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1. Platin-related Hearing Loss: Further Results from PanCareLIFE

Author

Parfitt, R, Matulat, P, Byrne, J, Langer, T, Deuster, D, Hesping, A, Clemens, E, Kaatsch, P, Grabow, D, O'Brien, K, Kaiser, M, Spix, C, Kremer, LC, van Dulmen-den Broeder, E, Calaminus, G, Baust, K, Kuehni, C, Weiss, A, Strebel, S, Kuonen, R, Elsner, S, Haupt, R, Garré, ML, Kepak, T, Kapakova, K, Falck Winther, J, Kenborg, L, Rechnitzer, C, Hasle, H, Kruseova, J, Luks, A, Lackner, H, Beilack, S, Hecker-Nolting, S, Beck, JD, van den Heuvel-Eibrink, M, Zolk, O, am Zehnhoff-Dinnesen, A, PanCareLIFE Consortium, Parfitt, R, Matulat, P, Byrne, J, Langer, T, Deuster, D, Hesping, A, Clemens, E, Kaatsch, P, Grabow, D, O'Brien, K, Kaiser, M, Spix, C, Kremer, LC, van Dulmen-den Broeder, E, Calaminus, G, Baust, K, Kuehni, C, Weiss, A, Strebel, S, Kuonen, R, Elsner, S, Haupt, R, Garré, ML, Kepak, T, Kapakova, K, Falck Winther, J, Kenborg, L, Rechnitzer, C, Hasle, H, Kruseova, J, Luks, A, Lackner, H, Beilack, S, Hecker-Nolting, S, Beck, JD, van den Heuvel-Eibrink, M, Zolk, O, am Zehnhoff-Dinnesen, A, and PanCareLIFE Consortium

Abstract

Background: Cisplatin and Carboplatin are widely-used in paediatric cancer treatment. Sensorineural hearing loss (SNHL) is one long-term side-effect. This study utilises a larger sample than previous research in order to investigate risk-factors for platin-related ototoxicity.Material and methods: Retrospective audiological and treatment data of 997 children and adolescents were gathered with the involvement of 18 pan-European institutions in 7 different countries as part of the PanCareLIFE consortium. Prior hearing loss was excluded. Conductive hearing losses were excluded where identified.Results: Prevalence rates of clinically-significant hearing loss (=> 2b Münster Classification) after treatment were 49 % (Cisplatin) and 15 % (Carboplatin). Where Cisplatin was administered prior to Carboplatin, prevalence rose to 76 %. Frequencies in the high and extended high-frequency range were predominantly affected, with mean threholds between 25-35 dB HL. Mean thresholds at frequencies below 3 kHz remained lower than 20 dB HL. No significant air-bone gap was apparent.50 % of clinically-significant hearing losses began within 3 years of start of treatment (Kaplan-Meier analysis). No significant difference in time-to-onset at different frequencies within the standard range was found. Further analyses, including multifactorial analysis to account for platin doses, presence of cranial radiotherapy, age and date of diagnosis will be conducted.Discussion: Analysis of this large sample was able to confirm the significant risk of SNHL posed by platin-based chemotherapeutics. Some quantitative and qualitative variation were present in this multi-centre retrospective dataset.Conclusion: This large sample confirms that platin-based chemotherapeutics, especially cisplatin, pose a significant risk of SNHL and underlines the necessity of audiological monitoring during and after end of chemotherapy.Acknowledgement: This work was supported by the PanCareLIFE consortium that has received

Published
2023

2. Perceived barriers and facilitators to health behaviors in European childhood cancer survivors: A qualitative PanCareFollowUp study.

Author

Bouwman, E., Pluijm, S.M.F., Stollman, I.D., Araujo-Soares, V., Blijlevens, N.M.A., Follin, C., Winther, J.F., Hjorth, L., Kepak, T., Kepakova, K., Kremer, L.C.M., Muraca, M., Pal, H.J.H. van der, Schneider, C., Uyttebroeck, A., Vercruysse, G., Skinner, R., Brown, M.C., Hermens, R.P., Groot-Loonen, J.J., Bouwman, E., Pluijm, S.M.F., Stollman, I.D., Araujo-Soares, V., Blijlevens, N.M.A., Follin, C., Winther, J.F., Hjorth, L., Kepak, T., Kepakova, K., Kremer, L.C.M., Muraca, M., Pal, H.J.H. van der, Schneider, C., Uyttebroeck, A., Vercruysse, G., Skinner, R., Brown, M.C., Hermens, R.P., and Groot-Loonen, J.J.

Abstract

01 juni 2023, Contains fulltext : upload_in_progress_2066_294199.pdf (Publisher’s version ) (Closed access), BACKGROUND: Healthy behaviors, that is, engaging in regular physical activities, maintaining a healthy diet, limiting alcohol consumption, and avoiding tobacco and drug use, decrease the risk of developing late adverse health conditions in childhood cancer survivors. However, childhood cancer survivors may experience barriers to adopting and maintaining healthy behaviors. This study aimed to assess these barriers and facilitators to health behavior adoption and maintenance in childhood cancer survivors. METHODS: A focus group ( n = 12) and semi-structured telephone interviews ( n = 20) were conducted with a selected sample of European and Dutch childhood cancer survivors, respectively. The Theoretical Domains Framework (TDF) was used to inform the topic guide and analysis. Inductive thematic analysis was applied to identify categories relating to barriers and facilitators of health behavior adoption and maintenance, after which they were deductively mapped onto the TDF. RESULTS: Ten TDF domains were identified in the data of which "Knowledge," "Beliefs about consequences," "Environmental context and resources," and "Social influences" were most commonly reported. Childhood cancer survivors expressed a need for knowledge on the importance of healthy behaviors, possibly provided by healthcare professionals. They indicated physical and long-term benefits of healthy behaviors, available professional support, and a supporting and health-consciously minded work and social environment to be facilitators. Barriers were mostly related to a lack of available time and an unhealthy environment. Lastly, (social) media was perceived as both a barrier and a facilitator to healthy behaviors. CONCLUSION: This study has identified education and available professional support in health behaviors and the relevance of healthy behaviors for childhood cancer survivors as key opportunities for stimulating health behavior adoption in childhood cancer survivors. Incorporating health behavi

Published
2023

3. Healthcare professionals' perceived barriers and facilitators of health behavior support provision: A qualitative study.

Author

Bouwman, E., Pluijm, S.M.F., Stollman, I.D., Araujo-Soares, V., Blijlevens, N.M.A., Follin, C., Falck Winther, J., Hjorth, L., Kepak, T., Kepakova, K., Kremer, L.C.M., Muraca, M., Pal, H.J. van der, Schneider, C., Uyttebroeck, A., Vercruysse, G., Skinner, R., Brown, M.C., Hermens, R.P., Loonen, J.J., Bouwman, E., Pluijm, S.M.F., Stollman, I.D., Araujo-Soares, V., Blijlevens, N.M.A., Follin, C., Falck Winther, J., Hjorth, L., Kepak, T., Kepakova, K., Kremer, L.C.M., Muraca, M., Pal, H.J. van der, Schneider, C., Uyttebroeck, A., Vercruysse, G., Skinner, R., Brown, M.C., Hermens, R.P., and Loonen, J.J.

Abstract

Contains fulltext : 291775.pdf (Publisher’s version ) (Open Access), BACKGROUND: Childhood cancer survivors (CCSs) have an increased risk of developing chronic health conditions. Evidence suggests that poor health behaviors further increase health risks. Healthcare professionals (HCPs) involved in survivorship care have a key role in providing health behavior support (HBS) but can feel limited in their ability to do so. This study aims to explore European HCPs perceived facilitators and barriers to providing HBS to CCSs. METHODS: Five focus groups with 30 HCPs from survivorship care clinics across Europe were conducted. Topic guides were informed by the Theoretical Domains Framework (TDF) to capture domains that may influence provision of HBS. Focus groups were analyzed with thematic analysis. Transcripts were inductively coded, after which axial coding was applied to organize codes into categories. Finally, categories were mapped onto the TDF domains. RESULTS: Nine TDF domains were identified in the data. The most commonly reported TDF domains were "Knowledge", "Skills", and "Environmental context and resources". HCPs indicated that their lack of knowledge of the association between late effects and health behaviors, besides time restrictions, were barriers to HBS. Facilitators for HBS included possession of skills needed to pass on health behavior information, good clinic organization, and an established network of HCPs. CONCLUSIONS: This study identified education and training of HCPs as key opportunities to improve HBS. Survivorship care clinics should work towards establishing well-integrated structured care with internal and external networks including HBS being part of routine care. Proper understanding of facilitators and barriers should lead to better survivorship care for CCSs.

Published
2023

4. The PanCareFollowUp Care Intervention: A European harmonised approach to person-centred guideline-based survivorship care after childhood, adolescent and young adult cancer

Author

Kalsbeek, R.J. van, Mulder, R.L., Haupt, R., Muraca, M., Hjorth, L., Follin, C., Kepak, T., Kepakova, K., Uyttebroeck, A., Mangelschots, M., Winther, J. Falck, Loonen, J.J., Michel, G., Bardi, E., Frederiksen, L. Elmerdahl, Hartogh, J. den, Mader, L., Roser, K., Schneider, C., Brown, M.C., Brunhofer, M., Göttgens, I.L.E., Hermens, R.P.M.G., Kienesberger, A., Korevaar, J.C., Skinner, R., Pal, H.J. van der, Kremer, L.C., Kalsbeek, R.J. van, Mulder, R.L., Haupt, R., Muraca, M., Hjorth, L., Follin, C., Kepak, T., Kepakova, K., Uyttebroeck, A., Mangelschots, M., Winther, J. Falck, Loonen, J.J., Michel, G., Bardi, E., Frederiksen, L. Elmerdahl, Hartogh, J. den, Mader, L., Roser, K., Schneider, C., Brown, M.C., Brunhofer, M., Göttgens, I.L.E., Hermens, R.P.M.G., Kienesberger, A., Korevaar, J.C., Skinner, R., Pal, H.J. van der, and Kremer, L.C.

Abstract

Item does not contain fulltext, BACKGROUND: Long-term follow-up (LTFU) care, although endorsed, is not available for the majority of adult survivors of childhood, adolescence and young adult (CAYA) cancer. Barriers to implementation include lack of time, knowledge, personnel and funding. Sustainable solutions are urgently needed to address the needs of CAYA cancer survivors to improve the quality of life and reduce the burden of late effects on survivors, health care systems and society. The European Union-funded PanCareFollowUp project, initiated by the Pan-European Network for Care of Survivors after Childhood and Adolescent Cancer, was established to facilitate the implementation of person-centred survivorship care across Europe. PATIENTS AND METHODS: The PanCareFollowUp Care Intervention was co-developed with survivors as part of the PanCareFollowUp project. It is a person-centred approach to survivorship care, supported by guidelines and with flexibility to adapt to local health care settings. The Care Intervention consists of three steps: (1) previsit completion of a Survivor Questionnaire (by the survivor) and Treatment Summary (by the health care provider [HCP]), (2) a clinic visit including shared decision-making, and (3) a follow-up call to finalise the individualised Survivorship Care Plan. RESULTS: We developed the key components of the PanCareFollowUp Care Intervention: a PanCareFollowUp Survivor Questionnaire, Treatment Summary template, Survivorship Care Plan template, and educational materials for HCPs and survivors. Wide implementation of the PanCareFollowUp Care Intervention will be supported with a freely distributed Replication Manual on completion of the PanCareFollowUp project. CONCLUSIONS: The PanCareFollowUp Care Intervention will support the implementation of person-centred, guideline-based LTFU care in different health care settings across Europe to improve survivors' health and well-being.

Published
2022

5. Person-centred online lifestyle coaching in childhood, adolescent, and young adult cancer survivors: protocol of the multicentre PanCareFollowUp lifestyle intervention feasibility study

Author

Bouwman, E., Hermens, R.P.M.G., Brown, M.C., Araujo-Soares, Vera, Blijlevens, N.M.A., Kepak, T., Pluijm, S.M.F., Loonen, J.J., Bouwman, E., Hermens, R.P.M.G., Brown, M.C., Araujo-Soares, Vera, Blijlevens, N.M.A., Kepak, T., Pluijm, S.M.F., and Loonen, J.J.

