Audiological monitoring.
Audiological monitoring was performed in our Institution by the same team of physicians and audiologists. At least a yearly evaluation was scheduled in patients with normal hearing whereas a six-monthly evaluation was performed in patients with a hearing loss diagnosis. Accordingly, with our previous paper [15], audiological evaluation included otoscopy and tympanometry and acoustic reflex measurements in order to exclude middle ear pathology (Grason Stadler, Eden Prairie Minn., USA).
Pure-tone air conduction thresholds were evaluated at frequencies of 0.25, 0.5, 1, 2, 4 and 8 kHz in decibel hearing level (dB HL). Pure-tone bone conduction thresholds were assessed at frequencies of 0.25, 0.5, 1, 2 and 4 kHz to determine the type of the hearing impairment (i.e. conductive, sensorineural or mixed). Visual reinforcement audiometry was performed in a calibrated sound field or via earphones for children 6–30 months of age. Sound-field results reflect hearing in the better ear if there is a difference in hearing between ears. In general, frequencies at 0.5, 1, 2 and 4 kHz were obtained when visual reinforcement audiometry was used to measure hearing. Conditioned play audiometry (train show) was used for children able to cooperate (30 months to 5 years). Standard pure-tone audiometry was used for older children (>5 years) under standard conditions using an Amplaid 319 audiometer (Amplaid Inc., Milan, Italy) in a double-walled, sound-proof room testing conventional frequency ranges from 0.25 to 8 kHz (see www.asha.org/policy).
Auditory brain response (ABR) evaluation consisted of threshold searches using 100-µs clicks as well as tone bursts at 1, 2 and 4 kHz (GN Otometrics, Copenhagen, Denmark). Responses were obtained by averaged electroencephalic responses via three scalp electrodes positioned during sleep. We considered these examinations normal as their threshold was 20 dB HL bilaterally. Patients who had their baseline evaluations recorded by ABR where subsequently monitored by behavioural audiometry, and thus no patient underwent exclusive ABR evaluation.
Audiological records were examined and classified according to the SIOP (International Society of Pediatric Oncology) Boston ototoxicity scale (grade 0–4). Families of children received adequate and comprehensible information about side effects of the administered therapy and scheduled audiological monitoring and gave their written consent to perform the tests. All protocol procedures were approved by the Ethical Committee of Fondazione Policlinico Universitario A. Gemelli IRCCS (Number of protocols: 0019971/20- ID 3074).