Prognostic factors of late ototoxicity outcomes.
According to our monitoring protocol, children treated with a second line carboplatin were those who shifted by cisplatin for the development of ototoxicity. Furthermore, children who underwent carboplatin therapy developed a SIOP grade 4 when subjected to prior or concurrent cranial irradiation for brain cancers. In fact, a significant difference (p = 0.002) existed between children who underwent exclusive carboplatin therapy and those who were subjected to exclusive carboplatin and radiotherapy. Irradiation independently, if combined with cisplatin or carboplatin, was associated with a greater ototoxicity SIOP grade (Fig. 2) with a p-value of 0.001. In addition, increasing age at treatment was correlated to greater hearing loss (p = 0.013) as seen in Fig. 3, even if the older children underwent irradiation (p = 0.012) as seen in Fig. 4. A severe late onset/progression ototoxicity was observed in 4/12 (33.3%) of patients treated by cisplatin and carboplatin and in 1/8 (12.5%) of patients treated by cisplatin alone (p > 0.05).
The relationship between cumulative dose and incidence of hearing impairment has been analysed. Despite it is well known that ototoxicity is dose-dependent [15], in this cohort late onset/progression of hearing loss was not significantly associated with the cumulative dose of platinum compounds (p > 0.05). In addition, no significant differences have been observed between genders (p > 0.05).
During follow-up, for five children (13.1%), all of which developed a progressive hearing loss, audiological counselling was performed to inform family on hearing aids indication and support decision on hearing rehabilitation. In two aided children the progression of hearing loss occurred after 5 years of follow-up (i.e. 72 and 84 months after the end treatment). All of them were affected by medulloblastoma and were treated with platinum-derived compounds and brain irradiation therapy. Namely, three children were treated with cisplatin but for the onset of ototoxicity during audiological monitoring, shifted to carboplatin. Taken together, these data demonstrate that the early onset of ototoxicity during chemotherapy and concomitant brain irradiation significantly affect long-term hearing outcomes. At the logistic regression analyses we observed that the irradiation was a significant prognostic factor for long-term ototoxicity outcomes with an Odds Ratio of 5.25 (CI: 1.26–21.86; p < 0.01).