Chemoradiation-induced hearing loss remains a major concern for head and neck cancer patients

Figures & data

Table 1. Summary of pertinent studies on hearing loss and tinnitus in head and neck cancer patients treated with platinum chemotherapy and/or radiation.

Study	Number of patients	Study design	Hearing loss criteria	Tumour sites included	Treatments	Hearing loss reported	Tinnitus assessed?
Bhandare et al (2007)	325	Retrospective review	≥15 dB threshold shift	Sinonasal, nasopharynx	RT, CRT (chemotherapy unspecified)	RT: 18% incidence CRT: 30% incidence	No
Cheraghi et al (2015)	29	Prospective study	CTCAE	Sinonasal, nasopharynx, parotid salivary	RT, CRT (low-dose cisplatin)	RT: 51% incidence CRT: 77% incidence	No
Hitchcock et al (2009)	62	Prospective study using mathematical modelling	≥10 dB threshold shift	Sinonasal, nasopharynx, oral cavity, oropharynx, larynx, hypopharynx	RT, CRT (low-dose or high-dose cisplatin)	Low-dose cisplatin:<10 Gy RT: 9.5 dB at 8 kHz40 Gy RT: 18.9 dB at 8 kHz High-dose cisplatin:<10 Gy RT: 21.5 dB at 8 kHz40 Gy RT: 38.4 dB at 8 kHz	No
Hwang et al (2015)	92	Prospective study	Threshold shifts recorded over time	Nasopharynx	RT, CRT (cisplatin, regimen not specified)	RT: 19.9 dB mean threshold shift byAC, 10.6 dB threshold shift by BC CRT: 14.3 dB mean threshold shift byAC, 9.6 dB threshold shift by BC	No
Ishikawa et al (2015)	18	Prospective study	Threshold shift >20 dB at one frequency	Sinonasal, nasopharynx, oropharynx, larynx, hypopharynx	RT with cisplatin (intra-arterial + sodium thiosulphate or high-dose intravenous)	RT + intra-arterial cisplatin: hearingloss criteria noted for meanthreshold shifts at 8 and 10 kHz RT intravenous, high dose cisplatin:hearing loss criteria noted for meanthreshold shifts at 8, 10 and 12 kHz	Yes
Lee et al (2015)	211	Prospective study	LENT-SOMA criteria for tinnitus	Nasopharynx, larynx, hypopharynx, oropharynx, oral cavity	RT	11.6% developed tinnitus	Yes
Low et al (2006)	115	Randomised, single-blinded, controlled trial of RT vs. CRT	Change in median thresholds for treatment group	Nasopharynx	RT vs. CRT (high-dose cisplatin)	CRT group had worse median thresholds at 0.5, 1, 2, and 4 kHz	No
Mujica-Mota et al (2013)	N/A	Systematic review of 20 publications	Variable	Primarily nasopharynx, parotid salivary	RT (variable techniques)	Incidence ranged from 0 to85% from 0.5 to 4 kHz, 27–95% in frequencies >4 kHz	No
Niemensivu et al (2016)	22	Prospective study	>10 dB threshold shift at 4 and 8 kHz or in PTA	Sinonasal, nasopharynx, oral cavity, oropharynx, larynx, hypopharynx	CRT (low-dose cisplatin)	13.6% incidence	Yes
Pan et al (2005)	35	Prospective study	Mean threshold shifts	Sinonasal, salivary gland, nasopharynx, oral cavity, oropharynx, skin	RT, CRT (chemotherapy not specified)	Mean threshold shifts of 8 dB at 2–4 kHz, 17.5 dB at 8 kHz after 24 months	No
Pearson et al (2006)	37 (15 with pre-/post-treatment audiograms)	Retrospective study	10 dB or greater threshold shift in PTA or at 4 or 8 kHz	Sinonasal, nasopharynx, oral cavity, oropharynx, larynx, hypopharynx	CRT (high-dose cisplatin)	53% incidence of change in PTA 100% incidence of change at 4 kHz 87% incidence of change at 8 kHz	Yes
Rades et al (2008)	128	Retrospective study	CTCAE	Nasopharynx, oral cavity, oropharynx, larynx, hypopharynx	CRT (high-dose cisplatin or cisplatin/5-FU)	Two patients in high-dose cisplatin group with grade 2–3 ototoxicity	No
Theunissen et al (2014)	158 (67 with data at 4.5 years)	Prospective study	CTCAE	Oral cavity, oropharynx, hypopharynx	CRT: intra-arterial or intravenous cisplatin	Intra-arterial cisplatin: 68% incidence (4.5 years) Intravenous cisplatin: 81% incidence at 4.5 years	No
Theunissen et al (2015a)	N/A	Systematic review of 21 publications	Variable	Variable	RT, CRT (variable)	Incidence ranging from 17 to88% depending on study and criteria used	No
Theunissen et al (2015b)	156	Retrospective study to create predictive model of hearing loss	BC hearing thresholds	Not specified	CRT (high-dose cisplatin)	N/A: predictive model created to predict hearing loss based on baseline thresholds, cumulative cisplatin dose and radiation dose to the cochlea	No
Zuur et al (2007a)	146	Retrospective study	Threshold shift ≥5 dB in PTA	Oral cavity, oropharynx, larynx, hypopharynx	CRT (intra-arterial cisplatin + sodium thiosulphate)	20% incidence	No
Zuur et al (2007b)	158	Randomized phase III trial	CTCAE	Oral cavity, oropharynx, hypopharynx	CRT (intra-arterial cisplatin vs. intravenous cisplatin + sodium thiosulphate)	Intra-arterial cisplatin: 91% incidence Intravenous cisplatin: 88% incidence	No

