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Brock PR, Maibach R, Childs M, Rajput K, Roebuck D, Sullivan MJ, Laithier V, Ronghe M, Dall'Igna P, Hiyama E, Brichard B, Skeen J, Mateos ME, Capra M, Rangaswami AA, Ansari M, Rechnitzer C, Veal GJ, Covezzoli A, Brugières L, Perilongo G, Czauderna P, Morland B, Neuwelt EA. Sodium Thiosulfate for Protection from Cisplatin-Induced Hearing Loss. N Engl J Med 2018; 378:2376-2385. [PMID: 29924955 PMCID: PMC6117111 DOI: 10.1056/nejmoa1801109] [Citation(s) in RCA: 246] [Impact Index Per Article: 35.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Cisplatin chemotherapy and surgery are effective treatments for children with standard-risk hepatoblastoma but may cause considerable and irreversible hearing loss. This trial compared cisplatin with cisplatin plus delayed administration of sodium thiosulfate, aiming to reduce the incidence and severity of cisplatin-related ototoxic effects without jeopardizing overall and event-free survival. METHODS We randomly assigned children older than 1 month and younger than 18 years of age who had standard-risk hepatoblastoma (≤3 involved liver sectors, no metastatic disease, and an alpha-fetoprotein level of >100 ng per milliliter) to receive cisplatin alone (at a dose of 80 mg per square meter of body-surface area, administered over a period of 6 hours) or cisplatin plus sodium thiosulfate (at a dose of 20 g per square meter, administered intravenously over a 15-minute period, 6 hours after the discontinuation of cisplatin) for four preoperative and two postoperative courses. The primary end point was the absolute hearing threshold, as measured by pure-tone audiometry, at a minimum age of 3.5 years. Hearing loss was assessed according to the Brock grade (on a scale from 0 to 4, with higher grades indicating greater hearing loss). The main secondary end points were overall survival and event-free survival at 3 years. RESULTS A total of 109 children were randomly assigned to receive cisplatin plus sodium thiosulfate (57 children) or cisplatin alone (52) and could be evaluated. Sodium thiosulfate was associated with few high-grade toxic effects. The absolute hearing threshold was assessed in 101 children. Hearing loss of grade 1 or higher occurred in 18 of 55 children (33%) in the cisplatin-sodium thiosulfate group, as compared with 29 of 46 (63%) in the cisplatin-alone group, indicating a 48% lower incidence of hearing loss in the cisplatin-sodium thiosulfate group (relative risk, 0.52; 95% confidence interval [CI], 0.33 to 0.81; P=0.002). At a median of 52 months of follow-up, the 3-year rates of event-free survival were 82% (95% CI, 69 to 90) in the cisplatin-sodium thiosulfate group and 79% (95% CI, 65 to 88) in the cisplatin-alone group, and the 3-year rates of overall survival were 98% (95% CI, 88 to 100) and 92% (95% CI, 81 to 97), respectively. CONCLUSIONS The addition of sodium thiosulfate, administered 6 hours after cisplatin chemotherapy, resulted in a lower incidence of cisplatin-induced hearing loss among children with standard-risk hepatoblastoma, without jeopardizing overall or event-free survival. (Funded by Cancer Research UK and others; SIOPEL 6 ClinicalTrials.gov number, NCT00652132 ; EudraCT number, 2007-002402-21 .).
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Affiliation(s)
- Penelope R Brock
- From Great Ormond Street Hospital, London (P.R.B., K.R., D.R.), Nottingham Clinical Trials Unit, Nottingham (M. Childs), Royal Hospital for Sick Children, Glasgow (M.R.), Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne (G.J.V.), and University of Birmingham, Birmingham (B.M.) - all in the United Kingdom; International Breast Cancer Study Group, Bern (R.M.), and Hôpital Universitaire de Genève, Geneva (M.A.) - both in Switzerland; University of Melbourne, Melbourne, VIC, Australia (M.J.S.); University of Otago, Christchurch (M.J.S.), and Starship Children's Hospital, Auckland (J.S.) - both in New Zealand; Centre Hospitalier Universitaire, Besançon (V.L.), and Institut de Cancerologie Gustave Roussy, Villejuif (L.B.) - both in France; University of Padua, Padua (P.D., G.P.), and Consorzio Interuniversitario (CINECA), Bologna (A.C.) - both in Italy; Hiroshima University, Hiroshima, Japan (E.H.); Cliniques Universitaires Saint Luc, Brussels (B.B.); University Hospital Reina Sofia, Cordoba, Spain (M.E.M.); Our Lady's Children's Hospital, Dublin (M. Capra); Stanford University Medical Center, Palo Alto, CA (A.A.R.); University Hospital Rigshospitalet, Copenhagen (C.R.); Medical University of Gdansk, Gdansk, Poland (P.C.); and Oregon Health and Science University, Portland (E.A.N.)
