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ORIGINAL ARTICLE
Year : 2013  |  Volume : 19  |  Issue : 3  |  Page : 136-139

The study of auditory effects after concomitant radiotherapy and chemotherapy in patients with head and neck cancer


Department of Otorhinolaryngology and Head and Neck Surgery, Goa Medical College, Bambolim, Goa, India

Date of Web Publication2-Sep-2013

Correspondence Address:
Harish Chander Goel
Department of Otorhinolaryngology and Head and Neck Surgery, Goa Medical College, Bambolim, Goa - 403 202
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-7749.117472

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  Abstract 

Aims and Objectives: The objective of this study was to assess the prevalence and patterns of hearing loss after concomitant radiochemotherapy in patients enrolled in a larynx preservation protocol. Materials and Methods: The study comprised of audiological evaluation of 30 patients prior to and at 1, 3, and 6 months after treatment using pure tone audiometry and impedance audiometry. Results: At the end of 6 months, 43.33% suffered sensorineural hearing loss (SNHL), 8.33% conductive hearing loss, 16.67% mixed hearing loss, and 6.67% showed improvement in hearing. Discussion: The possible mechanism for hearing loss are discussed and compared with the result of such studies in literature. Conclusion: There exist a small but definite potential risk of hearing loss after concomitant radiotherapy and chemotherapy in patients with head and neck cancer.

Keywords: Audiological, Audiometry, Concomitant radiochemotherapy, Head and neck cancer, Sensorineural


How to cite this article:
Goel HC, Laad P, Naik A. The study of auditory effects after concomitant radiotherapy and chemotherapy in patients with head and neck cancer. Indian J Otol 2013;19:136-9

How to cite this URL:
Goel HC, Laad P, Naik A. The study of auditory effects after concomitant radiotherapy and chemotherapy in patients with head and neck cancer. Indian J Otol [serial online] 2013 [cited 2019 Jun 18];19:136-9. Available from: http://www.indianjotol.org/text.asp?2013/19/3/136/117472


  Introduction Top


The worldwide incidence of head and neck cancers exceeds half a million cases and is ranked fifth most common malignancy in the world and the commonest malignancy in India. Radiotherapy is a major treatment modality for head and neck cancers and is used either exclusively or combined with surgery or chemotherapy. The treatment of these locally advanced head and neck cancers is a challenge in view of the limited response to radiation monotherapy in case of inoperable disease and the need to preserve vital functions in case of operable lesions. A combination of radiotherapy and concomitant chemotherapy (preferably cisplatin-based) shows improved response rates and allows for organ preservation. The temporal bone is frequently involved in the radiation field of head and neck cancers. Long-term survivors of cancers of the head and neck can experience sensorineural hearing loss (SNHL) induced by radiation, chemotherapy, or a combination of both.

Borsanyi et al., [1] and Leach [2] demonstrated that SNHL occurs following irradiation due to direct effect of radiation on post mitotic cells of sensory epithelium and altered vascular physiology interfering with cochlear supply of oxygen and metabolites. Conductive hearing loss was attributed to mucosal vascular dilatation and  Eustachian tube More Details edema with subsequent middle ear effusion and hemorrhage. Ossicular necrosis was also found to be a cause of conductive hearing loss secondary to radiotherapy.

In recent years, chemotherapy has increasingly been used in combination with radiotherapy for treatment of head and neck cancers. Cisplatin, 5-fluorouracil, paclitaxel, bleomycin, etc., are commonly used drugs. SNHL is a known complication of cisplatin treatment. [3],[4],[5] Thus, concurrent treatment with cisplatin with radiotherapy may add to the radiation induced SNHL. The objective of this study was to investigate the prevalence and patterns of hearing loss after concomitant radiochemotherapy in head and neck cancers.


  Materials and Methods Top


The present study comprised of audiological evaluation of 30 patients who presented in the Department of Ear, Nose, and Throat of our hospital which is a tertiary care hospital with advanced head and neck malignancy and were planned to treat with radiochemotherapy. Prior to treatment a detailed otological examination was done in each patient along with Head and Neck examination and investigations were carried out. Patients with history of hearing loss or ear diseases were excluded from the study. The study consisted of 25 males and five females with ages ranging from 26 years to 69 years. The site of lesion in relation to number of patients studied is shown in [Table 1].
Table 1: Site of the lesion in relation to the number of patients studied

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These patients were treated with cobalt-60 teletherapy unit and received doses between 60-65 Gy in 30-33 fractions over 6-6.5 weeks. They also received cisplatin 20 mg/m 2 concurrent with radiotherapy once weekly for 6 weeks.