Abstract

Item does not contain fulltext

Published
2022

6. 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

7. Genetic variation of cisplatin-induced ototoxicity in non-cranial-irradiated pediatric patients using a candidate gene approach: The International PanCareLIFE Study

Author

Clemens, Eva, Broer, Linda, Langer, Thorsten, Uitterlinden, André G., de Vries, Andrica C. H., van Grotel, Martine, Pluijm, Saskia F. M., Binder, Harald, Byrne, Julianne, Broeder, Eline van Dulmen-den, Crocco, Marco, Kaiser, Melanie, Kenborg, Line, Winther, Jeanette F., Rechnitzer, Catherine, Hasle, Henrik, van der Kooi, Anne-Lotte F., Kremer, Leontien C., van der Pal, Heleen, Parfitt, Ross, Deuster, Dirk, Matulat, Peter, Spix, Claudia, Tillmanns, Amelie, Tissing, Wim J. E., Maier, Lara, am Zehnhoff-Dinnesen, Antoinette, Zolk, Oliver, Kaatsch, P., Grabow, D., Campbell, H., O’Brien, K., Kremer, L.C.M., van Dulmen-den Broeder, E., van den Berg, M.H., van den Heuvel-Eibrink, M.M., Borgmann-Staudt, A., Kuehni, C.E., Haupt, R., Kepak, T., Berger, C., Winther, J.F., Kruseova, J., Calaminus, G., Baust, K., Dirksen, U., Kuehni, Claudia E., van den Heuvel-Eibrink, Marry M., Guided Treatment in Optimal Selected Cancer Patients (GUTS), Pediatric surgery, CCA - Cancer biology and immunology, Amsterdam Reproduction & Development (AR&D), Internal Medicine, Pediatrics, and Obstetrics & Gynecology

Subjects
Oncology, Male, Candidate gene, Internationality, Medizin, CHILDREN, VARIANTS, Neoplasms, TPMT, 610 Medicine & health, Child, SURVIVORS, Cumulative dose, Child, Preschool, Molecular Medicine, Sensorineural hearing loss, Female, 360 Social problems & social services, medicine.drug, medicine.medical_specialty, INDUCED HEARING-LOSS, Side effect, Adolescent, Single-nucleotide polymorphism, Antineoplastic Agents, PLATINUM CHEMOTHERAPY, ACYP2, Young Adult, Ototoxicity, Internal medicine, Genetics, medicine, Humans, Hearing Loss, Genetic Association Studies, Retrospective Studies, Pharmacology, Cisplatin, CHILDHOOD-CANCER, business.industry, Infant, Newborn, Genetic Variation, Infant, medicine.disease, COMT, REPLICATION, business
Abstract

Ototoxicity is a common side effect of platinum treatment and manifests as irreversible, high-frequency sensorineural hearing loss. Genetic association studies have suggested a role for SNPs in genes related to the disposition of cisplatin or deafness. In this study, 429 pediatric patients that were treated with cisplatin were genotyped for 10 candidate SNPs. Logistic regression analyses revealed that younger age at treatment (≤5 years vs >15 years: OR: 9.1; 95% CI: 3.8–21.5; P = 5.6 × 10−7) and higher cumulative dose of cisplatin (>450 vs ≤300 mg/m2: OR: 2.4; 95% CI: 1.3–4.6; P = 0.007) confer a significant risk of ototoxicity. Of the SNPs investigated, none of them were significantly associated with an increase of ototoxicity. In the meta-analysis, ACYP2 rs1872328 (OR: 3.94; 95% CI: 1.04–14.03; P = 0.04) and SLC22A2 rs316019 (OR: 1.46; 95% CI: 1.07–2.00; P = 0.02) were associated with ototoxicity. In order to increase the understanding of the association between SNPs and ototoxicity, we propose a polygenic model, which takes into account multiple interacting genes of the cisplatin pathway that together confer an increased risk of ototoxicity.

Published
2020

8. Incidence of Retinoblastoma Has Increased: Results from 40 European Countries

Author

Stacey AW, Bowman R, Foster A, Kivelä TT, Munier FL, Cassoux N, Fabian ID, Al Harby L, Alarcón Portabella S, Alia DB, All-Eriksson C, Antonino R, Astbury NJ, Balaguer J, Balwierz W, Barranco H, Bascaran C, Beck Popovic M, Biewald EM, Bobrova N, Bornfeld N, Brichard BG, Blum S, Capra M, Castela G, Catala J, Chantada G, Chernodrinska VS, Cieslik K, Comsa C, Correa Llano MG, Csóka M, De Potter P, Desjardins L, Dragomir MD, Fernández-Teijeiro A, García Aldana D, Gregersen PA, Gomel N, Hadjistilianou T, Hederova S, Hummlen M, Husakova K, Ida R, Ilic VR, Jenkinson H, Kapelushnik N, Kardava T, Keren-Froim N, Kepak T, Khotenashvili Z, Klett A, Krivaitiene D, Latinovic S, Lumbroso L, Lysytsia L, Maka E, Martín Begue N, Midena E, Moll AC, Murgoi G, Naumenko L, Neroev V, Nikitovic M, Olechowski A, Papyan R, Parrozzani R, Parulekar MV, Pawinska-Wasikowska K, Peric S, Pochop P, Polyakov VG, Reddy MA, Ritter-Sovinz P, Saakyan S, Sagoo MS, San Román Pacheco S, Seregard S, Silva S, Sorochynska T, Stathopoulos C, Stirn Kranjc B, Svojgr K, Tamamyan G, Tandili A, Tateshi B, Tekavcic Pompe M, Urbak SF, Ushakova TL, Valeina S, van Hoefen Wijsard M, Veleva-Krasteva NV, Viksnins M, Wackernagel W, Wolley Dod C, Yarovaya VA, Yarovoy AA, Zhilyaeva K, Zondervan M, and Global Retinoblastoma Study Group

Subjects
Incidence, Retinoblastoma, Familial, Genetic, Fitness
Published
2021

9. Health-related quality of life in European childhood cancer survivors: Protocol for a study within PanCareLIFE

Author

Calaminus, G. (Gabriele), Baust, K. (Katja), Berger, C. (Claire), Byrne, J. (Julianne), Binder, H. (Harald), Casagranda, L. (Leonie), Grabow, D. (Desiree), Grootenhuis, M.A. (Martha), Kaatsch, P. (Peter), Kaiser, M. (Melanie), Kepak, T. (Tomas), Kepáková, K. (Kateřina), Kremer, L.C.M. (Leontien), Kruseova, J. (Jarmila), Luks, A. (Ales), Spix, C. (Claudia), van den Berg, M. (Marleen), Heuvel-Eibrink, M.M. (Marry) van den, van Dulmen-Den Broeder, E. (Eline), Kuonen, R. (Rahel), Sommer, G. (Grit), Kuehni, C. (Claudia), Grabow, D. (D.), Byrne, J. (J.), Campbell, H. (H.), Clissmann, C. (C.), O'Brien, K. (K.), Kremer, L.C.M. (L. C.M.), Langer, T. (T.), Dulmen-den Broeder, E. (Eline) van, Berg, M.H. (Marleen) van den, van den Heuvel-Eibrink, M.M. (M. M.), Borgmann-Staudt, A. (Anja), am Zehnhoff-Dinnesen, A. (A.), Haupt, R. (R.), Berger, C. (C.), Winther, J.F. (J. F.), Dirksen, U. (Uta), Calaminus, G. (Gabriele), Baust, K. (Katja), Berger, C. (Claire), Byrne, J. (Julianne), Binder, H. (Harald), Casagranda, L. (Leonie), Grabow, D. (Desiree), Grootenhuis, M.A. (Martha), Kaatsch, P. (Peter), Kaiser, M. (Melanie), Kepak, T. (Tomas), Kepáková, K. (Kateřina), Kremer, L.C.M. (Leontien), Kruseova, J. (Jarmila), Luks, A. (Ales), Spix, C. (Claudia), van den Berg, M. (Marleen), Heuvel-Eibrink, M.M. (Marry) van den, van Dulmen-Den Broeder, E. (Eline), Kuonen, R. (Rahel), Sommer, G. (Grit), Kuehni, C. (Claudia), Grabow, D. (D.), Byrne, J. (J.), Campbell, H. (H.), Clissmann, C. (C.), O'Brien, K. (K.), Kremer, L.C.M. (L. C.M.), Langer, T. (T.), Dulmen-den Broeder, E. (Eline) van, Berg, M.H. (Marleen) van den, van den Heuvel-Eibrink, M.M. (M. M.), Borgmann-Staudt, A. (Anja), am Zehnhoff-Dinnesen, A. (A.), Haupt, R. (R.), Berger, C. (C.), Winther, J.F. (J. F.), and Dirksen, U. (Uta)

Abstract

Background: Survival after childhood cancer has improved to more than 80% during the last few years, leading to an increased number of childhood cancer survivors. Cancer itself, or its treatment, may cause chronic health conditions, including somatic and mental sequelae, which may affect survivors’ health-related quality of life (HRQoL). Objective: The project PanCareLIFE aims to establish a large database with comprehensive data on childhood cancer survivors from different European countries, including data on HRQoL. Within PanCareLIFE, this study aims to describe HRQoL in survivors, investigate predictors of HRQoL, and describe the association of HRQoL with hearing and female fertility impairment. This paper describes the design of the HRQoL study, the origin of data, strategies for data collection, and sampling characteristics of survivors from each contributing country. Methods: A total of 6 institutions from 5 European countries (the Czech Republic, France, Germany, the Netherlands, and Switzerland) provided data on HRQoL assessed with the Short Form 36 and on relevant predictors. The central PanCareLIFE data center aggregated the data and harmonized the variables between the institutions. Survivors were eligible if they received a diagnosis of cancer according to the 12 main groups of the International Classification of Childhood Cancer, 3rd edition, or Langerhans cell histiocytosis; were aged ≤18 years at the time of diagnosis; were residents of the respective country at the time of diagnosis; had survived ≥5 years after cancer diagnosis; were aged ≥18 years at the time of the questionnaire survey; and did not refuse to registration in the national or local childhood cancer cohort. Results: We identified 24,993 eligible survivors. Of those, 19,268 survivors received a questionnaire and 9871 survivors participated, resulting in response rates of 9871/24,993 (39.50%) of eligible survivors and of 9871/19,268 (51.23%) invited survivors. Most participants were dia

Published
2021
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10. TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study

Author

Meijer, A, Diepstraten, FA, Langer, T, Broer, L, Domingo, IK, Clemens, E, Uitterlinden, AG, de Vries, ACH, van Grotel, M, Vermeij, WP, Ozinga, RA, Binder, H, Byrne, J, van Dulmen-den Broeder, E, Garrè, ML, Grabow, D, Kaatsch, P, Kaiser, M, Kenborg, L, Falck-Winther, J, Rechnitzer, C, Hasle, H, Kepak, T, Kepakova, K, Tissing, WJE, van der Kooi, ALF, Kremer, LC, Kruseova, J, Pluijm, SMF, Kuehni, CF, van der Pal, H, Parfitt, R, Spix, C, Hesping, A, Deuster, D, Matulat, P, Calaminus, G, Hoetink, AE, Elsner, S, Gebauer, J, Haupt, R, Lackner, H, Blattmann, C, Neggers, SJCMM, Rassekh, SR, Wright, GEB, Brooks, B, Nagtegaal, AP, Drögemöller, BI, Ross, CJD, Bhavsar, AP, am Zehnhoff-Dinnesen, A, Carleton, BC, Zolk, O, van den Heuvel-Eibrink, M, Meijer, A, Diepstraten, FA, Langer, T, Broer, L, Domingo, IK, Clemens, E, Uitterlinden, AG, de Vries, ACH, van Grotel, M, Vermeij, WP, Ozinga, RA, Binder, H, Byrne, J, van Dulmen-den Broeder, E, Garrè, ML, Grabow, D, Kaatsch, P, Kaiser, M, Kenborg, L, Falck-Winther, J, Rechnitzer, C, Hasle, H, Kepak, T, Kepakova, K, Tissing, WJE, van der Kooi, ALF, Kremer, LC, Kruseova, J, Pluijm, SMF, Kuehni, CF, van der Pal, H, Parfitt, R, Spix, C, Hesping, A, Deuster, D, Matulat, P, Calaminus, G, Hoetink, AE, Elsner, S, Gebauer, J, Haupt, R, Lackner, H, Blattmann, C, Neggers, SJCMM, Rassekh, SR, Wright, GEB, Brooks, B, Nagtegaal, AP, Drögemöller, BI, Ross, CJD, Bhavsar, AP, am Zehnhoff-Dinnesen, A, Carleton, BC, Zolk, O, and van den Heuvel-Eibrink, M

Abstract

Background: Ototoxicity (hearing loss, tinnitus and/or vertigo) is a serious adverse event of cisplatin treatment in children with cancer. The heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. This study investigated the association between carriership of novel single nucleotide polymorphisms (SNPs) and cisplatin-induced hearing loss (CIHL) in childhood cancer patients.Material and methods: The discovery cohort included cisplatin treated, non-cranial irradiated pediatric cancer patients within the European PanCareLIFE (PCL) study (N=390). CIHL at end of cancer treatment was defined as Muenster grade >=2b, assessed by pure tone audiometry. DNA was genotyped using the Infinium© Global Screening Array. Logistic regression models were applied including age at diagnosis, sex, cisplatin total cumulative dose and principal components 1-4, assuming an additive effect of the minor allele. Replication of the findings was performed in two independent, similarly treated cohorts (N=192 and N=188). Functional validation experiments in cultured human HeLa cell lines were performed to determine the effect of knockdown of the SNPs nearest identified gene on cisplatin-induced toxicity.Results: In the PCL discovery cohort, 8 SNPs reached a suggestive significance of P<1.0x10-5. One variant (rs893507) within the TCERG1L gene showed evidence of replication (P=0.01) in the Canadian first replication cohort. Analysis in the PCL second replication cohort confirmed this finding (P=1.0x10-4). The combined analysis showed that carriership of the C-allele of this newly discovered variant increases the odds of CIHL with 3.11-fold (P=5.3x10-10, 95% CI 2.2-4.5). Modulating TCERG1L expression significantly altered cell viability in response to cisplatin treatment, where TCERG1L overexpression and silencing protected and sensitized cells to cisplatin toxicity, respectively.Discussion: Children with cancer who carry a variant in the TCERG1L g

Published
2021

11. TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study

Author

Meijer, A. J.M., Diepstraten, F. A., Langer, T., Broer, L., Domingo, I. K., Clemens, E., Uitterlinden, A. G., de Vries, A. C.H., van Grotel, M., Vermeij, W. P., Ozinga, R. A., Binder, H., Byrne, J., van Dulmen-den Broeder, E., Garrè, M. L., Grabow, D., Kaatsch, P., Kaiser, M., Kenborg, L., Winther, J. F., Rechnitzer, C., Hasle, H., Kepak, T., Kepakova, K., Tissing, W. J.E., van der Kooi, A. L.F., Kremer, L. C.M., Kruseova, J., Pluijm, S. M.F., Kuehni, C. E., van der Pal, H. J.H., Parfitt, R., Spix, C., Tillmanns, A., Deuster, D., Matulat, P., Calaminus, G., Hoetink, A. E., Elsner, S., Gebauer, J., Haupt, R., Lackner, H., Blattmann, C., Neggers, S. J.C.M.M., Rassekh, S. R., Wright, G. E.B., Brooks, B., Nagtegaal, A. P., Drögemöller, B. I., Ross, C. J.D., Meijer, A. J.M., Diepstraten, F. A., Langer, T., Broer, L., Domingo, I. K., Clemens, E., Uitterlinden, A. G., de Vries, A. C.H., van Grotel, M., Vermeij, W. P., Ozinga, R. A., Binder, H., Byrne, J., van Dulmen-den Broeder, E., Garrè, M. L., Grabow, D., Kaatsch, P., Kaiser, M., Kenborg, L., Winther, J. F., Rechnitzer, C., Hasle, H., Kepak, T., Kepakova, K., Tissing, W. J.E., van der Kooi, A. L.F., Kremer, L. C.M., Kruseova, J., Pluijm, S. M.F., Kuehni, C. E., van der Pal, H. J.H., Parfitt, R., Spix, C., Tillmanns, A., Deuster, D., Matulat, P., Calaminus, G., Hoetink, A. E., Elsner, S., Gebauer, J., Haupt, R., Lackner, H., Blattmann, C., Neggers, S. J.C.M.M., Rassekh, S. R., Wright, G. E.B., Brooks, B., Nagtegaal, A. P., Drögemöller, B. I., and Ross, C. J.D.