| | - Rudolf Maibach
- From Great Ormond Street Hospital, London (P.R.B., K.R., D.R.), Nottingham Clinical Trials Unit, Nottingham (M. Childs), Royal Hospital for Sick Children, Glasgow (M.R.), Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne (G.J.V.), and University of Birmingham, Birmingham (B.M.) - all in the United Kingdom; International Breast Cancer Study Group, Bern (R.M.), and Hôpital Universitaire de Genève, Geneva (M.A.) - both in Switzerland; University of Melbourne, Melbourne, VIC, Australia (M.J.S.); University of Otago, Christchurch (M.J.S.), and Starship Children's Hospital, Auckland (J.S.) - both in New Zealand; Centre Hospitalier Universitaire, Besançon (V.L.), and Institut de Cancerologie Gustave Roussy, Villejuif (L.B.) - both in France; University of Padua, Padua (P.D., G.P.), and Consorzio Interuniversitario (CINECA), Bologna (A.C.) - both in Italy; Hiroshima University, Hiroshima, Japan (E.H.); Cliniques Universitaires Saint Luc, Brussels (B.B.); University Hospital Reina Sofia, Cordoba, Spain (M.E.M.); Our Lady's Children's Hospital, Dublin (M. Capra); Stanford University Medical Center, Palo Alto, CA (A.A.R.); University Hospital Rigshospitalet, Copenhagen (C.R.); Medical University of Gdansk, Gdansk, Poland (P.C.); and Oregon Health and Science University, Portland (E.A.N.)
| | - Margaret Childs
- From Great Ormond Street Hospital, London (P.R.B., K.R., D.R.), Nottingham Clinical Trials Unit, Nottingham (M. Childs), Royal Hospital for Sick Children, Glasgow (M.R.), Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne (G.J.V.), and University of Birmingham, Birmingham (B.M.) - all in the United Kingdom; International Breast Cancer Study Group, Bern (R.M.), and Hôpital Universitaire de Genève, Geneva (M.A.) - both in Switzerland; University of Melbourne, Melbourne, VIC, Australia (M.J.S.); University of Otago, Christchurch (M.J.S.), and Starship Children's Hospital, Auckland (J.S.) - both in New Zealand; Centre Hospitalier Universitaire, Besançon (V.L.), and Institut de Cancerologie Gustave Roussy, Villejuif (L.B.) - both in France; University of Padua, Padua (P.D., G.P.), and Consorzio Interuniversitario (CINECA), Bologna (A.C.) - both in Italy; Hiroshima University, Hiroshima, Japan (E.H.); Cliniques Universitaires Saint Luc, Brussels (B.B.); University Hospital Reina Sofia, Cordoba, Spain (M.E.M.); Our Lady's Children's Hospital, Dublin (M. Capra); Stanford University Medical Center, Palo Alto, CA (A.A.R.); University Hospital Rigshospitalet, Copenhagen (C.R.); Medical University of Gdansk, Gdansk, Poland (P.C.); and Oregon Health and Science University, Portland (E.A.N.)
| | - Kaukab Rajput
- From Great Ormond Street Hospital, London (P.R.B., K.R., D.R.), Nottingham Clinical Trials Unit, Nottingham (M. Childs), Royal Hospital for Sick Children, Glasgow (M.R.), Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne (G.J.V.), and University of Birmingham, Birmingham (B.M.) - all in the United Kingdom; International Breast Cancer Study Group, Bern (R.M.), and Hôpital Universitaire de Genève, Geneva (M.A.) - both in Switzerland; University of Melbourne, Melbourne, VIC, Australia (M.J.S.); University of Otago, Christchurch (M.J.S.), and Starship Children's Hospital, Auckland (J.S.) - both in New Zealand; Centre Hospitalier Universitaire, Besançon (V.L.), and Institut de Cancerologie Gustave Roussy, Villejuif (L.B.) - both in France; University of Padua, Padua (P.D., G.P.), and Consorzio Interuniversitario (CINECA), Bologna (A.C.) - both in Italy; Hiroshima University, Hiroshima, Japan (E.H.); Cliniques Universitaires Saint Luc, Brussels (B.B.); University Hospital Reina Sofia, Cordoba, Spain (M.E.M.); Our Lady's Children's Hospital, Dublin (M. Capra); Stanford University Medical Center, Palo Alto, CA (A.A.R.); University Hospital Rigshospitalet, Copenhagen (C.R.); Medical University of Gdansk, Gdansk, Poland (P.C.); and Oregon Health and Science University, Portland (E.A.N.)
