author

Pritchard, K., primary, Chabot, J. P., additional, Robucci, R., additional, Choa, F. S., additional, Osovizky, A., additional, Ziegler, J., additional, Binkley, E., additional, Tsai, P., additional, Hadad, N., additional, Jackson, M., additional, Hurlbut, C., additional, Baltic, G. M., additional, Majkrzak, C. F., additional, and Maliszewskyj, N. C., additional

Published
2021
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10. 6LiF:ZnS(Ag) Mixture Optimization for a Highly Efficient Ultrathin Cold Neutron Detector

Author

Osovizky, A., primary, Pritchard, K., additional, Ziegler, J., additional, Binkley, E., additional, Yehuda-Zada, Y., additional, Tsai, P., additional, Thompson, A., additional, Cooksey, C., additional, Siebein, K., additional, Hadad, N., additional, Jackson, M., additional, Hurlbut, C., additional, Ibberson, R., additional, Baltic, G. M., additional, Majkrzak, C. F., additional, and Maliszewskyj, N. C., additional

Published
2018
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29. Effect of Phenylalanine-Restricted Diet in Phenylketonuria II

Author

HORNER, F. A., STREAMER, C. W., CLADER, D. E., HASSELL, L. L., BINKLEY, E. L., and DUMARS, K. W.

Abstract

In an earlier paper two of us (F. A. H. and C. W. S.) presented the short-term psychological and behavioral changes observed in two preschool phenylketonuric children treated with a phenylalanine-restricted diet.1 In addition, a newborn sibling of one of the cases, who had received dietary treatment since 8 weeks of age, was reported as developing normally through the first 9 months of life. The present paper offers an additional year of follow-up on these three patients. It also reports on the changes observed in a second newborn and two 18-month-old children under long-term therapy. DIETARY PROGRAM The phenylalanine-restricted diet used in this series is that outlined by Armstrong and Tyler.2,3 Patients are given a phenylalanine-free diet consisting of a protein hydrolysate basal mix* (4.2 gm/kg/day), fat in the form of a vegetable oil (3.0 gm/kg/day) and CHO (10 gm/kg/day) for three weeks. On such a diet

Published
1957
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31. Provocative Inhalant Testing and Treatment

Author

Lee, Carleton H., Williams, Russell I., and Binkley, E. L.

Abstract

THE PROVOCATIVE inhalant test is a deliberate intracutaneous injection of a potent inhalant extract of sufficient quantity and strength to provoke a mild systemic reaction, and the immediate injection of weaker (or, occasionally, stronger) dilutions of the identical antigen to relieve the provoked symptoms.Lee's experience with foods led him to believe that provocative testing for inhalants was feasible and would be of distinct value in testing and treatment, especially when the patient failed to show improvement with serial dilution antigen titration technique.Provocative inhalant testing is done for house dust, molds, animal danders, and the pollens of trees, grasses, and weeds.Atmospheric contaminants vary with seasonal changes. In inhalant-sensitive patients, sensitivities will show great variations with seasonal change and pollen toxicity. Foods can be controlled in the diet, but inhalants cannot be controlled by the patient.It is the opinion of the senior author that provocative testing and

Published
1969
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46. Belzutifan in Individuals with von Hippel-Lindau Retinal Hemangioblastomas: Institutional Experience and Review of the Literature.

Author

Jamshidi F, Lozano L, Tucker B, Andorf J, Sohn E, Stone E, Groves A, Zakharia Y, Boldt HC, and Binkley E