Abstract

In children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial irradiated, cisplatin-treated children with cancer. These results were replicated in two independent, similarly treated cohorts (n = 192 and 188, respectively) (combined cohort: P = 5.3 × 10−10, OR 3.11, 95% CI 2.2–4.5). Modulating TCERG1L expression in cultured human cells revealed significantly altered cellular responses to cisplatin-induced cytokine secretion and toxicity. These results contribute to insights into the genetic and pathophysiological basis of cisplatin-induced ototoxicity.

Published
2021

12. Health-related quality of life in European childhood cancer survivors: Protocol for a study within PanCareLIFE

Author

Calaminus, G, Baust, K, Berger, C, Byrne, J, Binder, H, Casagranda, L, Grabow, D, Grootenhuis, M, Kaatsch, P, Kaiser, M, Kepak, T, Kepáková, K, Kremer, LC, Kruseova, J, Luks, A, Spix, C, van den Berg, M, Van den Heuvel - Eibrink, Marry, van Dulmen-Den Broeder, E, Kuonen, R, Sommer, G, Kuehni, C, Calaminus, G, Baust, K, Berger, C, Byrne, J, Binder, H, Casagranda, L, Grabow, D, Grootenhuis, M, Kaatsch, P, Kaiser, M, Kepak, T, Kepáková, K, Kremer, LC, Kruseova, J, Luks, A, Spix, C, van den Berg, M, Van den Heuvel - Eibrink, Marry, van Dulmen-Den Broeder, E, Kuonen, R, Sommer, G, and Kuehni, C

Abstract

Background: Survival after childhood cancer has improved to more than 80% during the last few years, leading to an increased number of childhood cancer survivors. Cancer itself, or its treatment, may cause chronic health conditions, including somatic and mental sequelae, which may affect survivors’ health-related quality of life (HRQoL). Objective: The project PanCareLIFE aims to establish a large database with comprehensive data on childhood cancer survivors from different European countries, including data on HRQoL. Within PanCareLIFE, this study aims to describe HRQoL in survivors, investigate predictors of HRQoL, and describe the association of HRQoL with hearing and female fertility impairment. This paper describes the design of the HRQoL study, the origin of data, strategies for data collection, and sampling characteristics of survivors from each contributing country. Methods: A total of 6 institutions from 5 European countries (the Czech Republic, France, Germany, the Netherlands, and Switzerland) provided data on HRQoL assessed with the Short Form 36 and on relevant predictors. The central PanCareLIFE data center aggregated the data and harmonized the variables between the institutions. Survivors were eligible if they received a diagnosis of cancer according to the 12 main groups of the International Classification of Childhood Cancer, 3rd edition, or Langerhans cell histiocytosis; were aged ≤18 years at the time of diagnosis; were residents of the respective country at the time of diagnosis; had survived ≥5 years after cancer diagnosis; were aged ≥18 years at the time of the questionnaire survey; and did not refuse to registration in the national or local childhood cancer cohort. Results: We identified 24,993 eligible survivors. Of those, 19,268 survivors received a questionnaire and 9871 survivors participated, resulting in response rates of 9871/24,993 (39.50%) of eligible survivors and of 9871/19,268 (51.23%) invited survivors. Most participants were

Published
2021

13. Plerixafor combined with standard regimens for hematopoietic stem cell mobilization in pediatric patients with solid tumors eligible for autologous transplants: two-arm phase I/II study (MOZAIC)

Author

Morland, B., Kepak, T., Dallorso, S., Sevilla, J., Murphy, D., Luksch, R., Yaniv, I., Bader, P.I. (Peter), Rößler, J., Bisogno, G. (Gianni), Maecker-Kolhoff, B., Lang, P., Zwaan, C.M. (Michel), Sumerauer, D., Kriván, G., Bernard, J., Liu, Q., Doyle, E., Locatelli, F. (Franco), Morland, B., Kepak, T., Dallorso, S., Sevilla, J., Murphy, D., Luksch, R., Yaniv, I., Bader, P.I. (Peter), Rößler, J., Bisogno, G. (Gianni), Maecker-Kolhoff, B., Lang, P., Zwaan, C.M. (Michel), Sumerauer, D., Kriván, G., Bernard, J., Liu, Q., Doyle, E., and Locatelli, F. (Franco)

Abstract

This study (NCT01288573) investigated plerixafor’s safety and efficacy in children with cancer. Stage 1 investigated the dosage, pharmacokinetics (PK), pharmacodynamics (PD), and safety of plerixafor + standard mobilization (G-CSF ± chemotherapy). The stage 2 primary endpoint was successful mobilization (doubling of peripheral blood CD34+ cell count in the 24 h prior to first apheresis) in patients treated with plerixafor + standard mobilization vs. standard mobilization alone. In stage 1, three patients per age group (2–<6, 6–<12, and 12–<18 years) were treated at each dose level (160, 240, and 320 µg/kg). Based on PK and PD data, the dose proposed for stage 2 was 240 µg/kg (patients 1–<18 years), in which 45 patients were enrolled (30 plerixafor arm, 15 standard arm). Patient demographics and characteristics were well balanced across treatment arms. More patients in the plerixafor arm (24/30, 80%) met the primary endpoint of successful mobilization than in the standard arm (4/14, 28.6%, p = 0.0019). Adverse events reported as related to study treatment were mild, and no new safety concerns were identified. Plerixafor + standard G-CSF ± chemotherapy mobilization was generally well tolerated and efficacious when used to mobilize CD34+ cells in pediatric cancer patients.

Published
2020
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14. Association of candidate pharmacogenetic markers with platinum-induced ototoxicity: PanCareLIFE dataset

Author

Langer, T. (Thomas), Clemens, E. (Eva), Broer, L. (Linda), Maier, L. (Lara), Uitterlinden, A.G. (André), Vries, A.C.H. (Andrica) de, Grotel, M. (Martine) van, Pluijm, S.F.M. (Saskia F.M.), Binder, H. (Harald), Mayer, B. (Benjamin), von dem Knesebeck, A. (Annika), Byrne, J. (Julianne), Dulmen-den Broeder, E. (Eline) van, Crocco, M. (Marco), Grabow, D. (Desiree), Kaatsch, P. (Peter), Kaiser, M. (Melanie), Spix, C. (Claudia), Kenborg, L. (Line), Winther, J.F. (Jeanette F.), Rechnitzer, C. (Catherine), Hasle, H. (Henrik), Kepak, T. (Tomas), Kooi, A.L.F. (Anne-Lotte) van der, Kremer, L.C.M. (Leontien), Kruseova, J. (Jarmila), Bielack, S. (Stefan), Sorg, B. (Benjamin), Hecker-Nolting, S. (Stefanie), Kuehni, C. (Claudia), Ansari, M. (Marc), Kompis, M. (Martin), van der Pal, H.J. (Heleen J.), Parfitt, R. (Ross), Deuster, D. (Dirk), Matulat, P. (Peter), Tillmanns, A. (Amelie), Tissing, W.J.E. (Wim), Beck, J.D. (Jörn D.), Elsner, S. (Susanne), am Zehnhoff-Dinnesen, A. (Antoinette), Heuvel-Eibrink, M.M. (Marry) van den, Zolk, O. (Oliver), Langer, T. (Thomas), Clemens, E. (Eva), Broer, L. (Linda), Maier, L. (Lara), Uitterlinden, A.G. (André), Vries, A.C.H. (Andrica) de, Grotel, M. (Martine) van, Pluijm, S.F.M. (Saskia F.M.), Binder, H. (Harald), Mayer, B. (Benjamin), von dem Knesebeck, A. (Annika), Byrne, J. (Julianne), Dulmen-den Broeder, E. (Eline) van, Crocco, M. (Marco), Grabow, D. (Desiree), Kaatsch, P. (Peter), Kaiser, M. (Melanie), Spix, C. (Claudia), Kenborg, L. (Line), Winther, J.F. (Jeanette F.), Rechnitzer, C. (Catherine), Hasle, H. (Henrik), Kepak, T. (Tomas), Kooi, A.L.F. (Anne-Lotte) van der, Kremer, L.C.M. (Leontien), Kruseova, J. (Jarmila), Bielack, S. (Stefan), Sorg, B. (Benjamin), Hecker-Nolting, S. (Stefanie), Kuehni, C. (Claudia), Ansari, M. (Marc), Kompis, M. (Martin), van der Pal, H.J. (Heleen J.), Parfitt, R. (Ross), Deuster, D. (Dirk), Matulat, P. (Peter), Tillmanns, A. (Amelie), Tissing, W.J.E. (Wim), Beck, J.D. (Jörn D.), Elsner, S. (Susanne), am Zehnhoff-Dinnesen, A. (Antoinette), Heuvel-Eibrink, M.M. (Marry) van den, and Zolk, O. (Oliver)

Abstract

Genetic association studies suggest a genetic predisposition for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase (TPMT) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in a pharmacogenetic guideline. The PanCareLIFE cross-sectional cohort study evaluated the genetic associations in a large pan-European population and assessed the diagnostic accuracy of the genetic markers. 1,112 pediatric cancer survivors who had provided biomaterial for genotyping were screened for participation in the pharmacogenetic association study. 900 participants qualified for inclusion. Based on the assessment of original audiograms, patients were assigned to three phenotype categories: no, minor, and clinically relevant hearing loss. Fourteen variants in eleven candidate genes (ABCC3, OTOS, TPMT, SLC22A2, NFE2L2, SLC16A5, LRP2, GSTP1, SOD2, WFS1, and ACYP2) were genotyped. The genotype and phenotype data represent a resource for conducting meta-analyses to derive a more precise pooled estimate of the effects of genes on the risk of hearing loss due to platinum treatment.

Published
2020
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15. Guidance regarding COVID-19 for survivors of childhood, adolescent, and young adult cancer: A statement from the International Late Effects of Childhood Cancer Guideline Harmonization Group

Author

Verbruggen, LC, Wang, Y, Armenian, SH, Ehrhardt, MJ, van der Pal, HJH, van Dalen, EC, van As, JW, Bardi, E, Baust, K, Berger, C, Castagnola, E, Devine, KA, Gebauer, J, Marchak, JG, Glaser, AW, Groll, AH, Haeusler, GM, den Hartogh, J, Haupt, R, Hjorth, L, Kato, M, Kepak, T, Koopman, MMWR, Langer, T, Maeda, M, Michel, G, Muraca, M, Nathan, PC, van den Oever, SR, Pavasovic, V, Sato, S, Schulte, F, Sung, L, Tissing, W, Uyttebroeck, A, Mulder, RL, Kuehni, C, Skinner, R, Hudson, MM, Kremer, LCM, Verbruggen, LC, Wang, Y, Armenian, SH, Ehrhardt, MJ, van der Pal, HJH, van Dalen, EC, van As, JW, Bardi, E, Baust, K, Berger, C, Castagnola, E, Devine, KA, Gebauer, J, Marchak, JG, Glaser, AW, Groll, AH, Haeusler, GM, den Hartogh, J, Haupt, R, Hjorth, L, Kato, M, Kepak, T, Koopman, MMWR, Langer, T, Maeda, M, Michel, G, Muraca, M, Nathan, PC, van den Oever, SR, Pavasovic, V, Sato, S, Schulte, F, Sung, L, Tissing, W, Uyttebroeck, A, Mulder, RL, Kuehni, C, Skinner, R, Hudson, MM, and Kremer, LCM

Abstract

Childhood, adolescent, and young adult (CAYA) cancer survivors may be at risk for a severe course of COVID-19. Little is known about the clinical course of COVID-19 in CAYA cancer survivors, or if additional preventive measures are warranted. We established a working group within the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) to summarize existing evidence and worldwide recommendations regarding evidence about factors/conditions associated with risk for a severe course of COVID-19 in CAYA cancer survivors, and to develop a consensus statement to provide guidance for healthcare practitioners and CAYA cancer survivors regarding COVID-19.

