gms | German Medical Science

39. Wissenschaftliche Jahrestagung der Deutschen Gesellschaft für Phoniatrie und Pädaudiologie (DGPP)

Deutsche Gesellschaft für Phoniatrie und Pädaudiologie e. V.

28.09. - 01.10.2023, Köln

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Platin-related Hearing Loss: Further Results from PanCareLIFE

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  • corresponding author presenting/speaker Ross Parfitt - Klinik für Phoniatrie & Pädaudiologie, Uniklinikum Münster, Münster, Deutschland
  • Peter Matulat - Klinik für Phoniatrie & Pädaudiologie, Uniklinikum Münster, Münster, Deutschland
  • Julianne Byrne - Boyne Research Institute, Drogheda, Irland
  • Thorsten Langer - Pediatric Oncology and Hematology, University Hospital for Children and Adolescents, University zu Lübeck, Lübeck, Deutschland
  • Dirk Deuster - Klinik für Phoniatrie & Pädaudiologie, Uniklinikum Münster, Münster, Deutschland
  • Amélie Hesping - Klinik für Phoniatrie & Pädaudiologie, Uniklinikum Münster, Münster, Deutschland
  • Eva Clemens - Erasmus University Medical Centre (EMC), Rotterdam, Niederlande
  • Peter Kaatsch - German Childhood Cancer Registry (GCCR), Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Mainz, Deutschland
  • Desiree Grabow - German Childhood Cancer Registry (GCCR), Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Mainz, Deutschland
  • Kylie O'Brien - Pintail Ltd, Dublin, Irland
  • Melanie Kaiser - German Childhood Cancer Registry (GCCR), Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Mainz, Deutschland
  • Claudia Spix - German Childhood Cancer Registry (GCCR), Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Mainz, Deutschland
  • Leontien C. Kremer - Academisch Medisch Centrum bij de Universiteit van Amsterdam (AMC), Amsterdam, Niederlande
  • Eline van Dulmen-den Broeder - VU University Medical Centre (VUMC), Amsterdam, Niederlande
  • Gabriele Calaminus - Department of Paediatric Haematology and Oncology, Universitätsklinikum, Bonn, Deutschland
  • Katja Baust - Department of Paediatric Haematology and Oncology, Universitätsklinikum, Bonn, Deutschland
  • Claudia Kuehni - Pediatric Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Schweiz
  • Annette Weiss - Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; CANSEARCH research platform in pediatric oncology and hematology, Department of Pediatrics, Gynecology and Obstetrics, University of Geneva, Geneva, Schweiz
  • Sven Strebel - Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; CANSEARCH research platform in pediatric oncology and hematology, Department of Pediatrics, Gynecology and Obstetrics, University of Geneva, Geneva, Schweiz
  • Rahel Kuonen - Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; CANSEARCH research platform in pediatric oncology and hematology, Department of Pediatrics, Gynecology and Obstetrics, University of Geneva, Geneva, Schweiz
  • Susanne Elsner - Pediatric Oncology and Hematology, University Hospital for Children and Adolescents, University zu Lübeck, Lübeck, Deutschland
  • Riccardo Haupt - Epidemiology and Biostatistics Unit, Instituto Giannina Gaslini (IGG), Genoa, Italien
  • Marie-Luisa Garré - Epidemiology and Biostatistics Unit, Instituto Giannina Gaslini (IGG), Genoa, Italien
  • Tomas Kepak - University Hospital Brno, Brno, Tschech. Republik
  • Katerina Kapakova - University Hospital Brno, Brno, Tschech. Republik
  • Jeanette Falck Winther - Childhood Cancer Research Group, Danish Cancer Society Research Center, Copenhagen, Dänemark
  • Line Kenborg - Childhood Cancer Research Group, Danish Cancer Society Research Center, Copenhagen, Dänemark
  • Catherine Rechnitzer - Pediatric and Adolescent Medicine, Juliane Marie Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Dänemark
  • Henrik Hasle - Department of Pediatrics, Aarhus University Hospital, Arhus, Dänemark
  • Jarmila Kruseova - Motol Teaching Hospital, Prague, Tschech. Republik
  • Ales Luks - Motol Teaching Hospital, Prague, Tschech. Republik
  • Herwig Lackner - Medical University of Graz, Graz, Österreich
  • Stefan Beilack - Centre for Paediatric Medicine, Klinikum Stuttgart – Olgahospital, Stuttgart, Deutschland
  • Stefanie Hecker-Nolting - Centre for Paediatric Medicine, Klinikum Stuttgart – Olgahospital, Stuttgart, Deutschland
  • Jörn-Dirk Beck - Pediatric Oncology, University Hospital Erlangen, Erlangen, Deutschland
  • Marry van den Heuvel-Eibrink - Prinses Maxima Center for Pediatric Oncology (PMC), and University of Utrecht, Utrecht, Niederlande
  • Oliver Zolk - Medizinische Hochschule Brandenburg Theodor Fontane, Institut für Klinische Pharmakologie, Immanuel Klinik Rüdersdorf, Rüdersdorf, Deutschland
  • Antoinette am Zehnhoff-Dinnesen - Klinik für Phoniatrie & Pädaudiologie, Uniklinikum Münster, Münster, Deutschland
  • PanCareLIFE Consortium

