Occurrence and influencing factors of paranasal sinusitis in nasopharyngeal carcinoma patients after radiotherapy

www.landesbioscience.com Chinese Journal of Cancer 165

Background and objective: Radiation usually results in para-
nasal sinusitis in nasopharyngeal carcinoma (NPC) patients, which
influences patients quality of life. This study was to explore the
occurrence and influencing factors of paranasal sinusitis in NPC
patients before and after radiotherapy. Methods: Clinical data
of 381 NPC patients, treated in Cancer Center of Sun Yat-sen
University from January 1998 to July 2000, were reviewed. CT
images before and after radiotherapy were compared. The occur-
rence and influencing factors of paranasal sinusitis were analyzed.
Results: Of the 381 NPC patients, 176 (46.2%) suffered from
paranasal sinusitis before radiotherapy. Among the 205 NPC
patients without paranasal sinusitis before radiotherapy, 103
(50.2%) developed paranasal sinusitis after radiotherapy; the
occurrence rates of paranasal sinusitis at first month, third month,
six month and first year after radiotherapy were 21.0, 33.7, 41.5
and 29.3%, respectively (
2
= 20.918, p < 0.001). Logistic analysis
showed that T stage was related to the occurrence rate of paranasal
sinusitis. Conclusion: The incidence of paranasal sinusitis in NPC
patients after radiotherapy is high and related to T stage.
Nasopharyngeal carcinoma (NPC) is one of the most common
malignant tumors in China and occurs most frequently in Guangdong
Province. External-beam radiotherapy is the first choice in treating
NPC. When irradiating primary NPC lesion, the irradiation
also damages surrounding normal tissues, resulting in all kinds
of early and late complications. The occurrence rate of paranasal
sinusitis after radiotherapy for NPC is quite high. Purulent nasal
discharge and snuffles are the main symptoms of paranasal sinusitis,
which sometimes accompanied by headache, local tenderness, and
hyposmia or anosmia, which seriously affect patients quality of life.
The present study summarized the occurrence of paranasal sinusitis
after radiotherapy for NPC and explored the rules of occurrence
and development of and relevant influencing factors for paranasal
sinusitis through analyzing the clinical records of NPC patients, so
as to provide guidance for the prevention and treatment of paranasal
sinusitis after radiotherapy.
Patients and Methods
Patients. Clinical data of 381 patients with pathologically
confirmed NPC, treated at Cancer Center of Sun Yat-sen University
from January 1998 to July 2000 and received computed tomography
(CT) scan before and after radiotherapy, were reviewed. Of the 381
patients, 289 were men and 92 were women with a gender ratio of
3.14:1. Their age ranged from 14 to 76 years (median, 46 years).
According to the Chinese 1992 Staging System, 22 patients were at
Stage I, 99 at Stage II, 165 at Stage III and 95 at State IV.
Radiotherapy. The targeted nasopharynx (bilateral preauricular
portal or faciocervical portal) was radiated with ray from the
60
Co
machine or 6 MeV/8 MeV-X ray from the electron linear accelerator
using conventional fractional radiotherapy. The radiated primary
sites included the nasopharyngeal cavity, posterior ethmoid sinuses,
orbital apex, basilar ptergoid process, pterygopalatine fossa, posterior
nasal cavity, posterior 1/3 of maxillary sinus, clivus, sphenoid sinuses,
basilar part of sphenoid, great wing of sphenoid bone, apical petrous
and parapharyngeal space. Sixty-seven patients received additional
radiation over the anterior nasal portal. After external radiation of
5676 Gy, 24 patients underwent after loading radiation of 825
Gy by 24 fractions at the nasopharyngeal cavity from day 5 to day
25. The total radiation dosage ranged from 56 to 84 Gy (median, 70
Gy). A total of 135 stage IIIIV patients underwent 14 courses of
platinum-based neo-adjuvant or concurrent chemotherapy.
CT scan on nasopharynx and diagnosis criteria for paranasal
sinusitis. Before radiotherapy, and at first month, third month, six
month and first year after radiotherapy, transversal CT plain scan
plus enhanced scan on the nasopharynx were performed by the
ELSCINT CT2-FLASH double helical scanner with scan thickness
and space both of 5 mm. Because conventional transversal CT scan
on the nasopharynx could not reach the frontal sinus, this study
focused on the analysis of maxillary, ethmoid and sphenoidal sinuses.