Published
2020

16. 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

17. Association of candidate pharmacogenetic markers with platinum-induced ototoxicity: PanCareLIFE dataset

Author

Langer, T, Clemens, Eva, Broer, Linda, Maier, L, Uitterlinden, André, Vries, ACH, van Grotel, Martine, Pluijm, Saskia F.M., Binder, H, Mayer, Benjamin, von dem Knesebeck, A, Byrne, J, van Dulmen-den Broeder, E, Crocco, M, Grabow, D, Kaatsch, P, Kaiser, M, Spix, C, Kenborg, L, Winther, JF, Rechnitzer, C, Hasle, H, Kepak, T, Kooi, Anne-Lotte, Kremer, LC, Kruseova, J, Bielack, S, Sorg, B, Hecker-Nolting, S, Kuehni, CE, Ansari, M, Kompis, M, van der Pal, HJ, Parfitt, R, Deuster, D, Matulat, P, Tillmanns, A, Tissing, WJ, Beck, JD, Elsner, S, am Zehnhoff-Dinnesen, A, Eibrink, Marry, Zolk, O, Langer, T, Clemens, Eva, Broer, Linda, Maier, L, Uitterlinden, André, Vries, ACH, van Grotel, Martine, Pluijm, Saskia F.M., Binder, H, Mayer, Benjamin, von dem Knesebeck, A, Byrne, J, van Dulmen-den Broeder, E, Crocco, M, Grabow, D, Kaatsch, P, Kaiser, M, Spix, C, Kenborg, L, Winther, JF, Rechnitzer, C, Hasle, H, Kepak, T, Kooi, Anne-Lotte, Kremer, LC, Kruseova, J, Bielack, S, Sorg, B, Hecker-Nolting, S, Kuehni, CE, Ansari, M, Kompis, M, van der Pal, HJ, Parfitt, R, Deuster, D, Matulat, P, Tillmanns, A, Tissing, WJ, Beck, JD, Elsner, S, am Zehnhoff-Dinnesen, A, Eibrink, Marry, and Zolk, O

Published
2020

18. Plerixafor combined with standard regimens for hematopoietic stem cell mobilization in pediatric patients with solid tumors eligible for autologous transplants: two-arm phase I/II study (MOZAIC)

Author

Morland, B, Kepak, T, Dallorso, S, Sevilla, J, Murphy, D, Luksch, R, Yaniv, I, Bader, P, Rößler, J, Bisogno, G, Maecker-Kolhoff, B, Lang, P, Zwaan, C.M., Sumerauer, D, Kriván, G, Bernard, J, Liu, Q, Doyle, E, Locatelli, F (Franco), Morland, B, Kepak, T, Dallorso, S, Sevilla, J, Murphy, D, Luksch, R, Yaniv, I, Bader, P, Rößler, J, Bisogno, G, Maecker-Kolhoff, B, Lang, P, Zwaan, C.M., Sumerauer, D, Kriván, G, Bernard, J, Liu, Q, Doyle, E, and Locatelli, F (Franco)

Published
2020

20. Confirmation of genetic risk markers of platinum-induced ototoxicity

Author

Tillmanns, A, Parfitt, R, Matulat, P, Abdel-Kahaar, E, Maier, L, Zolk, O, Elsner, S, Wolschon, EM, Kuehni, CE, Kuonen, R, Weiss, A, Garré, ML, Kepak, T, Kepakova, K, Kruseova, J, Luks, A, Falck Winther, J, Kenborg, L, Lackner, H, Bielack, S, van den Heuvel-Eibrink, M, Calaminus, G, Baust, K, Beck, J, Kremer, L, Clemens, E, Langer, T, am Zehnhoff-Dinnesen, A, and PanCareLIFE consortium

Subjects
ddc: 610
Abstract

Background: Platinum compounds such as cisplatin or carboplatin are potent antineoplastic agents widely used for a variety of cancer types. Unfortunately, their use leads to dose-limiting side effects such as ototoxicity. Our study aimed at investigating the predictive value of 11 candidate genetic markers in a large non-selected pediatric population of cancer survivors who had been treated with cisplatin and/or carboplatin.Materials and Methods: As a part of the PanCareLIFE study, the ototoxicity study included 2,696 survivors from 7 European countries treated with cisplatin and/or carboplatin for childhood cancer, resulting in the largest clinical European cohort assembled for this late-effect study. Hearing loss was audiologically classified using the Münster Classification. Three groups were defined, i.e., no hearing loss, minor hearing loss, and clinically relevant hearing loss. Patients were genotyped for single nucleotide polymorphisms (SNPs) in 7 candidate genes. Genetic association analyses were performed considering non-genetic covariates.Results: 900 patients were included in the final genetic analysis. Multinomial logistic regression was performed to model the relationship between the predictors and membership in the hearing loss group. The model explained 25% of the variance in hearing loss and correctly classified 58% of cases. Significant unique contributions were made by SLC22A2 rs316019 (P=0.017), age at the start of platinum treatment (P=1.46x10-17), cranial radiation (P=5.42x10-6), and the cumulative dose of cisplatin (P=5.86x10-19). Addition of the rs316019 genetic marker to the non-genetic risk factors (age, dose, cranial radiation) improved the area under the ROC curve only marginally (0.731 vs. 0.730).Discussion: Our study confirmed one potential genetic marker, rs316019 in SLC22A2. Its predictive value, however, is low.Conclusion: Due to the heterogeneity of results from genetic association studies performed so far, the evidence seems not yet sufficient to recommend screening for specific markers. Advances in the understanding of the pathophysiologic mechanisms of cisplatin-induced ototoxicity, as well as future genome-wide association studies, may help identify suitable genetic markers.Acknowledgement: This work was supported by the PanCareLIFE project that has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 602030.

Published
2019

21. Platin treatment and hearing loss: initial audiological results from PanCareLIFE

Author

Parfitt, R, Tillmanns, A, Matulat, P, Deuster, D, Elsner, S, Wolschon, EM, Kuehni, CE, Kuonen, R, Weiss, A, Garré, ML, Kepak, T, Kepakova, K, Kruseova, J, Luks, A, Falck Winther, J, Kenborg, L, Lackner, H, Bielack, S, van den Heuvel-Eibrink, M, Calaminus, G, Baust, K, Beck, J, Kremer, L, Clemens, E, Langer, T, Zolk, O, and am Zehnhoff-Dinnesen, A

Subjects
ddc: 610
Abstract

Background: Cisplatin and carboplatin are widely used in paediatric cancer treatment. Cisplatin especially can have long-term side effects, including sensorineural hearing loss. The aim of this study is to define the risk factors for platin-related ototoxicity.Materials and Methods: As part of the PanCareLIFE consortium, we gathered audiological data from 13 pan-European clinics. Eligible patients were 20 dB HL at any frequency).A total of 2,696 patients with 10,320 audiograms from various stages of cancer treatment were obtained. Audiometric data were quality-checked and classified (Münster and SIOP classifications) and 736 patients with sufficient data were phenotyped. A logistic regression investigated the likelihood of developing a hearing loss >=Münster 2b (thresholds >40 dB HL at >=4 kHz) after treatment given age, gender, cisplatin dose and cranial irradiation.Results: 48.2% of 1,385 patients with a post-treatment audiogram had clinically-relevant hearing loss (defined as >=Münster 2b) after platin treatment.Children 15 years (odds ratio 2.7, 95% CI 1.5-4.9, p=0.0006). Patients with a cumulative cisplatin dose >450 mg/m2 were more likely to develop hearing loss than those treated with carboplatin alone (OR 12.5, 95% CI 6.8-23.0, p=3.7x10-16). Treatment with cranial irradiation was more likely to lead to hearing loss than without (OR 4.5, 95% CI 3.0-6.7, p=7.2x10-13).Discussion: This is the first study of platin ototoxicity with such a large sample size. The results support tendencies found in previous studies with smaller groups. The high risk groups identified here must be monitored regularly for ototoxicity. Further detailed analyses into audiological changes and possible pharmacogenetic confounders are planned.Conclusion: 48% of patients treated with cisplatin develop clinically-relevant hearing loss. Age

Published
2019

23. Genetic determinants of ototoxicity during and after childhood cancer treatment: Protocol for the pancarelife study

Author

Clemens, E. (Eva), Meijer, A.J.M. (Annelot J.M.), Broer, L. (Linda), Langer, T. (Thomas), Kooi, A.L.F. (Anne-Lotte) van der, Uitterlinden, A.G. (André), Vries, A.C.H. (Andrica) de, Kuehni, C. (Claudia), Garrè, M.L. (Maria L.), Kepak, T. (Tomas), Kruseova, J. (Jarmila), Winther, J.F. (Jeanette F.), Kremer, L.C.M. (Leontien), Dulmen-den Broeder, E. (Eline) van, Tissing, W.J.E. (Wim), Rechnitzer, C. (Catherine), Kenborg, L. (Line), Hasle, H. (Henrik), Grabow, D. (Desiree), Parfitt, R. (Ross), Binder, H. (Harald), Carleton, B.C. (Bruce), Byrne, J. (Julianne), Kaatsch, P. (Peter), Zehnhoff-Dinnesen, A. (Antoinetteam), Zolk, O. (Oliver), Heuvel-Eibrink, M.M. (Marry) van den, Clemens, E. (Eva), Meijer, A.J.M. (Annelot J.M.), Broer, L. (Linda), Langer, T. (Thomas), Kooi, A.L.F. (Anne-Lotte) van der, Uitterlinden, A.G. (André), Vries, A.C.H. (Andrica) de, Kuehni, C. (Claudia), Garrè, M.L. (Maria L.), Kepak, T. (Tomas), Kruseova, J. (Jarmila), Winther, J.F. (Jeanette F.), Kremer, L.C.M. (Leontien), Dulmen-den Broeder, E. (Eline) van, Tissing, W.J.E. (Wim), Rechnitzer, C. (Catherine), Kenborg, L. (Line), Hasle, H. (Henrik), Grabow, D. (Desiree), Parfitt, R. (Ross), Binder, H. (Harald), Carleton, B.C. (Bruce), Byrne, J. (Julianne), Kaatsch, P. (Peter), Zehnhoff-Dinnesen, A. (Antoinetteam), Zolk, O. (Oliver), and Heuvel-Eibrink, M.M. (Marry) van den

Abstract

Background: Survival rates after childhood cancer now reach nearly 80% in developed countries. However, treatments that lead to survival and cure can cause serious adverse effects with lifelong negative impacts on survivor quality of life. Hearing impairment is a common adverse effect in children treated with cisplatin-based chemotherapy or cranial radiotherapy. Ototoxicity can extend from high-tone hearing impairment to involvement of speech frequencies. Hearing impairment can impede speech and language and neurocognitive development. Although treatment-related risk factors for hearing loss following childhood cancer treatment have been identified, the individual variability in toxicity of adverse effects after similar treatment between childhood cancer patients suggests a role for genetic susceptibility. Currently, 12 candidate gene approach studies have been performed to identify polymorphisms predisposing to platinum-induced ototoxicity in children being treated for cancer. However, results were inconsistent and most studies were underpowered and/or lacked replication. Objective: We describe the design of the PanCareLIFE consortium's work packages that address the genetic susceptibility of platinum-induced ototoxicity. Methods: As a part of the PanCareLIFE study within the framework of the PanCare consortium, we addressed genetic susceptibility of treatment-induced ototoxicity during and after childhood cancer treatment in a large European cohort by a candidate gene approach and a genome-wide association screening. Results: This study included 1124 survivors treated with cisplatin, carboplatin, or cranial radiotherapy for childhood cancer, resulting in the largest clinical European cohort assembled for this late effect to date. Within this large cohort we defined a group of 598 cisplatin-treated childhood cancer patients not confounded by cranial radiotherapy. The PanCareLIFE initiative provided, for the first time, a unique opportunity to confirm already identi

Published
2019
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24. Genetic Determinants of Ototoxicity During and After Childhood Cancer Treatment: Protocol for the PanCareLIFE Study

Author

Clemens, Eva, Meijer, AJM, Broer, Linda, Langer, T, van der Kooi, Anne-Lotte, Uitterlinden, André, de Vries, A.C.H., Kuehni, CE, Garre, ML, Kepak, T, Kruseova, J, Winther, JF, Kremer, LC, van Dulmen-den Broeder, E, Tissing, WJ, Rechnitzer, C, Kenborg, L, Hasle, H, Grabow, D, Parfitt, R, Binder, H, Carleton, BC, Byrne, J, Kaatsch, P, Zehnhoff-Dinnesen, AA, Zolk, O, Van den Heuvel - Eibrink, Marry, Clemens, Eva, Meijer, AJM, Broer, Linda, Langer, T, van der Kooi, Anne-Lotte, Uitterlinden, André, de Vries, A.C.H., Kuehni, CE, Garre, ML, Kepak, T, Kruseova, J, Winther, JF, Kremer, LC, van Dulmen-den Broeder, E, Tissing, WJ, Rechnitzer, C, Kenborg, L, Hasle, H, Grabow, D, Parfitt, R, Binder, H, Carleton, BC, Byrne, J, Kaatsch, P, Zehnhoff-Dinnesen, AA, Zolk, O, and Van den Heuvel - Eibrink, Marry

Published
2019

25. Treatment-related fertility impairment in long-term female childhood, adolescent and young adult cancer survivors: investigating dose-effect relationships in a European case-control study (PanCareLIFE).

