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

Author

Fabian, Ido Didi, Abdallah, Elhassan, Abdullahi, Shehu U, Abdulqader, Rula A, Abdulrahaman, Aminatu A, Abouelnaga, Sherif, Ademola-Popoola, Dupe S, Adio, Adedayo, Afifi, Mahmoud A, Afshar, Armin R, Aggarwal, Priyanka, Aghaji, Ada E, Ahmad, Alia, Akib, Marliyanti NR, Akinsete, Adeseye, Al Harby, Lamis, Al Mesfer, Saleh, Al Ani, Mouroge H, Alarcón Portabella, Silvia, Al-Badri, Safaa AF, Alcasabas, Ana Patricia A, Al-Dahmash, Saad A, Alejos, Amanda, Alemany-Rubio, Ernesto, Alfa Bio, Amadou I, Alfonso Carreras, Yvania, Al-Haddad, Christiane E, Al-Hussaini, Hamoud HY, Ali, Amany M, Alia, Donjeta B, Al-Jadiry, Mazin F, Al-Jumaily, Usama, Alkatan, Hind M, All-Eriksson, Charlotta, Al-Mafrachi, Ali ARM, Almeida, Argentino A, Alsawidi, Khalifa M, Al-Shaheen, Athar ASM, Al-Shammary, Entissar H, Amankwaa-Frempong, Doreen, Amiruddin, Primawita O, Armytasari, Inggar, Astbury, Nicholas J, Atalay, Hatice T, Ataseven, Eda, Atchaneeyasakul, La-ongsri, Atsiaya, Rose, Autrata, Rudolf, Balaguer, Julia, Balayeva, Ruhengiz, Barranco, Honorio, Bartoszek, Paulina, Bartuma, Katarina, Bascaran, Covadonga, Bechrakis, Nikolaos E, Beck Popovic, Maja, Begimkulova, Ainura S, Benmiloud, Sarra, Berete, Rokia C, Berry, Jesse L, Bhaduri, Anirban, Bhat, Sunil, Bhattacharyya, Arpita, Biewald, Eva M, Binkley, Elaine, Blum, Sharon, Bobrova, Nadia, Boldt, H.C., Bonanomi, Maria Teresa BC, Bouda, Gabrielle C, Bouguila, Hédi, Brennan, Rachel C, Brichard, Bénédicte G, Buaboonnam, Jassada, Budiongo, Aléine, Burton, Matthew J, Calderón-Sotelo, Patricia, Calle Jara, Doris A, Camuglia, Jayne E, Cano, Miriam R, Capra, Michael, Caspi, Shani, Cassoux, Nathalie, Castela, Guilherme, Castillo, Luis, Català-Mora, Jaume, Cavieres, Isabel, Chandramohan, Arthika, Chantada, Guillermo L, Chaudhry, Shabana, Chawla, Bhavna, Chen, Wensi, Chiwanga, Faraja S, Chuluunbat, Tsengelmaa, Cieslik, Krzysztof, Clark, Antony, Cockcroft, Ruellyn L, Comsa, Codruta, Correa Llano, Maria G, Corson, Timothy W, Couitchere, Line, Cowan-Lyn, Kristin E, Csóka, Monika, Dangboon, Wantanee, Das, Anirban, Das, Pranab, Das, Sima, Davanzo, Jacquelyn M, Davidson, Alan, De Francesco, Sonia, De Potter, Patrick, Quintero D, Karina, Demirci, Hakan, Desjardins, Laurence, Díaz Coronado, Rosdali Y, Dimaras, Helen, Dodgshun, Andrew J, Donato Macedo, Carla R, Dragomir, Monica D, Du, Yi, Du Bruyn, Magritha, Du Plessis, Johannes, Dudeja, Gagan, Eerme, Katrin, Eka Sutyawan, I Wayan, El Kettani, Asmaa, Elbahi, Amal M, Elder, James E, Elhaddad, Alaa M, Elhassan, Moawia MA, Elzembely, Mahmoud M, Ericksen, Connor, Essuman, Vera A, Evina, Ted Grimbert A, Ezegwui, Ifeoma R, Fadoo, Zehra, Fandiño, Adriana C, Faranoush, Mohammad, Fasina, Oluyemi, Fernández, Delia DPG, Fernández-Teijeiro, Ana, Foster, Allen, Frenkel, Shahar, Fu, Ligia D, Fuentes-Alabi, Soad L, Garcia, Juan L, García Aldana, David, Garcia Pacheco, Henry N, Geel, Jennifer A, Ghassemi, Fariba, Girón, Ana V, Goenz, Marco A, Gold, Aaron S, Goldberg, Hila, Gole, Glen A, Gomel, Nir, Gonzalez, Efren, Gonzalez Perez, Graciela, González-Rodríguez, Liudmira, Gorfine, Malka, Graells, Jaime, Gregersen, Pernille A, Grigorovski, Nathalia DAK, Guedenon, Koffi M, Gunasekera, D Sanjeeva, Gündüz, Ahmet K, Gupta, Himika, Gupta, Sanjiv, Gupta, Vineeta, Hadjistilianou, Theodora, Hamel, Patrick, Hamid, Syed A, Hamzah, Norhafizah, Hansen, Eric D, Harbour, J William, Hartnett, M. Elizabeth, Hasanreisoglu, Murat, Muhammad, Hassan, Hassan, Sadiq, Hassan, Shadab, Hautz, Wojciech, Haydar, Huda, Hederova, Stanislava, Hessissen, Laila, Hongeng, Suradej, Hordofa, Diriba F, Hubbard, G. Baker, Hummelen, Marlies, Husakova, Kristina, Hussein Al-Janabi, Allawi N, Ibanga, Affiong, Ida, Russo, Ilic, Vesna R, Islamov, Ziyavuddin, Jairaj, Vivekaraj, Janjua, Teyyeb, Jeeva, Irfan, Ji, Xunda, Jo, Dong Hyun, Jones, Michael M, Kabesha Amani, Theophile B, Kabore, Rolande L, Kaliki, Swathi, Kalinaki, Abubakar, Kamsang, Pius, Kantar, Mehmet, Kapelushnik, Noa, Kardava, Tamar, Kebudi, Rejin, Keomisy, Jonny, Kepak, Tomas, Ketteler, Petra, Khan, Zohora J, Khaqan, Hussain A, Khetan, Vikas, Khodabande, Alireza, Khotenashvili, Zaza, Kim, Jonathan W, Kim, Jeong Hun, Kiratli, Hayyam, Kivela, Tero T., Klett, Artur, Koç, Irem, Kosh Komba Palet, Jess Elio, Krivaitiene, Dalia, Kruger, Mariana, Kulvichit, Kittisak, Kuntorini, Mayasari W, Kyara, Alice, Lam, Geoffrey C, Larson, Scott A, Latinović, Slobodanka, Laurenti, Kelly