Evidence map›Paper›PMID 29924955›Full record

Trial reportThe New England journal of medicine2018

Sodium Thiosulfate for Protection from Cisplatin-Induced Hearing Loss.

Penelope R Brock, Rudolf Maibach, Margaret Childs, Kaukab Rajput, Derek Roebuck, Michael J Sullivan, Véronique Laithier, Milind Ronghe, Patrizia Dall'Igna, Eiso Hiyama and 14 more

2 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The New England journal of medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 185 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
185citing papers in PubMed, 7 pooled it
12.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00652132 phase3completednot on this map

A Multi-centre Open-label Randomised Phase III Trial of the Efficacy of Sodium Thiosulphate in Reducing Ototoxicity in Patients Receiving Cisplatin Chemotherapy for Standard Risk Hepatoblastoma

TypeinterventionalSponsorUniversity of BirminghamRan2007 to 2018Enrolled116ConditionsLiver Cancer, OtotoxicityArmscisplatin, sodium thiosulfate
NCT04478292 phase3recruitingnot on this mapstarted 2021, after this paper: background citation

A Phase 3 Multi-institutional Study for Treatment of Children With Newly Diagnosed Hepatoblastoma Using a Modified PHITT Strategy Incorporating a Randomized Assessment of Sodium Thiosulfate as Otoprotection for Children With Localized Disease, and Response Adapted Therapy for Patients With Metastatic Disease

TypeinterventionalSponsorShanghai Children's Medical CenterRan2021 to 2027Enrolled330ConditionsHepatoblastomaArmsSodium Thiosulfate Injection, Primary surgery resection, mono CDDP-Group A2, Cisplatin, 5-Fluorouracil, Vincristine, Doxorubicin-Group C, Biopsy
3 · Its place in the literature

Who cites it

185 citing papers in PubMed, 7 syntheses or guidelines pooled it, 349 citations in OpenAlex.

  1. Pooled it
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  8. Randomized Phase Ib Clinical Trial of DB-020 Intratympanic Injections to Reduce High-Dose Cisplatin Ototoxicity.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025
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  19. Prestin as a potential biomarker for cochlear injury: Current evidence and future directions.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026
    Review
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125 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 20 institutions in 13 countries.

Penelope R BrockFrom 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 MaibachFrom 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 ChildsFrom 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 RajputFrom 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 RoebuckFrom 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 SullivanFrom 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 LaithierFrom 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 RongheFrom 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'IgnaFrom 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 HiyamaFrom 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 BrichardFrom 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 SkeenFrom 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 MateosFrom 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 CapraFrom 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 RangaswamiFrom 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 AnsariFrom 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 RechnitzerFrom 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 VealFrom 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 CovezzoliFrom 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 BrugièresFrom 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 PerilongoFrom 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 CzaudernaFrom 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 MorlandFrom 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 NeuweltFrom 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.).
Great Ormond Street Hospital · GBUniversity of Padua · ITCentre Hospitalier Universitaire de Besançon · FRCliniques Universitaires Saint-Luc · BEGdańsk Medical University · PLHiroshima University · JPHôpital Beau-Séjour · CHHospital Universitario Reina Sofía · ESInstitut Gustave Roussy · FRInternational Breast Cancer Study Group · CHNewcastle University · GBOregon Health & Science University · USOur Lady's Hospital · IERigshospitalet · DKRoyal Hospital for Children · GBStanford Medicine · USStarship Children's Health · NZUniversity College London · GBUniversity of Birmingham · GBUniversity of Otago · NZ

Funding

Two Compartment Models to Improve Brain Tumor TherapyR01CA137488 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI NEUWELT, EDWARD A. · 2008 to 2019
$7.3M
Opening of the Blood-Brain Barrier to Antitumor AgentsR01CA199111 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI NEUWELT, EDWARD A. · 2016 to 2020
$3.1M
THE ANNUAL BLOOD BRAIN BARRIER CONSORTIUM MEETINGR13CA086959 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI NEUWELT, EDWARD A. · 2000 to 2021
$429k
Chemoprotection and imaging for aminoglycoside and chemotherapy toxicitiesI01BX003897 · VA · PORTLAND VA MEDICAL CENTER · PI NEUWELT, EDWARD A. · 2018 to 2021
–
BLRD VA I01 BX003897Cancer Research UK 15958Cancer Research UK 8156NCI NIH HHS R01 CA137488NCI NIH HHS R01 CA199111NCI NIH HHS R13 CA086959
6 · The paper itself

Abstract

backgroundCisplatin 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.

methodsWe 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.

resultsA 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.

conclusionsThe 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 .).

Indexed as

AdolescentChildChild, PreschoolCisplatinDoxorubicinDrug Therapy, CombinationFemaleFollow-Up StudiesGlomerular Filtration RateHearing LossHepatoblastomaHumansIncidenceInfantLiver NeoplasmsMaleCisplatinDoxorubicinsodium thiosulfateThiosulfates

Identifiers

PMID29924955
PMCPMC6117111
OpenAlexW2809505594

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.