RT: radiation therapy; CRT: chemoradiation therapy; AC: air conduction; BC: bone conduction; PTA: pure tone average.

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Cheraghi S., Nikoofar P., Fadavi P., Bakhshandeh M., Khoie S., et al. 2015. Short-term cohort study on sensorineural hearing changes in head and neck radiotherapy. Med Oncol, 32, 200.

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Hitchcock Y.J., Tward J.D., Szabo A., Bentz B.G. & Shrieve D.C. 2009. Relative contributions of radiation and cisplatin-based chemotherapy to sensorineural hearing loss in head-and-neck cancer patients. Int J Radiat Oncol Biol Phys, 73, 779–788.

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Hwang C.-F., Fang F.-M., Zhuo M.-Y., Yang C.-H., Yang L.-N., et al. 2015. Hearing assessment after treatment of nasopharyngeal carcinoma with CRT and IMRT techniques. BioMed Res Int, 2015, 769806.

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Ishikawa E., Sugimoto H., Hatano M., Nakanishi Y., Tsuji A., et al. 2015. Protective effects of sodium thiosulfate for cisplatin-mediated ototoxicity in patients with head and neck cancer. Acta Oto-Laryngologica, 135, 919–924.

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Lee T.F., Yeh S.A., Chao P.J., Chang L., Chiu C.L., et al. 2015. Normal tissue complication probability modeling for cochlea constraints to avoid causing tinnitus after head-and-neck intensity-modulated radiation therapy . Radiat Oncol, 10, 194.

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Low W.K., Toh S.T., Wee J., Fook-Chong S.M.C. & Wang D.Y. 2006. Sensorineural hearing loss after radiotherapy and chemoradiotherapy: a single, blinded, randomized study. J Clin Oncol, 24, 1904–1908.

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Mujica-Moto M., Waissbluth S. & Daniel S.J. 2013. Characteristics of radiation-induced sensorineural hearing loss in head and neck cancer: a systematic review. Head Neck, 35, 1662–1668.

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Niemensivu R., Saarilahti K., Ylikoski J., Aarnisalo A. & Makitie A.A. 2016. Hearing and tinnitus in head and neck cancer patients after chemoradiotherapy. Eur Arch Otorhinolaryngol, 273, 2509–2514.

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Pan C.C., Eisbruch A., Lee J.S., Snorrason R.M., Ten Haken R.K., et al. 2005. Prospective study of inner ear radiation dose and hearing loss in head-and-neck cancer patients. Int J Radiation Oncology Biol Phys, 61, 1393–1402.

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Rades D., Fehlauer F., Sheikh-Sarraf M., Kazic N., Basic H., et al. 2008. Toxicity of two cisplatin-based radiochemotherapy regimens for the treatment of patients with stage III/IV head and neck cancer. Head Neck, 30, 235–241.

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Theunissen E.A., Zuur C.L., Lopez Yurda M., van der Baan S., Kornman A.F., et al. 2014. Cochlea sparing effects of intensity modulated radiation therapy in head and neck cancers patients: a long-term follow-up study. J Otolaryngol Head Neck Surg, 43, 30.

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Theunissen E.A., Bosma S.C., Zuur C.L., Spijker R., van der Baan S., et al. 2015a. Sensorineural hearing loss in patients with head and neck cancer after chemoradiotherapy and radiotherapy: a systematic review of the literature. Head Neck, 37, 281–292.

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Theunissen E.A., Zuur C.L., Jozwiak K., Lopez-Yurda M., Hauptmann M., et al. 2015b. Prediction of Hearing Loss Due to Cisplatin Chemoradiotherapy. JAMA Otolaryngol Head Neck Surg, 141, 810–815.

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Zuur C.L., Simis Y.J., Lansdaal P.E., Hart A.A., Rasch C.R., et al. 2007a. Risk factors of ototoxicity after cisplatin-based chemo-irradiation in patients with locally advanced head-and-neck cancer: a multivariate analysis. Int J Radiation Oncology Biol Phys, 68, 1320–1325.

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Zuur C.L., Simis Y.J., Lansdaal P.E., Hart A.A., Schornagel J.H., et al. 2007b. Ototoxicity in a randomized phase III trial of intra-arterial compared with intravenous cisplatin chemoradiation in patients with locally advanced head and neck cancer. J Clin Oncol, 25, 3759–3765.

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