D, Lavy, Yotam, Lavric Groznik, Alenka, Leverant, Amy A, Li, Cairui, Li, Kaijun, Limbu, Ben, Liu, Chun-Hsiu, Quah, BoonLong, López, Juan P, Lukamba, Robert M, Luna-Fineman, Sandra, Lutfi, Delfitri, Lysytsia, Lesia, Madgar, Shiran, Magrath, George N, Mahajan, Amita, Maitra, Puja, Maka, Erika, Makimbetov, Emil K, Maktabi, Azza, Maldonado, Carlos, Mallipatna, Ashwin, Manudhane, Rebecca, Manzhuova, Lyazat, Martín-Begue, Nieves, Masud, Sidra, Matende, Ibrahim O, Mattosinho, Clarissa CDS, Matua, Marchelo, Mayet, Ismail, Mbumba, Freddy B, McKenzie, John D, Mehrvar, Azim, Mengesha, Aemero A, Menon, Vikas, Mercado, Gary John V, Mets, Marilyn B, Midena, Edoardo, Miller, Audra, Mishra, Divyansh KC, Mndeme, Furahini G, Mohamedani, Ahmed A, Mohammad, Mona T, Moll, Annette C, Montero, Margarita M, Moreira, Claude, Mruthyunjaya, Prithvi, Msina, Mchikirwa S, Msukwa, Gerald, Mudaliar, Sangeeta S, Muma, Kangwa I M, Munier, Francis L, Murray, Timothy G, Musa, Kareem O, Mushtaq, Asma, Musika, Anne A, Mustak, Hamzah, Mustapha, Tajudeen, Muyen, Okwen M, Myezo, Khumo H, Naidu, Gita, Naidu, Natasha, Nair, Akshay Gopinathan, Natarajan, Sundaram, Naumenko, Larisa, Ndoye Roth, Paule Aïda, Nency, Yetty M, Neroev, Vladimir, Ng, Yvonne, Nikitovic, Marina, Nkanga, Elizabeth D, Nkumbe, Henry E, Numbi, Marcel N, Nummi, Kalle, Nuruddin, Murtuza, Nyaywa, Mutale, Nyirenda, Chinsisi, Obono-Obiang, Ghislaine, Oliver, Scott CN, Oporto, Joaquin, Ortega-Hernández, Miriam, Oscar, Alexander H, Ossandon, Diego, Pagarra, Halimah, Paintsil, Vivian, Paiva, Luisa, Palanivelu, Mahesh Shanmugam, Papyan, Ruzanna, Parrozzani, Raffaele, Pascual Morales, Claudia R, Paton, Katherine E, Pe'er, Jacob, Peralta Calvo, Jesús, Perić, Sanja, Pham, Chau TM, Philbert, Remezo, Plager, David A, Pochop, Pavel, Polania, Rodrigo A., Polyakov, Vladimir, Ponce, Jimena, Qadir, Ali O, Qayyum, Seema, Qian, Jiang, Refaeli, David, Rahman, Ardizal, Rajkarnikar, Purnima, Ramanjulu, Rajesh, Ramasubramanian, Aparna, Ramirez-Ortiz, Marco A, Randhawa, Jasmeen K, Randrianarisoa, Hoby Lalaina, Raobela, Léa, Rashid, Riffat, Reddy, M.A., Renner, Lorna A, Reynders, David, Ribadu, Dahiru, Ritter-Sovinz, Petra, Rogowska, Anna, Rojanaporn, Duangnate, Romero, Livia, Roy, Soma R, Saab, Raya H, Saakyan, Svetlana, Sabhan, Ahmed H, Sagoo, Mandeep S, Said, Azza MA, Saiju, Rohit, Salas, Beatriz, San Román Pacheco, Sonsoles, Sánchez, Gissela L, Sanchez Orozco, Alma Janeth, Sayalith, Phayvanh, Scanlan, Trish A, Schlüter, Sabrina, Schwab, Christoph, Sedaghat, Ahad, Seth, Rachna, Sgroi, Mariana, Shah, Ankoor S, Shakoor, Shawkat A, Sharma, Manoj K, Sherief, Sadik T, Shields, Carol L, Sia, David, Siddiqui, Sorath Noorani, Sidi cheikh, Sidi, Silva, Sónia, Singh, Arun D, Singh, Usha, Singha, Penny, Sitorus, Rita S, Skalet, Alison H, Soebagjo, Hendrian D, Sorochynska, Tetyana, Ssali, Grace, Stacey, Andrew W, Staffieri, Sandra E, Stahl, Erin D, Steinberg, David M, Stones, David K, Strahlendorf, Caron, Suarez, Maria Estela Coleoni, Sultana, Sadia, Sun, Xiantao, Superstein, Rosanne, Supriyadi, Eddy, Surukrattanaskul, Supawan, Suzuki, Shigenobu, Svojgr, Karel, Sylla, Fatoumata, Tamamyan, Gevorg, Tan, Deborah, Tandili, Alketa, Tang, Jing, Tarrillo Leiva, Fanny F, Tashvighi, Maryam, Tateshi, Bekim, Teh, Kok Hoi, Tehuteru, Edi S, Teixeira, Luiz F, Tekavcic Pompe, Manca, Thawaba, Abdullah Dahan M, Theophile, Tuyisabe, Toledano, Helen, Trang, Doan L, Traoré, Fousseyni, Tripathy, Devjyoti, Tuncer, Samuray, Tyau-Tyau, Harba, Umar, Ali B, Unal, Emel, Uner, Ogul E, Urbak, Steen F, Ushakova, Tatiana L, Usmanov, Rustam H, Valeina, Sandra, Valente, Paola, van Hoefen Wijsard, Milo, Vasquez Anchaya, Jacqueline Karina, Vaughan, Leon O, Veleva-Krasteva, Nevyana V, Verma, Nishant, Victor, Andi A, Viksnins, Maris, Villacís Chafla, Edwin G, Villegas, Victor M, Vishnevskia-Dai, Victoria, Waddell, Keith, Wali, Amina H, Wang, Yi-Zhuo, Wangtiraumnuay, Nutsuchar, Wetter, Julie, Widiarti, Widiarti, Wilson, Matthew W, Wime, Amelia DC, Wiwatwongwana, Atchareeya, Wiwatwongwana, Damrong, Wolley Dod, Charlotte, Wong, Emily S, Wongwai, Phanthipha, Wu, Si-qi, Xiang, Daoman, Xiao, Yishuang, Xu, Bing, Xue, Kang, Yaghy, Antonio, Yam, Jason C, Yang, Huasheng, Yanga, Jenny M, Yaqub, Muhammad A, Yarovaya, Vera A, Yarovoy, Andrey A, Ye, Huijing, Yee, Roberto I, Yousef, Yacoub A, Yuliawati, Putu, Zapata López, Arturo M, Zein, Ekhtelbenina, Zhang, Yi, Zhilyaeva, Katsiaryna, Zia, Nida, Ziko, Othman AO, Zondervan, Marcia, and Bowman, Richard

