Risk factors associated with tinnitus in 2948 Dutch survivors of childhood cancer: a Dutch LATER questionnaire study

Annelot J M Meijer; Marta F Fiocco; Geert O Janssens; Eva Clemens; Wim J E Tissing; Jacqueline J Loonen; Eline van Dulmen-den Broeder; Andrica C H de Vries; Dorine Bresters; Birgitta Versluys; Cécile M Ronckers; Leontien C M Kremer; Helena J van der Pal; Sebastian J C M M Neggers; Margriet van der Heiden-van der Loo; Robert J Stokroos; Alex E Hoetink; Martine van Grotel; Marry M van den Heuvel-Eibrink

doi:10.1093/noajnl/vdaa122

Risk factors associated with tinnitus in 2948 Dutch survivors of childhood cancer: a Dutch LATER questionnaire study

Neurooncol Adv. 2020 Sep 15;2(1):vdaa122. doi: 10.1093/noajnl/vdaa122. eCollection 2020 Jan-Dec.

Authors

Annelot J M Meijer¹, Marta F Fiocco^{1

2

3}, Geert O Janssens^{1

4}, Eva Clemens⁵, Wim J E Tissing^{1

6}, Jacqueline J Loonen^{1

7}, Eline van Dulmen-den Broeder^{1

8}, Andrica C H de Vries^{1

5}, Dorine Bresters¹, Birgitta Versluys^{1

9}, Cécile M Ronckers^{1

10

11}, Leontien C M Kremer^{1

10}, Helena J van der Pal^{1

10}, Sebastian J C M M Neggers^{1

12}, Margriet van der Heiden-van der Loo¹³, Robert J Stokroos¹⁴, Alex E Hoetink¹⁴, Martine van Grotel¹, Marry M van den Heuvel-Eibrink^{1

5}

Affiliations

¹ Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
² Department of Biomedical Data Science, Section Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands.
³ Institute of Mathematics, Leiden University, Leiden, The Netherlands.
⁴ Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
⁵ Department of Pediatric Oncology, Erasmus Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.
⁶ Department of Pediatric Oncology, University Medical Center Groningen - Beatrix Children's Hospital, Groningen, The Netherlands.
⁷ Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
⁸ Department of Pediatrics, VU University Medical Center, Amsterdam, The Netherlands.
⁹ Department of Pediatric Oncology, University Medical Center Utrecht - Wilhelmina Children's Hospital, Utrecht, The Netherlands.
¹⁰ Department of Pediatric Oncology, Academic Medical Center - Emma Children's Hospital, Amsterdam, The Netherlands.
¹¹ Institute of Biostatistics and Registry Research, Brandenburg Medical School Theodor Fontane, Neuruppin, Germany.
¹² Department of Medicine, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
¹³ Dutch Childhood Oncology Group - Late Effects after Childhood Cancer (LATER) Registry, Utrecht, The Netherlands.
¹⁴ Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Utrecht - Wilhelmina Children's Hospital, Utrecht, The Netherlands.

Abstract

Background: Tinnitus is a serious late effect of childhood cancer treatment. The aim of this study was to determine the occurrence and risk factors for tinnitus in a national cohort of childhood cancer survivors (CCS).

Methods: Data were collected within the national Dutch Childhood Oncology Group - Long-Term Effects after Childhood Cancer (DCOG-LATER) cohort by a self-reported health questionnaire among 5327 Dutch CCS treated between 1963 and 2002. Siblings (N = 1663) were invited to complete the same questionnaire. Relevant patient characteristics and treatment factors were obtained from the Dutch LATER database. The occurrence of tinnitus in survivors was compared to siblings. To study the effect of risk factors, multivariate logistic regression models were estimated.

Results: In total, 2948 CCS and 1055 siblings completed the tinnitus item. Tinnitus was reported in 9.5% of survivors and in 3.7% of siblings (odds ratio [OR] 3.0, 95% confidence interval [CI] 2.9-3.1). Risk factors associated with tinnitus in CCS were total cumulative dose cisplatin ≥400 mg/m² (OR 2.4, 95% CI 1.4-4.0), age at diagnosis (≥10 years: OR 2.1, 95% CI 1.6-2.8), cranial irradiation/total body irradiation (TBI; OR 1.9, 95% CI 1.5-2.5), and neuro/ear, nose, throat (ENT) surgery (OR 1.8, 95% CI 1.1-2.9). Fifty-one percent of CCS with tinnitus had received treatment with either cisplatin, cranial irradiation/TBI, and/or neuro/ENT surgery.

Conclusions: Tinnitus in CCS was present nearly 3 times more often than in siblings. Awareness in CCS previously treated with cisplatin, cranial irradiation/TBI, and/or neuro/ENT surgery is warranted. As only half of affected CCS had a history of these treatments, it seems that other factors might be associated with tinnitus occurrence in this population.

Keywords: ototoxicity; childhood cancer survivors; hearing aid; late effects; tinnitus.