Abstract

Introduction: The systemic HIF-2 alpha inhibitor, belzutifan, has been approved for use in patients with von Hippel-Lindau disease (VHL)-associated renal cell carcinoma, central nervous system (CNS) hemangioblastomas, and pancreatic neuroendocrine tumors. This drug has also shown promise in controlling VHL retinal hemangioblastomas (RHs), but little work has been published on the use of the drug in this setting., Methods: We conducted a retrospective review of patients with VHL-associated RHs followed by the retina service at our institution who were treated with systemic belzutifan. Patient age, gender, genotype, presence of systemic tumors, indication for the drug, initial dose, adjusted dose, side effects, and tumor response were recorded. We also conducted a literature search for all manuscripts describing the effect of belzutifan on VHL-associated ocular tumors., Results: We identified 12 eyes of 7 patients with VHL-associated ocular tumors who were treated with belzutifan at our institution. Of these, 5 eyes of 3 patients had progressing ocular tumors when belzutifan was started. Of the 7 total patients, 2 were treated for renal cell carcinoma, 2 for CNS hemangioblastomas, 2 for RHs, and one for pancreatic neuroendocrine tumors. Initial dose was 120 mg PO daily in 6 patients and 80 mg PO daily in 1 patient. The dose was reduced in all but 1 patient due to side effects. The ocular tumors were controlled in all patients with an average follow-up of 13 months (range 4-24 months). Literature review identified 7 manuscripts that described belzutifan-mediated control of ocular tumors in patients with VHL-associated RHs in 21 patients., Conclusion: The drug belzutifan shows great promise for controlling RHs and preventing vision loss in patients with VHL. Further work needs to address the optimal dose, role of the drug as a neoadjuvant therapy, and long-term efficacy and tolerability of the drug in a larger cohort of patients with ocular tumors., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Published
2024
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47. Primary central nervous system lymphoma: Inter-compartmental progression.

Author

Raval V, Binkley E, Aronow ME, Valenzuela J, Peereboom DM, Wei W, Srivastava S, Davanzo J, Boldt HC, McGarrey MP, Papaliodis GN, Sobrin L, Kim IK, Vavvas DG, Eliott D, Nayak L, Dodds E, Marco Del Pont F, and Singh AD

Abstract

There is limited understanding of the inter-compartmental progression and treatment outcomes of primary central nervous system lymphoma (PCNSL). In this multicenter retrospective cohort study on 234 patients with PCNSL (median age: 62.5 years [18-92]; median follow-up 35 months [0.1-237.0]) from 2000 till 2018 were divided into group 1 (ocular, 44 patients): 1A and 1B without and with CNS progression and group 2 (CNS, 190 patients): 2A and 2B without and with ocular progression, respectively. In group 1 (44 patients), 33 patients received local treatment, and 11 patients received systemic treatment. In group 2 (15 patients), six patients received combination treatment, while seven patients received only systemic treatment. A complete response was observed in 19 (43%) and 91 (48%) patients in groups 1 and 2, respectively. The 2-year progression-free survival (PFS) was 35% (95% CI: 0.23, 0.54) and 56% (95% CI: 0.49, 0.63) for groups 1 and 2, respectively ( p  < 0.0001). Age < 60 years was significantly associated with longer PFS (median PFS 48 vs. 24 months, p  = 0.01). The overall survival (OS) at 2-year was similar among groups 1 and 2 (83% and 67%), respectively ( p  = 0.06). Thus, Initial compartment of involvement does not influence local response rate or OS., (© 2021 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Published
2022
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48. Primary central nervous system lymphoma - ocular variant: an interdisciplinary review on management.

Author

Raval V, Binkley E, Aronow ME, Valenzuela J, Peereboom DM, and Singh AD

Subjects
Central Nervous System pathology, Humans, Methotrexate therapeutic use, Retina pathology, Central Nervous System Neoplasms therapy, Lymphoma therapy
Abstract

Primary central nervous system lymphoma-ophthalmic variant (PCNSL-O) is an ocular subset of PCNSL predominantly involving subretinal pigment epithelium space, retina, and vitreous. The ophthalmic manifestations can precede, occur simultaneously, or follow other compartments of the CNS. Clinical trials have resulted in a significantly improved outcome in PCNSL patients over the past 2 decades, with a higher proportion of patients receiving frontline high dose methotrexate-based polychemotherapy regimens with curative intent; however, the current management of PCNSL-O remains controversial owing to lack of prospective data. The goals of PCNSL-O treatment are both to achieve local (ocular) control and to prevent tumor-specific mortality from further CNS involvement. Despite achieving high rates of ocular control with intravitreal agents like methotrexate and rituximab, the overall survival is poor, as 65-85% of patients eventually succumb to CNS disease. Few studies define the role of systemic chemotherapy with/without local treatment as a first line induction treatment for PCNSL-O considering limiting factors such as ocular penetration of systemically administered drugs and treatment related neurotoxicity. Also, the role of adjuvant treatment for PCNSL-O to prevent CNS progression and to improve overall survival is unknown. In this systematic review of the literature, we analyze treatment outcomes of various regimens (local, systemic, and combination) in terms of local control, CNS progression, and overall survival., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Published
2021
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49. A prospective trial of adjuvant therapy for high-risk uveal melanoma: assessing 5-year survival outcomes.

