Table 1.
Overview of the characteristics of cisplatin-induced ototoxicity studies
| Ross et al. [8] | Pussegoda et al. [9] | Yang et al. [19] | Lanvers-Kaminsky et al. [21] | Hagleitner et al. [20] | Xu et al. [22] | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Discovery | Replication | Radiation | No radiation | Spanish | Dutch | Discovery | Replication | ||||
| Number of patients | 53 | 109 | 155 | 213 | 41 | 63 | 38 | 110 | 238 | 68 | |
| Treatment protocols | NS | NS | NS | SJMB-96; SJMB-03 | SJNB-97; SJNB-05; SJOS-08 | COSS-82/86/91; NB-90; MAHO-94; MAKEI-89; HIT-91 | NS | NS | SJMB-96; SJMB-03 | SJYC-07 | |
| Age [y], median (range) | |||||||||||
| Cases | 5 (0–16) | 6 (0–16) | 6 (1–25) | 7.6 (3.1–21.6) | 3–12 (0.8–18) | 11.8 (5–22) | 11.5 (4–29) | 15 (5–40) | 8.5 ± 3.8b | <5c | |
| Controls | 9 (0–16) | 9.5 (1–19) | 11(0–18) | 10.1 (3.3–19.8) | 10 (2–13) | 13.9 (5–20) | 14 (7–28) | 15 (7–39.3) | 10.0 ± 4.3b | ||
| Sex, male [%] | 67.9 | 57.8 | 49.7 | 66.2 | 70.7 | 60.3 | 55.3 | 50.0 | 62.2 | NS | |
| Ethnicity [%] | Caucasian 79.0a | Caucasian 80.0 | White 78.9; non-white 21.1 | White 61.0; non-white 39.0 | NS | European ancestry | Dutch ancestry | Mixed population | NS | ||
| Cancer type | Various cancers | Various cancers | Various cancers | Medulloblastoma | Neuroblastoma; osteosarcoma | Various cancers (mainly osteosarcoma) | Osteosarcoma | Osteosarcoma | Brain tumors | Brain tumors | |
| Follow up duration [y], median (range) or fixed number of years | Cases: 3 (0–18); controls: 2 (0–15)a | Cases: 5 (0–25); controls: 2 (0–16) | 1.7 | NS | 2.5 | NS | 5.2 (0.06–21.3) | 2.1 | 2.1 | ||
| Craniospinal irradiation (%) | 17.0 | 19.3 | 18.1 | 100 | 0 | NS | 0 | 0 | 100 | NS | |
| Concurrent drug therapy | |||||||||||
| Use of ototoxic antibiotics | Yes | Yes | Yes | NS | NS | NS | Yes | No | NS | NS | |
| Vincristine (%) | 39.5a | 49.7 | 100 | 0 | NS | 15.8 | 4.5 | 100 | 100 | ||
| Otoprotectants (%) | NS | NS | NS | 90.6 | 0 | NS | 0 | 0 | >87 | 0 | |
| Cumulative cisplatin dose [mg/m2], median (range) | |||||||||||
| Cases | 360 (180–630) | 400 (120–720) | 400 (92–800) | 300 (77–313) | 390–618 (113–1105) | 412 (120–644) | 504 (120–870) | 500 (100–600) | 287 ± 35b | ±300c | |
| Controls | 360 (180–720) | 410 (100–700) | 400 (20–768) | 300 (79–312) | 254 (225–815) | 418 (161–560) | 515 (140–720) | 480 (200–600) | 289 ± 36b | ||
| Ototoxicity grading scale and comparison groups | CTCAE >1 vs CTCAE = 0 | CTCAE >1 vs CTCAE = 0 | CTCAE >0 vs CTCAE = 0 + ordinal and Chang score = 0 vs >0; 2a vs ≥2a and ordinal | CTCAE ordinal | NS | CTCAE >1 vs CTCAE = 0; SIOP Boston ototoxicity scale | Chang score >0 vs Chang score = 0 | ||||
| Outcome | |||||||||||
| Association COMT | Yes | Yes | No | No | No | No | Yes | No | No | No | |
| Association TPMT | Yes | Yes | Yes | No | No | No | No | No | No | No | |
CTCAE common terminology criteria for adverse events, NS not specified, SIOP international society of pediatric oncology, y years
aBased on combined cohort (discovery + replication) [9]
bMean and standard deviation given instead of median and range
cBased on combined cohort (cases + controls)