| | - Derek Roebuck
- From Great Ormond Street Hospital, London (P.R.B., K.R., D.R.), Nottingham Clinical Trials Unit, Nottingham (M. Childs), Royal Hospital for Sick Children, Glasgow (M.R.), Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne (G.J.V.), and University of Birmingham, Birmingham (B.M.) - all in the United Kingdom; International Breast Cancer Study Group, Bern (R.M.), and Hôpital Universitaire de Genève, Geneva (M.A.) - both in Switzerland; University of Melbourne, Melbourne, VIC, Australia (M.J.S.); University of Otago, Christchurch (M.J.S.), and Starship Children's Hospital, Auckland (J.S.) - both in New Zealand; Centre Hospitalier Universitaire, Besançon (V.L.), and Institut de Cancerologie Gustave Roussy, Villejuif (L.B.) - both in France; University of Padua, Padua (P.D., G.P.), and Consorzio Interuniversitario (CINECA), Bologna (A.C.) - both in Italy; Hiroshima University, Hiroshima, Japan (E.H.); Cliniques Universitaires Saint Luc, Brussels (B.B.); University Hospital Reina Sofia, Cordoba, Spain (M.E.M.); Our Lady's Children's Hospital, Dublin (M. Capra); Stanford University Medical Center, Palo Alto, CA (A.A.R.); University Hospital Rigshospitalet, Copenhagen (C.R.); Medical University of Gdansk, Gdansk, Poland (P.C.); and Oregon Health and Science University, Portland (E.A.N.)
| | - Michael J Sullivan
- From Great Ormond Street Hospital, London (P.R.B., K.R., D.R.), Nottingham Clinical Trials Unit, Nottingham (M. Childs), Royal Hospital for Sick Children, Glasgow (M.R.), Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne (G.J.V.), and University of Birmingham, Birmingham (B.M.) - all in the United Kingdom; International Breast Cancer Study Group, Bern (R.M.), and Hôpital Universitaire de Genève, Geneva (M.A.) - both in Switzerland; University of Melbourne, Melbourne, VIC, Australia (M.J.S.); University of Otago, Christchurch (M.J.S.), and Starship Children's Hospital, Auckland (J.S.) - both in New Zealand; Centre Hospitalier Universitaire, Besançon (V.L.), and Institut de Cancerologie Gustave Roussy, Villejuif (L.B.) - both in France; University of Padua, Padua (P.D., G.P.), and Consorzio Interuniversitario (CINECA), Bologna (A.C.) - both in Italy; Hiroshima University, Hiroshima, Japan (E.H.); Cliniques Universitaires Saint Luc, Brussels (B.B.); University Hospital Reina Sofia, Cordoba, Spain (M.E.M.); Our Lady's Children's Hospital, Dublin (M. Capra); Stanford University Medical Center, Palo Alto, CA (A.A.R.); University Hospital Rigshospitalet, Copenhagen (C.R.); Medical University of Gdansk, Gdansk, Poland (P.C.); and Oregon Health and Science University, Portland (E.A.N.)
| | - Véronique Laithier
- From Great Ormond Street Hospital, London (P.R.B., K.R., D.R.), Nottingham Clinical Trials Unit, Nottingham (M. Childs), Royal Hospital for Sick Children, Glasgow (M.R.), Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne (G.J.V.), and University of Birmingham, Birmingham (B.M.) - all in the United Kingdom; International Breast Cancer Study Group, Bern (R.M.), and Hôpital Universitaire de Genève, Geneva (M.A.) - both in Switzerland; University of Melbourne, Melbourne, VIC, Australia (M.J.S.); University of Otago, Christchurch (M.J.S.), and Starship Children's Hospital, Auckland (J.S.) - both in New Zealand; Centre Hospitalier Universitaire, Besançon (V.L.), and Institut de Cancerologie Gustave Roussy, Villejuif (L.B.) - both in France; University of Padua, Padua (P.D., G.P.), and Consorzio Interuniversitario (CINECA), Bologna (A.C.) - both in Italy; Hiroshima University, Hiroshima, Japan (E.H.); Cliniques Universitaires Saint Luc, Brussels (B.B.); University Hospital Reina Sofia, Cordoba, Spain (M.E.M.); Our Lady's Children's Hospital, Dublin (M. Capra); Stanford University Medical Center, Palo Alto, CA (A.A.R.); University Hospital Rigshospitalet, Copenhagen (C.R.); Medical University of Gdansk, Gdansk, Poland (P.C.); and Oregon Health and Science University, Portland (E.A.N.)
| | - Milind Ronghe
- From Great Ormond Street Hospital, London (P.R.B., K.R., D.R.), Nottingham Clinical Trials Unit, Nottingham (M. Childs), Royal Hospital for Sick Children, Glasgow (M.R.), Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne (G.J.V.), and University of Birmingham, Birmingham (B.M.) - all in the United Kingdom; International Breast Cancer Study Group, Bern (R.M.), and Hôpital Universitaire de Genève, Geneva (M.A.) - both in Switzerland; University of Melbourne, Melbourne, VIC, Australia (M.J.S.); University of Otago, Christchurch (M.J.S.), and Starship Children's Hospital, Auckland (J.S.) - both in New Zealand; Centre Hospitalier Universitaire, Besançon (V.L.), and Institut de Cancerologie Gustave Roussy, Villejuif (L.B.) - both in France; University of Padua, Padua (P.D., G.P.), and Consorzio Interuniversitario (CINECA), Bologna (A.C.) - both in Italy; Hiroshima University, Hiroshima, Japan (E.H.); Cliniques Universitaires Saint Luc, Brussels (B.B.); University Hospital Reina Sofia, Cordoba, Spain (M.E.M.); Our Lady's Children's Hospital, Dublin (M. Capra); Stanford University Medical Center, Palo Alto, CA (A.A.R.); University Hospital Rigshospitalet, Copenhagen (C.R.); Medical University of Gdansk, Gdansk, Poland (P.C.); and Oregon Health and Science University, Portland (E.A.N.)