Author

Berg, M H van den, Dijk, M van, Byrne, J, Berger, C, Dirksen, U, Winther, J F, Fossa, S D, Grabow, D, Grandage, V L, Haupt, R, Heuvel-Eibrink, M M van den, Kaiser, M, Kepak, T, Kooi, A L F van der, Kremer, L C M, Kruseova, J, Lambalk, C B, Leeuwen, F E van, Leiper, A, and Modan-Moses, D

Subjects
YOUNG adults, TEENAGERS, FERTILITY, CANCER survivors, CANCER patients, INFERTILITY, CASE-control method, COMPARATIVE studies, FERTILITY preservation, TUMORS, LONGITUDINAL method
Abstract

Study Question: Which chemotherapeutic agents and body site-specific radiation fields are dose-dependently associated with an increased risk of fertility impairment in long-term female childhood, adolescent and young adulthood (CAYA) cancer survivors?Summary Answer: Busulfan, lower abdominal radiotherapy (RT) and total body irradiation (TBI) seem to be associated with fertility impairment at any dose, whereas gonadotoxicity of melphalan and procarbazine is suggested at medium/high (>140 mg/m2) or high dose (>5600 mg/m2) therapy, respectively.What Is Known Already: Several treatment-related fertility deficits, as assessed by both self-reported outcomes and hormonal markers are known to occur following treatment of CAYA cancer. However, knowledge regarding precise dose-related estimates of these treatment-related risks are scarce.Study Design, Size, Duration: The current case-control study was nested within the PanCareLIFE cohort study. In total, 1332 CAYA survivors from 8 countries, 9 institutions and 11 cohorts, participated in and contributed data to the study.Participants/materials, Setting, Methods: All participants were female 5-year CAYA cancer survivors. In total, 450 cases (fertility impaired survivors) and 882 matched controls (not fertility impaired survivors) were included. Fertility impairment was defined using both questionnaire data (primary or secondary amenorrhea; use of artificial reproductive techniques; unfulfilled wish to conceive) and hormonal data (FSH and anti-Müllerian hormone (AMH)). Multivariable logistic regression models were used to investigate the effect of (i) alkylating agent exposure, and (ii) dose categories for individual chemotherapeutic agents and for RT-exposed body sites.Main Results and the Role Of Chance: A positive dose-effect relationship between cyclophosphamide equivalent dose (CED) score and fertility impairment was found, with survivors with a CED score > 7121 mg/m2 being at a significantly increased risk of fertility impairment (odds ratio (95% CI) = 2.6 (1.9-3.6) P < 0.001). Moreover, cumulative dose variables of the following treatments were significantly associated with fertility impairment: busulfan, carmustine, cyclophosphamide, melphalan, procarbazine, lower abdominal RT and TBI. Busulfan, lower abdominal RT and TBI seem to be associated with fertility impairment at any dose, whereas gonadotoxicity of melphalan and procarbazine is suggested at medium/high (>140 mg/m2) or high dose (>5600 mg/m2) therapy, respectively.Limitations, Reasons For Caution: Our study may have been subject to selection bias since data from about half of the original base cohorts were available for the current study. This could impact the generalizability of our study results.Wider Implications Of the Findings: We identified survivors at high risk for fertility impairment and, consequently, for a reduced or even absent reproductive life span. Both girls and young women who are about to start anti-cancer treatment, as well as adult female survivors, should be counselled about future parenthood and referred to a reproductive specialist for fertility preservation, if desired.Study Funding/competing Interest(s): This study has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 602030. There are no competing interests.Trial Registration Number: n/a. [ABSTRACT FROM AUTHOR]

Published
2021
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26. Incidence and course of ototoxic hearing loss in a big European cohort of childhood cancer patients – subproject of PanCareLIFE

Author

Tillmanns, A, Parfitt, R, Matulat, P, Deuster, D, Clemens, E, Langer, T, Bielack, S, van Dulmen-den Broeder, E, Kuehni, C, Lackner, H, Kepak, T, Kruseova, J, Haupt, R, Falck-Winther, J, Kremer, L, Calaminus, G, Broer, L, Uitterlinden, A, Zolk, O, Van den Heuvel-Eibrink, M, Byrne, J, Kaatsch, P, and am Zehnhoff-Dinnesen, A

Subjects
ddc: 610, otorhinolaryngologic diseases, 610 Medical sciences, Medicine
Abstract

Background Ototoxicity is a common side effect after platin chemotherapy and existing studies are limited due to small cohorts and a variety of confounding factors [ref:1], [ref:2]. Therefore, studies that enrolled greater numbers of patients will help us to learn more about incidence[for full text, please go to the a.m. URL], 4. Dreiländertagung D-A-CH, 35. Wissenschaftliche Jahrestagung der Deutschen Gesellschaft für Phoniatrie und Pädaudiologie (DGPP)

Published
2018
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27. Genetic variation in gonadal impairment in female survivors of childhood cancer: a PanCareLIFE study protocol

Author

Kooi, A.L.F. (Anne-Lotte) van der, Clemens, E. (Eva), Broer, L. (Linda), Zolk, O. (Oliver), Byrne, J. (Julianne), Campbell, H. (Helen), Berg, M.H. (Marleen) van den, Berger, C. (Claire), Calaminus, G. (Gabriele), Dirksen, U. (Uta), Winther, J.F. (Jeanette Falck), Fossa, S.D. (Sophie), Grabow, D. (Desiree), Haupt, R. (Riccardo), Kaiser, M. (Melanie), Kepak, T. (Tomas), Kremer, L.C.M. (Leontien), Kruseova, J. (Jarmila), Modan-Moses, D. (Dalit), Ranft, A. (Andreas), Spix, C. (Claudia), Kaatsch, P. (Peter), Laven, J.S.E. (Joop), Dulmen-den Broeder, E. (Eline) van, Uitterlinden, A.G. (André G), Heuvel-Eibrink, M.M. (Marry) van den, Kooi, A.L.F. (Anne-Lotte) van der, Clemens, E. (Eva), Broer, L. (Linda), Zolk, O. (Oliver), Byrne, J. (Julianne), Campbell, H. (Helen), Berg, M.H. (Marleen) van den, Berger, C. (Claire), Calaminus, G. (Gabriele), Dirksen, U. (Uta), Winther, J.F. (Jeanette Falck), Fossa, S.D. (Sophie), Grabow, D. (Desiree), Haupt, R. (Riccardo), Kaiser, M. (Melanie), Kepak, T. (Tomas), Kremer, L.C.M. (Leontien), Kruseova, J. (Jarmila), Modan-Moses, D. (Dalit), Ranft, A. (Andreas), Spix, C. (Claudia), Kaatsch, P. (Peter), Laven, J.S.E. (Joop), Dulmen-den Broeder, E. (Eline) van, Uitterlinden, A.G. (André G), and Heuvel-Eibrink, M.M. (Marry) van den

Abstract

BACKGROUND: Improved risk stratification, more effective therapy and better supportive care have resulted in survival rates after childhood cancer of around 80% in developed countries. Treatment however can be harsh, and three in every four childhood cancer survivors (CCS) develop at least one late effect, such as gonadal impairment. Gonadal impairment can cause involuntary childlessness, with serious consequences for the well-being of CCS. In addition, early menopause increases the risk of comorbidities such as cardiovascular disease and osteoporosis. Inter-individual variability in susceptibility to therapy related gonadal impairment suggests a role for genetic variation. Currently, only one candidate gene study investigated genetic determinants in relation to gonadal impairment in female CCS; it yielded one single nucleotide polymorphism (SNP) that was previously linked with the predicted age at menopause in the general population of women, now associated with gonadal impairment in CCS. Additionally, one genome wide association study (GWAS) evaluated an association with premature menopause, but no GWAS has been performed using endocrine measurements for gonadal impairment as the primary outcome in CCS.METHODS: As part of the PanCareLIFE study, the genetic variability of chemotherapy induced gonadal impairment among CCS will be addressed. Gonadal impairment will be determined by anti-Müllerian hormone (AMH) levels or alternatively by fertility and reproductive medical history retrieved by questionnaire. Clinical and genetic data from 837 non-brain or non-bilateral gonadal irradiated long-term CCS will result in the largest clinical European cohort assembled for this late-effect study to date. A candidate gene study will examine SNPs that have already been associated with age at natural menopause and DNA maintenance in the general population. In addition, a GWAS will be performed to identify novel allelic variants. The results will be validated in an independent C

Published
2018
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28. Genetic variation in gonadal impairment in female survivors of childhood cancer: a PanCareLIFE study protocol

Author

van der Kooi, Anne-Lotte, Clemens, Eva, Broer, Linda, Zolk, O, Byrne, J, Campbell, H, Berg, M, Berger, C, Calaminus, G, Dirksen, U, Winther, JF, Fossa, SD, Grabow, D, Haupt, R, Kaiser, M, Kepak, T, Kremer, L, Kruseova, J, Modan-Moses, D, Ranft, A, Spix, C, Kaatsch, P, Laven, Joop, van Dulmen-den Broeder, E, Uitterlinden, André, Van den Heuvel - Eibrink, Marry, van der Kooi, Anne-Lotte, Clemens, Eva, Broer, Linda, Zolk, O, Byrne, J, Campbell, H, Berg, M, Berger, C, Calaminus, G, Dirksen, U, Winther, JF, Fossa, SD, Grabow, D, Haupt, R, Kaiser, M, Kepak, T, Kremer, L, Kruseova, J, Modan-Moses, D, Ranft, A, Spix, C, Kaatsch, P, Laven, Joop, van Dulmen-den Broeder, E, Uitterlinden, André, and Van den Heuvel - Eibrink, Marry

Published
2018

29. PanCareLIFE: The scientific basis for a European project to improve long-term care regarding fertility, ototoxicity and health-related quality of life after cancer occurring among children and adolescents

Author

Byrne, Julianne, primary, Grabow, Desiree, additional, Campbell, Helen, additional, O'Brien, Kylie, additional, Bielack, Stefan, additional, am Zehnhoff-Dinnesen, Antoinette, additional, Calaminus, Gabriele, additional, Kremer, Leontien, additional, Langer, Thorsten, additional, van den Heuvel-Eibrink, Marry M., additional, van Dulmen-den Broeder, Eline, additional, Baust, Katja, additional, Bautz, Andrea, additional, Beck, Jörn D., additional, Berger, Claire, additional, Binder, Harald, additional, Borgmann-Staudt, Anja, additional, Broer, Linda, additional, Cario, Holger, additional, Casagranda, Leonie, additional, Clemens, Eva, additional, Deuster, Dirk, additional, de Vries, Andrica, additional, Dirksen, Uta, additional, Winther, Jeanette Falck, additional, Fosså, Sophie, additional, Font-Gonzalez, Anna, additional, Grandage, Victoria, additional, Haupt, Riccardo, additional, Hecker-Nolting, Stefanie, additional, Hjorth, Lars, additional, Kaiser, Melanie, additional, Kenborg, Line, additional, Kepak, Tomas, additional, Kepáková, Kateřina, additional, Knudsen, Lisbeth E., additional, Krawczuk-Rybak, Maryna, additional, Kruseova, Jarmila, additional, Kuehni, Claudia E., additional, Kunstreich, Marina, additional, Kuonen, Rahel, additional, Lackner, Herwig, additional, Leiper, Alison, additional, Loeffen, Erik A.H., additional, Luks, Ales, additional, Modan-Moses, Dalit, additional, Mulder, Renee, additional, Parfitt, Ross, additional, Paul, Norbert W., additional, Ranft, Andreas, additional, Ruud, Ellen, additional, Schilling, Ralph, additional, Spix, Claudia, additional, Stefanowicz, Joanna, additional, Strauβ, Gabriele, additional, Uitterlinden, Andre G., additional, van den Berg, Marleen, additional, van der Kooi, Anne-Lotte, additional, van Dijk, Marloes, additional, van Leeuwen, Flora, additional, Zolk, Oliver, additional, Zöller, Daniela, additional, Kaatsch, Peter, additional, Kaatsch, P., additional, Grabow, D., additional, Byrne, J., additional, Campbell, H., additional, Clissmann, C., additional, O'Brien, K., additional, Kremer, L.C.M., additional, Langer, T., additional, van Dulmen-den Broeder, E., additional, van den Berg, Dr. MH., additional, van den Heuvel-Eibrink, M.M., additional, Borgmann-Staudt, A., additional, am Zehnhoff-Dinnesen, A., additional, Kuehni, C.E., additional, Haupt, R., additional, Kepak, T., additional, Berger, C., additional, Winther, J.F., additional, Kruseova, J., additional, Calaminus, G., additional, Baust, K., additional, Dirksen, U., additional, van Leeuwen, F., additional, Schilling, R., additional, Strauss, G., additional, Ranft, A., additional, Garré, M.-L., additional, Fosså, S., additional, Leiper, A., additional, Lackner, H., additional, Panasiuk, A., additional, Krawczuk-Rybak, Dr. M., additional, Kunstreich, M., additional, Cario, H., additional, Zolk, O., additional, Bielack, S., additional, Stefanowicz, J., additional, Grandage, V., additional, and Modan, D., additional

Published
2018
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30. Metronomic Chemotherapy with the COMBAT Regimen in Advanced Pediatric Malignancies: A Multicenter Experience

Author

Zapletalova, D., primary, André, N., additional, Deak, L., additional, Kyr, M., additional, Bajciova, V., additional, Mudry, P., additional, Dubska, L., additional, Demlova, R., additional, Pavelka, Z., additional, Zitterbart, K., additional, Skotakova, J., additional, Husek, K., additional, Martincekova, A., additional, Mazanek, P., additional, Kepak, T., additional, Doubek, M., additional, Kutnikova, L., additional, Valik, D., additional, and Sterba, J., additional

Published
2012
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34. Healthcare providers' expected barriers and facilitators to the implementation of person-centered long-term follow-up care for childhood cancer survivors: A PanCareFollowUp study.