39. Wissenschaftliche Jahrestagung der Deutschen Gesellschaft für Phoniatrie und Pädaudiologie (DGPP). Köln, 28.09.-01.10.2023. Düsseldorf: German Medical Science GMS Publishing House; 2023. DocV35

doi: 10.3205/23dgpp63, urn:nbn:de:0183-23dgpp637

Veröffentlicht: 20. September 2023

© 2023 Parfitt et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.

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 funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 602030.

Gliederung

Text

Background

Cisplatin and carboplatin are widely-used in paediatric cancer treatment. Sensorineural hearing loss (SNHL) is one long-term side-effect (Langer et al. [1], amongst others). This study utilises a larger sample than previous research in order to investigate risk-factors for platin-related ototoxicity as part of the PanCareLIFE consortium.

Material and Methods

Retrospective audiological and treatment data of 933 children and adolescents treated with cisplatin and/or carboplatin (mean age at diagnosis 8.3 years, 55 % male) were gathered with the involvement of 18 pan-European institutions in 7 different countries. Prior hearing loss was excluded. Conductive hearing losses were excluded where identified.

Mean cumulative cisplatin dose was 390 mg/m2 (body surface area); mean carboplatin dose was 3025 mg/m2.

Results

Prevalence rates of clinically-significant hearing loss (=> 2b Münster Classification [2]) after treatment were 49 % (cisplatin alone) and 15 % (carboplatin alone). 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 thresholds in the group with significant hearing loss of 40 dB HL at 4 kHz and 50-60 dB HL at 6 and 8 kHz. Mean thresholds at frequencies below 3 kHz remained lower than 20 dB HL. No significant asymmetry or air-bone gap was apparent.

An ordinal regression was highly significant for larger cumulative cisplatin dose and younger age on hearing classification after the end of treatment (p=0.000) and not significant for sex or cumulative carboplatin dose. A MANOVA was also highly significant for cumulative cisplatin dose and younger age on thresholds at 4 and 8 kHz (N=563, p=0.000 to p=0.009, good model fit), though not at 1 and 2 kHz. The effect size was moderate for both factors.

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 are planned as part of this study.

Discussion

Analysis of this large sample was able to confirm the significant risk of high-frequency SNHL posed by treatment involving cisplatin in this large sample. Some quantitative and qualitative variation was present in this multi-centre retrospective dataset.

Conclusions

This large sample confirms that treatment involving cisplatin poses a significant risk of SNHL, especially at a younger age, and underlines the necessity of audiological monitoring during and after the end of chemotherapy.

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.

Gliederung

References

1.
Langer T, am Zehnhoff-Dinnesen A, Radtke S, Meitert J, Zolk O. Understanding platinum-induced ototoxicity. Trends Pharmacol Sci. 2013;34(8):458-69.
2.
Schmidt CM, Bartholomaus E, Deuster D, Heinecke A, Dinnesen AG. Die „Münsteraner Klassifikation“. Eine neue Einteilung der Hochtonschwerhörigkeit nach Cisplatingabe[The "Muenster classification" of high frequency hearing loss following cisplatin chemotherapy]. HNO. 2007;55(4):299-306.