Artikel
Platin treatment and hearing loss: initial audiological results from PanCareLIFE
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Autoren
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Ross Parfitt
- Department of Phoniatrics and Pedaudiology, Münster University Hospital, Münster, Germany
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Amelie Tillmanns
- Department of Phoniatrics and Pedaudiology, Münster University Hospital, Münster, Germany
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Peter Matulat
- Department of Phoniatrics and Pedaudiology, Münster University Hospital, Münster, Germany
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Dirk Deuster
- Department of Phoniatrics and Pedaudiology, Münster University Hospital, Münster, Germany
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Susanne Elsner
- Department of Pediatric Oncology and Hematology, University Hospital for Children and Adolescents, Lübeck, Germany
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Eva-Maria Wolschon
- Department of Pediatric Oncology and Hematology, University Hospital for Children and Adolescents, Lübeck, Germany
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Claudia E. Kuehni
- Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
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Rahel Kuonen
- Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
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Annette Weiss
- Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
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Marie-Luisa Garré
- Instituto Giannina Gaslini, Genova, Italy
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Tomas Kepak
- University Hospital Brno & International Clinical Research Center (FNUSA-ICRC), Masaryk University, Brno, Czech Republic
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Katerina Kepakova
- University Hospital Brno & International Clinical Research Center (FNUSA-ICRC), Masaryk University, Brno, Czech Republic
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Jarmila Kruseova
- Department of Children Hemato-Oncology, Motol Teaching Hospital, Prague, Czech Republic
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Ales Luks
- Department of Children Hemato-Oncology, Motol Teaching Hospital, Prague, Czech Republic
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Jeanette Falck Winther
- Danish Cancer Society Research Center & Department of Clinical Medicine, Faculty of Health, Aarhus University and University Hospital, Copenhagen & Aarhus, Denmark
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Line Kenborg
- Danish Cancer Society Research Center & Department of Clinical Medicine, Faculty of Health, Aarhus University and University Hospital, Copenhagen & Aarhus, Denmark
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Herwig Lackner
- Department of Paediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria
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Stefan Bielack
- Department of Paediatrics & Oncology, Hematology and Immunology, Centre for Paediatric, Adolescent and Women’s Medicine, Klinikum Stuttgart Olgahospital, Stuttgart, Germany
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Marry van den Heuvel-Eibrink
- Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands
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Gabriele Calaminus
- Department of Paediatric Haematology and Oncology, University Hospital Bonn, Bonn, Germany
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Katja Baust
- Department of Paediatric Haematology and Oncology, University Hospital Bonn, Bonn, Germany
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Jörn Beck
- Hospital for Children and Adolescents, University of Erlangen-Nürnberg, Erlangen, Germany
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Leontien Kremer
- Department Pediatric Oncology, Emma Children’s Hospital/Academic Medical Center, Amsterdam, Netherlands
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Eva Clemens
- Department of Pediatric Hematology and Oncology, Erasmus MC – Sophia Children’s Hospital, Rotterdam, Netherlands
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Thorsten Langer
- Department of Pediatric Oncology and Hematology, University Hospital for Children and Adolescents, Lübeck, Germany
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Oliver Zolk
- Institute of Pharmacology of Natural Products and Clinical Pharmacology, University of Ulm, Ulm, Germany
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Antoinette am Zehnhoff-Dinnesen
- Department of Phoniatrics and Pedaudiology, Münster University Hospital, Münster, Germany
| Veröffentlicht: | 13. September 2019 |
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Gliederung
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 <18 years old at diagnosis, underwent treatment with cisplatin or carboplatin and had no evidence of pre-treatment hearing loss (>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 <5 years old were more likely to develop hearing loss than those >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 <5 years old, higher cumulative cisplatin doses and cranial irradiation present especially high risks.
Acknowledgement: This work was supported by the PanCareLIFE consortium that has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 602030.
Text
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 <18 years old at diagnosis, underwent treatment with cisplatin or carboplatin and had no evidence of pre-treatment hearing loss (>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 <5 years old were more likely to develop hearing loss than those >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 <5 years old, higher cumulative cisplatin doses and cranial irradiation present especially high risks.
Acknowledgement: This work was supported by the PanCareLIFE consortium that has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 602030.