Author

Breij D, Hjorth L, Bouwman E, Walraven I, Kepak T, Kepakova K, Haupt R, Muraca M, Göttgens I, Stollman I, Winther JF, Kienesberger A, Gsell H, Michel G, Blijlevens N, Pluijm SMF, Roser K, Skinner R, Renard M, Uyttebroeck A, Follin C, van der Pal HJH, Kremer LCM, Loonen J, and Hermens R

Subjects
Humans, Female, Male, Focus Groups, Child, Patient-Centered Care, Quality of Life, Follow-Up Studies, Neoplasms psychology, Neoplasms therapy, Adult, Attitude of Health Personnel, Long-Term Care, Aftercare, Cancer Survivors psychology, Health Personnel psychology, Qualitative Research
Abstract

Background: Childhood cancer survivors face high risks of adverse late health effects. Long-term follow-up care for childhood cancer survivors is crucial to improve their health and quality of life. However, implementation remains a challenge. To support implementation of high-quality long-term follow-up care, we explored expected barriers and facilitators for establishing this follow-up care among healthcare providers from four European clinics., Methods: A qualitative study was conducted using four focus groups comprising 30 healthcare providers in total. The semi-structured interview guide was developed based on the Grol and Wensing framework. Data was analyzed following a thematic analysis, combining both inductive and deductive approaches to identify barriers and facilitators across the six levels of Grol and Wensing: innovation, professional, patient, social, organizational and economic and political., Results: Most barriers were identified on the organizational level, including insufficient staff, time, capacity and psychosocial support. Other main barriers included limited knowledge of late effects among healthcare providers outside the long-term follow-up care team, inability of some survivors to complete the survivor questionnaire and financial resources. Main facilitators included motivated healthcare providers and survivors, a skilled hospital team, collaborations with important stakeholders like general practitioners, and psychosocial care facilities, utilization of the international collaboration and reporting long-term follow-up care results to convince hospital managers., Conclusion: This study identified several factors for successful implementation of long-term follow-up care for childhood cancer survivors. Our findings showed that specific attention should be given to knowledge, capacity, and financial issues, along with addressing psychosocial issues of survivors., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Published
2024
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35. Barriers, facilitators, and other factors associated with health behaviors in childhood, adolescent, and young adult cancer survivors: A systematic review.

Author

de Beijer IAE, Bouwman E, Mulder RL, Steensma P, Brown MC, Araújo-Soares V, Balcerek M, Bardi E, Falck Winther J, Frederiksen LE, van Gorp M, Oberti S, van Kalsbeek RJ, Kepak T, Kepakova K, Gsell H, Kienesberger A, van Litsenburg R, Mader L, Michel G, Muraca M, van den Oever SR, van der Pal HJH, Roser K, Skinner R, Stolman I, Uyttebroeck A, Kremer LCM, Loonen J, van Dalen EC, and Pluijm SMF

Subjects
Adolescent, Adult, Child, Female, Humans, Male, Middle Aged, Young Adult, Alcohol Drinking epidemiology, Diet, Neoplasms psychology, Neoplasms epidemiology, Smoking epidemiology, Smoking adverse effects, Cancer Survivors psychology, Exercise, Health Behavior
Abstract

Background: Healthy behaviors are paramount in preventing long-term adverse health outcomes in childhood, adolescent, and young adult (CAYA) cancer survivors. We systematically reviewed and synthesized existing literature on barriers, facilitators, and other factors associated with health behaviors in this population., Methods: MEDLINE and PsycInfo were searched for qualitative and quantitative studies including survivors aged 16-50 years at study, a cancer diagnosis ≤25 years and ≥2 years post diagnosis. Health behaviors included physical activity, smoking, diet, alcohol consumption, sun exposure, and a combination of these behaviors (defined as health behaviors in general)., Results: Barriers, facilitators, and other factors reported in ≥2 two studies were considered relevant. Out of 4529 studies, 27 were included (n = 31,905 participants). Physical activity was the most frequently examined behavior (n = 12 studies), followed by smoking (n = 7), diet (n = 7), alcohol (n = 4), sun exposure (n = 4), and health behavior in general (n = 4). Relevant barriers to physical activity were fatigue, lack of motivation, time constraints, and current smoking. Relevant facilitators were perceived health benefits and motivation. Influence of the social environment and poor mental health were associated with more smoking, while increased energy was associated with less smoking. No relevant barriers and facilitators were identified for diet, alcohol consumption, and sun exposure. Barriers to healthy behavior in general were unmet information needs and time constraints whereas lifestyle advice, information, and discussions with a healthcare professional facilitated healthy behavior in general. Concerning other factors, women were more likely to be physically inactive, but less likely to drink alcohol and more likely to comply with sun protection recommendations than men. Higher education was associated with more physical activity, and lower education with more smoking., Conclusion: This knowledge can be used as a starting point to develop health behavior interventions, inform lifestyle coaches, and increase awareness among healthcare providers regarding which survivors are most at risk of unhealthy behaviors., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Published
2024
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36. The impact of the temporal sequence of cranial radiotherapy and platin-based chemotherapy on hearing impairment in pediatric and adolescent CNS and head-and-neck cancer patients: A report from the PanCareLIFE consortium.

Author

Scobioala S, Parfitt R, Matulat P, Byrne J, Langer T, Troschel FM, Hesping AE, Clemens E, Kaatsch P, Grabow D, Kaiser M, Spix C, Kremer LC, Calaminus G, Baust K, Kuehni CE, Weiss A, Strebel S, Kuonen R, Elsner S, Haupt R, Garré ML, Gruhn B, Kepak T, Kepakova K, Winther JF, Kenborg L, Rechnitzer C, Hasle H, Kruseova J, Luks A, Lackner H, Bielack S, Beck JD, Jürgens H, van den Heuvel-Eibrink MM, Zolk O, Eich HT, and Am Zehnhoff-Dinnesen A

Subjects
Humans, Child, Adolescent, Central Nervous System, Cranial Irradiation, Hearing Loss chemically induced, Hearing Loss epidemiology, Hearing Loss, Sensorineural chemically induced, Hearing Loss, Sensorineural epidemiology, Head and Neck Neoplasms drug therapy, Head and Neck Neoplasms radiotherapy
Abstract

The impact of the temporal sequence by which cranial radiotherapy (CRT) and platin-based chemotherapy (PCth) are administered on sensorineural hearing loss (SNHL) in pediatric and adolescent central nervous system (CNS) and head-and-neck (HN) cancer patients has not yet been studied in detail. We examined the ototoxic effects of sequentially applied CRT and PCth. This study included children and adolescents with CNS and HN tumors who participated in the multicountry PanCareLIFE (PCL) consortium. Audiological outcomes were compared between patients who received CRT prior to PCth and those who received it afterwards. The incidence, degree and posttreatment progression of SNHL, defined as Muenster classification grade ≥MS2b, were evaluated in 141 patients. One hundred and nineteen patients were included in a time-to-onset analysis. Eighty-eight patients received CRT prior to PCth (Group 1) and 53 patients received PCth before CRT (Group 2). Over a median follow-up time of 1.6 years, 72.7% of patients in Group 1 experienced SNHL ≥ MS2b compared to 33.9% in Group 2 (P < .01). A time-to-onset analysis was performed for 74 patients from Group 1 and 45 patients from Group 2. Median time to hearing loss (HL) ≥ MS2b was 1.2 years in Group 1 and 4.4 years in Group 2 (P < .01). Thus, audiological outcomes were better for patients who received CRT after PCth than before. This finding should be further evaluated and considered within clinical practice in order to minimize hearing loss in children and adolescents with CNS and HN tumors., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Published
2024
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37. Auditory complications among childhood cancer survivors and health-related quality of life: a PanCareLIFE study.

Author

Strebel S, Baust K, Grabow D, Byrne J, Langer T, Am Zehnhoff-Dinnesen A, Kuonen R, Weiss A, Kepak T, Kruseova J, Berger C, Calaminus G, Sommer G, and Kuehni CE

Abstract

Purpose: Auditory complications are potential side effects from childhood cancer treatment. Yet, limited evidence exists about the impact of auditory complications-particularly tinnitus-on health-related quality of life (HRQoL) among childhood cancer survivors (CCS). We determined the prevalence of hearing loss and tinnitus in the European PanCareLIFE cohort of CCS and examined its effect on HRQoL., Methods: We included CCS from four European countries who were diagnosed at age ≤ 18 years; survived ≥ 5 years; and aged 25-44 years at study. We assessed HRQoL (Short Form 36), hearing loss, and tinnitus using questionnaires. We used multivariable linear regression to examine associations between these two auditory complications and HRQoL adjusting for socio-demographic and clinical factors., Results: Our study population consisted of 6,318 CCS (53% female; median age at cancer diagnosis 9 years interquartile range [IQR] 5-13 years) with median age at survey of 31 years (IQR 28-35 years). Prevalence was 7.5% (476/6,318; confidence interval [CI]: 6.9-8.2) for hearing loss and 7.6% (127/1,668; CI: 6.4-9.0) for tinnitus. CCS with hearing loss had impaired physical (coefficient [coef.] -4.3, CI: -7.0 to -1.6) and mental (coef. -3.2, CI: -5.5 to -0.8) HRQoL when compared with CCS with normal hearing. Tinnitus was associated with impaired physical (coef. -8.2, CI: -11.8 to -4.7) and mental (coef. -5.9, CI: -8.8 to -3.1) HRQoL., Conclusion: We observed reduced HRQoL among CCS with hearing loss and tinnitus. Our findings indicate timely treatment of hearing loss and tinnitus may contribute to quality of life of survivors., Implications for Cancer Survivors: CCS who experience auditory complications should be counseled about possible therapeutic and supportive measures during follow-up care., (© 2023. The Author(s).)

Published
2023
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38. Perceived barriers and facilitators to health behaviors in European childhood cancer survivors: A qualitative PanCareFollowUp study.

Author

Bouwman E, Pluijm SMF, Stollman I, Araujo-Soares V, Blijlevens NMA, Follin C, Winther JF, Hjorth L, Kepak T, Kepakova K, Kremer LCM, Muraca M, van der Pal HJH, Schneider C, Uyttebroeck A, Vercruysse G, Skinner R, Brown MC, Hermens RPMG, and Loonen JJ

Subjects
Humans, Child, Health Behavior, Qualitative Research, Focus Groups, Cancer Survivors, Neoplasms epidemiology, Neoplasms therapy
Abstract

Background: Healthy behaviors, that is, engaging in regular physical activities, maintaining a healthy diet, limiting alcohol consumption, and avoiding tobacco and drug use, decrease the risk of developing late adverse health conditions in childhood cancer survivors. However, childhood cancer survivors may experience barriers to adopting and maintaining healthy behaviors. This study aimed to assess these barriers and facilitators to health behavior adoption and maintenance in childhood cancer survivors., Methods: A focus group ( n  = 12) and semi-structured telephone interviews ( n  = 20) were conducted with a selected sample of European and Dutch childhood cancer survivors, respectively. The Theoretical Domains Framework (TDF) was used to inform the topic guide and analysis. Inductive thematic analysis was applied to identify categories relating to barriers and facilitators of health behavior adoption and maintenance, after which they were deductively mapped onto the TDF., Results: Ten TDF domains were identified in the data of which "Knowledge," "Beliefs about consequences," "Environmental context and resources," and "Social influences" were most commonly reported. Childhood cancer survivors expressed a need for knowledge on the importance of healthy behaviors, possibly provided by healthcare professionals. They indicated physical and long-term benefits of healthy behaviors, available professional support, and a supporting and health-consciously minded work and social environment to be facilitators. Barriers were mostly related to a lack of available time and an unhealthy environment. Lastly, (social) media was perceived as both a barrier and a facilitator to healthy behaviors., Conclusion: This study has identified education and available professional support in health behaviors and the relevance of healthy behaviors for childhood cancer survivors as key opportunities for stimulating health behavior adoption in childhood cancer survivors. Incorporating health behavior support and interventions for this population should therefore be a high priority., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Published
2023
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39. Healthcare professionals' perceived barriers and facilitators of health behavior support provision: A qualitative study.

Author

Bouwman E, Pluijm SMF, Stollman I, Araujo-Soares V, Blijlevens NMA, Follin C, Winther JF, Hjorth L, Kepak T, Kepakova K, Kremer LCM, Muraca M, van der Pal HJH, Schneider C, Uyttebroeck A, Vercruysse G, Skinner R, Brown MC, Hermens RPMG, and Loonen JJ

Subjects
Humans, Child, Qualitative Research, Focus Groups, Delivery of Health Care, Health Personnel education, Health Behavior
Abstract

Background: Childhood cancer survivors (CCSs) have an increased risk of developing chronic health conditions. Evidence suggests that poor health behaviors further increase health risks. Healthcare professionals (HCPs) involved in survivorship care have a key role in providing health behavior support (HBS) but can feel limited in their ability to do so. This study aims to explore European HCPs perceived facilitators and barriers to providing HBS to CCSs., Methods: Five focus groups with 30 HCPs from survivorship care clinics across Europe were conducted. Topic guides were informed by the Theoretical Domains Framework (TDF) to capture domains that may influence provision of HBS. Focus groups were analyzed with thematic analysis. Transcripts were inductively coded, after which axial coding was applied to organize codes into categories. Finally, categories were mapped onto the TDF domains., Results: Nine TDF domains were identified in the data. The most commonly reported TDF domains were "Knowledge", "Skills", and "Environmental context and resources". HCPs indicated that their lack of knowledge of the association between late effects and health behaviors, besides time restrictions, were barriers to HBS. Facilitators for HBS included possession of skills needed to pass on health behavior information, good clinic organization, and an established network of HCPs., Conclusions: This study identified education and training of HCPs as key opportunities to improve HBS. Survivorship care clinics should work towards establishing well-integrated structured care with internal and external networks including HBS being part of routine care. Proper understanding of facilitators and barriers should lead to better survivorship care for CCSs., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Published
2023
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40. Person-centred online lifestyle coaching in childhood, adolescent, and young adult cancer survivors: protocol of the multicentre PanCareFollowUp lifestyle intervention feasibility study.

