ORIGINAL ARTICLE
Olfactory change aer intensity-modulated radiotherapy for nasopharyngeal carcinoma Jing-Jie Wang, MD1 , Kai-Li Liang, MD1,2,3 , Chih-Wen Twu, MD, PhD1,3 , Jin-Ching Lin, MD, PhD4 and Rong-San Jiang, MD, PhD1,2,3
Background: Radiotherapy is the mainstay of treatment for nasopharyngeal cancer (NPC), but many side effects were reported in NPC patients receiving radiotherapy. This study was conducted to evaluate the long-term effects of intensity-modulated radiotherapy (IMRT) on olfactory function. Methods: The olfactory function of 41 NPC patients was assessed by a traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC). The patients also filled out a Taiwanese version of the 22-item Sino-Nasal Outcome Test (TWSNOT-22) questionnaire and received imaging examinations of the sinuses before IMRT and 1 year aer IMRT. The sinus imaging was scored according to the Lund-Mackay system. Results: The mean UPSIT-TC scores were 30.6 before IMRT and 28.0 aer IMRT and the decrease in UPSIT-TC scores was significant (p = 0.001). The mean TWSNOT-22 scores were 32.1 before IMRT and 28.8 aer IMRT. The change in TWSNOT-22 scores was not significant, but the scores for item 5 “loss of smell or taste” significantly increased aer IMRT (p = 0.035). The mean total computed tomography
N
asopharyngeal carcinoma (NPC) is prevalent in southeast China and Taiwan.1 Radiotherapy is the mainstay of treatment for NPC.2 However, conventional radiotherapy results in significant side effects such as
1 Department
of Otolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan; 2 School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 3 Faculty of Medicine, National Yang-Ming Medical University, Taipei, Taiwan; 4 Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan
Correspondence to: Rong-San Jiang, MD, PhD, Department of Otolaryngology, Taichung Veterans General Hospital, 1650, Sec. 4, Taiwan Boulevard, Taichung, Taiwan 40705; e-mail: [email protected] Potential conflict of interest: None provided. Presented at the 13th Asia-Oceania ORL-HNS Congress, March 19-22, 2015, in Taipei, Taiwan. Received: 18 March 2015; Revised: 8 May 2015; Accepted: 14 May 2015 DOI: 10.1002/alr.21575 View this article online at wileyonlinelibrary.com.
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(CT) scores were 1.7 before IMRT and 3.2 aer IMRT, and the mean ethmoid CT scores were 0.5 before IMRT and 1.2 aer IMRT. The increase in total CT and ethmoid CT scores was both significant (p = 0.004 and 0.002). The decrease in UPSIT-TC scores was moderately negatively correlated with the increase in total CT and ethmoid CT scores (r = −0.348 and −0.423). Conclusion: Our results showed that the olfactory function of NPC patients was mildly impaired aer IMRT, which can C 2015 ARS-AAOA, LLC. cause rhinosinusitis.
Key Words: imaging; intensity-modulated radiotherapy; nasopharyngeal carcinoma; olfactory function; questionnaire; rhinosinusitis; University of Pennsylvania Smell Identification Test How to Cite this Article: Wang JJ, Liang KL, Twu CW, Lin JC, Jiang RS. Olfactory change aer intensity-modulated radiotherapy for nasopharyngeal carcinoma. Int Forum Allergy Rhinol. 2015;5:1059–1062.
xerostomia.3 Because the irradiated fields encompass the posterior nasal cavity, ethmoid sinuses, and sphenoid sinuses,4 the nasal epithelium is often damaged by radiotherapy, resulting in rhinosinusitis.5 The olfactory epithelium is located in the upper nasal vault and is thus included in the irradiated field. This might be a reason why NPC patients experience olfactory loss postirradiation.6 Over the past 20 years, advances in modern radiotherapy techniques for treating NPC have emerged with the development of 3-dimensional conformal radiotherapy.7 Threedimensional conformal radiotherapy relies on computed tomography (CT) or magnetic resonance imaging–guided 3-dimensional planning, which allows better delineation of tumor tissue. Intensity-modulated radiotherapy (IMRT) represents an advanced form of 3-dimensional conformal radiotherapy. It employs inverse planning algorithms and iterative computer-driven optimization to generate treatment fields with varying beam intensity.7 Therefore, the
Wang et al.