| | - Patrizia Dall'Igna
- From Great Ormond Street Hospital, London (P.R.B., K.R., D.R.), Nottingham Clinical Trials Unit, Nottingham (M. Childs), Royal Hospital for Sick Children, Glasgow (M.R.), Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne (G.J.V.), and University of Birmingham, Birmingham (B.M.) - all in the United Kingdom; International Breast Cancer Study Group, Bern (R.M.), and Hôpital Universitaire de Genève, Geneva (M.A.) - both in Switzerland; University of Melbourne, Melbourne, VIC, Australia (M.J.S.); University of Otago, Christchurch (M.J.S.), and Starship Children's Hospital, Auckland (J.S.) - both in New Zealand; Centre Hospitalier Universitaire, Besançon (V.L.), and Institut de Cancerologie Gustave Roussy, Villejuif (L.B.) - both in France; University of Padua, Padua (P.D., G.P.), and Consorzio Interuniversitario (CINECA), Bologna (A.C.) - both in Italy; Hiroshima University, Hiroshima, Japan (E.H.); Cliniques Universitaires Saint Luc, Brussels (B.B.); University Hospital Reina Sofia, Cordoba, Spain (M.E.M.); Our Lady's Children's Hospital, Dublin (M. Capra); Stanford University Medical Center, Palo Alto, CA (A.A.R.); University Hospital Rigshospitalet, Copenhagen (C.R.); Medical University of Gdansk, Gdansk, Poland (P.C.); and Oregon Health and Science University, Portland (E.A.N.)
| | - Eiso Hiyama
- From Great Ormond Street Hospital, London (P.R.B., K.R., D.R.), Nottingham Clinical Trials Unit, Nottingham (M. Childs), Royal Hospital for Sick Children, Glasgow (M.R.), Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne (G.J.V.), and University of Birmingham, Birmingham (B.M.) - all in the United Kingdom; International Breast Cancer Study Group, Bern (R.M.), and Hôpital Universitaire de Genève, Geneva (M.A.) - both in Switzerland; University of Melbourne, Melbourne, VIC, Australia (M.J.S.); University of Otago, Christchurch (M.J.S.), and Starship Children's Hospital, Auckland (J.S.) - both in New Zealand; Centre Hospitalier Universitaire, Besançon (V.L.), and Institut de Cancerologie Gustave Roussy, Villejuif (L.B.) - both in France; University of Padua, Padua (P.D., G.P.), and Consorzio Interuniversitario (CINECA), Bologna (A.C.) - both in Italy; Hiroshima University, Hiroshima, Japan (E.H.); Cliniques Universitaires Saint Luc, Brussels (B.B.); University Hospital Reina Sofia, Cordoba, Spain (M.E.M.); Our Lady's Children's Hospital, Dublin (M. Capra); Stanford University Medical Center, Palo Alto, CA (A.A.R.); University Hospital Rigshospitalet, Copenhagen (C.R.); Medical University of Gdansk, Gdansk, Poland (P.C.); and Oregon Health and Science University, Portland (E.A.N.)
| | - Bénédicte Brichard
- From Great Ormond Street Hospital, London (P.R.B., K.R., D.R.), Nottingham Clinical Trials Unit, Nottingham (M. Childs), Royal Hospital for Sick Children, Glasgow (M.R.), Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne (G.J.V.), and University of Birmingham, Birmingham (B.M.) - all in the United Kingdom; International Breast Cancer Study Group, Bern (R.M.), and Hôpital Universitaire de Genève, Geneva (M.A.) - both in Switzerland; University of Melbourne, Melbourne, VIC, Australia (M.J.S.); University of Otago, Christchurch (M.J.S.), and Starship Children's Hospital, Auckland (J.S.) - both in New Zealand; Centre Hospitalier Universitaire, Besançon (V.L.), and Institut de Cancerologie Gustave Roussy, Villejuif (L.B.) - both in France; University of Padua, Padua (P.D., G.P.), and Consorzio Interuniversitario (CINECA), Bologna (A.C.) - both in Italy; Hiroshima University, Hiroshima, Japan (E.H.); Cliniques Universitaires Saint Luc, Brussels (B.B.); University Hospital Reina Sofia, Cordoba, Spain (M.E.M.); Our Lady's Children's Hospital, Dublin (M. Capra); Stanford University Medical Center, Palo Alto, CA (A.A.R.); University Hospital Rigshospitalet, Copenhagen (C.R.); Medical University of Gdansk, Gdansk, Poland (P.C.); and Oregon Health and Science University, Portland (E.A.N.)