Published
2022
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7. MR Imaging of Adverse Effects and Ocular Growth Decline after Selective Intra-Arterial Chemotherapy for Retinoblastoma

Author

de Bloeme, Christiaan M; https://orcid.org/0000-0002-4901-0301, van Elst, Sabien; https://orcid.org/0000-0003-2784-1988, Galluzzi, Paolo; https://orcid.org/0000-0002-7553-5064, Jansen, Robin W; https://orcid.org/0000-0003-0347-1919, de Haan, Joeka; https://orcid.org/0009-0008-3050-6703, Göricke, Sophia, Moll, Annette C; https://orcid.org/0000-0002-9313-8345, Bot, Joseph C J, Munier, Francis L; https://orcid.org/0000-0002-8928-1050, Beck-Popovic, Maja; https://orcid.org/0000-0001-9502-5697, Puccinelli, Francesco, Aerts, Isabelle, Hadjistilianou, Theodora, Sirin, Selma; https://orcid.org/0000-0003-4555-0367, Koob, Mériam, Brisse, Hervé J; https://orcid.org/0000-0003-2794-5875, Cardoen, Liesbeth; https://orcid.org/0000-0001-7842-8638, Maeder, Philippe; https://orcid.org/0000-0002-2875-4889, de Jong, Marcus C; https://orcid.org/0000-0002-8524-5108, de Graaf, Pim; https://orcid.org/0000-0003-1938-0747, de Bloeme, Christiaan M; https://orcid.org/0000-0002-4901-0301, van Elst, Sabien; https://orcid.org/0000-0003-2784-1988, Galluzzi, Paolo; https://orcid.org/0000-0002-7553-5064, Jansen, Robin W; https://orcid.org/0000-0003-0347-1919, de Haan, Joeka; https://orcid.org/0009-0008-3050-6703, Göricke, Sophia, Moll, Annette C; https://orcid.org/0000-0002-9313-8345, Bot, Joseph C J, Munier, Francis L; https://orcid.org/0000-0002-8928-1050, Beck-Popovic, Maja; https://orcid.org/0000-0001-9502-5697, Puccinelli, Francesco, Aerts, Isabelle, Hadjistilianou, Theodora, Sirin, Selma; https://orcid.org/0000-0003-4555-0367, Koob, Mériam, Brisse, Hervé J; https://orcid.org/0000-0003-2794-5875, Cardoen, Liesbeth; https://orcid.org/0000-0001-7842-8638, Maeder, Philippe; https://orcid.org/0000-0002-2875-4889, de Jong, Marcus C; https://orcid.org/0000-0002-8524-5108, and de Graaf, Pim; https://orcid.org/0000-0003-1938-0747

Abstract

This retrospective multicenter study examines therapy-induced orbital and ocular MRI findings in retinoblastoma patients following selective intra-arterial chemotherapy (SIAC) and quantifies the impact of SIAC on ocular and optic nerve growth. Patients were selected based on medical chart review, with inclusion criteria requiring the availability of posttreatment MR imaging encompassing T2-weighted and T1-weighted images (pre- and post-intravenous gadolinium administration). Qualitative features and quantitative measurements were independently scored by experienced radiologists, with deep learning segmentation aiding total eye volume assessment. Eyes were categorized into three groups: eyes receiving SIAC (Rb-SIAC), eyes treated with other eye-saving methods (Rb-control), and healthy eyes. The most prevalent adverse effects post-SIAC were inflammatory and vascular features, with therapy-induced contrast enhancement observed in the intraorbital optic nerve segment in 6% of patients. Quantitative analysis revealed significant growth arrest in Rb-SIAC eyes, particularly when treatment commenced ≤ 12 months of age. Optic nerve atrophy was a significant complication in Rb-SIAC eyes. In conclusion, this study highlights the vascular and inflammatory adverse effects observed post-SIAC in retinoblastoma patients and demonstrates a negative impact on eye and optic nerve growth, particularly in children treated ≤ 12 months of age, providing crucial insights for clinical management and future research.

Published
2024

8. Conservative management of retinoblastoma: Challenging orthodoxy without compromising the state of metastatic grace. “Alive, with good vision and no comorbidity”

Author

Munier, Francis L., Beck-Popovic, Maja, Chantada, Guillermo L., Cobrinik, David, Kivelä, Tero T., Lohmann, Dietmar, Maeder, Philippe, Moll, Annette C., Carcaboso, Angel Montero, Moulin, Alexandre, Schaiquevich, Paula, Bergin, Ciara, Dyson, Paul J., Houghton, Susan, Puccinelli, Francesco, Vial, Yvan, Gaillard, Marie-Claire, and Stathopoulos, Christina

Published
2019
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9. Anti-MAPK Targeted Therapy for Ameloblastoma: Case Report with a Systematic Review.

Author

Raemy, Anton, May, Laurence, Sala, Nathalie, Diezi, Manuel, Beck-Popovic, Maja, and Broome, Martin

Subjects
PROTEIN kinase inhibitors, MITOGEN-activated protein kinases, PATIENT safety, CANCER relapse, CANCER invasiveness, DISEASE remission, SYSTEMATIC reviews, METASTASIS, DRUG efficacy, AMELOBLASTOMA, PHARMACODYNAMICS
Abstract

Simple Summary: Ameloblastoma is a type of tumor that usually forms in the jaw; while typically benign, it grows aggressively and often recurs after treatment. Traditional treatment involves extensive surgery, which can significantly affect a patient's quality of life. Recent research has focused on a new approach, targeting a specific cellular pathway known as the MAPK pathway, which appears to be involved in the development of these tumors. In this study, we reviewed the outcomes of 23 patients treated with this targeted therapy to assess its safety and effectiveness. The results were promising: most patients experienced significant tumor reduction, and the side effects were generally mild. This suggests that MAPK pathway inhibitors could be a viable alternative to surgery, potentially offering improved outcomes for patients with ameloblastoma, minimizing surgical risks, and preserving quality of life. This advancement could greatly impact the approach to treating this challenging condition. Ameloblastoma, a benign yet aggressive odontogenic tumor known for its recurrence and the severe morbidity from radical surgeries, may benefit from advancements in targeted therapy. We present a case of a 15-year-old girl with ameloblastoma successfully treated with targeted therapy and review the literature with this question: Is anti-MAPK targeted therapy safe and effective for treating ameloblastoma? This systematic review was registered in PROSPERO, adhered to PRISMA guidelines, and searched multiple databases up to December 2023, identifying 13 relevant studies out of 647 records, covering 23 patients treated with MAPK inhibitor therapies. The results were promising as nearly all patients showed a positive treatment response, with four achieving complete radiological remission and others showing substantial reductions in primary, recurrent, and metastatic ameloblastoma sizes. Side effects were mostly mild to moderate. This study presents anti-MAPK therapy as a significant shift from invasive surgical treatments, potentially enhancing life quality and clinical outcomes by offering a less invasive yet effective treatment alternative. This approach could signify a breakthrough in managing this challenging tumor, emphasizing the need for further research into molecular-targeted therapies. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Absorbable gelatin compressed sponge (Gelfoam) embolization of distal external carotid artery branches in intra- arterial chemotherapy for retinoblastoma.