Pure tone audiograms (PTA) were obtained before treatment to assess individual baseline hearing thresholds. The hearing assessment included audiologic history, air and bone conduction threshold, and impedance audiometry. Testing was performed in a sound treated audiometric testing suite. Masking was used, if indicated. Bone and air conduction thresholds (250-4,000 and 250-8,000 Hz; respectively) were obtained using a pure tone audiometer (Arphi Diagnostic 2001 model). Impedance audiometry (Maico MI 34) was performed in patients showing conductive hearing loss. Posttreatment audiograms were obtained at various intervals 1, 3, and 6 months after completion of radiochemotherapy. Patients with audiograms less than 6 months after completion of radiochemotherapy were excluded.

Ototoxicity was measured using intrasubject audiogram comparisons. Each patient served as his/her control with the pretreatment audiogram serving as the baseline. Hearing threshold change was determined relative to each patient's baseline.


  Results Top


Results of type of hearing loss as analyzed at 6 months posttreatment are as shown in [Table 2].
Table 2: Audiometric results 6 months after concomitant radiochemotherapy

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Results of degree of hearing loss at 1, 3, and 6 months after treatment are as shown in [Table 3].
Table 3: Degree of hearing loss posttreatment

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Impedance audiometry showed altered tympanogram type B/C in five patients (16.67%) and acoustic reflexes were absent in 2 patients (6.67%).

The frequency range, which showed maximum hearing loss was between 4,000 and 8,000 Hz. Maximum loss occurred at 8,000 Hz in almost 35 ears (75%). Least affected frequency was 2,000 Hz in 23 ears (38.33%).


  Discussion Top


As combined modality therapy becomes the standard of care in the treatment of many head and neck cancers, there are increasing concerns of ototoxicity, as cisplatin and radiation are known to cause hearing loss independently.

Irreversible hearing loss as a consequence of cisplatin administration has been closely investigated, with numerous causative factors identified, including: The cumulative dose of cisplatin received, mode of drug administration, concurrent use of aminoglycosides and diuretics, and renal dysfunction.

Whereas; the precise mechanism of radiation-induced hearing loss is obscure, studies of irradiated animal cochleae have also shown ultrastructural changes in the outer hair cells (OHCs) and stria vascularis of the basal turn. [6]

Whereas; many have focused on the individual toxicities of radiation and cisplatin on the auditory apparatus, few clinical studies have evaluated the synergistic ototoxic effects of radiation and cisplatin chemotherapy. Some have demonstrated that combined modality protocols with cochleotoxic compounds such as cisplatin may increase the detrimental effects of radiation on the inner ear, [7],[8],[9],[10],[11],[12] with SNHL both immediate and delayed. [13],[14] In examining the results, it is thus important to differentiate between radiation- and cisplatin-induced ototoxicity.

Typically, cisplatin ototoxicity occurs acutely, with effects seen as early as 3-4 days after administration. Audiologic threshold shifts are greatest initially in the high frequencies, with threshold changes extending to lower frequencies as the duration of cisplatin administration lengthen. The audiometric abnormalities are typically bilateral, irreversible, and progressive. As the cumulative dose of cisplatin reaches 200 mg/m 2 , significant hearing loss begins to occur in the range of 6,000-8,000 Hz and the 2,000-4,000 Hz range also appears susceptible to changes. [3],[4],[5] In our series, patients received a cumulative cisplatin dose of 120 mg/m 2 .

Radiation-induced ototoxicity, meanwhile, is typically evident 6-12 months after completion of radiotherapy. [15],[16],[17] Predisposing factors include older age and coexisting otitis media. [16],[18],[19] Grau et al., [18] and Chen et al., [20] suggested cochlea tolerance doses in human patients of 50 and 60 Gy, respectively, showing significant increase of severe SNHL in patients receiving greater than the reported thresholds. Recently, Honoré et al., [21] and Pan et al., [22] showed increased risk of SNHL with increased patient age and decreased pretherapeutic hearing level as well. Conversely, Liberman et al., [23] concluded that SNHL was not associated with total radiation dose or with dose to the ear region; the study was, however, limited by size (11 patients) and follow-up (audiograms range, 5-10 months). It is important to note that these observations were made in patients receiving radiation only and no chemotherapy.