TABLE 1. Patient characteristics
radiation doses to the nasal cavity and normal tissue surrounding the nasopharyngeal tumor tissue are expected to be lower.5 It has been reported that IMRT is superior to conventional radiotherapy in preserving parotid function and results in less severe delayed xerostomia.8 However, the influence of IMRT on the olfactory function in NPC patients has not been reported. In this study we investigated the change in olfactory function in NPC patients receiving IMRT treatment.
Characteristic
Gender Male
31 (76)
Female
10 (24)
Age (years)
Patients and methods
Median
45
Range
29–77
T stage
Seventy patients with histologically proven NPC who received IMRT for treatment at our hospital from April 2010 to October 2013 were recruited in the study. They all underwent a detailed nasoendoscopic examination before having a nasopharyngeal specimen taken for histological analysis. Before receiving IMRT, they were asked about their olfactory function and filled out a Taiwanese version of the 22-item Sino-Nasal Outcome Test (TWSNOT-22).9 No patient had a history of loss of olfactory function caused by congenital olfactory dysfunction, head trauma, upper respiratory infection, or psychiatric or neurological disorders. The olfactory function was evaluated by a traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC).10 A head and neck CT scan was arranged to examine tumor extent and sinusitis severity before IMRT. One year after IMRT, 41 patients returned to retake the TWSNOT-22 questionnaire and their olfactory function was evaluated again by the UPSIT-TC. A head and neck CT scan was also arranged to examine tumor status and sinusitis severity. This study was approved by the Ethics Committee of Taichung Veterans General Hospital. Written consent was obtained from each patient.
T1
15 (37)
T2
11 (27)
T3
7 (17)
T4
8 (20)
N stage N0
4 (10)
N1
4 (10)
N2
25 (61)
N3 Stage
8 (20) a
I
1 (2)
II
5 (12)
III
17 (41)
IVA
10 (24)
IVB
8 (20)
*
Values are n (%) except where indicated otherwise. Staging based on the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 7th edition (2010). a
Patient characteristics The TNM classification system of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 7th edition (2010), was used to stage our patients. None of the patients had distant metastatic disease at presentation. Local radiotherapy was administered to the primary tumor and neck region via an IMRT technique. The total dose to the primary tumor was 70 Gy/35 fractions/7 weeks for T1 to T3 lesions, and 76.8 Gy by a hyperfractionated (1.2 Gy twice per day [bid] × 64 fractions) schedule for T4 tumors. Thirty-seven patients received induction chemotherapy before IMRT, 2 received concurrent chemoradiotherapy, and 2 received IMRT alone (Table 1).
Evaluation of rhinosinusitis severity
from 0 to 5 (0 for no problem, 5 for the problem as bad as it can be). The total score is the sum of the scores of all the items (range, 0-110).11 The sinus CT scan findings were quantified according to the staging method described by Lund and Mackay.12 The CT findings of maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal sinus were graded as 0, 1, or 2 (0 = clear sinus, 1 = partial opacification, and 2 = total opacification) and the osteomeatal complex was scored as 0 or 2 (0 = not obstructed and 2 = obstructed). The total CT score is the sum of the all the scores of the bilateral sinuses (range, 0-24), and the ethmoid CT score is the sum of the all the scores of the bilateral anterior and posterior ethmoids (range, 0-8).
