Sub-analyses on the late onset/progression cases.
Median time of the late onset/progression of ototoxicity was 24 months by the end of treatment (range: 3–84 months).
In the group of five children with a “late onset hearing loss” (Median age 10years; range 4-12; male/female ratio 4), four children showed a SIOP grade 1-2 and only one child a SIOP grade 4 at the end of 5-year follow-up. In this group four patient were exposed to cisplatin (no one with a cumulative dose > 400 mg/sqm), and one to carboplatin therapy.
In the group of ten children (median age: 12.5 years; range: 2–18, male/female ratio was 2.33) that worsened over time a “progressive hearing loss”, eight children developed a SIOP grade 4 and 2 children a SIOP grade 1-2. In this group five patients (50%) were exposed to cisplatin plus carboplatin therapy (one with a cisplatin’s cumulative dose > 400 mg/sqm), one patient was exposed to cisplatin alone with a cumulative dose > 400 mg/sqm, and four patients were exposed to carboplatin plus cranial irradiation therapy.
These results demonstrated that proportion of patients with SIOP grade 4 hearing loss was significantly higher in patients with hearing loss at the end of chemotherapy compared with patients with new late onset of ototoxicity, respectively 8/10 (80%) versus 1/5 (20%) (p<0.05).
Finally, at the logistic regression analyses we observed that the presence of hearing loss at the end of treatment was a significant prognostic factor for long-term ototoxicity outcomes with an Odds Ratio of 7.2 (CI: 1.67–31.1; p < 0.01).