Association Between Tinnitus and Hearing Loss in Locally Advanced Head and Neck Cancer Treated by Radiotherapy Alone or With Chemotherapy: a Prospective and Multicenter Study

Study Overview
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Brief Summary
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The aim of the AURACCO study is to evaluate the association between the onset of tinnitus and hearing loss in patients with locally advanced head and neck cancer treated by concomitant chemoradiotherapy or exclusive radiotherapy

Detailed Description
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Radiotherapy with or without concomitant chemotherapy is the standard of care for patients diagnosed with locally advanced head and neck cancer. This treatment is associated with many side effects, especially tinnitus and hearing loss affecting patients' quality of life. Theses toxicities are due to chemotherapy and radiotherapy, with a synergic effect. The effects of chemoradiotherapy on hearing loss are already well documented but very limited data are available on the onset of tinnitus. Currently, no study established a correlation between tinnitus and hearing loss after treatment by chemoradiotherapy or exclusive radiotherapy. The main question we aim to answer is whether the development of tinnitus during treatment can be a precursor to hearing loss? Clinical data will be collected prospectively in 4 centers in Paris (Hôpital Tenon, Hôpital La Pitié-Salpêtrrière, Hôpital Saint-Louis and Hôpital Européen Georges Pompidou) to collect : Patient data : Birth date (age at diagnosis) Tobacco use (active : yes/no, quantity in pack-year) Alcohol use (active : yes/no, quantity in g/day) Sex Disease data : Primitive site (oral cavity, nasopharynx, oropharynx, larynx, sinus, salivary gland, carcinoma with unknown primitive) Histological type HPV status TNM stage Data at diagnosis Treatment data : Post-operative situation (yes/no) Radiotherapy dose received and number of fraction Mean and max doses received in Gy on the right and left cochleas Other otototoxic treatment taken during radiotherapy Evaluation data : Tinnitus evaluation (using SOMA-LENT criteria) Audiogram with measures at 0,25, 0,5, 1, 2, 4, 6, 8, 10 and 12,5 kHz Check for hearing microloss If tinnitus present : acouphénométrie If hearing aid fitting indication : APHAB (Abbreviated Profile of Hearing Aid Benefit) questionnaire

Official Title
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Association Between Tinnitus and Hearing Loss in Patients With Locally Advanced Head and Neck Cancer Treated by Concomitant Chemoradiotherapy or Exclusive Radiotherapy: a Prospective and Multicenter Study

Conditions
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Head Cancer, Neck Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with locally advanced or post-operative ENT cancer with high risk of recurrence Patient ≥ 18 years Absence of prior chemotherapy or radiotherapy Patient eligible for chemotherapy with cisplatin according to the standard regimen: radiotherapy delivering 60-70 Gy in 30-35 fractions spread over 6 to 7 weeks associated with chemotherapy with cisplatin 100 mg/m2 every 3 weeks (i.e. at week 1, 4 and 7) Patient ineligible for cisplatin chemotherapy receiving: Either exclusive radiotherapy (age > 70 years, contraindication: renal failure, patient wearing a device): radiotherapy delivering 60-70 Gy in 30-35 fractions spread over 6 to 7 weeks. either chemoradiotherapy with a chemotherapy protocol different from the standard scheme (due to a contraindication to cisplatin): radiotherapy delivering 60-70 Gy in 30-35 fractions spread over 6 to 7 weeks associated with non-standard chemotherapy ototoxic (cetuximab or carboplatin-5FU) Exclusion Criteria: Tinnitus grade ≥ 2 according to the SOMA-LENT scale Patient fitted for hearing disorders Significant cognitive disorders that may compromise the performance of the various assessments Patients treated with weekly cisplatin Patient's refusal to participate in research

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients treated by chemoradiotherapy with high dose of cisplatin<br>radiotherapy 60-70 Gy in 30-35 fractions with concomitant chemotherapy by cisplatin 100 mg/m2 every 3 weeks (week 1, 3 and 7) | |
| Patients treated with exclusive radiotherapy or radiotherapy with non-ototoxic chemotherapy<br>patient ineligible for chemotherapy with cisplatin: exclusive radiotherapy: 60-70 Gy in 30-35 fractions radiotherapy with a non-ototoxic chemotherapy (due to contraindication to cisplatin): 60-70 Gy in 30-35 fractions | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association between the onset of tinnitus and hearing loss at 3 months after treatment | Evaluation of the tinnitus on each ear. Hearing loss is defined as a loss of more than 20 dB compared to the measurement made at inclusion | 3 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tinnitus incidence | According to Subjective, Objective, Management, Analytic- Late Effects Normal Tissue scales :SOMA-LENT scale (grade 1 to 4). | at inclusion, at 3 weeks, at 6 weeks, 3 months after treatment, 6 months, 12 months and 18 months | 
| Hearing loss incidence | audiogram with measures at 0,25, 0,5, 1, 2, 4, 6, 8, 10 and 12,5 kHz | at inclusion, at 3 weeks, 6 weeks, 3 months after treatment, 6 months, 12 months and 18 months | 
| Association between the onset of tinnitus and/or hearing loss and quality of life | Evaluation quality of life (Tinnitus Handicap Inventory) | at inclusion, at 3 weeks, 6 weeks, 3 months after treatment, 6 months, 12 months and 18 months | 
| Association between the onset of tinnitus and/or hearing loss and quality of life | Evaluation quality of life: EVA intensity and discomfort | at inclusion, at 3 weeks, 6 weeks, 3 months after treatment, 6 months, 12 months and 18 months | 
| Association between the onset of tinnitus and/or hearing loss and quality of life | Evaluation quality of life: EQ-5D-5L questionnaire | at inclusion, at 3 weeks, 6 weeks, 3 months after treatment, 6 months, 12 months and 18 months | 
| Evolution of hearing disorders (tinnitus and/or hearing loss) | using SOMA-LENT criteria and audiogram | at inclusion, at 3 weeks, 6 weeks, 3 months after treatment, 6 months, 12 months and 18 months | 
| Association between radiotherapy dose received on the cochlea and the onset of tinnitus | mean dose and max dose | 3 months after treatment | 
| Association between radiotherapy dose received on the cochlea and hearing loss | mean dose and max dose | 3 months after treatment | 
| Association between cisplatin dose received and the onset of tinnitus and/or hearing loss | dose in mg/m2 | 3 months after treatment | 
| Quality of life after hearing aid fitting in patients requiring hearing aid during/after treatment | APHAB (Abbreviated Profile of Hearing Aid Benefit) questionnaire | at 3 weeks, 6 weeks, 3 months after treatment, 6 months, 12 months and 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cisplatin, Ototoxicity, Head and neck cancer, HNSCC, Undifferentiated nasopharyngeal cancer, UCNT, Salivary gland cancer, Radiotherapy, Chemoradiotherapy, Radiochemotherapy, Chemotherapy, Tinnitus, Hearing loss