Radiologists observed the CT films. The diagnosis criteria for para-
nasal sinusitis were as follow: (1) the sinus mucosa was thickened
Clinical Research Paper
Occurrence and influencing factors of paranasal sinusitis
in nasopharyngeal carcinoma patients after radiotherapy
Tai-Ze Yuan,
1,2
Xiang Guo,
1,2,
* Lie Zheng,
1,3
Su-Mei Cao,
1,2
Ning-Wei Li
1,2
and Yan-Qun Xiang
1,2
State Key Laboratory of Oncology in South China; Guangzhou, Guangdong P.R. China;
2
Department of Nasopharyngeal Carcinoma;
3
Medical Imaging and Interventional Center;
Sun Yat-sen University Cancer Center; Guangzhou, Guangdong, P.R. China
Key words: nasopharyngeal neoplasm, radiotherapy, paranasal sinusitis, complication, influencing factor
*Correspondence to: Xiang Guo; State Key Laboratory of Oncology in South China;
Department of Nasopharyngeal Carcinoma; Sun Yat-sen University Cancer Center;
Guangzhou, Guangdong 510060 P.R. China; Tel.: 87343359; Fax: 87343392;
Email: guoxiang@mail.sysu.edu.cn
Submitted: 07/19/07; Revised: 11/20/07; Accepted: 11/20/07
This paper was translated into English from its original publication in Chinese.
Translated by: Beijing Xinglin Meditrans Center and Wei Liu on 06/02/08.
The original Chinese version of this paper is published in: Ai Zheng(Chinese
Journal of Cancer), 27(8); http://www.cjcsysu.cn/cn/article.asp?id=13930
Previously published online as a Chinese Journal of Cancer E-publication:
http://www.landesbioscience.com/journals/cjc/article/6449
[Chinese Journal of Cancer 27:8, 165-168; August 2008]; 2008 Sun Yat-Sen University Cancer Center
Occurrence and influencing factors of paranasal sinusitis in nasopharyngeal carcinoma patients after radiotherapy
166 Chinese Journal of Cancer 2008; Vol. 27 Issue 8
for >3 mm with effusion or liquid-gas level in the sinus cavity; (2)
enhanced scan showed thickened and strengthened sinus mucosa,
but without the indication of bone erosion.
Statistical analysis. The statistical software package SPSS10.0
was applied for all analyses.
2
test was used for rate comparison.
Univariate analysis was used to analyze the correlations of age, sex,
tumor morphology, T stage, invasion of nasal cavity, radiation dose
for the nasopharynx, radiation for anterior nasal portal, after loading
radiation, chemotherapy and radiation resources to the occurrence
of paranasal sinusitis after radiotherapy. Multivariate analysis with
Logsitic regression model was used to screen the influencing factors
for occurrence of paranasal sinusitis after radiotherapy. A p value of
< 0.05 was considered significant.
Results
Occurrence of paranasal sinusitis before and after radiotherapy.
Among the 381 patients, 176 (46.2%) had paranasal sinusitis before
radiotherapy. Among the 205 patients without paranasal sinusitis
before radiotherapy, 103 (50.2%) developed paranasal sinusitis after
radiotherapy: the occurrence rates of paranasal sinusitis at first month,
third month, sixth month and first year after radiotherapy were 21.0,
33.7, 41.5 and 29.3%, respectively (
2
= 20.92, p < 0.001).
Among the 176 patients with paranasal sinusitis before radio-
therapy, 24 (13.6%) had the paranasal sinusitis alleviated after
radiotherapy, while the other 152 still suffered from paranasal
sinusitis after radiotherapy.
Comparison of occurrence of paranasal sinusitis at different
time points after radiotherapy. Among the 381 patients, 108, 107,
96 and 71 patients had paranasal sinusitis in one single sinus at first
month, third month, sixth month and first year after radiotherapy,
respectively. The occurrence rate of maxillary sinusitis was the highest
at different time points (Table 1). In the patients with paranasal
sinusitis in multiple sinuses, maxillary-ethmoid-sphenoid sinusitis
was the most frequently observed and then maxillary-ethmoid
sinusitis (Table 2).
