Global burden of ototoxic hearing loss associated with platinum-based cancer treatment: A systematic review and meta-analysis

Dillard, Lauren K; Lopez-Perez, Lucero; Martinez, Ricardo X; Fullerton, Amanda M.; Chadha, Shelly; McMahon, Catherine M.

doi:10.1016/j.canep.2022.102203

Cited by 44 publications

(34 citation statements)

References 96 publications

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“…According to the 2018 Ototoxicity Working Group of Pharmaceutical Interventions for Hearing Loss, ototoxicity is defined as “…damage to the inner ear, targeting cochlear and vestibular structures and sensory function, due to exposure to certain pharmaceuticals, chemicals, and/or ionizing radiation” [ 8 ]. In a recent meta-analysis of data from over 5077 patients receiving cisplatin and/or carboplatin, hearing loss occurred in 38–49% of patients pooled across age and tumor type [ 9 ]. Cisplatin, the most ototoxic of these drugs, causes some combination of ototoxic hearing loss (prevalence 50–80% [ 10 , 11 ]), tinnitus (prevalence 11–40%; [ 10 , 12 ]), and/or balance problems (prevalence 0% to 50%; [ 7 ]) in the majority of those who receive it.…”

Section: Introductionmentioning

confidence: 99%

Audiologists’ perceived value of ototoxicity management and barriers to implementation for at-risk cancer patients in VA: the OtoMIC survey

et al. 2023

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Purpose Platinum-based chemotherapies used to treat many types of cancers are ototoxic. Ototoxicity management (OtoM) to mitigate the ototoxic outcomes of cancer survivors is recommended practice yet it is not a standard part of oncologic care. Although more than 10,000 patients each year are treated with platinum-based chemotherapies at the US Veterans Health Administration (VA), the current state of OtoM in VA is not well-defined. This study reports on a national survey of VA audiologists’ perceptions regarding OtoM in cancer patients. Methods A 26-item online survey was administered to VA audiologists and service chiefs across the VA’s 18 regional systems of care. Descriptive statistics and deductive thematic analysis were used to analyze the data. Results The 61 respondents included at least one from each VA region. All reported they felt some form of OtoM was necessary for at-risk cancer patients. A pre-treatment baseline, the ability to detect ototoxicity early, and management of ototoxic effects both during and after treatment were considered high value objectives of OtoM by respondents. Roughly half reported routinely providing these services for patients receiving cisplatin and carboplatin. Respondents disagreed regarding appropriate hearing testing schedules and how to co-manage OtoM responsibilities with oncology. They identified barriers to care that conformed to three themes: care and referral coordination with oncology, audiology workload, and lack of protocols. Conclusions Although VA audiologists value providing OtoM for cancer patients, only about half perform OtoM for highly ototoxic treatment regimens. The OtoMIC survey provides clinician perspectives to benchmark and address OtoM care gaps. Implications for cancer survivors Collaboration between oncology and audiology is needed to improve current OtoM processes, so that cancer survivors can have more control over their long term hearing health.

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Section: Introductionmentioning

confidence: 99%

Audiologists’ perceived value of ototoxicity management and barriers to implementation for at-risk cancer patients in VA: the OtoMIC survey

et al. 2023

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“…Despite its effectiveness against solid tumors, cisplatin presents with high prevalence dose-limiting adverse side effects due to its action in non-proliferating cells; it is toxic to liver, kidney, nervous system and the cochlea, affecting hair cells and spiral ganglion neurons ( Callejo et al, 2015 ; Rybak et al, 2019 ; Prayuenyong et al, 2021 ). Close to half a million cases of hearing loss associated to the treatment with cisplatin per year globally have been estimated ( Dillard et al, 2022 ).…”

Section: Cisplatin Ototoxicity In Zebrafishmentioning

confidence: 99%

Hair cell toxicology: With the help of a little fish

Barrallo-Gimeno

Llorens

2022

Front. Cell Dev. Biol.