Author

Binkley E, Triozzi PL, Rybicki L, Achberger S, Aldrich W, and Singh A

Subjects
Adult, Aged, Aged, 80 and over, Chemotherapy, Adjuvant, Disease-Free Survival, Female, Humans, Infusions, Intravenous, Injections, Subcutaneous, Interferon alpha-2, Male, Melanoma pathology, Middle Aged, Prospective Studies, Survival Rate, Uveal Neoplasms pathology, Young Adult, Antineoplastic Agents, Alkylating administration & dosage, Dacarbazine administration & dosage, Interferon-alpha administration & dosage, Melanoma drug therapy, Melanoma mortality, Uveal Neoplasms drug therapy, Uveal Neoplasms mortality
Abstract

Background/aims: Survival after diagnosis of metastasis from uveal melanoma is poor. Identifying individuals at high risk for metastasis and developing adjuvant therapy to prevent clinically apparent metastasis could improve survival. We conducted an adjuvant trial of sequential, low-dose dacarbazine (DTIC) and interferon-alpha-2b (IFN-α-2b) in patients with cytogenetic high-risk uveal melanoma., Methods: Patients diagnosed with iris, ciliary body or choroidal melanoma with high-risk tumour cytogenetics (monosomy 3) were offered adjuvant treatment with low-dose DTIC and IFN-α-2b following primary therapy. Eligible but not enrolled patients were observed for comparison. DTIC was administered at 850 mg/m 2 intravenously on days 1 and 28. IFN-α-2b was administered at 3 million units three times a week subcutaneously for 24 weeks beginning at week 9. Hepatic imaging was performed prior to adjuvant therapy and then at least every 6 months. Survival data were collected for 5 years after enrolment., Results: 33 patients (22%) were enrolled (treatment group), 29 (19%) were eligible but did not enrol (observation group) and 88 (59%) were not eligible. The 5-year metastasis-free survival (MFS) was 64%±9% for treated and 33%±10% for observed patients (p=0.05). The 5-year overall survival (OS) rate was 66%±9% for treated and 37%±10% for observed patients (p=0.02)., Conclusions: When adjusted for differences in age, tumour size and initial treatment, survival between treated and observed patients was no longer significant (p=0.56 MFS and p=0.92 OS). Differences in baseline tumour characteristics between treated and observed patients can influence interpretation of results., Trial Registration Number: NCT01100528., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2020
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50. Single-Cell RNA Sequencing in Human Retinal Degeneration Reveals Distinct Glial Cell Populations.

Author

Voigt AP, Binkley E, Flamme-Wiese MJ, Zeng S, DeLuca AP, Scheetz TE, Tucker BA, Mullins RF, and Stone EM

Subjects
Aged, Humans, Male, Neuroglia metabolism, Retinal Degeneration genetics, Sequence Analysis, RNA methods
Abstract

Degenerative diseases affecting retinal photoreceptor cells have numerous etiologies and clinical presentations. We clinically and molecularly studied the retina of a 70-year-old patient with retinal degeneration attributed to autoimmune retinopathy. The patient was followed for 19 years for progressive peripheral visual field loss and pigmentary changes. Single-cell RNA sequencing was performed on foveal and peripheral retina from this patient and four control patients, and cell-specific gene expression differences were identified between healthy and degenerating retina. Distinct populations of glial cells, including astrocytes and Müller cells, were identified in the tissue from the retinal degeneration patient. The glial cell populations demonstrated an expression profile consistent with reactive gliosis. This report provides evidence that glial cells have a distinct transcriptome in the setting of human retinal degeneration and represents a complementary clinical and molecular investigation of a case of progressive retinal disease., Competing Interests: The authors declare no conflict of interest.

Published
2020
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