| | - Jane Skeen
- From Great Ormond Street Hospital, London (P.R.B., K.R., D.R.), Nottingham Clinical Trials Unit, Nottingham (M. Childs), Royal Hospital for Sick Children, Glasgow (M.R.), Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne (G.J.V.), and University of Birmingham, Birmingham (B.M.) - all in the United Kingdom; International Breast Cancer Study Group, Bern (R.M.), and Hôpital Universitaire de Genève, Geneva (M.A.) - both in Switzerland; University of Melbourne, Melbourne, VIC, Australia (M.J.S.); University of Otago, Christchurch (M.J.S.), and Starship Children's Hospital, Auckland (J.S.) - both in New Zealand; Centre Hospitalier Universitaire, Besançon (V.L.), and Institut de Cancerologie Gustave Roussy, Villejuif (L.B.) - both in France; University of Padua, Padua (P.D., G.P.), and Consorzio Interuniversitario (CINECA), Bologna (A.C.) - both in Italy; Hiroshima University, Hiroshima, Japan (E.H.); Cliniques Universitaires Saint Luc, Brussels (B.B.); University Hospital Reina Sofia, Cordoba, Spain (M.E.M.); Our Lady's Children's Hospital, Dublin (M. Capra); Stanford University Medical Center, Palo Alto, CA (A.A.R.); University Hospital Rigshospitalet, Copenhagen (C.R.); Medical University of Gdansk, Gdansk, Poland (P.C.); and Oregon Health and Science University, Portland (E.A.N.)
| | - M Elena Mateos
- From Great Ormond Street Hospital, London (P.R.B., K.R., D.R.), Nottingham Clinical Trials Unit, Nottingham (M. Childs), Royal Hospital for Sick Children, Glasgow (M.R.), Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne (G.J.V.), and University of Birmingham, Birmingham (B.M.) - all in the United Kingdom; International Breast Cancer Study Group, Bern (R.M.), and Hôpital Universitaire de Genève, Geneva (M.A.) - both in Switzerland; University of Melbourne, Melbourne, VIC, Australia (M.J.S.); University of Otago, Christchurch (M.J.S.), and Starship Children's Hospital, Auckland (J.S.) - both in New Zealand; Centre Hospitalier Universitaire, Besançon (V.L.), and Institut de Cancerologie Gustave Roussy, Villejuif (L.B.) - both in France; University of Padua, Padua (P.D., G.P.), and Consorzio Interuniversitario (CINECA), Bologna (A.C.) - both in Italy; Hiroshima University, Hiroshima, Japan (E.H.); Cliniques Universitaires Saint Luc, Brussels (B.B.); University Hospital Reina Sofia, Cordoba, Spain (M.E.M.); Our Lady's Children's Hospital, Dublin (M. Capra); Stanford University Medical Center, Palo Alto, CA (A.A.R.); University Hospital Rigshospitalet, Copenhagen (C.R.); Medical University of Gdansk, Gdansk, Poland (P.C.); and Oregon Health and Science University, Portland (E.A.N.)
| | - Michael Capra
- From Great Ormond Street Hospital, London (P.R.B., K.R., D.R.), Nottingham Clinical Trials Unit, Nottingham (M. Childs), Royal Hospital for Sick Children, Glasgow (M.R.), Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne (G.J.V.), and University of Birmingham, Birmingham (B.M.) - all in the United Kingdom; International Breast Cancer Study Group, Bern (R.M.), and Hôpital Universitaire de Genève, Geneva (M.A.) - both in Switzerland; University of Melbourne, Melbourne, VIC, Australia (M.J.S.); University of Otago, Christchurch (M.J.S.), and Starship Children's Hospital, Auckland (J.S.) - both in New Zealand; Centre Hospitalier Universitaire, Besançon (V.L.), and Institut de Cancerologie Gustave Roussy, Villejuif (L.B.) - both in France; University of Padua, Padua (P.D., G.P.), and Consorzio Interuniversitario (CINECA), Bologna (A.C.) - both in Italy; Hiroshima University, Hiroshima, Japan (E.H.); Cliniques Universitaires Saint Luc, Brussels (B.B.); University Hospital Reina Sofia, Cordoba, Spain (M.E.M.); Our Lady's Children's Hospital, Dublin (M. Capra); Stanford University Medical Center, Palo Alto, CA (A.A.R.); University Hospital Rigshospitalet, Copenhagen (C.R.); Medical University of Gdansk, Gdansk, Poland (P.C.); and Oregon Health and Science University, Portland (E.A.N.)