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Hearing or balance loss are disabling conditions that have a serious impact in those suffering them, especially when they appear in children. Their ultimate cause is frequently the loss of function of mechanosensory hair cells in the inner ear. Hair cells can be damaged by environmental insults, like noise or chemical agents, known as ototoxins. Two of the most common ototoxins are life-saving medications: cisplatin against solid tumors, and aminoglycoside antibiotics to treat infections. However, due to their localization inside the temporal bone, hair cells are difficult to study in mammals. As an alternative animal model, zebrafish larvae have hair cells similar to those in mammals, some of which are located in a fish specific organ on the surface of the skin, the lateral line. This makes them easy to observe in vivo and readily accessible for ototoxins or otoprotective substances. These features have made possible advances in the study of the mechanisms mediating ototoxicity or identifying new potential ototoxins. Most importantly, the small size of the zebrafish larvae has allowed screening thousands of molecules searching for otoprotective agents in a scale that would be highly impractical in rodent models. The positive hits found can then start the long road to reach clinical settings to prevent hearing or balance loss.

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“… 28 The incidence of hearing loss associated with carboplatin is estimated to be approximately 13.8% (95% confidence interval, CI: 8.7–20.3%). 10 For cisplatin, conventional regimens are associated with a 49.2% (95% CI: 42.6–55.8%) incidence of hearing loss, and combination therapy with cisplatin is associated with a 56.1% (95% CI: 45.1–66.4%) incidence of hearing loss. 10 , 15 The guidelines of the National Cancer Institute Common Terminology Criteria for Adverse Events are commonly applied when investigating ototoxicity for platinum-based compounds.…”

Section: Ototoxic Drugsmentioning

confidence: 99%

“… 10 For cisplatin, conventional regimens are associated with a 49.2% (95% CI: 42.6–55.8%) incidence of hearing loss, and combination therapy with cisplatin is associated with a 56.1% (95% CI: 45.1–66.4%) incidence of hearing loss. 10 , 15 The guidelines of the National Cancer Institute Common Terminology Criteria for Adverse Events are commonly applied when investigating ototoxicity for platinum-based compounds. However, the guidelines do not include high frequency hearing loss and may lead to underestimation of the true incidence of hearing loss.…”

Section: Ototoxic Drugsmentioning

confidence: 99%

“…Globally, platinum-based chemotherapies and aminoglycosides are associated with over 500 000 and 50 000 annual cases of hearing loss, respectively. 4 , 15 Currently, there are no international guidelines or protocols for the screening and management of hearing loss during treatment. 7 Examination of several countries’ guidance for detection of ototoxicity shows that there is no universal approach to screening or diagnosing hearing loss.…”

Section: Introductionmentioning

confidence: 99%

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Prevention and management of hearing loss in patients receiving ototoxic medications

Lindeborg¹,

Jung²,

Chan³

et al. 2022

Bull World Health Org

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Following the efforts of patient advocates, the World Health Organization published updated guidelines for management of multidrug-resistant tuberculosis in 2018 that advised against the routine use of ototoxic second-line injectable drugs (amikacin, capreomycin and kanamycin). Although hearing loss is no longer considered an unavoidable harm for patients with multidrug-resistant tuberculosis, ototoxic medications continue to be used for several infectious and oncological disorders around the world. These drugs contribute to more than a half a million cases of hearing loss worldwide annually. Currently, there are no international standards for preventing and managing hearing loss associated with ototoxic medications. We present recent data on the prevention and management of hearing loss related to these drugs and highlight the variability in care across settings. More importantly, we aim to provide an evidence-based framework for evaluating, screening and preventing ototoxicity. Finally, we identify avenues for future research so that patients no longer have to choose between hearing loss and a disease cure. There remain significant gaps in our understanding about optimal screening and treatment of ototoxic hearing loss. Here we aim to inspire future international guidelines to address gaps in ototoxicity care and establish research agendas for eliminating ototoxic medications.

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Global burden of ototoxic hearing loss associated with platinum-based cancer treatment: A systematic review and meta-analysis

Cited by 44 publications

References 96 publications

Audiologists’ perceived value of ototoxicity management and barriers to implementation for at-risk cancer patients in VA: the OtoMIC survey

Audiologists’ perceived value of ototoxicity management and barriers to implementation for at-risk cancer patients in VA: the OtoMIC survey

Hair cell toxicology: With the help of a little fish

Prevention and management of hearing loss in patients receiving ototoxic medications

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