CLINICAL INVESTIGATION Head and Neck
SENSORINEURAL HEARING LOSS AFTER TREATMENT OF NASOPHARYNGEAL
CARCINOMA: A LONGITUDINAL ANALYSIS
S. H. C
W. T. N
K. L. K
C. H. L
C. W. C
T. K. Y
W. M. L
S. K. C
Departments of *Clinical Oncology and
Otorhinolaryngology, Pamela Youde Nethersole Eastern Hospital, Hong Kong
Purpose: To analyze the effects of radiotherapy (RT) and chemotherapy in relation to sensorineural hearing loss
(SNHL) after contemporary treatment of nasopharyngeal carcinoma.
Methods and Materials: A total of 87 nasopharyngeal carcinoma patients were treated with RTor chemoradiother-
apy using either three-dimensional conformal RT or intensity-modulated RT between 2004 and 2005. Tympanom-
etry and pure-tone audiogram assessments were performed before treatment and then serially at 6-month
intervals. The dose–volume data of the cochlea were analyzed. The effects of cisplatin administered in concurrent
and nonconcurrent phases was explored.
Results: Of the 170 eligible ears, RT (n = 30) and chemoradiotherapy (n = 140) resulted in 40% (n = 12) and 56.4%
(n = 79) persistent SNHL ($15 dB loss), respectively, after a median follow-up of 2 years. SNHL at a high frequency
was more frequent statistically in the chemoradiotherapy group than in the RT-alone group (55% vs. 33.3%,
p < 0.01), but not at a low frequency (7.9% vs. 16.7%, p = 0.14). Within the chemoradiotherapy group, the
mean cochlea dose and concurrent cisplatin dose were important determinants of high-frequency SNHL, with
an odds ratio of 1.07/Gy increase (p = 0.01) and an odds ratio of 1.008/mg/m
increase (p < 0.01), respectively.
Age, gender, and nonconcurrent cisplatin dose were not statistically signiﬁcant factors. A mean radiation dose
to the cochlea of <47 Gy would result in <15% of patients developing severe ($30 dB) high-frequency SNHL.
Conclusion: The results of our study have shown that high-frequency SNHL is signiﬁcantly related to the mean
cochlea dose and the concurrent cisplatin dose. A mean dose constraint of 47 Gy to the cochlea is recommended
to minimize SNHL after chemoradiotherapy. Ó 2009 Elsevier Inc.
Sensorineural hearing loss, Nasopharyngeal carcinoma, Prognostic factors, Chemoradiotherapy, Dose constraint.
Sensorineural hearing loss (SNHL) is a common and impor-
tant complication after radiotherapy (RT) in patients with na-
sopharyngeal carcinoma (NPC) that signiﬁcantly affects their
quality of life. The auditory apparatus lies in close proximity
to the nasopharynx and usually receives a signiﬁcant dose of
radiation, leading to destruction of the sensory hair cells
within the cochlea and resulting in permanent sensorineural
hearing loss (1, 2).
Since the landmark study of Al-Sarraf et al. (3), many sub-
sequent Phase III clinical trials (4–7) have echoed the ﬁnd-
ings that concurrent cisplatin with RT signiﬁcantly
improves the clinical outcomes for NPC patients. However,
it is well known that cisplatin is ototoxic, especially affecting
high-frequency hearing. Thus, the concurrent use of cisplatin
and RT might act in synergy and result in an increase in the
incidence and severity of SNHL and a reduction in the ther-
apeutic index. Although concurrent chemoradiotherapy has
become the standard of care for advanced NPC, clinical
data on the ototoxicity after chemoradiotherapy are sparse.
The dose tolerance of the cochlea remains undeﬁned.
A longitudinal study was conducted to quantitatively ana-
lyze the effect of RT with or without chemotherapy in rela-
tion to the probability of SNHL development and to derive
a cochlea tolerance dose in the setting of concurrent chemo-
METHODS AND MATERIALS
A total of 97 consecutive, newly diagnosed, nonmetastatic NPC
patients were treated in a single regional hospital between Septem-
ber 2004 and December 2005. Of these 194 ears, 24 ears with a base-
line threshold dose >55 dB were excluded, because accurate
Reprint requests to: S. H. Chan, F.R.C.R., Department of Clinical
Oncology, Pamela Youde Nethersole Eastern Hospital, 3 Lok Man
Rd., Chai Wan, Hong Kong. Tel: (852) 2595-4180; Fax: (852)
2515-1266; E-mail: email@example.com
Accepted as a poster presentation at European Society for Thera-
peutic Radiology and Oncology Annual Congress, Goteborg,
Conﬂict of interest: none.
Acknowledgments—We thank Ms. Mandy Wong, Ms. Betty Wong,
Mr. Albert Hung, Mr. Patrick Chan, and Mr. Peter Lee for data col-
lection and Ms. Connie Chan for graphics preparation.
Received May 24, 2008, and in revised form July 7, 2008.
Accepted for publication July 8, 2008.
Int. J. Radiation Oncology Biol. Phys., Vol. 73, No. 5, pp. 1335–1342, 2009
Copyright Ó 2009 Elsevier Inc.
Printed in the USA. All rights reserved
0360-3016/09/$–see front matter