Univariate analysis. Univariate analysis revealed that the occur-
rence rate of paranasal sinusitis after radiotherapy was significantly
higher in stage T3/T4 patients than in stage T1/T2 patients (60.2%
vs. 41.1%,
2
= 6.71, p = 0.006), and significantly lower in the
patients received external radiation of 70 Gy than in those received
external radiation of >70 Gy (38.0% vs. 54.2%, p = 0.046); no rela-
tionship was found between the occurrence rate of paranasal sinusitis
and age, sex, radiation sources, after loading radiation and radiation
for anterior nasal portal (Table 3).
Multivariate analysis of factors influencing the occurrence of
paranasal sinusitis after radiotherapy. T stage and external radiation
dose entered the Logistic regression model, but only T stage was
positively correlated with the occurrence of paranasal sinusitis after
radiotherapy (Table 4).
Discussion
Radiotherapy is the preferred treatment for NPC. The main
reason of early occurrence of paranasal sinusitis after radiotherapy
is mucosa edema and increased excretion caused by acute mucosa
reactions, which affect nasal drainage. Kamel et al.
1
measured the
nasal mucociliary clearance in NPC patients using saccharin before
and after radiotherapy, and revealed that the nasal mucociliary
injury persisted after radiotherapy and deteriorated until stabilized
at six months later. This finding is a reached consensus for the main
cause of paranasal sinusitis after radiotherapy, that is, intra-sinus
factors. The refractory anaphase paranasal sinusitis may result from
the adhesion and granulation tissue obstruction in the middle nasal
meatus, which are extra-sinus factors. Additionally, general physical
constitution cannot be neglected. The immune functions in the
patients with advanced cancers are suppressed, and the immune
functions in NPC patients are further damaged by radiotherapy.
Wang et al.
2
found significant decrease of IgA after radiotherapy for
NPC patients and the redistribution of T lymphocytes that led to
immune disorder.
Zhang et al.
3
observed 513 NPC patients who received radio-
therapy, and found that the occurrence rate of paranasal sinusitis was
9.9% before radiotherapy and increased to 86.8% after radiotherapy.
The present study found an occurrence rate of 46.2% for paranasal
sinusitis in NPC patients before radiotherapy, and most of these
patients still suffered from paranasal sinusitis after radiotherapy;
however, paranasal sinusitis faded away in some patients, which
may resulted from the decreased tumor size due to external radia-
tion, smooth sinus drainage, and gradually decreased sinus effusion.
The patients without paranasal sinusitis before radiotherapy had an
occurrence rate of 50.2% for paranasal sinusitis after radiotherapy.
Zhang et al.
4
found that maxillary sinusitis was the most
common inflammation after radiotherapy, accounting for 84.85%
of the patients with paranasal sinusitis after radiotherapy, followed
by ethmoid sinusitis (71.21%) and sphenoid sinusitis (34.85%).
This finding is consistent with our results. The maxillary sinus, the
lowest sinus below drainage opening of the nasal cavity, is vulner-
able to tumor invasion resulting in drainage obstacle, which leads
to paranasal sinusitis. After radiotherapy, the swollen sinus mucosa
and increased excretions aggravate the retention of excretions in the
sinuses. But Chen et al.
5
claimed that the occurrence rate of ethmoid
sinusitis is the highest because the ethmoid air cells, numerous but
small, are likely to be swollen and lead to drainage obstacle when the
mucosa is damaged by radiation. In our study, multiple paranasal
sinusitis existed after radiotherapy; maxillary-ethmoid-sphenoid
sinusitis was the most common type followed by maxillary-ethmoid
sinusitis. Our results are consistent with the results reported by Chen
et al.
5
The high occurrence rate of multiple paranasal sinusitis may
result from the wide extent of radiotherapy for NPC that covers the
posterior 1/3 part of maxillary sinus, the posterior ethmoid sinuses
and the whole sphenoid sinus.