Author

Akkari, Fouad Georges, Stathopoulos, Christina, Puccinelli, Francesco, Hajdu, Steven D., Beck-Popovic, Maja, Munier, Francis L., Saliou, Guillaume, and Bartolini, Bruno

Subjects
CAROTID artery surgery, RETINAL detachment, OPHTHALMIC artery, PATIENT safety, THERAPEUTIC embolization, TREATMENT effectiveness, CANCER chemotherapy, RETINOBLASTOMA, LONGITUDINAL method, SURGICAL sponges, INTRA-arterial infusions, PATHOLOGIC neovascularization
Abstract

Background In intra-arterial chemotherapy for retinoblastoma, a backflow from unreachable external carotid artery branches in the ophthalmic artery can be challenging. Objective To describe a new endovascular technique using Gelfoam pledgets to temporarily occlude distal branches of the external carotid artery to reverse the competitive backflow into the ophthalmic artery in order to perform intra-arterial chemotherapy via the ostium of the ophthalmic artery in selected cases. Methods We queried our prospectively collected database of 327 consecutive patients treated for retinoblastoma by intra-arterial chemotherapy and identified those employing Gelfoam pledgets. We describe this new technique with emphasis on feasibility and safety. Results We treated 11 eyes with 14 infusions of intra-arterial chemotherapy using Gelfoam pledgets to occlude the distal branches of the external carotid artery. We report no perioperative complications due to this occlusion technique. At the ophthalmologic follow-up 1 month after the injection of Gelfoam pledgets, all cases showed tumor regression or stable disease. Two injections into the same eye as the rescue intra-arterial chemotherapy infusion resulted in a transient exudative retinal detachment, and one injection in a heavily pretreated case was followed by iris neovascularization and retinal ischemia. None of the pledget injections led to irreversible vision-threatening intraocular complications. Conclusions Intra-arterial chemotherapy in retinoblastoma using Gelfoam to transiently occlude the distal branches of the external carotid artery and reverse the backflow into the ophthalmic artery seems feasible and safe. Larges series will help to confirm the effectiveness of this new technique. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Interleukin 2 with anti-GD2 antibody ch14.18/CHO (dinutuximab beta) in patients with high-risk neuroblastoma (HR-NBL1/SIOPEN): a multicentre, randomised, phase 3 trial

Author

Ladenstein, Ruth, Pötschger, Ulrike, Valteau-Couanet, Dominique, Luksch, Roberto, Castel, Victoria, Yaniv, Isaac, Laureys, Genevieve, Brock, Penelope, Michon, Jean Marie, Owens, Cormac, Trahair, Toby, Chan, Godfrey Chi Fung, Ruud, Ellen, Schroeder, Henrik, Beck Popovic, Maja, Schreier, Guenter, Loibner, Hans, Ambros, Peter, Holmes, Keith, Castellani, Maria Rita, Gaze, Mark N, Garaventa, Alberto, Pearson, Andrew D J, and Lode, Holger N

Published
2018
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12. Risk factors for overweight and obesity after childhood acute lymphoblastic leukemia in North America and Switzerland: A comparison of two cohort studies

Author

Belle, Fabiën N., primary, Schindera, Christina, additional, Ansari, Marc, additional, Armstrong, Gregory T., additional, Beck‐Popovic, Maja, additional, Howell, Rebecca, additional, Leisenring, Wendy M., additional, Meacham, Lillian R., additional, Rössler, Jochen, additional, Spycher, Ben D., additional, Tonorezos, Emily, additional, von der Weid, Nicolas X., additional, Yasui, Yutaka, additional, Oeffinger, Kevin C., additional, and Kuehni, Claudia E., additional

Published
2023
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13. Low adherence to dietary recommendations in adult childhood cancer survivors

Author

Ammann, R., Angst, R., Ansari, M., Beck Popovic, M., Bergstraesser, E., Brazzola, P., Greiner, J., Grotzer, M., Hengartner, H., Kuehne, T., Leibundgut, K., Niggli, F., Rischewski, J., von der Weid, N., Belle, Fabiën, Wengenroth, Laura, Weiss, Annette, Sommer, Grit, Beck Popovic, Maja, Ansari, Marc, Bochud, Murielle, and Kuehni, Claudia

Published
2017
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14. Spinal Canal Involvement in Neuroblastoma

Author

Trahair, Toby, Sorrentino, Stefania, Russell, Susan J., Sampaio, Hugo, Selek, Laurent, Plantaz, Dominique, Freycon, Claire, Simon, Thorsten, Kraal, Kathelijne, Beck-Popovic, Maja, Haupt, Riccardo, Ash, Shifra, and De Bernardi, Bruno

Published
2017
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15. Busulfan and melphalan versus carboplatin, etoposide, and melphalan as high-dose chemotherapy for high-risk neuroblastoma (HR-NBL1/SIOPEN): an international, randomised, multi-arm, open-label, phase 3 trial

Author

Ladenstein, Ruth, Pötschger, Ulrike, Pearson, Andrew D J, Brock, Penelope, Luksch, Roberto, Castel, Victoria, Yaniv, Isaac, Papadakis, Vassilios, Laureys, Geneviève, Malis, Josef, Balwierz, Walentyna, Ruud, Ellen, Kogner, Per, Schroeder, Henrik, de Lacerda, Ana Forjaz, Beck-Popovic, Maja, Bician, Pavel, Garami, Miklós, Trahair, Toby, Canete, Adela, Ambros, Peter F, Holmes, Keith, Gaze, Mark, Schreier, Günter, Garaventa, Alberto, Vassal, Gilles, Michon, Jean, and Valteau-Couanet, Dominique

Published
2017
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16. MR Imaging of Adverse Effects and Ocular Growth Decline after Selective Intra-Arterial Chemotherapy for Retinoblastoma.

Author

de Bloeme, Christiaan M., van Elst, Sabien, Galluzzi, Paolo, Jansen, Robin W., de Haan, Joeka, Göricke, Sophia, Moll, Annette C., Bot, Joseph C. J., Munier, Francis L., Beck-Popovic, Maja, Puccinelli, Francesco, Aerts, Isabelle, Hadjistilianou, Theodora, Sirin, Selma, Koob, Mériam, Brisse, Hervé J., Cardoen, Liesbeth, Maeder, Philippe, de Jong, Marcus C., and de Graaf, Pim

Subjects
OPTIC nerve diseases, VISION disorders, EYE, QUALITATIVE research, RESEARCH funding, DISEASE management, MAGNETIC resonance imaging, RETROSPECTIVE studies, QUANTITATIVE research, TREATMENT effectiveness, RETINOBLASTOMA, CANCER chemotherapy, RESEARCH, DEEP learning, COMPARATIVE studies, INFLAMMATION
Abstract

