Hearing loss after platinum treatment is irreversible in noncranial irradiated childhood cancer survivors

Abstract

Cisplatin and carboplatin are effective antineoplastic agents. They are also considered to be potentially highly ototoxic. To date, no long-term follow-up data from well-documented cohorts with substantial numbers of childhood cancer survivors (CCS) with platinum-related hearing loss are available. Therefore, in this study, we studied the reversibility of ototoxicity from discontinuation of treatment onwards in a national cohort of platinum-treated survivors with hearing loss at the end of cancer treatment. Of the 168 CCS with follow-up audiograms, we longitudinally evaluated the course of hearing function in 61 CCS who showed hearing impairment at discontinuation of treatment according to the Münster criteria (>20 dB at ࣙ4-8 kHz). Survivors were treated with platinum (median total cumulative dose cisplatin: 480 mg/m 2 and median total cumulative dose carboplatin: 2520 mg/m 2 ). Median followup time was 5.5 years (range: 1.0-28.8 years). The results showed that none of these survivors revealed improvement of hearing function even till 28.8 years after discontinuation of treatment (grade <2b during longterm follow-up). An increase in hearing loss with two or three Münster degrees was observed in five of 61 survivors after 1.6-19.6 years. Overall, this indicates that ototoxicity after platinum treatment may be irreversible and that longitudinal clinical audiological monitoring and care is required in long-term survivors of childhood cancer on a large scale.

Ototoxicity after platinum‑based chemotherapy in the treatment of melanotic neuroectodermal tumour of infancy

“…destructive effect on external auditory cells, which are not capable of regeneration (18). The means that the hearing loss after cisplatin-based treatment is irreversible (19). In this study, a patient with a mesenchymal-neuroectodermal tumor who had been treated with cisplatin was diagnosed with bilateral high-frequency hearing loss, which is consistent with literature reports (10)(11)(12)(13).…”

“…Unfortunately, in our case no previous pure-tone audiometry tests were performed, which makes it impossible to determine whether the hearing loss is progressive or whether it has remained at the same level since the end of chemotherapy. In the literature, reports are stating that after the completion of treating hearing loss is permanent and stable (19,23). However, many authors have observed progressive hearing loss following chemotherapy with platinum compounds in children treated for solid tumors (15,21,22).…”

Pregnancy and Cancer: the INCIP Project

“…However, the evidence regarding cardiac function on children prenatally exposed to anthracyclines is reassuring: non-clinically relevant differences in echocardiographic findings have been reported in exposed children compared with non-exposed ones [8,42,51,52]. Concerns related to hearing function throughout infancy are mainly based on data from young cancer survivors [53,54]. However, on indication, the use of carboplatinum during pregnancy is preferred, as there are case reports of impaired hearing in children prenatally exposed to cisplatin [8,41,55].…”

Recommendations for ototoxicity surveillance for childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCare Consortium

“…There is low quality evidence that hearing function in CAYA cancer survivors may deteriorate over time after treatment with platinum agents 34,35,[53][54][55][56] , head/brain radiotherapy, or a CSF shunt (level C evidence). 5,10,[57][58][59] However, in some survivors hearing function remains stable or even improves over time.…”

“…5,10,[57][58][59] However, in some survivors hearing function remains stable or even improves over time. 34,35,[53][54][55][56]60 The predictors for change of hearing function over time are unknown. From existing literature, it is difficult to define an appropriate surveillance interval indicating the length of time during which testing should be performed.…”