In our study, the occurrence rate of paranasal sinusitis increased
gradually after radiotherapy and reached the peak at sixth month
Table 1 The occurrence of single paranasal sinusitis
in nasopharyngeal carcinoma (NPC) patients
after radiotherapy [cases (%)]
Time Cases Maxillary Ethmoid Sphenoid
2
p
sinusitis inusitis sinusitis
1 month 381 46 (12.1) 35 (9.2) 27 (7.1) 5.58 0.061
3 months 381 65 (17.1) 21 (5.5) 21 (5.5) 39.92 <0.001
6 months 350 69 (19.7) 22 (6.3) 5 (1.4) 75.60 <0.001
1 year 315 44 (14.0) 7 (2.2) 20 (6.3) 32.19 <0.001
Occurrence and influencing factors of paranasal sinusitis in nasopharyngeal carcinoma patients after radiotherapy
www.landesbioscience.com Chinese Journal of Cancer 167
Table 2 The occurrence of multiple paranasal sinusitis in NPC patients after radiotherapy [cases (%)]
Time Cases Maxillary-ethmoid Maxillary-sphenoid Ethmoid-sphenoid Maxillary-ethmoid-sphenoid 2 p
sinusitis sinusitis sinusitis sinusitis
1 month 381 34 (8.9) 17 (4.5) 14 (3.7) 53 (13.9) 35.60 <0.001
3 months 381 65 (17.1) 15 (3.9) 12 (3.1) 65 (17.1) 75.46 <0.001
6 months 350 78 (22.3) 22 (6.3) 11 (3.1) 84 (24.0) 101.020 <0.001
1 year 315 24 (7.6) 24 (7.6) 7 (2.2) 71 (22.5) 80.18 <0.001
Table 3 Univariate prognostic analysis of paranasal sinusitis in NPC patients after radiotherapy
Parameter Cases Paranasal sinusitis after radiotherapy Occurrence rate (%)
2
p
No Yes
Age
46 102 56 46 49.8
> 46 103 46 57 50.2 2.15 0.143
Sex
Male 150 77 73 48.7
Female 55 25 30 54.5 0.56 0.456
Tumor type
Nodular 96 45 51 53.1
Fungating 17 11 6 35.3
Infiltrating 45 19 26 57.8
Protrude 47 27 20 42.6 3.97 0.264
Nasal cavity invasion
No 174 88 86 49.4
Yes 31 14 17 54.8 0.31 0.579
T stage
T1/T2 107 63 44 41.4
T3/T4 98 39 59 60.2 7.45 0.006
Dose
70 Gy 50 31 19 38.0
> 70 Gy 155 71 84 54.25 3.97 0.046
Anterior nasal portal radiation
No 165 80 85 51.5
Yes 40 22 18 45.0 0.55 0.460
After loading
No 189 92 97 51.3
Yes 16 10 6 37.5 1.13 0.288
Radiation source
60
Co 144 73 71 49.3
Linear accelerator 61 29 32 52.5 0.17 0.680
Chemotherapy
No 141 76 65 46.1
Yes 64 26 38 59.4 3.10 0.078
Table 4 Multivariate prognostic analysis of paranasal sinusitis in NPC patients after radiotherapy
Parameter B SE Wald p
T stage 0.386 0.172 7.358 0.007
Dose 0.015 0.302 0.003 0.960
Constant -0.745 0.312 5.699 0.017
Occurrence and influencing factors of paranasal sinusitis in nasopharyngeal carcinoma patients after radiotherapy
168 Chinese Journal of Cancer 2008; Vol. 27 Issue 8
after radiotherapy, and then it gradually decreased to 29.3% at first
year after radiotherapy. The occurrence of paranasal sinusitis in NPC
patients after radiotherapy is a continual and lasting process, which
is composed of acute phase and chronic phase. Acute paranasal sinus-
itis mainly results from swollen mucosa, increased excretions and
suppressed excretion function of cilia that leads to retention of excre-
tions. While radiation-induced choanal atresia, chronic hyperemia
and hypertrophy of the turbinates, and nasal adhesion, especially
complex adhesion near the nasal sinuses may be the main causes for
chronic paranasal sinusitis. However, there is no definite borderline
between the acute and chronic phases.
As T stage climbs, the tumor invasion scope increases gradu-
ally, the radiation field is expanded accordingly and the tolerance
dose for normal tissues decreases,
6
therefore, the occurrence rate
of paranasal sinusitis after radiotherapy increases. In this study,
the occurrence rate of paranasal sinusitis after radiotherapy was
higher in stage T3T4 patients than in stage T1T2 patients. As
radiation dose increases, the exposure to radiation for different
paranasal sinus mucosa increases and the occurrence rate of para-
nasal sinusitis increases. Chemotherapy suppresses the immune
functions of tumor patients. Additionally, in spite of kill tumor cells,
chemotherapeutic drugs also injure local normal tissues at different
degrees (for example, 5-fluorouracil can induce mucositis), leading
to increased occurrence of paranasal sinusitis after chemotherapy in
advanced tumor patients. Regarding radiation sources, the radia-
tion energy of ray from
60
Co is 1.25 MeV, while the radiation
energy from conventional electron linear accelerator is 6 MeV or 8
MeV. The percentage depth dose is higher for the latter. With the
same radiation fields, the patients radiated by conventional electron
linear accelerator should be more vulnerable to paranasal sinusitis.
