Long-term audiologic follow-up of carboplatin-treated children with retinoblastoma

Figures & data

Table 1. Current overview on carboplatin-induced ototoxicity in retinoblastoma patients.

Study	Qaddoumi et al. 2012^20	Liberman et al. 2011^26	Bhagat et al. 2010^24	Jehanne et al. 2009^25	Lambert et al. 2008^27	Friedman et al. 2000^14	Smits et al. 2006^1	Current study
No. of patients	60	15	10	175	116	47	25	22
Ototoxicity (no. of patients)	10	1	None	8	None	None	None	1
Follow-up (months)	73	NA	NA	60	40	13	25	139
Mean age first carboplatin dose (months)	8.6ª	19.2	7.6	8	10	5.5	7^c	11^d
Mean cumulative dose (mg/m^2)	3850	2538	1660	2880	3348	3360	2240	2240
Mean number of carboplatin courses	8	NA	4	5	6	6	5	5
Audiologic methods	NA	TEOAE	DPOAE	OAE; PTA	ABR; OAE; PTA	NA	OAE; VRA; PA	PTA
Up to frequecy (kHz)	NA	NA	8	8	NA	NA	NA	16
Grading system	CCG; Brock; NCI-CTCAE	Brock	NA	Brock	NA	NA	NA	Brock; SIOP
Confounders:
Ototoxic medication	NA	NA	NA	Yes	Yes	Yes	None	Yes
Cisplatin administration	NA	None	NA	None	NA	NA	None	None
Renal failure	Low GFR^b	NA	NA	Yes	NA	NA	None	Yes

ªMean age since start treatment, not specifically since start carboplatin.

^bThe 10 children with hearing loss had a mean GFR of 44 ml/min/m^{2 (29 −69.7)}.

^cMean age is based on start of treatment.

^dMean age is based on start of carboplatin treatment.

CCG, Children’s Cancer Group; HL, hearing loss; NCI-CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; NA, not available/not applicable; PTA, pure-tone audiogram; OAE, otoacoustic emission; DPOAE, distortion product otoacoustic emission; TEOA, transient evoked otoacoustic emissions; VRA, visual reinforcement audiometry; PA, play audiometry; kHz, kiloHertz; SIOP, International Society of Paediatric Oncology; ABR, auditory brainstem response.

Table 2. Overview according to the systems used.

Grade	Brock system^a	SIOP Boston ototoxicity scale^b
0	< 40 dB HL at all frequencies	≤ 20 dB HL at all frequencies
1	≥ 40 dB HL at 8 kHz only	> 20 dB HL above 4 kHz
2	≥ 40 dB HL at 4 kHz and above	> 20 dB HL at 4 kHz and above
3	≥ 40 dB HL at 2 kHz and above	> 20 dB HL at 2 kHz or 3 kHz and above
4	≥ 40 dB HL at 1 kHz and above	> 40 dB HL at 2 kHz and above

^aScale based on absolute hearing loss; ^bScale based on bone conduction or on air conduction with a normal tympanogram.

dB, decibel; kHz, kilohertz; HL, hearing loss; SIOP, International Society of Paediatric Oncology.

Table 3. Patient characteristics of the included and excluded children.

Patient	Gender	RB	Age at therapy initiation (months)	Regimen^a	Number of courses	Cumulative carboplatin dose (mg/m^2)	Follow-up (years)	Age at most recent test (years)	Number of audiologic tests	Highest frequency tested (kHz)	Ototoxic medication^b	Current hearing status^c
1	F	BI	2	D	5	2250	14	15	6	12	None	0
2	M	BI	15	B	3	900	13	14	8	12	None	0
3	F	BI	35	C	6	3360	16	19	7	16	None	0
4	F	BI	13	B	3	1350	11	12	4	16	None	0
5	F	UN	33	B	3	1350	17	20	5	16	None	0
6	F	UN	10	B	3	1350	11	12	4	12	None	0
7	M	UN	15	B	3	1350	16	18	7	16	None	0
8	M	BI	4	C	8	2660	9	10	7	12	None	0
9	F	BI	1	C	6	1800	16	16	9	16	None	1
10	M	BI	13	C	4	1805	11	12	8	16	A + G	2
11	M	UN	43	B	3	1350	14	18	6	16	None	0
12	F	BI	6	A	3	1680	10	11	6	16	None	0
13	M	BI	0.7	A + B	4	1720	10	11	7	14	None	0
14	F	BI	0.8	A	6	3360	11	11	5	14	None	0
15	F	BI	0.5	A	10	5600	12	13	9	16	G	0
16	M	BI	7	A	5	2800	9	10	7	12	G	0
17	M	BI	4	A	4	2240	13	13	9	16	None	0
18	F	BI	8	A	5	2800	5.4	6.4	7	16	None	0
19	M	UN	16	B	3	1050	6	8	7	12	None	0
20	F	BI	31	A	4	2240	8	11	5	14	None	0
21	F	BI	2	A	7	3760	12	12	8	16	None	0
22	M	BI	0.7	A	8	4480	12	13	8	16	None	0
23^d	M	BI	28	D	9	3150	1 month	3	4	8	None
24^d	F	BI	4	A	3	1680	1	1.5	3	8	None
25^d	M	BI	36	D	3	6580	2	5	3	8	None

^aChemotherapy regimens as in Table II of Smits and colleagues, 2006¹; ^bFor instance aminoglycosides, glycopeptides, cisplatin, loop diuretics; ^c0 = normal hearing; 1 = mixed hearing loss; 2 = bilateral sensorineural hearing loss; ^dCharacteristics of excluded children.

F, female; M, male; kHz, kiloHertz; RB, retinoblastoma; UN, unilateral; BI, bilateral; A, aminoglycosides; G, glycopeptides.

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