Simple Summary: This study investigates the adverse effects of selective intra-arterial chemotherapy (SIAC) on the eyes and optic nerves of retinoblastoma patients using magnetic resonance imaging (MRI). We aim to understand the post-SIAC changes in orbital and ocular structures and evaluate their impact on eye and optic nerve growth. Experienced radiologists analyzed MR images of retinoblastoma eyes treated with SIAC, comparing them to eyes treated with other eye-saving methods and healthy eyes. Results reveal common adverse effects like inflammation and vascular changes, along with significant ocular growth arrest and optic nerve atrophy in eyes treated with SIAC, especially in children treated ≤ 12 months of age. This study underscores the importance of careful consideration when utilizing SIAC, particularly in young patients, due to its potential negative effects on eye and optic nerve development. This retrospective multicenter study examines therapy-induced orbital and ocular MRI findings in retinoblastoma patients following selective intra-arterial chemotherapy (SIAC) and quantifies the impact of SIAC on ocular and optic nerve growth. Patients were selected based on medical chart review, with inclusion criteria requiring the availability of posttreatment MR imaging encompassing T2-weighted and T1-weighted images (pre- and post-intravenous gadolinium administration). Qualitative features and quantitative measurements were independently scored by experienced radiologists, with deep learning segmentation aiding total eye volume assessment. Eyes were categorized into three groups: eyes receiving SIAC (Rb-SIAC), eyes treated with other eye-saving methods (Rb-control), and healthy eyes. The most prevalent adverse effects post-SIAC were inflammatory and vascular features, with therapy-induced contrast enhancement observed in the intraorbital optic nerve segment in 6% of patients. Quantitative analysis revealed significant growth arrest in Rb-SIAC eyes, particularly when treatment commenced ≤ 12 months of age. Optic nerve atrophy was a significant complication in Rb-SIAC eyes. In conclusion, this study highlights the vascular and inflammatory adverse effects observed post-SIAC in retinoblastoma patients and demonstrates a negative impact on eye and optic nerve growth, particularly in children treated ≤ 12 months of age, providing crucial insights for clinical management and future research. [ABSTRACT FROM AUTHOR]

Published
2024
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20. Ten-year experience with intracameral chemotherapy for aqueous seeding in retinoblastoma: long-term efficacy, safety and toxicity.

Author

Stathopoulos, Christina, Beck-Popovic, Maja, Moulin, Alexandre P., and Munier, Francis L.

Abstract

Aims To report long-term results of intracameral chemotherapy (ICC) for aqueous seeding (AS) in retinoblastoma. Methods Retrospective study including 20 patients with primary (n=4) or secondary non-iatrogenic (n=16) AS treated with ICC according to a previously described technique between 2011 and 2020 with at least 1-year follow-up. Results AS control was initially achieved in all cases with a mean 5 injections of melphalan (n=13) or topotecan (n=7). Three eyes had an isolated AS relapse at a mean interval of 8 months after the first ICC course, which regressed with a second course of intracameral melphalan. Concomitant interciliary process seed implantation was treated with additional brachytherapy if sectorial (n=3) or proton therapy if annular (n=1). Other therapies including systemic, intra-arterial chemotherapy and/or focal treatments were given in 15 eyes to treat concomitant tumour sites. Eye preservation was achieved in 85% of the eyes (n=17/20) at a mean event-free follow-up of 45 months for aqueous disease, and 40 months for any other intraocular tumour activity. Three cases were enucleated due to refractory non-aqueous disease. All patients are alive without metastasis (mean follow-up of 48 months after first ICC). ICC-related intraocular toxicity included iris atrophy (n=5), cataract (n=4), posterior synechiae (n=2) and iris heterochromia (n=1). No patient suffered irreversible vision loss. Useful to normal vision was found in 82% of the cases (n=14/17). Conclusion ICC appears to be safe and efficient for AS without irreversible vision-threatening adverse effects. More data are needed to determine any superiority in efficiency/toxicity of topotecan versus melphalan. [ABSTRACT FROM AUTHOR]

Published
2024
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22. CUDC-907, a dual PI3K/histone deacetylase inhibitor, increases meta-iodobenzylguanidine uptake (123/131I-mIBG) in vitro and in vivo: a promising candidate for advancing theranostics in neuroendocrine tumors

Author

Grand-Guillaume, Joana, primary, Mansi, Rosalba, additional, Gaonkar, Raghuvirharidas, additional, Zanger, sandra, additional, Fani, Melpomeni, additional, Eugster, Philippe, additional, Beck-Popovic, Maja, additional, Grouzmann, Eric, additional, and Abid, karim, additional

Published
2023
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29. Essential medicines for childhood cancer in Europe: a pan-European, systematic analysis by SIOPE

Author

Otth, Maria, primary, Brack, Eva, additional, Kearns, Pamela R, additional, Kozhaeva, Olga, additional, Ocokoljic, Marko, additional, Schoot, Reineke A, additional, Vassal, Gilles, additional, Achini, Federica, additional, Balduzzi, Adriana, additional, Beck Popovic, Maja, additional, Beishuizen, Auke, additional, Bergamaschi, Luca, additional, Biondi, Andrea, additional, Bourdeaut, Franck, additional, Braicu, Elena, additional, Brok, Jesper, additional, Brugières, Laurence, additional, Burke, Amos, additional, Calaminus, Gabriele, additional, Casanova, Michela, additional, Choucair, Marie-Louise, additional, Cleirec, Morgane, additional, Corbaciouglu, Selim, additional, Correa Llano, Maria Genoveva, additional, De Rojas, Teresa, additional, Domínguez Pinilla, Nerea, additional, Elmaraghi, Caroline, additional, Ferrari, Andrea, additional, Fossa, Alexander, additional, Gaspar, Nathalie, additional, Herold, Nikolas, additional, Karapiperi, Kyriaki, additional, Karu, Maarja, additional, Kjærsgaar, Mimi, additional, Knörr, Fabian, additional, Koenig, Christa, additional, Kranjcec, Izabela, additional, Krawczyk, Malgorzata, additional, Lehmberg, Kai, additional, Lehrnbecher, Thomas, additional, Lunesink, Maaike, additional, Massano, Davide, additional, Matijasic, Nuša, additional, Merks, Hans, additional, Metzler, Markus, additional, Michalski, Anthony, additional, Minkov, Milen, additional, Morland, Bruce, additional, Niktoreh, Naghmeh, additional, Oltenau, Elena, additional, Orbach, Daniel, additional, Owens, Cormac, additional, Papachristidou, Smaragda, additional, Pasqualini, Claudia, additional, Pavlovic, Maja, additional, Perez Albert, Paula, additional, Poyer, Fiona, additional, Radulovic, Ivana, additional, Reinhardt, Dirk, additional, Rebelo, Joana, additional, Roser, Eva, additional, Russo, Ida, additional, Scheinemann, Katrin, additional, Schindera, Christina, additional, Schrappe, Martin, additional, Sehested, Astrid, additional, Sehouli, Jalid, additional, Spreafico, Filippo, additional, Strauss, Sandra J, additional, Stutterheim, Janine, additional, Svojgr, Karel, additional, Tzotzola, Vasiliki, additional, Van Ewijk, Roelof, additional, Verschuur, Arnauld, additional, Vora, Ajay, additional, Woessmann, Willi, additional, Zajac-Spychala, Olga, additional, and Zwaan, Michel, additional

Published
2022
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31. Acute and long-term psychosocial consequences in grandparents when a grandchild is diagnosed with cancer – the GROKids Project: a population-based mixed-methods study protocol.