The severity of rhinosinusitis in these patients was rated by scores on a TWSNOT-22 questionnaire and sinus CT. TWSNOT-22 is a 22-item questionnaire that has been used as a tool in assessing the degree and effect of treating patients with rhinitis and rhinosinusitis.9 Based on the frequency and severity of symptoms, each question is graded
The olfactory function was subjectively evaluated by the score for the 5th item of the TWSNOT-22 (loss of smell or taste). The olfactory function was objectively measured by the UPSIT-TC, which is a modified version of the
Evaluation of olfactory function
International Forum of Allergy & Rhinology, Vol. 5, No. 11, November 2015
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Olfactory change after IMRT for NPC
TABLE 2. Comparison of scores pre-IMRT, and 1 year
post-IMRT Pre-IMRT (mean ± SD) Post-IMRT (mean ± SD)
p
32.1 ± 15.3
28.8 ± 19.9
0.27
Total CT score
1.7 ± 2.3
3.2 ± 3.7
0.004
Ethmoid CT score
0.5 ± 0.9
1.2 ± 1.4
0.002
Loss of smell/taste
1.1 ± 1.4
1.7 ± 1.4
0.035
30.6 ± 5.2
28.0 ± 6.0
0.001
TWSNOT-22
UPSIT-TC
CT = computed tomography; Ethmoid CT score = bilateral ethmoid score by Lund-Mackay staging method; IMRT = intensity-modulated radiotherapy; Total CT score = total CT score by Lund-Mackay staging method; TWSNOT-22 = Taiwanese version of the 22-item Sino-Nasal Outcome Test; UPSIT-TC = traditional Chinese version of the University of Pennsylvania Smell Identification Test.
UPSIT for Taiwanese patients.13 The test is comprised of four 10-odorant booklets. Each of the 40 “scratch and sniff” odorants is embedded in 10 to 50 μm of ureaformaldehyde polymer microcapsules fixed in a propriety binder and positioned on brown strips located at the bottom of the pages of each test booklet. When the examinee takes the UPSIT-TC, he/she releases each of the 40 odorants by scratching the strip with a pencil tip in a standardized manner. The identity of the released odorant is signified by choosing a name from a set of 4 odor descriptors. The test is scored as the number of odors identified correctly. The normative data were 29 for males aged 20 to 49 years and 22 for males aged 50 to 79 years; 29 for females aged 20 to 49 years and 21 for females aged 50 to 79 years.14
Statistical analysis All data are presented as mean ± standard deviation. The pre-IMRT and post-IMRT scores of the TWSNOT-22, the fifth item of the TWSNOT-22 (loss of smell or taste), total CT score, ethmoid CT score, and UPSIT-TC were compared by Wilcoxon signed-rank test. The correlation between the change of UPSIT-C scores after IMRT and the T stage, and the correlation between the change of UPSIT-C scores after IMRT and the change of total CT scores as well as ethmoid CT scores after IMRT were evaluated by Spearman’s correlation coefficient. All computations were performed using SPSS version 17.0 (SPSS, Inc., Chicago, IL). Two-tailed p values < 0.05 were considered statistically significant.
Results Table 2 shows the comparison of the scores of the TWSNOT-22, the 5th item of the TWSNOT-22 (loss of smell or taste), total CT score, ethmoid CT score, and UPSIT-TC before IMRT and 1 year after IMRT. The TWSNOT-22 scores ranged from 3 to 61 with a mean of 32.1 before IMRT and from 0 to 75 with a mean of 28.8 after IMRT. The total CT scores ranged from 0 to 11 with a mean of 1.7 before IMRT and from 0 to 16 with a mean of 3.2 after IMRT, and the ethmoid CT scores ranged from
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0 to 3 with a mean of 0.5 before IMRT and from 0 to 5 with a mean of 1.2 after IMRT. The total CT scores and ethmoid CT score increased significantly after IMRT. The scores for the 5th item of the TWSNOT-22 ranged from 0 to 5 with a mean of 1.1 before IMRT and from 0 to 5 with a mean of 1.7 after IMRT. The scores for the 5th item of the TWSNOT-22 increased significantly after IMRT. The UPSIT-TC scores ranged from 11 to 37 with a mean of 30.6 before IMRT and from 13 to 35 with a mean of 28 after IMRT. The UPSIT-TC scores decreased significantly after IMRT. According to our normative data, 34 (82.9%) patients were classified as normosmic before IMRT, and 31 (75.6%) were normosmic after IMRT. When the change of UPSIT-C scores after IMRT was correlated with the T stage, the correlation was not significant (r = −0.169, p = 0.29). When the change of UPSIT-TC scores after IMRT was correlated with the change of CT scores after IMRT, there was a moderately negative correlation for total CT scores (r = −0.348, p = 0.026) as well as ethmoid CT scores (r = −0.423, p = 0.006).
