Diagnostic of Various Ototoxicity Induced by Cancer Treatment

Ototoxicity refers to all the auditory and vestibular consequences of a mechanical, radiological and/or chemical aggressor, which can affect these functions via common or specific mechanisms.

Quantification of auditory damage (whatever the type of aggressor) is currently mainly assessed by pure tone audiometry (TTA). However, apart from its subjectivity, LTA only takes into account the audibility of auditory signals - most often only the frequencies of the speech spectrum - and not an individual's ability to analyze and interpret these signals. From an objective point of view, apart from acoustic otoemissions, which have revolutionized neonatal hypoacusis screening, ototoxicity assessment suffers from the absence of reliable biomarkers, objective witnesses of a lesion more or less specific to the type of aggression.

Patients undergoing treatment for cancer are exposed to numerous iatrogenic risks that potentially impact quality of life, whether in a curative or palliative context. In terms of ototoxicity to anticancer drugs (mainly platinum salts), less than half of patients benefit from follow-up during and after exposure to these treatments, despite existing recommendations for cisplatin. There are no recommendations for other anti-cancer drugs (including other platinum salts and neurotoxic drugs) in the absence of clear evidence of a reduction in ATL scores, but the analysis of the literature shows above all a lack of screening for other forms of ototoxicity. Yet the potential consequences of failing to treat hypoacusis can be dramatic: a strong statistical link has been demonstrated, notably with the risk of dementia and mortality, which could also be impacted by the increased risk of falls caused by impaired balance due to vestibulotoxicity (the investigation of which is exceptional in the absence of a vertigo attack).

Areas for improvement include prevention recommendations, improved accessibility to audiometric monitoring, and the development of robust, time-saving diagnostic tests (in patients who often present with other iatrogenic or cancer-induced problems) - the main focus of our study - and the identification of effective treatments.

Vocal noise audiometry (VNA) is an ideal candidate for describing hearing impairment in cancer patients, because :

• Difficulty understanding speech in noise is one of the first signs of hearing loss in the case of peripheral disorders such as presbycusis (linked to ageing) or central auditory disorders, making it possible to account for ototoxicity linked to different mechanisms or damage to different compartments of the auditory system.
• AVB allows assessment under more ecological conditions, i.e., closer to situations encountered in everyday life, than those of tone or voice audiometry in silence, and in a less restrictive way (in terms of time taken to perform the test, and not requiring access to an audiometric booth).

However, the various reference techniques used to assess AVB differ in complexity (comprehension of sentences, syllables, dissyllabic words or logatomes), normative value, conditions and duration, making analysis of intelligibility functions all the more complex. It is generally accepted that logatomes enable us to test the periphery of the auditory system, whereas words and sentences involve mental substitution and the subject's semantic knowledge, and therefore enable us to test hearing in conditions closer to those encountered in everyday life.

In a population particularly exposed to the risk of fatigue and cognitive disorders (chemo-induced cognitive disorders), it is therefore necessary to carry out a study incorporating quality of life questionnaires to take these associated factors into account. In addition, depending on the treatment (and its intensity) and cancer location, different compartments of the auditory system may be affected by the risk of ototoxicity, requiring objective tests (at least on part of our study population) to assess the vestibule, inner ear - in particular to differentiate ciliopathy from cochlear synaptopathy - and middle ear, in order to clarify their respective involvement in functional loss.

The investigators propose to study these parameters in several patient populations, exposed - or not - to ototoxic and/or neurotoxic agents. Comparison within and between these different populations will enable us to assess the specificity and sensitivity of the subjective and objective tests proposed in this study, as well as the validity of composite biomarkers constructed from results on specific groups.

Inclusion criteria

• Age 18 and over
• Registered with social security
• Signed consents
• Absence of presbycusis prior to cancer treatment (groups A and C)
• No known presbycusis (group B)
• Previous exposure to an ototoxic/neurotoxic agent (group A)
• Indication for initiation of ototoxic/neurotoxic therapy (group C)

Exclusion criteria

• - Subjects deprived of liberty
• Subjects unable to read or write the French language
• Pregnant and breast-feeding women
• Previous treatment for ototoxicity
• History of bilateral auditory pathology, in particular otosclerosis, perilymphatic fistula, ruptured tympanic membrane, autoimmune hearing loss, acoustic neuroma.
• History of severe head trauma (Glasgow Coma Score <= 8)
• Abnormal otoscopy or tympanometry In addition for group B
• Previous chemotherapy
• Previous ENT radiotherapy
• Ongoing ototoxic drug therapy (quinine, diuretics, aminoglycosides, aspirin, NSAIDs) or corticosteroid therapy