Author

Michel, Gisela, Raguindin, Peter Francis, Priboi, Cristina, Ilic, Anica, Holmer, Pauline, Scheinemann, Katrin, the GROKids Project, von der Weid, Nicolas, Brazzola, Pierluigi, Roessler, Jochen, Ansari, Marc, Diezi, Manuel, Beck-Popovic, Maja, Schilling, Freimut, Greiner, Jeanette, and Hengartner, Heinz

Subjects
GRANDPARENTS, GRANDCHILDREN, GRANDPARENT-grandchild relationships, CANCER diagnosis, RESEARCH protocols, PATIENT advocacy, PSYCHOSOCIAL factors, MEDICAL personnel
Abstract

Background: Grandparents play a crucial role in providing their families with love, support, and wisdom, often also supporting them in practical and financial ways. The psychosocial effects experienced by grandparents when a grandchild is diagnosed with an illness can be significant, including increased stress, anxiety, grief, and disruptions in their own lives. Yet, the experience of grandparents is often overlooked in the literature. Methods/design: The GROKids Project aims to investigate how grandparents are affected by a grandchild's cancer diagnosis. It employs a mixed-methods approach and consists of three studies: a longitudinal cohort study (Study 1) and a qualitative study (Study 2) involving grandparents of children with a recent cancer diagnosis, and a cross-sectional study (Study 3) of grandparents of childhood cancer survivors. Study 1 covers four time points over two years after the cancer diagnosis, while Study 2 explores the lived experiences of a subsample of these grandparents. Study 3 collects data from grandparents of childhood cancer survivors diagnosed 3 to 10 years ago. Participants are recruited across eight pediatric oncology centers in Switzerland, and through patient advocacy and support groups. Eligibility criteria include having a grandchild diagnosed with cancer and being fluent in German, French, or Italian. Study procedures involve requesting grandparents' contacts from eligible families, and later contacting grandparents, providing study information, obtaining informed consent, and sending out questionnaires by post or online. Reminder calls and mails are used to improve response rates. Data analysis includes multilevel regression (Study 1), thematic analysis (Study 2), and regression analyses (Study 3). Various validated questionnaires are used to assess physical health and overall well-being, psychological health, internal, and external factors. Discussion: This project addresses the gaps in understanding the psychosocial effects on grandparents having a grandchild diagnosed with cancer. It utilizes a comprehensive approach, including multiple methodologies and considering the broader family context. The project's strengths lie in its mixed-methods design, longitudinal approach, and inclusion of the perspectives of the sick children, siblings, and parents, besides grandparents. By gaining a more profound understanding of grandparents' experiences, researchers and healthcare professionals can develop targeted interventions and support services to address grandparents' unique needs. [ABSTRACT FROM AUTHOR]

Published
2023
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32. CUDC-907, a dual PI3K/histone deacetylase inhibitor, increases meta-iodobenzylguanidine uptake (123/131I-mIBG) in vitro and in vivo: a promising candidate for advancing theranostics in neuroendocrine tumors.

Author

Grand-Guillaume, Joana, Mansi, Rosalba, Gaonkar, Raghuvir H., Zanger, Sandra, Fani, Melpomeni, Eugster, Philippe J., Beck Popovic, Maja, Grouzmann, Eric, and Abid, Karim

Subjects
NEUROENDOCRINE tumors, MONOAMINE transporters, HISTONE deacetylase inhibitors, COMPANION diagnostics, HISTONE deacetylase, ORAL drug administration
Abstract

Background: Neuroblastoma (NB) and pheochromocytoma/paraganglioma (PHEO/PGL) are neuroendocrine tumors. Imaging of these neoplasms is performed by scintigraphy after injection of radiolabeled meta-iodobenzylguanidine (mIBG), a norepinephrine analog taken up by tumoral cells through monoamine transporters. The pharmacological induction of these transporters is a promising approach to improve the imaging and therapy (theranostics) of these tumors. Methods: Transporters involved in mIBG internalization were identified by using transfected Human Embryonic Kidney (HEK) cells. Histone deacetylase inhibitors (HDACi) and inhibitors of the PI3K/AKT/mTOR pathway were tested in cell lines to study their effect on mIBG internalization. Studies in xenografted mice were performed to assess the effect of the most promising HDACi on 123I-mIBG uptake. Results: Transfected HEK cells demonstrated that the norepinephrine and dopamine transporter (NET and DAT) avidly internalizes mIBG. Sodium-4-phenylbutyrate (an HDACi), CUDC-907 (a dual HDACi and PI3K inhibitor), BGT226 (a PI3K inhibitor) and VS-5584 and rapamycin (two inhibitors of mTOR) increased mIBG internalization in a neuroblastoma cell line (IGR-NB8) by 2.9-, 2.1-, 2.5-, 1.5- and 1.3-fold, respectively, compared with untreated cells. CUDC-907 also increased mIBG internalization in two other NB cell lines and in one PHEO cell line. We demonstrated that mIBG internalization occurs primarily through the NET. In xenografted mice with IGR-NB8 cells, oral treatment with 5 mg/kg of CUDC-907 increased the tumor uptake of 123I-mIBG by 2.3- and 1.9-fold at 4 and 24 h post-injection, respectively, compared to the untreated group. Conclusions: Upregulation of the NET by CUDC-907 lead to a better internalization of mIBG in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Published
2023
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36. Presenting features of neuroblastoma with spinal canal invasion. A prospective study of the International Society of Pediatric Oncology Europe - Neuroblastoma (SIOPEN)

Author

Sorrentino, Stefania, primary, Ash, Shifra, additional, Haupt, Riccardo, additional, Plantaz, Dominique, additional, Schiff, Isabelle, additional, Hero, Barbara, additional, Simon, Thorsten, additional, Kachanov, Denis, additional, Shamanskaya, Tatyana, additional, Kraal, Katheljine, additional, Littooij, Annemieke, additional, Wieczoreck, Alexsandra, additional, Balwierz, Walentyna, additional, Laureys, Geneviève, additional, Trager, Catherine, additional, Sertorio, Fiammetta, additional, Erminio, Giovanni, additional, Fragola, Martina, additional, Beck Popovic, Maja, additional, De Bernardi, Bruno, additional, and Trahair, Toby, additional

Published
2022
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39. Presenting features of neuroblastoma with spinal canal invasion. A prospective study of the International Society of Pediatric Oncology Europe-Neuroblastoma (SIOPEN)