Discussion Conventional radiotherapy results in significant side effects in NPC patients postirradiation. The incidence of sinus mucosal abnormality was approximately doubled after radiotherapy.15 Therefore, chronic rhinosinusitis has become 1 of the most common side effects of radiotherapy.16 Because the olfactory epithelium and some of the brain structure such as olfactory bulbs are included in the irradiated field, olfactory dysfunction and diminished volume of olfactory bulbs have been reported following radiotherapy.2, 17 The olfactory loss was considered to be most likely sensorineural.6 IMRT is an advanced form of 3-dimensional conformal radiotherapy. The radiation doses to the nasal cavity and normal tissue surrounding the nasopharyngeal tumor are expected to decrease. Our results showed that the TWSNOT-22 scores did not increase after IMRT. This implied that overall sinonasal symptoms did not worsen after IMRT, and a mean score of 28.8 indicated a very mildto-mild sinonasal problem. On the other hand, CT scores increased after IMRT, which meant that rhinosinusitis became worse after IMRT. However, a mean score of 3.2 indicated mild rhinosinusitis. In summary, our results suggested IMRT might lessen rhinosinusitis side effects. One year after IMRT, our patients considered their olfactory function was worse, but a mean score of 1.7 for the 5th item of the TWSNOT-22 (loss of smell or taste) indicated a very mild-to-mild problem. UPSIT-TC scores decreased after IMRT, which meant that olfactory function was impaired after IMRT. Nevertheless, 75.6% of patients still had normal olfactory function, and this showed that the olfactory function of most NPC patients was not affected by IMRT. When the change of UPSIT-TC scores after IMRT was correlated with the change of total CT scores and ethmoid
Wang et al.
CT scores after IMRT, the correlation was moderately negative. This implied that olfactory change after IMRT might result from rhinosinusitis caused by IMRT. Ho et al.6 considered that the olfactory dysfunction in NPC patients after radiotherapy was most likely sensorineural and not conductive, but their patients received conventional radiotherapy. Veyseller et al.2 reported diminished volume of olfactory bulbs following radiotherapy, but all of their patients except 2 also received conventional radiotherapy. In this study, we did not measure the volume of olfactory bulbs. Therefore, we did not evaluate the influence of IMRT on olfactory bulbs, and were not able to exclude the
possibility of sensorineural olfactory dysfunction caused by IMRT.
Conclusion Our results showed that IMRT caused rhinosinusitis side effects but the severity might not be as serious as that with conventional radiotherapy. IMRT also mildly impaired the olfactory function of NPC patients and this might result from the rhinosinusitis side effects caused by IMRT, but we were not able to exclude the possibility of sensorineural olfactory dysfunction caused by IMRT.
References 1.
2.
3.
4.
5.
6.
Hu KH, Tan CT, Lin KN, et al. Effect of endoscopic sinus surgery on irradiation-induced rhinosinusitis in patients with nasopharyngeal carcinoma. Otolaryngol Head Neck Surg. 2008;139:575–579. Veyseller B, Ozucer B, Degirmenci N, et al. Olfactory bulb volume and olfactory function after radiotherapy in patients with nasopharyngeal cancer. Auris Nasus Larynx. 2014;41:436–440. Lu H, Yao M. The current status of intensitymodulated radiation therapy in the treatment of nasopharyngeal carcinoma. Cancer Treat Rev. 2008;34:27–36. Su MC, Jiang RS, Chiang JL, Lin JC. Endoscopic sinus surgery for the treatment of chronic rhinosinusitis in patients with postirradiated nasopharyngeal carcinoma. Am J Otolaryngol. 2006;27:46–99. Yin GD, Xiong GX, Zhao C, Chen YY. Damage of nasal mucociliary movement after intensitymodulated radiation therapy of nasopharyngeal carcinoma. Chin J Cancer. 2010;29:824–829. Ho WK, Kwong DL, Wei WI, Sham JS. Change in olfaction after radiotherapy for nasopharyngeal cancera prospective study. Am J Otolaryngol. 2002;23:209– 214.
