Comparative Study of Sensorineural Hearing Loss

A Comparative Study of Sensorineural Hearing Loss in the

Treatment of Nasopharyngeal Carcinoma:

Conventional Radiation Vs IMRT Technique

Introduction

The standard treatment for nasopharyngeal

carcinoma is de

fi nitive radiotherapy with or without

chemotherapy where chemotherapy is reserved for

more advanced lesions [1]. Intensity modulated

radiation therapy (IMRT), a type of 3D conformal

radiotherapy, has gained its popularity in the treatment

of nasopharyngeal carcinoma. With this technique,

radiation beams can be modulated such that a high

dose can be delivered to the tumor while signi

fi cantly

reducing the dose to the surrounding normal tissue

[2-5]. Favorable toxicity pro

fi les were described with

IMRT that may be due to the reduced volumes of

normal tissue irradiated.

Due to the auditory apparatus especially cochlea

lies in close proximity to the nasopharynx and

usually receives a significant dose of radiation.

Sensory neural hearing loss (SNHL) is a common

toxicity after treatment in patients with nasopharyngeal

carcinoma that signi

fi cantly affects their quality of

life. Moreover, the addition of chemotherapy also

decrease local, regional and distant recurrence rate

while increase some toxicities include SNHL.

Because it is well known that Cisplatin is ototoxic

with affect high-frequency hearing, the concurrent

use of Cisplatin and radiation might act in synergy and

result in an increase in the incidence of SNHL [6].

In previous reports, the incidence of hearing loss

following radiation treatment (with and without

chemotherapy) of nasopharyngeal carcinoma is about

18-49% [7-16]. With IMRT techniques, the incidence

of radiation induced SNHL would expect to be

decline as a result of fewer dose of radiation to

normal tissue causing capability to spare the cochlea.

But there is no randomized control trial that comparing

about incidence of SNHL from each radiation

techniques. This is the

fi rst study that prospectively

to compare the incidence and severity of SNHL in

the nasopharyngeal carcinoma patients who received

radiation treatment between conventional twodimensional

(2D) radiation and IMRT technique.

Methods and materials

Patient population

Patients with newly diagnosed stage IIB-III

nasopharyngeal carcinoma who were treated between

November 2009 and August 2010 at Chiang Mai

University were included. Eligible patients were age

18-70 years, histological proven, non-metastatic

stage IIB-III nasopharyngeal carcinoma (AJCC

staging 2002, 6th edition) receive treatment with

combination of radiation and Cisplatin chemotherapy,

ECOG (Eastern Cooperative Oncology Group)

performance Status 0-1 and adequate haematological,

renal, and hepatic function. Patients with history of

other malignancies or head and neck radiotherapy

or conductive hearing loss in either ear before

treatment were excluded.

Study design and procedure

Patients were randomly assigned to receive

either conventional two-dimensional (2D) radiation

technique or IMRT technique. Data of patients’

characteristics, computed tomography scans, AJCC

2002 stage distribution and pure-tone audiogram

were collected.

Chemotherapy

Cisplatin at 100 mg/m2 infusion over 3 hr was

given on days 1, 22 and 43 concurrently with radiotherapy.

Adjuvant chemotherapy consisting of

Cisplatin 80 mg/m2 intravenously and 5-FU infusion

at 1000 mg/m2/day by 96 hr infusion was given

every 4 weeks for a total of 3 cycles, beginning 4

weeks after the end of radiation therapy.

Radiotherapy

Patients were randomized to receive:

Arm 1: Conventional two-dimensional (2D)

radiation technique

All patients were treated with 6-MV photon

linear accelerator. Parallel opposed portals were used

for the primary tumor site and the upper neck with

spinal cord and brainstem shielding at the dose of 40

Gy. The lower neck was treated with the anterior

split

fi eld with central shielding. Radiation therapy

was delivered at 2 Gy per fraction, 5 fractions per

week with dose 70 Gy to gross tumor and involved

lymph nodes with a 2 cm margin, and dose 50 Gy to

clivus, skull base, inferior sphenoid sinus, posterior

third of nasal cavity, maxillary sinus, pterygoid

fossa, cervical nodal regions level I-V and supraclavicular

nodal regions.

Arm 2: IMRT technique

A computed tomography (CT) was used for

simulation and treatment planning. CT images indexed

every 3 mm were obtained. Thermoplastic

masks were used for immobilization. Patients were

treated with 6-MV photon linear accelerator and a

step and shoot IMRT technique. Target and organ at

risk were contoured and prescribed radiation dose

according to RTOG Guideline, Report No. 0225 [24]

Pure-tone Audiometry

Standard pure tone audiometry was done in a

soundproof room. Baseline pre-treatment audiograms

were obtained. Post-treatment audiograms were

scheduled at completion of concurrent chemoradiation.

The audiograms included assessment of bone

conduction thresholds at 0.5, 1, 2, and 4 kHz. As in

previous reports by other authors [9,17,21], high and

lower frequencies in the speech range were represented

by the threshold at 4 kHz and the average of

0.5, 1, and 2 kHz (PTA: pure tone average) thresholds,

respectively. For each patient, the left and right

hearing levels were analyzed separately.

Hearing threshold change was determined

relatively to each patient’s baseline. An increase in

bone conduction (BC) threshold more than 15 dB

from baseline was considered as significant

represented SNHL in the present analysis.

Statistical Analysis

The data was analyzed using SPSS version 15

(Chicago IL, USA). Each ear was analyzed independently.

Differences in the incidence of SNHL

between conventional radiation and IMRT group

were analyzed using Fisher’s exact test. Differences

in hearing level between pre and post-radiotherapy

in each technique were analyzed using paired sample

t-test. The Mann-Whitney U test was performed to

compare the hearing levels between the conventional

radiation and IMRT group groups at pre and

post-radiotherapy. A p-value of < 0.05 was considered

signi

fi cant.

Results

Between November 2009 and August 2010, 19

nasopharyngeal carcinoma patients were enrolled

into the study and randomly assigned to receive radiotherapy

by conventional radiation (n=10) and

IMRT technique (n=9). One patient in IMRT arm

were excluded due to GFR <40 which is not suitable

for receiving Cisplatin chemotherapy. Therefore data

from 18 patients (36 ears), 10 for conventional

radiation and 8 for IMRT arm were analyzed. Patient

characteristics are given in Table 1. There were

comparability in both arms, including age, gender,

tumor staging, and Cisplatin dose.

Baseline pre-treatment audiograms (Table 2)

showed that number of ears which had abnormal

hearing loss (BC threshold >20 dB without AB gap)

before treatment at the pure tone average (PTA) of

0.5, 1, 2 kHz or low speech frequencies were 8 and

5 for conventional and IMRT groups, respectively.

At 4 kHz or high speech frequency, they showed

abnormal hearing in 13 ears for

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