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• Visit the clinic once every 2 weeks for checkups and tests The goal of this clinical trial is to learn if systematic hearing tests (eg fonctional assesment, electrophysiology and seric biomarkers) can diagnose hidden hearing loss or vestibular troubles in a population of patients treated for cancer; population study will include different population in terms of sex/gender, age, medical condition (cancer patients treated with surgery alone and/or radiotherapy and/or chemotherapy, and healthy volunteers).
The main question it aims to answer is:
• To assess the ototoxicity of anticancer drugs using a combination of auditory functional tests (including speech audiometry in noise), vestibular test , plasmatic samples and electrophysiological measures.
Participants will be studied:
Either only after exposition (single visit) Or before, during and after the exposition to potential otototoxic agents with a 4 times Visit the clinic checkups and tests (one before, two while ongoing potential ototoxic agents and 1 post exposition)
Participants will complete questionnaires, undergo audiometric and electrophysiological tests, and their routine biomedical data will be studied, without any modification of the routine care (planned 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 :
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A:Previously exposed to CISPLATIN with significant ATL damage | Groupe A |
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| A:Previously exposed to CISPLATIN without significant ATL damage | Groupe A |
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| A:Previously exposed to cochlear RADIOTHERAPY with significant ATL damage | Groupe A |
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| A:Previously exposed to cochlear RADIOTHERAPY WITHOUT significant ATL damage | Groupe A |
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| A:Previously exposed to cochlear RADIOTHERAPY & CISPLATIN with significant ATL damage | Groupe A |
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| A:Previously exposed to cochlear RADIOTHERAPY & CISPLATIN WITHOUT significant ATL damage |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Auditory, vestibular and electrophysiological investigations | Diagnostic Test | otoacoustic emissions, electrocochleography, vocal audiometry in noise and high-frequency tonal audiometry, impedancemetry |
| Measure | Description | Time Frame |
|---|---|---|
| Descriptive statistics for audiometry of the various groups | Percentage of correct consonant identification as a function of signal-to-noise ratio for speech audiometry in noise | Day 0-Day1 (groups A, B, C) & Day 2, Day 0+7-14-21, Day 0+180-270 (for group C) |
| Descriptive statistics for electrophysiological tests of the various groups | amplitudes of the acoustic distortion products collected during the measurement of induced acoustic otoemissions | Day 0-Day1 (groups A, B, C) & Day 2, Day 0+7-14-21, Day 0+180-270 (for group C) |
| Descriptive statistics for protein analyses of the various groups | Concentration of selected proteins in plasma (/mL) | Day 0-Day1 (groups A, B, C) & Day 2, Day 0+7-14-21, Day 0+180-270 (for group C) |
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Inclusion Criteria:
Exclusion Criteria:
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patients treated, not treated or to be treated for cancer or hematologic recquiring neurotoxic treatment
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| François-Régis FERRAND | Contact | 0178651249 | francois-regis.ferrand@def.gouv.fr |
| Name | Affiliation | Role |
|---|---|---|
| François Régis FERRAND | IRBA, 1 place Valérie André, 91 223 Brétigny-sur-Orge cedex | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| HIA Bégin | Recruiting | Paris | France |
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| ID | Term |
|---|---|
| D000081015 | Ototoxicity |
| ID | Term |
|---|---|
| D004427 | Ear Diseases |
| D010038 | Otorhinolaryngologic Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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proteins
Groupe A |
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| A:Previously exposed to OXALIPLATIN | Groupe A |
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| A:Previously exposed to CARBOPLATIN | Groupe A |
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| A:Previously exposed to TAXANES | Groupe A |
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| A:Previously exposed to VINCALCALOIDS | Groupe A |
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| A:Previously exposed to other neurotoxicant | Groupe A |
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| B:Patients cured of cancer without ototoxic or neurotoxic exposure | Groupe B |
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| B:Companions without ototoxic or neurotoxic exposure | Groupe B |
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| A:Hyperacusic patients following cancer treatment | Groupe A |
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| A:Tinnitus patients following cancer treatment | Groupe A |
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| A:Patients with vestibular disorders following cancer treatment | Groupe A |
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| C:Patients with an indication for CISPLATIN recruited prior to any treatment | Groupe C |
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| C:Patients indicated for cochlear radiotherapy and recruited prior to treatmen | Groupe C |
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| C:Patients with indication for CISPLATIN and cochlear radiotherapy recruited prior any treatment | Groupe C |
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| C:Patients with an indication for OXALIPLATIN treatment recruited prior to any treatment | Groupe C |
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| C:Patients with indication for CARBOPLATIN recruited prior to any treatment | Groupe C |
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| C:Patients with indication for TAXANES therapy recruited prior to any treatment | Groupe C |
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| C:Patients with indication for VINCALCALOIDES or other neurotoxicant | Groupe C |
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| Biologic investigations; seric proteins | Diagnostic Test | seric proteins |
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| D064420 | Drug-Related Side Effects and Adverse Reactions |
| D064419 | Chemically-Induced Disorders |
| D011832 | Radiation Injuries |
| D014947 | Wounds and Injuries |