| | - Arun A Rangaswami
- From Great Ormond Street Hospital, London (P.R.B., K.R., D.R.), Nottingham Clinical Trials Unit, Nottingham (M. Childs), Royal Hospital for Sick Children, Glasgow (M.R.), Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne (G.J.V.), and University of Birmingham, Birmingham (B.M.) - all in the United Kingdom; International Breast Cancer Study Group, Bern (R.M.), and Hôpital Universitaire de Genève, Geneva (M.A.) - both in Switzerland; University of Melbourne, Melbourne, VIC, Australia (M.J.S.); University of Otago, Christchurch (M.J.S.), and Starship Children's Hospital, Auckland (J.S.) - both in New Zealand; Centre Hospitalier Universitaire, Besançon (V.L.), and Institut de Cancerologie Gustave Roussy, Villejuif (L.B.) - both in France; University of Padua, Padua (P.D., G.P.), and Consorzio Interuniversitario (CINECA), Bologna (A.C.) - both in Italy; Hiroshima University, Hiroshima, Japan (E.H.); Cliniques Universitaires Saint Luc, Brussels (B.B.); University Hospital Reina Sofia, Cordoba, Spain (M.E.M.); Our Lady's Children's Hospital, Dublin (M. Capra); Stanford University Medical Center, Palo Alto, CA (A.A.R.); University Hospital Rigshospitalet, Copenhagen (C.R.); Medical University of Gdansk, Gdansk, Poland (P.C.); and Oregon Health and Science University, Portland (E.A.N.)
| | - Marc Ansari
- From Great Ormond Street Hospital, London (P.R.B., K.R., D.R.), Nottingham Clinical Trials Unit, Nottingham (M. Childs), Royal Hospital for Sick Children, Glasgow (M.R.), Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne (G.J.V.), and University of Birmingham, Birmingham (B.M.) - all in the United Kingdom; International Breast Cancer Study Group, Bern (R.M.), and Hôpital Universitaire de Genève, Geneva (M.A.) - both in Switzerland; University of Melbourne, Melbourne, VIC, Australia (M.J.S.); University of Otago, Christchurch (M.J.S.), and Starship Children's Hospital, Auckland (J.S.) - both in New Zealand; Centre Hospitalier Universitaire, Besançon (V.L.), and Institut de Cancerologie Gustave Roussy, Villejuif (L.B.) - both in France; University of Padua, Padua (P.D., G.P.), and Consorzio Interuniversitario (CINECA), Bologna (A.C.) - both in Italy; Hiroshima University, Hiroshima, Japan (E.H.); Cliniques Universitaires Saint Luc, Brussels (B.B.); University Hospital Reina Sofia, Cordoba, Spain (M.E.M.); Our Lady's Children's Hospital, Dublin (M. Capra); Stanford University Medical Center, Palo Alto, CA (A.A.R.); University Hospital Rigshospitalet, Copenhagen (C.R.); Medical University of Gdansk, Gdansk, Poland (P.C.); and Oregon Health and Science University, Portland (E.A.N.)
| | - Catherine Rechnitzer
- From Great Ormond Street Hospital, London (P.R.B., K.R., D.R.), Nottingham Clinical Trials Unit, Nottingham (M. Childs), Royal Hospital for Sick Children, Glasgow (M.R.), Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne (G.J.V.), and University of Birmingham, Birmingham (B.M.) - all in the United Kingdom; International Breast Cancer Study Group, Bern (R.M.), and Hôpital Universitaire de Genève, Geneva (M.A.) - both in Switzerland; University of Melbourne, Melbourne, VIC, Australia (M.J.S.); University of Otago, Christchurch (M.J.S.), and Starship Children's Hospital, Auckland (J.S.) - both in New Zealand; Centre Hospitalier Universitaire, Besançon (V.L.), and Institut de Cancerologie Gustave Roussy, Villejuif (L.B.) - both in France; University of Padua, Padua (P.D., G.P.), and Consorzio Interuniversitario (CINECA), Bologna (A.C.) - both in Italy; Hiroshima University, Hiroshima, Japan (E.H.); Cliniques Universitaires Saint Luc, Brussels (B.B.); University Hospital Reina Sofia, Cordoba, Spain (M.E.M.); Our Lady's Children's Hospital, Dublin (M. Capra); Stanford University Medical Center, Palo Alto, CA (A.A.R.); University Hospital Rigshospitalet, Copenhagen (C.R.); Medical University of Gdansk, Gdansk, Poland (P.C.); and Oregon Health and Science University, Portland (E.A.N.)
