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).