Article
A retrospective study of paediatric hearing loss in cranial radiotherapy combined with platin-based chemotherapy
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Published: | September 7, 2015 |
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Outline
Abstract
Objective: Cranial Radiotherapy (CRT) is a common aspect of treatment for brain tumours in childhood. Larger cochlear dose of radiation correlates with greater hearing loss (eg. Hua et al., 2008), especially in combination with Cisplatin chemotherapy (eg. Paulinho et al, 2010). Animal studies and clinical studies in adults suggest asymmetrical hearing loss (Miller et al., 2007; Van der Putten, 2006).
Materials and Methods: We initiated a retrospective study in a pediatric population with brain tumours to investigate the effects of CRT on audiological thresholds, as part of our involvement in PANCare-Life. Initial results include a comparison of post-chemotherapy thresholds of 186 patients (57 who had CRT, 129 who did not) to investigate progressive audiological changes after cessation of platin treatment. Thresholds were categorized according to the Münster system, focusing on minimal high-frequency changes (Schmidt et al., 2007).
Results: The CRT and non-CRT groups were characterized by asymmetrical vs symmetrical post-treatment hearing losses respectively. A robust tendency (p= 0.05, Fisher’s exact) towards asymmetrical deterioration was found in the CRT group.
No significant differences were found in the estimated mean cochlear dose of CRT per ear (means of 42.5 and 47 Gy (t=0.18) for the least and most irradiated ears respectively) given to a group of 19 CRT patients. Inter-ear hearing thresholds for this group also showed no significant difference which, although it does not directly support the idea of asymmetrical cranial radiation as a cause of increased asymmetrical hearing loss (Van den Putten, 2006), does take a complimentary position.
Conclusion: These findings underline the necessity of audiological follow up after cessation of platin therapy, especially in children with combined cranial irradiation.
Text
Background
In Cranial Radiotherapy (CRT), high-energy radiation beams are employed to damage the DNA of cancerous cells in order to restrict their spread. Cancerous cells are more susceptible to this damage than normal cells and various techniques to target tumours with minimal effect on normal cells exist [1]. Despite this, risks of damage are still present for normal tissue.
Otological side-effects of CRT have been reported to affect the middle-ear [5], [9], [2] and the cochlea ([11], [4] amongst others). The severity of the effect on cochlear hearing thresholds seems to depend upon the total cochlear dose of radiation (Dmean) and the order in which CRT and Cisplatin chemotherapy are administered. The correlation of increased risk of sensorineural hearing loss (SNHL) and a higher Dmean was reported by Bhandare et al. [3], Hua et al. [6] and Van der Putten et al. [10]. Hua et al. [6] made specific recommendations for paediatric practice, such as a cochlear dose of less than 35 Gy even when Platin therapy does not form part of the patient’s treatment. Kretschmar et al. [7] and Low et al. [8] reported an increased risk of hearing loss when CRT is administered prior to Cisplatin but that CRT following Cisplatin presents no greater risk of hearing loss than Cisplatin alone.
Material and Method
Post-treatment change in hearing thresholds, especially regarding symmetry, following Platin-based chemotherapy with and without CRT was investigated using retrospective data of 186 children and adolescents (57 with CRT, 129 without CRT). A sub-group of 19 patients was analysed with reference to the estimated cochlear dose of CRT given.
Results
A significant difference (p=0.035) in the improvement or decline of audiometric classification was found, with greater deterioration and significantly fewer improvements in the CRT group. No difference was found in rates of bilateral change between the groups, however a robust tendency towards asymmetrical decline was found in the CRT group (p=0.05) in this post-treatment period. Both groups saw some reversal of earlier decline in hearing classification, but significantly less often in the CRT group.
No significant asymmetry in cochlear dose was found between the least/most irradiated ears (means of 42.5 and 47 Gy respectively (T=0.18)) of a sub-group of 19 for whom estimated cochlear dose figures were available. Nor was a difference found in rates of change in hearing classification between ears in this group over the post-CRT-treatment period. Although it does not directly support the idea of asymmetrical cranial radiation as a cause of increased asymmetrical hearing loss [10], this finding takes a complimentary position. Mean estimated cochlear dose was 45 Gy (sd=15.5 Gy) which is higher than Hua et al.’s [6] recommendation but lower than the risk level of 50 Gy proposed by Van der Putten [10].
Discussion
As different diagnoses require different treatments, the populations of our CRT and non-CRT groups necessarily had different diagnoses. Possible effects of this could have played a role in our findings, as could variation in the number of post-treatment audiological tests for each patient. Next steps will incorporate more data on CRT and Platin and will investigate further the role of their relative timing.
Conclusion
The possible role of CRT combined with Platin-based chemotherapy in the development of asymmetrical post-treatment changes in hearing was demonstrated. These findings underline the necessity of audiological follow up after the cessation of platin therapy, especially in children with combined cranial irradiation.
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