| | - Gareth J Veal
- From Great Ormond Street Hospital, London (P.R.B., K.R., D.R.), Nottingham Clinical Trials Unit, Nottingham (M. Childs), Royal Hospital for Sick Children, Glasgow (M.R.), Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne (G.J.V.), and University of Birmingham, Birmingham (B.M.) - all in the United Kingdom; International Breast Cancer Study Group, Bern (R.M.), and Hôpital Universitaire de Genève, Geneva (M.A.) - both in Switzerland; University of Melbourne, Melbourne, VIC, Australia (M.J.S.); University of Otago, Christchurch (M.J.S.), and Starship Children's Hospital, Auckland (J.S.) - both in New Zealand; Centre Hospitalier Universitaire, Besançon (V.L.), and Institut de Cancerologie Gustave Roussy, Villejuif (L.B.) - both in France; University of Padua, Padua (P.D., G.P.), and Consorzio Interuniversitario (CINECA), Bologna (A.C.) - both in Italy; Hiroshima University, Hiroshima, Japan (E.H.); Cliniques Universitaires Saint Luc, Brussels (B.B.); University Hospital Reina Sofia, Cordoba, Spain (M.E.M.); Our Lady's Children's Hospital, Dublin (M. Capra); Stanford University Medical Center, Palo Alto, CA (A.A.R.); University Hospital Rigshospitalet, Copenhagen (C.R.); Medical University of Gdansk, Gdansk, Poland (P.C.); and Oregon Health and Science University, Portland (E.A.N.)
| | - Anna Covezzoli
- From Great Ormond Street Hospital, London (P.R.B., K.R., D.R.), Nottingham Clinical Trials Unit, Nottingham (M. Childs), Royal Hospital for Sick Children, Glasgow (M.R.), Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne (G.J.V.), and University of Birmingham, Birmingham (B.M.) - all in the United Kingdom; International Breast Cancer Study Group, Bern (R.M.), and Hôpital Universitaire de Genève, Geneva (M.A.) - both in Switzerland; University of Melbourne, Melbourne, VIC, Australia (M.J.S.); University of Otago, Christchurch (M.J.S.), and Starship Children's Hospital, Auckland (J.S.) - both in New Zealand; Centre Hospitalier Universitaire, Besançon (V.L.), and Institut de Cancerologie Gustave Roussy, Villejuif (L.B.) - both in France; University of Padua, Padua (P.D., G.P.), and Consorzio Interuniversitario (CINECA), Bologna (A.C.) - both in Italy; Hiroshima University, Hiroshima, Japan (E.H.); Cliniques Universitaires Saint Luc, Brussels (B.B.); University Hospital Reina Sofia, Cordoba, Spain (M.E.M.); Our Lady's Children's Hospital, Dublin (M. Capra); Stanford University Medical Center, Palo Alto, CA (A.A.R.); University Hospital Rigshospitalet, Copenhagen (C.R.); Medical University of Gdansk, Gdansk, Poland (P.C.); and Oregon Health and Science University, Portland (E.A.N.)
| | - Laurence Brugières
- From Great Ormond Street Hospital, London (P.R.B., K.R., D.R.), Nottingham Clinical Trials Unit, Nottingham (M. Childs), Royal Hospital for Sick Children, Glasgow (M.R.), Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne (G.J.V.), and University of Birmingham, Birmingham (B.M.) - all in the United Kingdom; International Breast Cancer Study Group, Bern (R.M.), and Hôpital Universitaire de Genève, Geneva (M.A.) - both in Switzerland; University of Melbourne, Melbourne, VIC, Australia (M.J.S.); University of Otago, Christchurch (M.J.S.), and Starship Children's Hospital, Auckland (J.S.) - both in New Zealand; Centre Hospitalier Universitaire, Besançon (V.L.), and Institut de Cancerologie Gustave Roussy, Villejuif (L.B.) - both in France; University of Padua, Padua (P.D., G.P.), and Consorzio Interuniversitario (CINECA), Bologna (A.C.) - both in Italy; Hiroshima University, Hiroshima, Japan (E.H.); Cliniques Universitaires Saint Luc, Brussels (B.B.); University Hospital Reina Sofia, Cordoba, Spain (M.E.M.); Our Lady's Children's Hospital, Dublin (M. Capra); Stanford University Medical Center, Palo Alto, CA (A.A.R.); University Hospital Rigshospitalet, Copenhagen (C.R.); Medical University of Gdansk, Gdansk, Poland (P.C.); and Oregon Health and Science University, Portland (E.A.N.)
| | - Giorgio Perilongo
- From Great Ormond Street Hospital, London (P.R.B., K.R., D.R.), Nottingham Clinical Trials Unit, Nottingham (M. Childs), Royal Hospital for Sick Children, Glasgow (M.R.), Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne (G.J.V.), and University of Birmingham, Birmingham (B.M.) - all in the United Kingdom; International Breast Cancer Study Group, Bern (R.M.), and Hôpital Universitaire de Genève, Geneva (M.A.) - both in Switzerland; University of Melbourne, Melbourne, VIC, Australia (M.J.S.); University of Otago, Christchurch (M.J.S.), and Starship Children's Hospital, Auckland (J.S.) - both in New Zealand; Centre Hospitalier Universitaire, Besançon (V.L.), and Institut de Cancerologie Gustave Roussy, Villejuif (L.B.) - both in France; University of Padua, Padua (P.D., G.P.), and Consorzio Interuniversitario (CINECA), Bologna (A.C.) - both in Italy; Hiroshima University, Hiroshima, Japan (E.H.); Cliniques Universitaires Saint Luc, Brussels (B.B.); University Hospital Reina Sofia, Cordoba, Spain (M.E.M.); Our Lady's Children's Hospital, Dublin (M. Capra); Stanford University Medical Center, Palo Alto, CA (A.A.R.); University Hospital Rigshospitalet, Copenhagen (C.R.); Medical University of Gdansk, Gdansk, Poland (P.C.); and Oregon Health and Science University, Portland (E.A.N.)