Author

Sorrentino, Stefania, Ash, Shifra, Haupt, Riccardo, Plantaz, Dominique, Schiff, Isabelle, Hero, Barbara, Simon, Thorsten, Kachanov, Denis, Shamanskaya, Tatyana, Kraal, Katheljine, Littooij, Annemieke, Wieczoreck, Alexsandra, Balwierz, Walentyna, Laureys, Genevieve, Trager, Catherine, Sertorio, Fiammetta, Erminio, Giovanni, Fragola, Martina, Beck Popovic, Maja, De Bernardi, Bruno, Trahair, Toby, Sorrentino, Stefania, Ash, Shifra, Haupt, Riccardo, Plantaz, Dominique, Schiff, Isabelle, Hero, Barbara, Simon, Thorsten, Kachanov, Denis, Shamanskaya, Tatyana, Kraal, Katheljine, Littooij, Annemieke, Wieczoreck, Alexsandra, Balwierz, Walentyna, Laureys, Genevieve, Trager, Catherine, Sertorio, Fiammetta, Erminio, Giovanni, Fragola, Martina, Beck Popovic, Maja, De Bernardi, Bruno, and Trahair, Toby

Abstract

IntroductionBetween 5 and 15% of children with neuroblastoma (NB) present with or develop spinal canal invasion (SCI). The majority of these children have symptoms of epidural compression of spinal cord and/or spinal nerves. Treatment of NB-SCI is considered an emergency but its modalities are not yet well-established. Independently of treatment, NB-SCI may result in significant long-term disabilities. We report on the first prospective study of NB-SCI focused on presenting characteristics of both symptomatic and asymptomatic patients and correlation between SCI-related symptoms and imaging features. Materials and methodsThis SIOPEN prospective NB-SCI study opened in June 2014. Patient data including SCI symptoms evaluated by standardized measures and spinal cord imaging studies were collected for each patient. For the purpose of this study data entry was locked on July 2021. ResultsOf the 208 NB-SCI patients registered, 196 were evaluable for this analysis of whom 67% were symptomatic and 33% asymptomatic. Median age was 11 months. The thorax was the commonest primary tumor site. The median intervals between initial symptoms and diagnosis and between first medical visit and diagnosis were 14 and 3 days, respectively. The was no statistical difference in frequency of presenting characteristics between symptomatic and asymptomatic patients. Presenting features of NB-SCI patients differed from other NBs for older median age, prevalence of thoracic vs. abdominal primary site, prevalence of localized vs. metastatic disease and lower incidence of MYCN gene amplification. The most common SCI features were motor deficit in the younger and pain in the older patients that correlated on imaging with both transverse and longitudinal extent but not with the level of intraspinal tumor. Spinal cord T2-hyperintensity was more frequently detected in symptomatic patients (not significant). ConclusionThis prospective study confirms that children with NB-SCI differ from NBs without SC

Published
2022

44. PASTEC - a prospective, single-center, randomized, cross-over trial of pure physical versus physical plus attentional training in children with cancer

Author

Fontana, Andrea, primary, Matthey, Sonia, additional, Mayor, Claire, additional, Dufour, Céline, additional, Destaillats, Alice, additional, Ballabeni, Pierluigi, additional, Maeder, Stéphane, additional, Newman, Christopher J., additional, Beck Popovic, Maja, additional, Renella, Raffaele, additional, and Diezi, Manuel, additional

Published
2021
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46. Corrigendum to “Conservative management of retinoblastoma: Challenging orthodoxy without compromising the state of metastatic grace. “Alive, with good vision and no comorbidity”” [Prog. Retina Eye Res. 73 (2019) 100764]

Author

Munier, Francis L., Beck-Popovic, Maja, Chantada, Guillermo L., Cobrinik, David, Kivelä, Tero T., Lohmann, Dietmar, Maeder, Philippe, Moll, Annette C., Carcaboso, Angel Montero, Moulin, Alexandre, Schaiquevich, Paula, Bergin, Ciara, Dyson, Paul J., Houghton, Susan, Puccinelli, Francesco, Vial, Yvan, Gaillard, Marie-Claire, and Stathopoulos, Christina

Published
2020
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47. Randomized Trial of Two Induction Therapy Regimens for High-Risk Neuroblastoma: HR-NBL1.5 International Society of Pediatric Oncology European Neuroblastoma Group Study

Author

Garaventa, Alberto, primary, Poetschger, Ulrike, additional, Valteau-Couanet, Dominique, additional, Luksch, Roberto, additional, Castel, Victoria, additional, Elliott, Martin, additional, Ash, Shifra, additional, Chan, Godfrey C. F., additional, Laureys, Geneviève, additional, Beck-Popovic, Maja, additional, Vettenranta, Kim, additional, Balwierz, Walentyna, additional, Schroeder, Henrik, additional, Owens, Cormac, additional, Cesen, Maja, additional, Papadakis, Vassilios, additional, Trahair, Toby, additional, Schleiermacher, Gudrun, additional, Ambros, Peter, additional, Sorrentino, Stefania, additional, Pearson, Andrew D. J., additional, and Ladenstein, Ruth Lydia, additional

Published
2021
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48. Current Indications of Secondary Enucleation in Retinoblastoma Management: A Position Paper on Behalf of the European Retinoblastoma Group (EURbG)

Author

Stathopoulos, Christina, primary, Lumbroso-Le Rouic, Livia, additional, Moll, Annette C., additional, Parulekar, Manoj, additional, Maeder, Philippe, additional, Doz, François, additional, Jenkinson, Helen, additional, Beck Popovic, Maja, additional, Chantada, Guillermo, additional, and Munier, Francis L., additional

Published
2021
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49. Corrigendum to 'Conservative management of retinoblastoma:Challenging orthodoxy without compromising the state of metastatic grace. 'Alive, with good vision and no comorbidity'' [Prog. Retina Eye Res. 73 (2019) 100764] (Progress in Retinal and Eye Research (2019) 73, (S1350946218300739), (10.1016/j.preteyeres.2019.05.005))

Author

Munier, Francis L., Beck-Popovic, Maja, Chantada, Guillermo L., Cobrinik, David, Kivelä, Tero T., Lohmann, Dietmar, Maeder, Philippe, Moll, Annette C., Carcaboso, Angel Montero, Moulin, Alexandre, Schaiquevich, Paula, Bergin, Ciara, Dyson, Paul J., Houghton, Susan, Puccinelli, Francesco, Vial, Yvan, Gaillard, Marie Claire, and Stathopoulos, Christina

