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  • 1
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  4. Dreiländertagung D-A-CH, 35. Wissenschaftliche Jahrestagung der Deutschen Gesellschaft für Phoniatrie und Pädaudiologie (DGPP); 20180920-20180923; Innsbruck, Österreich; DOCV27 /20180914/
    Publication Date: 2018-09-15
    Description: Background: Ototoxicity is a common side effect after platin chemotherapy and existing studies are limited due to small cohorts and a variety of confounding factors (Grewal et al. , Langer et al. ). Therefore, studies that enrolled greater numbers of patients will help us to learn more about incidence and course of ototoxic hearing loss, clinical and genetic risk factors.Material and Methods: In the PanCare LIFE Project, data were collected about chemotherapy, radiation, other ototoxic medicaments and audiological follow-up from a number of European centers to create a cohort of childhood cancer patients who were treated with platin chemotherapy. The audiological tests of 2525 patients were evaluated by the Clinic for Phoniatrics and Pedaudiology at the University Hospital Münster as an audiological reference center and the hearing loss severity was classified according to the Muenster and the SIOP schemes (Schmidt et al. , Brock et al. ). The hearing loss course of all patients with sufficient audiological tests was analyzed by two pedaudiologists separately. Patients were assigned to the following phenotype groups: no hearing impairment (〈/= Muenster 1); progression of hearing impairment during chemotherapy; early onset of hearing impairment (〉0 (Muenster classification) after 2nd/before 3rd cycle); hearing loss 〉=2b (Muenster classification) on at least one ear at end of chemotherapy; progression of hearing impairment after end of chemotherapy.Results: Phenotyping was possible in 513 patients. In total, 234 patients had no hearing loss during the whole observation period. During therapy, 263 patients suffered from a progressive hearing loss. Of these, 83 had an early onset hearing loss and 182 developed a hearing loss 〉=2b (Muenster classification) at the post-treatment evaluation. A progression of hearing loss later than 15 months after the end of therapy could be observed in 52 cases. Odds ratios between early onset hearing loss, severe hearing loss at the end of chemotherapy and posttherapeutic progression will be presented with detailed information on extent, rate and time course of hearing loss progression.Discussion: These data are the first preliminary results from a big European cohort of childhood cancer patients treated with platin chemotherapy, providing information about incidence and course of hearing loss in one of the biggest studies existing up to now. The predefined audiological phenotypes are discussed on the basis of different degrees and time courses of hearing loss progression.
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 2
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  36. Wissenschaftliche Jahrestagung der Deutschen Gesellschaft für Phoniatrie und Pädaudiologie (DGPP); 20190919-20190922; Göttingen; DOCV4 /20190913/
    Publication Date: 2019-09-14
    Description: 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.
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject , info:eu-repo/semantics/article
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  • 3
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  36. Wissenschaftliche Jahrestagung der Deutschen Gesellschaft für Phoniatrie und Pädaudiologie (DGPP); 20190919-20190922; Göttingen; DOCV5 /20190913/
    Publication Date: 2019-09-14
    Description: Background: Platinum compounds such as cisplatin or carboplatin are potent antineoplastic agents widely used for a variety of cancer types. Unfortunately, their use leads to dose-limiting side effects such as ototoxicity. Our study aimed at investigating the predictive value of 11 candidate genetic markers in a large non-selected pediatric population of cancer survivors who had been treated with cisplatin and/or carboplatin.Materials and Methods: As a part of the PanCareLIFE study, the ototoxicity study included 2,696 survivors from 7 European countries treated with cisplatin and/or carboplatin for childhood cancer, resulting in the largest clinical European cohort assembled for this late-effect study. Hearing loss was audiologically classified using the Münster Classification. Three groups were defined, i.e., no hearing loss, minor hearing loss, and clinically relevant hearing loss. Patients were genotyped for single nucleotide polymorphisms (SNPs) in 7 candidate genes. Genetic association analyses were performed considering non-genetic covariates.Results: 900 patients were included in the final genetic analysis. Multinomial logistic regression was performed to model the relationship between the predictors and membership in the hearing loss group. The model explained 25% of the variance in hearing loss and correctly classified 58% of cases. Significant unique contributions were made by SLC22A2 rs316019 (P=0.017), age at the start of platinum treatment (P=1.46x10-17), cranial radiation (P=5.42x10-6), and the cumulative dose of cisplatin (P=5.86x10-19). Addition of the rs316019 genetic marker to the non-genetic risk factors (age, dose, cranial radiation) improved the area under the ROC curve only marginally (0.731 vs. 0.730).Discussion: Our study confirmed one potential genetic marker, rs316019 in SLC22A2. Its predictive value, however, is low.Conclusion: Due to the heterogeneity of results from genetic association studies performed so far, the evidence seems not yet sufficient to recommend screening for specific markers. Advances in the understanding of the pathophysiologic mechanisms of cisplatin-induced ototoxicity, as well as future genome-wide association studies, may help identify suitable genetic markers.Acknowledgement: This work was supported by the PanCareLIFE project that has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 602030.
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject , info:eu-repo/semantics/article
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