| | - Piotr Czauderna
- From Great Ormond Street Hospital, London (P.R.B., K.R., D.R.), Nottingham Clinical Trials Unit, Nottingham (M. Childs), Royal Hospital for Sick Children, Glasgow (M.R.), Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne (G.J.V.), and University of Birmingham, Birmingham (B.M.) - all in the United Kingdom; International Breast Cancer Study Group, Bern (R.M.), and Hôpital Universitaire de Genève, Geneva (M.A.) - both in Switzerland; University of Melbourne, Melbourne, VIC, Australia (M.J.S.); University of Otago, Christchurch (M.J.S.), and Starship Children's Hospital, Auckland (J.S.) - both in New Zealand; Centre Hospitalier Universitaire, Besançon (V.L.), and Institut de Cancerologie Gustave Roussy, Villejuif (L.B.) - both in France; University of Padua, Padua (P.D., G.P.), and Consorzio Interuniversitario (CINECA), Bologna (A.C.) - both in Italy; Hiroshima University, Hiroshima, Japan (E.H.); Cliniques Universitaires Saint Luc, Brussels (B.B.); University Hospital Reina Sofia, Cordoba, Spain (M.E.M.); Our Lady's Children's Hospital, Dublin (M. Capra); Stanford University Medical Center, Palo Alto, CA (A.A.R.); University Hospital Rigshospitalet, Copenhagen (C.R.); Medical University of Gdansk, Gdansk, Poland (P.C.); and Oregon Health and Science University, Portland (E.A.N.)
| | - Bruce Morland
- From Great Ormond Street Hospital, London (P.R.B., K.R., D.R.), Nottingham Clinical Trials Unit, Nottingham (M. Childs), Royal Hospital for Sick Children, Glasgow (M.R.), Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne (G.J.V.), and University of Birmingham, Birmingham (B.M.) - all in the United Kingdom; International Breast Cancer Study Group, Bern (R.M.), and Hôpital Universitaire de Genève, Geneva (M.A.) - both in Switzerland; University of Melbourne, Melbourne, VIC, Australia (M.J.S.); University of Otago, Christchurch (M.J.S.), and Starship Children's Hospital, Auckland (J.S.) - both in New Zealand; Centre Hospitalier Universitaire, Besançon (V.L.), and Institut de Cancerologie Gustave Roussy, Villejuif (L.B.) - both in France; University of Padua, Padua (P.D., G.P.), and Consorzio Interuniversitario (CINECA), Bologna (A.C.) - both in Italy; Hiroshima University, Hiroshima, Japan (E.H.); Cliniques Universitaires Saint Luc, Brussels (B.B.); University Hospital Reina Sofia, Cordoba, Spain (M.E.M.); Our Lady's Children's Hospital, Dublin (M. Capra); Stanford University Medical Center, Palo Alto, CA (A.A.R.); University Hospital Rigshospitalet, Copenhagen (C.R.); Medical University of Gdansk, Gdansk, Poland (P.C.); and Oregon Health and Science University, Portland (E.A.N.)
| | - Edward A Neuwelt
- From Great Ormond Street Hospital, London (P.R.B., K.R., D.R.), Nottingham Clinical Trials Unit, Nottingham (M. Childs), Royal Hospital for Sick Children, Glasgow (M.R.), Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne (G.J.V.), and University of Birmingham, Birmingham (B.M.) - all in the United Kingdom; International Breast Cancer Study Group, Bern (R.M.), and Hôpital Universitaire de Genève, Geneva (M.A.) - both in Switzerland; University of Melbourne, Melbourne, VIC, Australia (M.J.S.); University of Otago, Christchurch (M.J.S.), and Starship Children's Hospital, Auckland (J.S.) - both in New Zealand; Centre Hospitalier Universitaire, Besançon (V.L.), and Institut de Cancerologie Gustave Roussy, Villejuif (L.B.) - both in France; University of Padua, Padua (P.D., G.P.), and Consorzio Interuniversitario (CINECA), Bologna (A.C.) - both in Italy; Hiroshima University, Hiroshima, Japan (E.H.); Cliniques Universitaires Saint Luc, Brussels (B.B.); University Hospital Reina Sofia, Cordoba, Spain (M.E.M.); Our Lady's Children's Hospital, Dublin (M. Capra); Stanford University Medical Center, Palo Alto, CA (A.A.R.); University Hospital Rigshospitalet, Copenhagen (C.R.); Medical University of Gdansk, Gdansk, Poland (P.C.); and Oregon Health and Science University, Portland (E.A.N.)
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