In the study by Pan et al., [22] patients with various head and neck tumors were treated with radiotherapy alone; with ipsilateral mean cochlear doses ranging from 14.1-68.8 Gy and contralateral doses ranging from 0.4-31.3 Gy. An increase in the mean radiation dose to the inner ear was associated with increased hearing loss.

We have observed that average hearing loss ranged between 5-15 dB and frequency range between 4,000-8,000 Hz was maximally affected. SNHL occurred in 43.33% of patients, 16.67% had mixed hearing loss, and 8.33% had conductive hearing loss at 6 months after treatment. Borsanyi et al., [1] reported that 4,000 Hz showed greatest hearing loss and least affected frequency was 2,000 Hz. Novotony [24] also observed 8.4 dB loss localized in 4,000-8,000 Hz. Kwong et al., [16] in their study of hearing loss in patients treated with nasopharyngeal carcinoma with radiotherapy alone and with radiotherapy and cisplatin together reported SNHL for higher frequency in 43.1 and 54.8% patients, respectively.

In our study, we had five patients with conductive hearing loss. Postirradiation secretory otitis media is considered a complication of radiotherapy arising from Eustachian tube dysfunction, accounting for conductive hearing loss. [2],[25],[26] Two patients, who were having mild conductive deafness at the start of radiochemotherapy, had improvement in their hearing which we are unable to explain. Duration of our study was limited to 6 months, studies with longer follow-ups and with more number of patients are recommended to get clearer picture.


  Conclusion Top


The prevalence of hearing loss after radiochemotherapy for head and neck cancers is high; but, is mild and asymptomatic and severe hearing loss is gradual over years. Doctors and patients are less attentive to this ailment as it does not affect survival. Hearing loss is a small price to pay for cure of a malignant disease; but for patients with preexisting hearing loss, further loss can cause impairment in their daily functioning. Each patient undergoing concurrent radiochemotherapy should be counseled for the possibility of hearing loss or its deterioration.

 
  References Top

1.Borsanyi S, Blanchard CL, Thorne B. Effect of ionizing radiation on the ear. Ann Otol Rhinol Laryngol 1962;70:255-62.  Back to cited text no. 1
    
2.Leach W. Irradiation of the ear. J Laryngol Otol 1965;79:870-80.  Back to cited text no. 2
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3.Kopelman J, Budnick AS, Sessions RB, Kramer MB, Wong GY. Ototoxicity of high-dose cisplatin by bolus administration in patients with advanced cancers and normal hearing. Laryngoscope 1988;98:858-64.  Back to cited text no. 3
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4.Fausti SA, Schechter MA, Rappaport BZ, Frey RH, Mass RE. Early detection of cisplatin ototoxicity. Selected case reports. Cancer 1984;53:224-31.  Back to cited text no. 4
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5.Piel I, Meyer D, Perlia CP, Wolfe VI. Effects of cis-diamminedichloriplatinum (NSC-119875) on hearing function in man. Cancer Chemother Rep 1974;58:871-5.  Back to cited text no. 5
    
6.Akmansu H, Eryilmaz A, Korkmaz H, Sennaro g¢lu G, Akmansu M, GöÇer C, et al. Ultrastructural and electrophysiologic changes of rat cochlea after irradiation. Laryngoscope 2004;114:1276-80.  Back to cited text no. 6
    