Subjects
eye diseases
Abstract

The authors regret that Science Direct is not formatted to display the full content of the paper synopsis. This is now fixed with the publication of this corrigendum. List of contents 1. Introduction2. Epidemiology 2.1. Incidence2.2. Prevalence2.3. Predisposing factors for sporadic retinoblastoma3. Diagnosis 3.1. Presenting features3.2. Clinical examination and ancillary testing 3.2.1. Fundus documentation and fluorescein angiography3.2.2. Ultrasonic biomicroscopy (UBM)3.2.3. Optic coherence tomography (OCT)3.2.4. Magnetic Resonance Imaging (MRI)3.3. Classifications 3.3.1. Grouping of the eye at presentation (RE, IIRC, ICRB, COG, TNMH)3.3.2. Patient staging at presentation (IRSS, TNMH)3.3.3. Classification of retinoblastoma at relapse (RSU classification)3.4. Differential diagnosis3.5. Prenatal diagnosis of retinoblastoma3.6. Trilateral retinoblastoma 3.6.1. Incidence, early detection and screening3.6.2. Influence of the retinoblastoma treatment on the incidence of trilateral retinoblastoma3.6.3. Improved treatment of trilateral retinoblastoma: high-dose chemotherapy3.6.4. Differential diagnosis: pineal cysts3.7. Metastatic retinoblastoma 3.7.1. Diagnosis of metastatic retinoblastoma3.7.2. Treatment of metastatic retinoblastoma3.7.3. Influence of conservative retinoblastoma treatment in the occurrence of metastasis3.8. Second primary neoplasms 3.8.1. Incidence and mortality of second primary neoplasms3.8.2. Characteristics of secondary primary neoplasms3.8.3. Factors influencing the risk of secondary primary neoplasms 3.8.3.1. Genetic predisposition3.8.3.2. Influence of therapy3.8.3.2.1. Radiotherapy3.8.3.2.2. Chemotherapy3.8.4. Long-term follow-up in heritable retinoblastoma survivors 4. Retinoblastoma genesis 4.1. Mutational inactivation of the RB1 gene initiates retinoblastoma tumorigenesis4.2. Most retinoblastomas show more than two-hits4.3. RB1 mutations initiate tumorigenesis in the retinoblastoma cell-of-origin 4.3.1. First hints pointing towards a photoreceptor cell-of-origin4.3.2. Efforts to identify the retinoblastoma origin using genetically engineered mice4.3.3. Circumstantial and direct evidence for a cone precursor cell-of-origin4.3.4. Reconciling the cone precursor cell-of-origin with apparently contradictory observations4.4. Collaboration between RB1 inactivation and the cell-of-origin circuitry5. Retinoblastoma genetics and genetic counseling 5.1. Genetic presentations of retinoblastoma 5.1.1. Inherited heritable retinoblastoma (familial retinoblastoma) 5.1.1.1. Familial retinoblastoma with complete retinoblastoma5.1.1.2. Familial retinoblastoma with incomplete penetrance5.1.2. Isolated heritable retinoblastoma 5.1.2.1. Isolated bilateral retinoblastoma (full expressivity)5.1.2.2. Isolated retinoblastoma with genomic 13q14 deletion (reduced expressivity)5.1.3. Mosaic retinoblastoma5.1.4. Non-heritable retinoblastoma 5.1.4.1. Isolated unilateral retinoblastoma with somatic biallelic RB1 mutation5.1.4.2. Retinoblastoma without alterations of the RB1 gene 5.2. Genetic counseling and testing 5.2.1. Familial retinoblastoma5.2.2. Isolated bilateral retinoblastoma5.2.3. Isolated unilateral retinoblastoma 6. Clinical growth and seeding patterns 6.1. Retinoblastoma growth patterns 6.1.1. Classic growth patterns of primary retinoblastoma: endophytic, exophytic, mixed growth6.1.2. Rare variants of retinoblastoma 6.1.2.1. Cavitary retinoblastoma6.1.2.2. Diffuse infiltrating retinoblastoma6.1.2.3. Diffuse anterior retinoblastoma 6.2. Intra-ocular seeding 6.2.1. Vitreous seeding6.2.2. Retrohyaloid seeding6.2.3. Subretinal seeding6.2.4. Aqueous seeding 6.2.4.1. Prevalence of anterior chamber seeding6.2.4.2. Prevalence of anterior uvea invasion6.2.4.3. Invasion mechanisms of the aqueous humor 6.3. Retinoma/retinocytoma and phthisis bulbi 6.3.1. Prevalence and relationship with retinoblastoma6.3.2. Clinical features and risk of malignant transformation. 7. Conservative management of intraocular retinoblastoma 7.1. Pharmacokinetics 7.1.1. Intravenous drug delivery7.1.2. Intra-arterial drug delivery 7.1.2.1. Intraocular distribution of intra-arterial melphalan and topotecan7.1.2.2. Systemic adverse effects of intra-arterial delivered drugs7.1.3. Intravitreal drug delivery 7.1.3.1. Intraocular distribution of intravitreal melphalan7.1.3.2. Intraocular distribution of intravitreal topotecan7.1.4. Intracameral drug delivery7.1.5. Periocular drug delivery7.1.6. Suprachoroidal drug delivery7.2. Treatment modalities 7.2.1. Intravenous chemotherapy 7.2.1.1. Drug regimen and number of cycles7.2.1.2. Indications 7.2.1.2.1. Current indications7.2.1.2.2. Potential future indications 7.2.2. Treatment outcomes of intravenous chemotherapy 7.2.2.1. Relapse rate and role of consolidation by focal treatments7.2.2.2. Eye preservation without external beam radiotherapy7.2.3. Chemotherapy-related toxicity of intravenous chemotherapy 7.2.3.1. Expected toxicities7.2.3.2. Long-term toxicities7.2.4. Intra-arterial chemotherapy 7.2.4.1. Drug regimen and number of cycles7.2.4.2. Indications 7.2.4.2.1. Current indications7.2.4.2.2. Potential future indications7.2.4.3. Treatment outcomes 7.2.4.3.1. Recurrence rate and salvage therapy7.2.4.3.2. Eye preservation without external beam radiotherapy7.2.4.4. Adverse effects7.2.5. Intravitreal chemotherapy 7.2.5.1. Drug regimen and number of injections7.2.5.2. Safety7.2.5.3. Treatment outcomes7.2.5.4. Adverse effects7.2.6. Intracameral chemotherapy 7.2.6.1. Treatment outcomes7.2.6.2. Treatment-related adverse effects7.2.6.3. Potential alternatives to intracameral chemotherapy for aqueous seeding7.2.7. Periocular chemotherapy7.2.8. Focal treatments 7.2.8.1. Cryotherapy7.2.8.2. Hyperthermia7.2.8.3. Photocoagulation7.2.8.4. Brachytherapy 7.3. Disease and treatment-related complications 7.3.1. Amblyopia7.3.2. Cataract 7.3.2.1. Incidence7.3.2.2. Cataract surgery7.3.3. Rhegmatogenous retinal detachment 7.3.3.1. Incidence7.3.3.2. Surgical repair7.3.4. Secondary neovascularization7.3.5. Chorioretinal complications 7.3.5.1. Intravitreal melphalan-induced chorioretinopathy 7.3.5.1.1. Clinical presentation, classification system and incidence7.3.5.1.2. Risk factors associated with intravitreal melphalan-induced chorioretinopathy 7.3.5.1.2.1. Intravitreal concentration7.3.5.1.2.2. Para-vitreal injections7.3.5.1.2.3. Intraocular pigmentation7.3.5.1.2.4. Concomitant drug interactions 7.3.5.2. Choroidal occlusive vasculopathy 7.3.5.2.1. Clinical presentation, classification system and incidence.7.3.5.2.2. Factors associated with choroidal occlusive vasculopathy 7.4. Evaluation of quality of life8. Future directions and conclusion 8.1. Animal models8.2. Gene therapy8.3. Cell-of-origin targeted therapy8.4. Personalized therapy and liquid biopsy8.5. New drugs or combinations of drugs8.6. New Galenic formulation of known drugs8.7. Conclusion

Published
2020
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