HEARING IMPAIRMENT IN NASOPHARYNGEAL CARCINOMA PATIENTS
Background and purpose
As the prognosis of nasopharyngeal carcinoma (NPC) has improved with the introduction of concurrent high-dose chemoradiotherapy (CRT), the prevention of side effects of CRT has become increasingly emphasized. Ear symptoms such as otitis media with effusion (OME) and progressive sensorineural hearing loss (SNHL) are major complications and seriously erode the quality of life of NPC patients. We retrospectively analyzed the factors affecting progressive SNHL in NPC.
Objective and methods
Fifty-three NPC patients were treated in Kumamoto University Hospital between April 1996 and December 2010. Follow-up pure-tone audiometry was performed in 58 ears of 29 patients (23 males and six females), who were then enrolled in this study. The mean age at diagnosis was 59.3 (range 18–86) years. The standard treatment protocol for NPC in our hospital is concurrent CRT, based on cis-diamminedichloroplatinum (II) (CDDP) and 5-fluorouracil (5-FU). Three subjects received radiotherapy (RT) alone due to patient factors and the others received concurrent CRT. We assessed the pre-treatment and time-dependent bone conductive hearing threshold and endoscopic findings of the ear. The mean hearing level was calculated as the hearing at (500 Hz + 1 kHz×2 + 2 kHz)/4 (dB). The NPC patients were classified into two groups based on the follow-up audiometry: the SNHL group had a > 10 dB increase in the bone-conduction hearing threshold (29 ears), and the non-SNHL group had a < 10 dB increment in the bone-conduction hearing threshold (15 ears). Fourteen ears were excluded because their bone-conduction hearing threshold was beyond the measuring limits of the audiometer at the start of CRT. Age, tumor stage according to the International Union Against Cancer (UICC) T category (6th edition, 2002), radiation dose to the cochlea, and total CDDP dose were compared between the two groups. Significance was analyzed using the Mann-Whitney U-test or chi-square test and p-values < 0.05 were considered to indicate significance.
Results
Age, local tumor stage, and pretreatment bone conductive hearing threshold differed significantly between the SNHL and non-SNHL groups. The mean age of the SNHL and non-SNHL groups was 66.0 (range 43–79) and 54.0 (range 18–72) years, respectively. The difference was significant (p = 0.0042, Mann-Whitney U-test). Figure 1 shows the patients’ UICC T categories. The proportions of T3 and T4 were 55.2% (SNHL) and 13.3% (non-SNHL), respectively. The proportion of locally advanced tumors (T3 and T4) was significantly larger in the SNHL group (p = 0.0075, χ2 test). The pretreatment bone-conduction hearing threshold also differed significantly between the two groups (Fig. 2). The median hearing level in the SNHL group was 25.0 (range 6.7–41.7) dB versus 6.7 (range 0–35.0) dB in the non-SNHL group (p = 0.0038, Mann-Whitney U-test). The radiation dose to the cochlea and total dose of CDDP did not differ significantly (Figs. 3 and 4). Persistent otorrhea after RT was observed in 15 ears in the SNHL group, while no patients in the non-SNHL group suffered from post-irradiation otorrhea. Fifteen ears in the SNHL group showed progressive deterioration of hearing over two years after RT or CRT (Fig. 5).
Fig. 1. T category according to the 6th UICC, 2006.
Fig. 2. Pretreatment BC threshold.
Fig. 3. Radiation dose to the cochle.
Fig. 4. Total CDDP dose.
Fig. 5. Time from the end of therapy to the onset of SNHL.
Discussion
Nasopharyngeal carcinoma is a common disease in East and Southeast Asians. Standard therapy is concurrent CRT. The radiation field extends from the skull base to the lower neck, and high-dose cisplatin-based chemotherapy is given simultaneously. Consequently, most NPC patients suffer from side effects. SNHL is one of the most common late complications, and occurs more than 80% of NPC patients, including non-complaining patients.1 It is reported that post-radiation SNHL is related to patient age.1–3 Our data also suggest that old age is a risk factor for post-treatment SNHL. Moreover, the condition of patients who have pretreatment SNHL tends to worsen after the treatment. Inner-ear fragility might be related to the post-treatment SNHL. Periodic audiometric examinations are important in post-treatment NPC patients.