Author

Bouwman E, Hermens RPMG, Brown MC, Araújo-Soares V, Blijlevens NMA, Kepak T, Kepakova K, Kremer LCM, van den Oever SR, van der Pal HJH, Skinner R, Pluijm SMF, and Loonen JJ

Abstract

Background: Physical inactivity and unhealthy dietary habits are known to be disadvantageous for the development of late adverse effects in survivors of childhood, adolescent, and young adult cancer. To make interventions, aimed at improving lifestyle, fit into the daily life of survivors, interventions should be designed and delivered in a person-centred way with a limited time burden. As part of the European PanCareFollowUp project, an eHealth intervention was developed to support sustainable changes to physical activity levels and/or diet of childhood, adolescent, and young adult cancer survivors. This feasibility study aims to gain insight into the feasibility and potential effect sizes of the PanCareFollowUp lifestyle intervention., Methods: The PanCareFollowUp lifestyle intervention consists of person-centred 3-6 screen-to-screen sessions with a certified lifestyle coach. The intervention will be evaluated with a single-arm pre-post feasibility study conducted at two survivorship care clinics in the Netherlands. A total of 60 participants who are (i) diagnosed with cancer <25 years, (ii) ≥ 5 years post-treatment, (iii) aged 16-55 years, and (iv) have a low physical activity level and/or unhealthy dietary intake manifested by overweight will be recruited. Using reports, hospital records, and questionnaires for survivors, coaches, and late effect doctors, feasibility will be based on (i) adherence to intervention, (ii) acceptability, (iii) practicality, (iv) integration/implementation, (v) demand, and (vi) attrition. The potential effect sizes of the intervention will be explored by determining the percentage of survivors that reach the personalized lifestyle goals that were set with the coach. Physical activity level, dietary intake, BMI, general self-efficacy, self-management, and motivation level will be assessed at three time points with questionnaires, reports, and/or an accelerometer., Discussion: Data of this study will be gathered to assess the feasibility and potential effect sizes. This will allow for further intervention refinement as needed as well as to inform a future large-scale intervention study and a manual for implementation at other centres., Trial Registration: International Clinical Trial Registry Platform (ICTRP) number: NL8932 (ICTRP Search Portal (who.int)). Registered on September 29, 2020., (© 2022. The Author(s).)

Published
2022
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41. Childhood cancer survivorship care during the COVID-19 pandemic: an international report of practice implications and provider concerns.

Author

van den Oever SR, Pluijm SMF, Skinner R, Glaser A, Mulder RL, Armenian S, Bardi E, Berger C, Ehrhardt MJ, Gilleland Marchak J, Haeusler GM, Hartogh JD, Hjorth L, Kepak T, Kriviene I, Langer T, Maeda M, Márquez-Vega C, Michel G, Muraca M, Najib M, Nathan PC, Panasiuk A, Prasad M, Roganovic J, Uyttebroeck A, Winther JF, Zadravec Zaletel L, van Dalen EC, van der Pal HJH, Hudson MM, and Kremer LCM

Subjects
Child, Humans, Pandemics, Survivors, Cancer Survivors psychology, Neoplasms psychology, COVID-19 epidemiology
Abstract

Purpose: Long-term follow-up (LTFU) care is essential to optimise health outcomes in childhood cancer survivors (CCS). We aimed to assess the impact of the COVID-19 pandemic on LTFU services and providers., Methods: A COVID-19 working group within the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) distributed a questionnaire to LTFU service providers in 37 countries across Europe, Asia, North America, Central/South America, and Australia. The questionnaire assessed how care delivery methods changed during the pandemic and respondents' level of worry about the pandemic's impact on LTFU care delivery, their finances, their health, and that of their family and friends., Results: Among 226 institutions, providers from 178 (79%) responded. Shortly after the initial outbreak, 42% of LTFU clinics closed. Restrictions during the pandemic resulted in fewer in-person consultations and an increased use of telemedicine, telephone, and email consultations. The use of a risk assessment to prioritise the method of LTFU consultation for individual CCS increased from 12 to 47%. While respondents anticipated in-person consultations to remain the primary method for LTFU service delivery, they expected significantly increased use of telemedicine and telephone consultations after the pandemic. On average, respondents reported highest levels of worry about psychosocial well-being of survivors., Conclusions: The pandemic necessitated changes in LTFU service delivery, including greater use of virtual LTFU care and risk-stratification to identify CCS that need in-person evaluations., Implications for Cancer Survivors: Increased utilisation of virtual LTFU care and risk stratification is likely to persist post-pandemic., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Published
2022
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42. The Use of Assisted Reproductive Technology by European Childhood Cancer Survivors.

Author

Borgmann-Staudt A, Michael S, Sommerhaeuser G, Fernández-González MJ, Friedrich LA, Klco-Brosius S, Kepak T, Kruseova J, Michel G, Panasiuk A, Schmidt S, Lotz L, and Balcerek M

Subjects
Child, Female, Humans, Infant, Newborn, Male, Pregnancy, Pregnancy Outcome, Prospective Studies, Reproductive Techniques, Assisted adverse effects, Semen, Cancer Survivors, Neoplasms epidemiology, Premature Birth epidemiology
Abstract

CCS often wish to have biological children yet harbour concerns about fertility impairment, pregnancy risks and the general health risks of prospective offspring. To clarify these concerns, health outcomes in survivor offspring born following ART (n = 74, 4.5%) or after spontaneous conception (n = 1585) were assessed in our European offspring study by descriptive and bivariate analysis. Outcomes were compared to a sibling offspring cohort (n = 387) in a 4:1 matched-pair analysis (n = 1681). (i) Survivors were more likely to employ ART than their siblings (4.5% vs. 3.7%, p = 0.501). Successful pregnancies were achieved after a median of one cycle with, most commonly, intracytoplasmic sperm injection (ICSI) using non-cryopreserved oocytes/sperm. (ii) Multiple-sibling births (p < 0.001, 29.7% vs. 2.5%), low birth weight (p < 0.001; OR = 3.035, 95%-CI = 1.615−5.706), and preterm birth (p < 0.001; OR = 2.499, 95%-CI = 1.401−4.459) occurred significantly more often in survivor offspring following ART utilisation than in spontaneously conceived children. ART did not increase the prevalence of childhood cancer, congenital malformations or heart defects. (iii) These outcomes had similar prevalences in the sibling population. In our explorative study, we could not detect an influence on health outcomes when known confounders, such as multiple births, were taken into account.

Published
2022
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43. Late effects of childhood cancer recorded at a single outpatient clinic over the course of one year: implications for the follow-up care.

Author

Kepak T, Hrstkova H, Bajciova V, Dusek V, Holikova M, Strublova L, and Kepakova K

Subjects
Adolescent, Adult, Aftercare, Ambulatory Care Facilities, Child, Disease Progression, Humans, Middle Aged, Survivors, Young Adult, Cancer Survivors psychology, Neoplasms complications, Neoplasms therapy
Abstract

The paper provides a descriptive analysis of medical data and selected patient-reported outcomes from a group of 133 survivors of childhood cancer recruited at St. Anne's University Hospital in Brno, Czech Republic, over the course of one year. The participants were 18-53 years old (mean age 27.9 years) and had been diagnosed with childhood cancer in the period 1979-2016. Treatment data and data on relevant health outcomes were extracted from the medical records and categorized. Patient-reported outcomes were measured using the clinic's questionnaires completed by survivors prior to the medical examination. The most frequent adverse health outcomes in the study were dyslipidemia (50%) and overweight, obesity, and even morbid obesity (45%, 15%, and 1.5%, respectively). Endocrinopathies were observed in more than one-third (35.3%) of the survivors, followed by nephropathy (33.8%). Cardiovascular abnormalities were found in 9.7% of the survivors and fertility impairment in 9%. 38% of the survivors reported chronic fatigue and one-half (51%) reported pain. 20% of the cohort face mobility impairment. A remarkably high percentage of the survivors (70%) communicated some level of mental health issues. Moderate to severe anxiety and/or depression was reported by 25% of the survivors. 40% of the survivors experienced strong fears of disease recurrence, another 40% reported mild or moderate fears. Fear of late effects was communicated by 83% of the survivors, with 38% experiencing high levels of concerns. Only 8% of the survivors had no adverse health outcome. The rate of somatic and mental health outcomes identified in our sample is high. Some of the most frequent outcomes are mutually interconnected and modifiable, which highlights the need for patient education on a healthy lifestyle. There is also a clear need for improved psychological support for childhood cancer survivors to mitigate unnecessary anxieties resulting from unsubstantiated health concerns. Dissemination of personalized and positive messages should be part of routine follow-up care.

Published
2022
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44. The PanCareFollowUp Care Intervention: A European harmonised approach to person-centred guideline-based survivorship care after childhood, adolescent and young adult cancer.

Author

van Kalsbeek RJ, Mulder RL, Haupt R, Muraca M, Hjorth L, Follin C, Kepak T, Kepakova K, Uyttebroeck A, Mangelschots M, Winther JF, Loonen JJ, Michel G, Bardi E, Elmerdahl Frederiksen L, den Hartogh J, Mader L, Roser K, Schneider C, Brown MC, Brunhofer M, Göttgens I, Hermens RPMG, Kienesberger A, Korevaar JC, Skinner R, van der Pal HJH, and Kremer LCM

Subjects
Adolescent, Humans, Quality of Life, Survivors, Survivorship, Young Adult, Cancer Survivors, Neoplasms therapy
Abstract

Background: Long-term follow-up (LTFU) care, although endorsed, is not available for the majority of adult survivors of childhood, adolescence and young adult (CAYA) cancer. Barriers to implementation include lack of time, knowledge, personnel and funding. Sustainable solutions are urgently needed to address the needs of CAYA cancer survivors to improve the quality of life and reduce the burden of late effects on survivors, health care systems and society. The European Union-funded PanCareFollowUp project, initiated by the Pan-European Network for Care of Survivors after Childhood and Adolescent Cancer, was established to facilitate the implementation of person-centred survivorship care across Europe., Patients and Methods: The PanCareFollowUp Care Intervention was co-developed with survivors as part of the PanCareFollowUp project. It is a person-centred approach to survivorship care, supported by guidelines and with flexibility to adapt to local health care settings. The Care Intervention consists of three steps: (1) previsit completion of a Survivor Questionnaire (by the survivor) and Treatment Summary (by the health care provider [HCP]), (2) a clinic visit including shared decision-making, and (3) a follow-up call to finalise the individualised Survivorship Care Plan., Results: We developed the key components of the PanCareFollowUp Care Intervention: a PanCareFollowUp Survivor Questionnaire, Treatment Summary template, Survivorship Care Plan template, and educational materials for HCPs and survivors. Wide implementation of the PanCareFollowUp Care Intervention will be supported with a freely distributed Replication Manual on completion of the PanCareFollowUp project., Conclusions: The PanCareFollowUp Care Intervention will support the implementation of person-centred, guideline-based LTFU care in different health care settings across Europe to improve survivors' health and well-being., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2022
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45. Health of children born to childhood cancer survivors: Participant characteristics and methods of the Multicenter Offspring Study.

Author

Sommerhäuser G, Borgmann-Staudt A, Schilling R, Frey E, Hak J, Janhubová V, Kepakova K, Kepak T, Klco-Brosius S, Krawczuk-Rybak M, Kruseova J, Lackner H, Luks A, Michel G, Panasiuk A, Tamesberger M, Vetsch J, and Balcerek M

Subjects
Child, Female, Humans, Male, Prospective Studies, Siblings, Survivors, Cancer Survivors, Neoplasms epidemiology
Abstract

Introduction: Research on childhood cancer survivor offspring has been limited to genetic disease occurrence, malformations or non-hereditary cancers. However, previous surveys indicated that survivors harbor fears about their (prospective) children's overall health. Our Multicenter Offspring Study examined extensive health aspects in children born to survivors and their siblings providing comprehensive information to be used in patient counseling to elucidate and alleviate existing concerns., Methods: Using a specifically designed questionnaire, childhood cancer survivors and their siblings were surveyed on their offspring's health (Supplementary material). Recruitment strategies depended on local infrastructures and standards of participating centers, including registry-based and direct approaches. Group differences were tested non-parametrically and effect sizes were calculated., Results: In total, 1126 survivors reported on 1780 offspring and 271 siblings reported on 441 offspring. Response rates ranged from 32.1% (Czech Republic) to 85.0% (Austria). Respondents were more likely to be female (p = .007), older at time of survey (p < .001), diagnosed 1980-1999 (p < .001) and treated with chemotherapy (p < .001). Compared to siblings, survivors were younger at time of survey (35 years vs. 39 years, p < .001) and at first birth (29 years vs. 30 years, p < .001). Survivor and sibling offspring only differed in terms of age at survey (6.3 years vs. 8.9 years, p < .001)., Conclusion: The Multicenter Offspring Study investigates a wide variety of health aspects in offspring born to survivors and their siblings in five European countries. Our study cohorts form a solid basis for future analyses; yet, certain limitations, due to differences in approach among participating centers, must be considered when interpreting findings., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Published
2021
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46. Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries.

