Ototoxicity in patients treated with the RADPLAT-protocol

Researcher(s): C.L. Zuur, MSc., Y.J.W. Simis, PhD.
Supervisor(s): prof. A.J.M. Balm, PhD., (NKI/AvL) and

prof. W.A. Dreschler, PhD.

Aim:
This project focuses primarily on the assessment of ototoxicity in patients with tumors in the head and neck, treated with a combination of radiation and cisplatinum according to the RADPLAT-protocol. Parts of this study are dose-effect relationships and patterns of recovery after treatment. An additional issue is the value of otoacoustic emissions that possibly can be used to increase the sensitivity of monitoring the status of hearing, detecting ototoxicity in an earlier phase, and reducing the patient load.

Method:
The project consists of the following parts:

Retrospective analyses of ototoxicity in patients treated according to the RADPLAT-protocol. This concerns a group of 75 patients treated in 6 different hospitals. In these patients a series of 5 audiometric tests is available and the analysis focuses on specific patterns of damage.
In the same group the dose-effect relationship will be investigated and the project aims to separate the effects of cisplatinum and radiation.
The added value of otoacoustic emissions in monitoring ototoxicity is still unclear from literature. OAE’s can be able to increase the sensitivity in detecting ototoxicity and reduce the load of audiological examinations for the patient. The added value and additional advantages will be investigated in different patient groups in the AMC. Also we will investigate the sensitivity, the reliability, and the reproducibility of different types of OAE measurements.
In a new group of 250 patients treated according to the RADPLAT-protocol cisplatinum will be delivered at randomly according to different protocols. The results will be evaluated by means of OAE-measurements.
A third group of patients receives a relatively low dose of cisplatinum, but according to a more frequent delivery scheme. The effects of this alternative delivery will be evaluated using tone audiometry and OAE-measurements.
The patients from the retroprospective and prospective studies that showed hearing damage will be followed as far as possible post treatment in order to find information about the long-term effects. Long-term effects can be influenced by delayed expression of damage due to the cisplatinum and radiation. On the other hand some recovery may show up.

Results:
The results in the group of 146 patients clearly show the pattern of damage caused by ototoxicity due to the combined treatment with cisplatinum and radio therapy. After treatment 23% of the ears is eligible for a hearing aid. Also we found a conductive hearing loss in about a quarter of the patients, possibly due to radiation. It was possible to design a formula that predicts the hearing damage based on the base line audiogram age and sex. It turns out that deterioration on average is larger for younger patients with a normal pre-treatment audiogram.

Future research:
Other aspects of this project focus on the differences in damage patterns between treatments with intra - arterial versus intra - venous delivery of cisplatinum. A special group consists of patients with a low dose cisplatinum genoradiation, in which we also will evaluate the patterns of audiological damage. In part of the patients oto acoustic emissions are available. These data will be used to investigate whether oto acoustic emissions have an added value in the monitoring of ototoxic damage. The results will be presented in a series of papers and in the PhD thesis of C.L. Zuur.


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General Otology Prevention of hearing loss Ototoxicity in patients treated with the RADPLAT-protocol Noise exposure in classical musicians Prevention of noise-induced hearing loss I Prevention of noise-induced hearing loss II Auditory profile Rehabilitation Hearing at work Publications Presentations	Ototoxicity in patients treated with the RADPLAT-protocol Researcher(s): C.L. Zuur, MSc., Y.J.W. Simis, PhD. Supervisor(s): prof. A.J.M. Balm, PhD., (NKI/AvL) and prof. W.A. Dreschler, PhD. Aim: This project focuses primarily on the assessment of ototoxicity in patients with tumors in the head and neck, treated with a combination of radiation and cisplatinum according to the RADPLAT-protocol. Parts of this study are dose-effect relationships and patterns of recovery after treatment. An additional issue is the value of otoacoustic emissions that possibly can be used to increase the sensitivity of monitoring the status of hearing, detecting ototoxicity in an earlier phase, and reducing the patient load. Method: The project consists of the following parts: Retrospective analyses of ototoxicity in patients treated according to the RADPLAT-protocol. This concerns a group of 75 patients treated in 6 different hospitals. In these patients a series of 5 audiometric tests is available and the analysis focuses on specific patterns of damage. In the same group the dose-effect relationship will be investigated and the project aims to separate the effects of cisplatinum and radiation. The added value of otoacoustic emissions in monitoring ototoxicity is still unclear from literature. OAE’s can be able to increase the sensitivity in detecting ototoxicity and reduce the load of audiological examinations for the patient. The added value and additional advantages will be investigated in different patient groups in the AMC. Also we will investigate the sensitivity, the reliability, and the reproducibility of different types of OAE measurements. In a new group of 250 patients treated according to the RADPLAT-protocol cisplatinum will be delivered at randomly according to different protocols. The results will be evaluated by means of OAE-measurements. A third group of patients receives a relatively low dose of cisplatinum, but according to a more frequent delivery scheme. The effects of this alternative delivery will be evaluated using tone audiometry and OAE-measurements. The patients from the retroprospective and prospective studies that showed hearing damage will be followed as far as possible post treatment in order to find information about the long-term effects. Long-term effects can be influenced by delayed expression of damage due to the cisplatinum and radiation. On the other hand some recovery may show up. Results: The results in the group of 146 patients clearly show the pattern of damage caused by ototoxicity due to the combined treatment with cisplatinum and radio therapy. After treatment 23% of the ears is eligible for a hearing aid. Also we found a conductive hearing loss in about a quarter of the patients, possibly due to radiation. It was possible to design a formula that predicts the hearing damage based on the base line audiogram age and sex. It turns out that deterioration on average is larger for younger patients with a normal pre-treatment audiogram. Future research: Other aspects of this project focus on the differences in damage patterns between treatments with intra - arterial versus intra - venous delivery of cisplatinum. A special group consists of patients with a low dose cisplatinum genoradiation, in which we also will evaluate the patterns of audiological damage. In part of the patients oto acoustic emissions are available. These data will be used to investigate whether oto acoustic emissions have an added value in the monitoring of ototoxic damage. The results will be presented in a series of papers and in the PhD thesis of C.L. Zuur.