In this study, the radiation dose to the cochlea and total dose of CDDP did not differ significantly between the SNHL and non-SNHL groups. There are numerous reports that radiation might be related to the postradiation SNHL, especially high-frequency SNHL.1–4 In our study, the prescribed irradiation dose was completed in all patients, so the median dose of radiation to the cochlea was similar: 58.8 Gy (SNHL) and 54.9 Gy (non-SNHL). Chen et al. recommend a mean cochlea radiation dose of < 47 Gy to control the ototoxicity of CRT for NPC patients.2 In our study, the radiation dose to 28 of 29 ears exceeded 47 Gy in the SNHL group. In comparison, five of 15 ears in the non-SNHL group had doses < 47 Gy. Such high-dose radiation to the cochlea might have led to the SNHL. To prevent late complications of RT, intensity-modulated radiation therapy (IMRT) is commonly used for NPC therapy. We started IMRT in 2008, but the mean radiation dose to the cochlea has not decreased (data not shown). A complete cure of their NPC is the most important issue for the patients, so there are practical limits to decreasing the radiation dose.
Continuous otorrhea has been suggested to be a risk factor for gradually progressive SNHL. RT causes immune or mucosal changes in the nasopharynx and middle ear,5 so many NPC patients are tormented by stubborn otorrhea. However, the treatment of post-radiation OME remains controversial. Tympanoplasty or grommet insertion was ineffective in some recalcitrant OME cases.6 As the prognosis of NPC has improved, more patients suffer from continuous otorrhea and progressive SNHL. Further investigation is needed to control post-radiation OME.
Conclusions
Our data suggest that inner ear fragility and persistent otorrhea are risk factors for progressive post-treatment SNHL. In addition, the radiation dose to the cochlea is related to SNHL. Unfortunately, there is no effective method for preventing post-treatment SNHL. This remains a future challenge.
References
1.Sumitsawan Y, Chaiyasate S, Chitapanarux I, et al. Late complications of radiotherapy for nasopharyngeal carcinoma. Auris Nasus Larynx 36:205–209, 2009
2.Chan SH, Ng WT, Kam KL, et al. Sensorineural hearing loss after treatment of nasopharyngeal carcinoma: a longitudinal analysis. Int J Radiation Oncology Biol Phys 73(5):1335–1342, 2009
3.Lee AWM, Ng WT, Hung WM, et al. Major late toxicities after conformal radiotherapy for nasopharyngeal carcinoma – patient-and treatment-related risk factors. Int J Radiation Oncology Biol Phys 73(4):1121–1128, 2009
4.Hitchcock YJ, Tward JD, Szabo A, Bentz BG, Shrieve DC. Relative contributions of radiation and cisplatin-based chemotherapy to sensorineural hearing loss in head-and-neck cancer patients. Int J Radiation Oncology Biol Phys 73(3):779–788, 2009
5.Young YH, Lu YC. Mechanism of hearing loss in irradiated ears: a long-term longitudinal study. Ann Otol Rhinol Laryngol 110(10):904–906, 2001
6.Liang KL, Su MC, Twu CW, Jiang RS, Lin JC, Shiao JY. Long-term result of management of otitis media with effusion in patients with post-irradiated nasopharyngeal carcinoma. Eur Arch Otorhinolaryngol 268(2):213–217, 2011
Address for correspondence: Masako Masuda, MD, 1–1-1 Honjo Chuo-ku Kumamoto 860–8556, Japan. masakom@fc.kuh.kumamoto-u.ac.jp
Cholesteatoma and Ear Surgery - An Update, pp. 399–402
Edited by Haruo Takahashi
2013 © Kugler Publications, Amsterdam, The Netherlands