However, our results showed that the occurrence rate of paranasal
sinusitis after chemotherapy was only slightly higher in the patients
radiated by conventional electron linear accelerator than in the
patients radiated by
60
Co ray (p = 0.680). And we did not find
that the occurrence rate of paranasal sinusitis was affected by radia-
tion for anterior nasal portal or by additional after loading radiation,
which might be due to limited cases.
We found that the occurrence rate of paranasal sinusitis reached
the peak at the sixth month after radiotherapy and the symptoms
alleviated spontaneously in some patients later. We advocate conser-
vative therapy for paranasal sinusitis after radiotherapy; if paranasal
sinusitis lasts for over one year and severely influences the quality of
life, surgical operation could be performed to release nasal adhesion
and complex adhesion in the nasal sinuses, and smooth the drainage
in the nasal sinuses. On the basis of thoroughly removing lesions
by operation, the normal mucosa and structures of the nasal cavity
and nasal sinuses are proposed to be maintained to open the sinuses
for favorable airing and drainage, so as to promote the formation of
mucosa in the nasal cavity and nasal sinuses and the recovery of their
physiological functions. Zhou et al.
7
found favorable results with a
general effective rate of 100% and a cure rate of 36.4% when treating
22 patients with radiation-related paranasal sinusitis by operation.
In conclusion, the normal tissues and organs surrounding NPC
lesions are inevitably injured when the NPC patients are treated
actively by radiotherapy. Paranasal sinusitis, with a high occurrence
rate, severely affects the quality of patients life. With technological
development of radiotherapy, we should adopt the radiotherapy
protocol with high efficacy and low complication rate, such as
three-dimensional conformal radiotherapy and intensity-modulated
radiotherapy. In the meantime, sinus-opening operation should be
considered for the patients with paranasal sinusitis before radio-
therapy. During chemotherapy, the nasal cavity and nasopharynx
should be washed to keep the nasal cavity smooth in order to
decrease the occurrence rate of paranasal sinusitis.
References
[1] Kamel R, Al-Badawy S, Kandil T, et al. Nasal and paranasal sinus changes after radiotherapy
for nasopharyngeal carcinoma [J]. Acta Otolaryngol, 2004,124(4):532-535.
[2] Wang JY, Gao S, Cui L, et al. Preliminary observation for the changes of immune compe-
tence of patients with advanced cancer before and after radiotherapy [J]. Cancer Res Clinic,
2000,12(5):313-314. [Article in Chinese]
[3] Zhang XH, Huang JN, Fu XJ, et al. Analysis of relevant factors concerning nasosinus-
itis after radiotherapy of nasopharyngeal carcinoma [J]. Chin J Otorhinolaryngology,
2004,39(12):730-732. [Article in Chinese]
[4] Zhang WJ, Wang JQ, Wang ZW, et al. Analysis of risk factors for nasosinusitis after radio-
therapy of nasopharyngeal carcinoma [J]. Chin J Radiol Med Protection, 2003,23(1):33-35.
[Article in Chinese]
[5] Chen YL, Huang GW, Wen WS, et al. An analysis of nasal diseases in 113 patients with
nasopharyngeal carcinoma before and after radiotherapy [J]. Chin Arch Otolaryngology-
Head Neck Surg, 2003,10 (1):32-35. [Article in Chinese]
[6] Wang WZ. Injuries of normal tissues [M]. Yin WB, Gu XZ, eds. Radiation Oncology.
Beijing: Beijing Union Medical College Press, 2002:307-320. [Book in Chinese]
[7] Zhou Y, Tang A Z, Lan XH, et al. Surgery for nasosinusitis after radiotherapy of nasopha-
ryngeal carcinoma [J]. Ai Zheng, 2003,22(1):102-103. [Article in Chinese]