Author

Fabian ID, Stacey AW, Foster A, Kivelä TT, Munier FL, Keren-Froim N, Gomel N, Cassoux N, Sagoo MS, Reddy MA, Harby LA, Zondervan M, Bascaran C, Abdallah E, Abdullahi SU, Boubacar SA, Ademola-Popoola DS, Adio A, Aghaji AE, Portabella SA, Alfa Bio AI, Ali AM, Alia DB, All-Eriksson C, Almeida AA, Alsawidi KM, Antonino R, Astbury NJ, Atsiaya R, Balaguer J, Balwierz W, Barranco H, Popovic MB, Benmiloud S, Guebessi NB, Berete RC, Biddulph SJ, Biewald EM, Blum S, Bobrova N, Boehme M, Bornfeld N, Bouda GC, Bouguila H, Boumedane A, Brichard BG, L MC, Castela G, Català-Mora J, Chantada GL, Chernodrinska VS, Chiwanga FS, Cieslik K, Comsa C, Correa Llano MG, Csóka M, Da Gama IV, Davidson A, Potter P, Desjardins L, Dragomir MD, Bruyn MD, Kettani AE, Elbahi AM, Elgalaly D, Elhaddad AM, Ali Elhassan MM, Elzembely MM, Essuman VA, Evina TGA, Fasina O, Fernández-Teijeiro A, Gandiwa M, Aldana DG, Geel JA, Gizachew Z, Gregersen PA, Guedenon KM, Hadjistilianou T, Hassan S, Hederova S, Hessissen L, Hordofa DF, Hummlen M, Husakova K, Ida R, Ilic VR, Jenkinson H, Amani Kabesha TB, Kabore RL, Kalinaki A, Kapelushnik N, Kardava T, Kemilev PK, Kepak T, Khotenashvili Z, Klett A, Kosh Komba Palet JE, Krivaitiene D, Kruger M, Kyara A, Lachmann ES, Latinović S, Lecuona K, Lukamba RM, Lumbroso L, Lysytsia L, Maka E, Makan M, Manda C, Begue NM, Matende IO, Matua M, Mayet I, Mbumba FB, Mengesha AA, Midena E, Mndeme FG, Mohamedani AA, Moll AC, Moreira C, Msina MS, Msukwa G, Muma KI, Murgoi G, Musa KO, Mustak H, Muyen OM, Naidu G, Naumenko L, Ndoye Roth PA, Neroev V, Nikitovic M, Nkanga ED, Nkumbe H, Nyaywa M, Obono-Obiang G, Oguego NC, Olechowski A, Oscar AH, Osei-Bonsu P, Painter SL, Paintsil V, Paiva L, Papyan R, Parrozzani R, Parulekar M, Pawinska-Wasikowska K, Perić S, Philbert R, Pochop P, Polyakov VG, Pompe MT, Pons JJ, Raobela L, Renner LA, Reynders D, Ribadu D, Riheia MM, Ritter-Sovinz P, Saakyan S, Said AM, Román Pacheco SS, Scanlan TA, Schoeman J, Seregard S, Sherief ST, Cheikh SS, Silva S, Sorochynska T, Ssali G, Stathopoulos C, Kranjc BS, Stones DK, Svojgr K, Sylla F, Tamamyan G, Tandili A, Tateshi B, Theophile T, Traoré F, Tyau-Tyau H, Umar AB, Urbak SF, Ushakova TL, Valeina S, Hoefen Wijsard MV, Veleva-Krasteva NV, Viksnins M, Wackernagel W, Waddell K, Wade PD, Wali Nigeria AH, Wime AD, Dod CW, Yanga JM, Yarovaya VA, Yarovoy AA, Zein E, Sharabi S, Zhilyaeva K, Ziko OA, and Bowman R

Subjects
Africa epidemiology, Cross-Sectional Studies, Humans, Risk Factors, Retinal Neoplasms diagnosis, Retinal Neoplasms epidemiology, Retinoblastoma diagnosis, Retinoblastoma epidemiology
Abstract

Background: The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe., Methods: A cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries., Results: Capture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI -12.4 to -5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease., Conclusions: Fewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2021
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47. European PanCareFollowUp Recommendations for surveillance of late effects of childhood, adolescent, and young adult cancer.

Author

van Kalsbeek RJ, van der Pal HJH, Kremer LCM, Bardi E, Brown MC, Effeney R, Winther JF, Follin C, den Hartogh J, Haupt R, Hjorth L, Kepak T, Kepakova K, Levitt G, Loonen JJ, Mangelschots M, Muraca M, Renard M, Sabic H, Schneider CU, Uyttebroeck A, Skinner R, and Mulder RL

Subjects
Adolescent, Humans, Quality of Life, Young Adult, Cancer Survivors psychology, Neoplasms therapy, Practice Guidelines as Topic
Abstract

Background: Long-term follow-up (LTFU) care for childhood, adolescent, and young adult (CAYA) cancer survivors is essential to preserve health and quality of life (QoL). Evidence-based guidelines are needed to inform optimal surveillance strategies, but many topics are yet to be addressed by the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG). Therefore, the PanCareFollowUp Recommendations Working Group collaborated with stakeholders to develop European harmonised recommendations in anticipation of evidence-based IGHG guidelines., Methods: The PanCareFollowUp Recommendations Working Group, consisting of 23 late effects specialists, researchers, and survivor representatives from nine countries, collaborated in the first Europe-wide effort to provide unified recommendations in anticipation of evidence-based guidelines. A pragmatic methodology was used to define recommendations for topics where no evidence-based IGHG recommendations exist. The objective was to describe the surveillance requirements for high-quality care while balancing the different infrastructures and resources across European health care systems. The process included two face-to-face meetings and an external consultation round involving 18 experts from 14 countries., Results: Twenty-five harmonised recommendations for LTFU care were developed collaboratively and address topics requiring awareness only (n = 6), awareness, history and/or physical examination (n = 9), or additional surveillance tests (n = 10)., Conclusions: The PanCareFollowUp Recommendations, representing a unique agreement across European stakeholders, emphasise awareness among survivors and health care providers in addition to tailored clinical evaluation and/or surveillance tests. They include existing IGHG guidelines and additional recommendations developed by a pragmatic methodology and will be used in the Horizon 2020-funded PanCareFollowUp project to improve health and QoL of CAYA cancer survivors., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2021
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48. The European multistakeholder PanCareFollowUp project: novel, person-centred survivorship care to improve care quality, effectiveness, cost-effectiveness and accessibility for cancer survivors and caregivers.

Author

van Kalsbeek RJ, van der Pal HJH, Hjorth L, Winther JF, Michel G, Haupt R, Uyttebroeck A, O'Brien K, Kepakova K, Follin C, Muraca M, Kepak T, Araujo-Soares V, Bardi E, Blondeel A, Bouwman E, Brown MC, Frederiksen LE, Essiaf S, Hermens RPMG, Kienesberger A, Korevaar JC, Mader L, Mangelschots M, Mulder RL, van den Oever S, Rijken M, Roser K, Skinner R, Pluijm SMF, Loonen JJ, and Kremer LCM

Subjects
Europe, Humans, Quality of Health Care, Cancer Survivors statistics & numerical data, Caregivers economics, Caregivers psychology, Survivorship
Abstract

Background: The majority of childhood cancer survivors are at risk of treatment-related adverse health outcomes. Survivorship care to mitigate these late effects is endorsed, but it is not available for many adult survivors of childhood cancer in Europe. The PanCareFollowUp project was initiated to improve their health and quality of life (QoL) by facilitating person-centred survivorship care., Methods: The PanCareFollowUp consortium was established in 2018, consisting of 14 project partners from ten European countries, including survivor representatives. The consortium will develop two PanCareFollowUp Interventions, including a person-centred guideline-based model of care (Care Intervention) and eHealth lifestyle coaching (Lifestyle Intervention). Their development will be informed by several qualitative studies and systematic reviews on barriers and facilitators for implementation and needs and preferences of healthcare providers (HCPs) and survivors. Implementation of the PanCareFollowUp Care Intervention as usual care will be evaluated prospectively among 800 survivors from Belgium, Czech Republic, Italy and Sweden for survivor empowerment, detection of adverse health conditions, satisfaction among survivors and HCPs, cost-effectiveness and feasibility. The feasibility of the PanCareFollowUp Lifestyle Intervention will be evaluated in the Netherlands among 60 survivors., Results: Replication manuals, allowing for replication of the PanCareFollowUp Care and Lifestyle Intervention, will be published and made freely available after the project. Moreover, results of the corresponding studies are expected within the next five years., Conclusions: The PanCareFollowUp project is a novel European collaboration aiming to improve the health and QoL of all survivors across Europe by developing and prospectively evaluating the person-centred PanCareFollowUp Care and Lifestyle Interventions., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Published
2021
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49. TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study.

Author

Meijer AJM, Diepstraten FA, Langer T, Broer L, Domingo IK, Clemens E, Uitterlinden AG, de Vries ACH, van Grotel M, Vermeij WP, Ozinga RA, Binder H, Byrne J, van Dulmen-den Broeder E, Garrè ML, Grabow D, Kaatsch P, Kaiser M, Kenborg L, Winther JF, Rechnitzer C, Hasle H, Kepak T, Kepakova K, Tissing WJE, van der Kooi ALF, Kremer LCM, Kruseova J, Pluijm SMF, Kuehni CE, van der Pal HJH, Parfitt R, Spix C, Tillmanns A, Deuster D, Matulat P, Calaminus G, Hoetink AE, Elsner S, Gebauer J, Haupt R, Lackner H, Blattmann C, Neggers SJCMM, Rassekh SR, Wright GEB, Brooks B, Nagtegaal AP, Drögemöller BI, Ross CJD, Bhavsar AP, Am Zehnhoff-Dinnesen AG, Carleton BC, Zolk O, and van den Heuvel-Eibrink MM

Abstract

In children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial irradiated, cisplatin-treated children with cancer. These results were replicated in two independent, similarly treated cohorts (n = 192 and 188, respectively) (combined cohort: P = 5.3 × 10 -10 , OR 3.11, 95% CI 2.2-4.5). Modulating TCERG1L expression in cultured human cells revealed significantly altered cellular responses to cisplatin-induced cytokine secretion and toxicity. These results contribute to insights into the genetic and pathophysiological basis of cisplatin-induced ototoxicity., (© 2021. The Author(s).)

Published
2021
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50. Treatment-related fertility impairment in long-term female childhood, adolescent and young adult cancer survivors: investigating dose-effect relationships in a European case-control study (PanCareLIFE).

Author

van den Berg MH, van Dijk M, Byrne J, Berger C, Dirksen U, Winther JF, Fossa SD, Grabow D, Grandage VL, Haupt R, van den Heuvel-Eibrink MM, Kaiser M, Kepak T, van der Kooi ALF, Kremer LCM, Kruseova J, Lambalk CB, van Leeuwen FE, Leiper A, Modan-Moses D, Spix C, Twisk JWR, Ronckers CM, Kaatsch P, and van Dulmen-den Broeder E

Subjects
Adolescent, Adult, Case-Control Studies, Child, Cohort Studies, Female, Fertility, Humans, Young Adult, Cancer Survivors, Fertility Preservation, Neoplasms drug therapy
Abstract

Study Question: Which chemotherapeutic agents and body site-specific radiation fields are dose-dependently associated with an increased risk of fertility impairment in long-term female childhood, adolescent and young adulthood (CAYA) cancer survivors?, Summary Answer: Busulfan, lower abdominal radiotherapy (RT) and total body irradiation (TBI) seem to be associated with fertility impairment at any dose, whereas gonadotoxicity of melphalan and procarbazine is suggested at medium/high (>140 mg/m2) or high dose (>5600 mg/m2) therapy, respectively., What Is Known Already: Several treatment-related fertility deficits, as assessed by both self-reported outcomes and hormonal markers are known to occur following treatment of CAYA cancer. However, knowledge regarding precise dose-related estimates of these treatment-related risks are scarce., Study Design, Size, Duration: The current case-control study was nested within the PanCareLIFE cohort study. In total, 1332 CAYA survivors from 8 countries, 9 institutions and 11 cohorts, participated in and contributed data to the study., Participants/materials, Setting, Methods: All participants were female 5-year CAYA cancer survivors. In total, 450 cases (fertility impaired survivors) and 882 matched controls (not fertility impaired survivors) were included. Fertility impairment was defined using both questionnaire data (primary or secondary amenorrhea; use of artificial reproductive techniques; unfulfilled wish to conceive) and hormonal data (FSH and anti-Müllerian hormone (AMH)). Multivariable logistic regression models were used to investigate the effect of (i) alkylating agent exposure, and (ii) dose categories for individual chemotherapeutic agents and for RT-exposed body sites., Main Results and the Role of Chance: A positive dose-effect relationship between cyclophosphamide equivalent dose (CED) score and fertility impairment was found, with survivors with a CED score > 7121 mg/m2 being at a significantly increased risk of fertility impairment (odds ratio (95% CI) = 2.6 (1.9-3.6) P < 0.001). Moreover, cumulative dose variables of the following treatments were significantly associated with fertility impairment: busulfan, carmustine, cyclophosphamide, melphalan, procarbazine, lower abdominal RT and TBI. Busulfan, lower abdominal RT and TBI seem to be associated with fertility impairment at any dose, whereas gonadotoxicity of melphalan and procarbazine is suggested at medium/high (>140 mg/m2) or high dose (>5600 mg/m2) therapy, respectively., Limitations, Reasons for Caution: Our study may have been subject to selection bias since data from about half of the original base cohorts were available for the current study. This could impact the generalizability of our study results., Wider Implications of the Findings: We identified survivors at high risk for fertility impairment and, consequently, for a reduced or even absent reproductive life span. Both girls and young women who are about to start anti-cancer treatment, as well as adult female survivors, should be counselled about future parenthood and referred to a reproductive specialist for fertility preservation, if desired., Study Funding/competing Interest(s): This study has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 602030. There are no competing interests., Trial Registration Number: n/a., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2021
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