7.Grau C, Overgaard J. Postirradiation sensorineural hearing loss: A common but ignored late radiation complication. Int J Radiat Oncol Biol Phys 1996;36:515-7.  Back to cited text no. 7
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8.Plowman PN. Post-radiation sensorineural hearing loss. Int J Radiat Oncol Biol Phys 2002;52:589-91.  Back to cited text no. 8
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9.Schell MJ, McHaney VA, Green AA, Kun LE, Hayes FA, Horowitz M, et al. Hearing loss in children and young adults receiving cisplatin with or without prior cranial irradiation. J Clin Oncol 1989;7:754-60.  Back to cited text no. 9
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10.Miettinen S, Laurikainen E, Johansson R, Minn H, Laurell G, Salmi TT. Radiotherapy enhanced ototoxicity of cisplatin in children. Acta Otolaryngol Suppl 1997;529:90-4.  Back to cited text no. 10
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11.Fukunaga-Johnson N, Sandler HM, Marsh R, Martel MK. The use of 3D conformal radiotherapy to spare the cochlea in patients with medulloblastoma. Int J Radiat Oncol Biol Phys 1998;41:77-82.  Back to cited text no. 11
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12.Huang E, Teh BS, Strother DR, Davis QG, Chiu JK, Lu HH, et al. Intensity-modulated radiation therapy for pediatric medulloblastoma: Early report on the reduction of ototoxicity. Int J Radiat Oncol Biol Phys 2002;52:599-605.  Back to cited text no. 12
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13.Sataloff RT, Rosen DC. Effects of cranial irradiation on hearing acuity: A review of the literature. Am J Otol 1994;15:772-80.  Back to cited text no. 13
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14.Fong RS, Beste DJ, Murray KJ. Pediatric sensorineural hearing loss after temporal bone radiation. Am J Otol 1995;16:793-6.  Back to cited text no. 14
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15.Ho WK, Wei WI, Kwong DL, Sham JS, Tai PT, Yuen AP, et al. Long-term sensorineural hearing deficit following radiotherapy in patients suffering from nasopharyngeal carcinoma: A prospective study. Head Neck 1999;21:547-53.  Back to cited text no. 15
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16.Kwong DL, Wei WI, Sham JS, Ho WK, Yuen PW, Chua DT, et al. Sensorineural hearing loss in patients treated for nasopharyngeal carcinoma: A prospective study of the effect of radiation and Cisplatin treatment. Int J Radiat Oncol Biol Phys 1996;36:281-9.  Back to cited text no. 16
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17.Fuss M, Debus J, Lohr F, Huber P, Rhein B, Engenhart-Cabillic R, et al. Conventionally fractionated stereotactic radiotherapy (FSRT) for acoustic neuromas. Int J Radiat Oncol Biol Phys 2000;48:1381-7.  Back to cited text no. 17
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18.Grau C, Moller K, Overgaard M, Overgaard J, Elbrønd O. Sensori-neural hearing loss in patients treated with irradiation for nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 1991;21:723-8.  Back to cited text no. 18
    
19.Oh YT, Kim CH, Choi JH, Kang SH, Chun M. Sensory neural hearing loss after concurrent cisplatin and radiation therapy for nasopharyngeal carcinoma. Radiother Oncol 2004;72:79-82.  Back to cited text no. 19
    
20.Chen WC, Liao CT, Tsai HC, Yeh JY, Wang CC, Tang SG, et al. Radiation-induced hearing impairment in patients treated for malignant parotid tumour. Ann Otol Rhinol Laryngol 1999;108:1159-64.  Back to cited text no. 20
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21.Honoré HB, Bentzen SM, Moller K, Grau C. Sensori-neural hearing loss after radiotherapy for nasopharyngeal carcinoma: Individualized risk estimation. Radiother Oncol 2002;65:9-16.  Back to cited text no. 21
    
22.Pan CC, Eisbruch A, Lee JS, Snorrason RM, Ten Haken RK, Kileny PR. Prospective study of inner ear radiation dose and hearing loss in head-and-neck cancer patients. Int J Radiat Oncol Biol Phys 2005;61:1393-402.  Back to cited text no. 22
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23.Liberman PH, Schultz C, Gomez MV, Carvalho AL, Pellizzon AC, Testa JR, et al. Auditory effects after organ preservation protocol for laryngeal/hypopharyngeal carcinomas. Arch Otolaryngol Head Neck Surg 2004;130:1265-8.  Back to cited text no. 23
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24.Novotony O. Effect of x-rays on cochlea of guinea pig. Arch Ital Otol Rinol Laringol 1951;62:15-9.  Back to cited text no. 24
    
25.Dias A. Effects on hearing of patients treated with irradiation of head and neck area. J Laryngol Otol 1966;80:276-87.  Back to cited text no. 25
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26.Young YH, Cheng PW, Ko JY. A 10 year longitudinal study of tubal function in patients with nasopharyngeal carcinoma after irradiation. Arch Otolaryngol Head Neck Surg 1997;123:945-8.  Back to cited text no. 26
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    Tables

  [Table 1], [Table 2], [Table 3]


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[Pubmed] | [DOI]



 

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