7.
Fang FM, Chien CY, Tsai WL, et al. Quality of life and survival outcome for patients with nasopharyngeal carcinoma receiving three-dimensional conformal radiotherapy vs. intensity-modulated radiotherapy-a longitudinal study. Int J Radiat Oncol Biol Phys. 2008;72:356–364. 8. Kam MK, Leung SF, Zee B, et al. Prospective randomized study of intensity-modulated radiotherapy on salivary gland function in early-stage nasopharyngeal carcinoma patients. J Clin Oncol. 2007;25:4873– 4879. 9. Hsu MY, Jiang RS, Hsin CH, Liang KL. Validation of the Taiwanese version of the 22-item Sino-nasal Outcome Test. J Taiwan Otolaryngol Head Neck Surg. 2013;48:55–63. 10. Jiang RS, Su MC, Liang KL, et al. A pilot study of a traditional Chinese version of the University of Pennsylvania Smell Identification Test for application in Taiwan. Am J Rhinol Allergy. 2010;24: 45–50. 11. Jalessi M, Farhadi M, Kamrava SK, et al. The reliability and validity of the Persian version of sinonasal outcome test 22 (SNOT 22) questionnaires. Iran Red Crescent Med J. 2013;15:404–408.
12. Lund VJ, Mackay IS. Staging in rhinosinusitus. Rhinology. 1993;31:183–184. 13. Jiang RS, Kuo LT, Wu SH, et al. Validation of the applicability of the traditional Chinese version of the University of Pennsylvania Smell Identification Test in patients with chronic rhinosinusitis. Allergy Rhinol. 2014;5:e28–e35. 14. Jiang RS. Establishment of normative data for a traditional Chinese version of the University of Pennsylvania Smell Identification Test. J Taiwan Otolaryngol Head Neck Surg. 2013;48:302–306. 15. Porter MJ, Leung SF, Ambrose R, et al. The paranasal sinuses before and after radiotherapy for nasopharyngeal carcinoma: a computed tomographic study. J Laryngol Otol. 1996;110:19–22. 16. Zubizarreta PA, D’Antonio G, Raslawski E, et al. Nasopharyngeal carcinoma in childhood and adolescence: a single-institution experience with combined therapy. Cancer. 2000;89:690–695. 17. Hua MS, Chen ST, Tang LM, Leung WM. Olfactory function in patients with nasopharyngeal carcinoma following radiotherapy. Brain Inj. 1999;13: 905–915.
International Forum of Allergy & Rhinology, Vol. 5, No. 11, November 2015
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Olfactory change aer intensity-modulated radiotherapy for nasopharyngeal carcinoma Jing-Jie Wang, MD1 , Kai-Li Liang, MD1,2,3 , Chih-Wen Twu, MD, PhD1,3 , Jin-Ching Lin, MD, PhD4 and Rong-San Jiang, MD, PhD1,2,3
Background: Radiotherapy is the mainstay of treatment for nasopharyngeal cancer (NPC), but many side effects were reported in NPC patients receiving radiotherapy. This study was conducted to evaluate the long-term effects of intensity-modulated radiotherapy (IMRT) on olfactory function. Methods: The olfactory function of 41 NPC patients was assessed by a traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC). The patients also filled out a Taiwanese version of the 22-item Sino-Nasal Outcome Test (TWSNOT-22) questionnaire and received imaging examinations of the sinuses before IMRT and 1 year aer IMRT. The sinus imaging was scored according to the Lund-Mackay system. Results: The mean UPSIT-TC scores were 30.6 before IMRT and 28.0 aer IMRT and the decrease in UPSIT-TC scores was significant (p = 0.001). The mean TWSNOT-22 scores were 32.1 before IMRT and 28.8 aer IMRT. The change in TWSNOT-22 scores was not significant, but the scores for item 5 “loss of smell or taste” significantly increased aer IMRT (p = 0.035). The mean total computed tomography
N
asopharyngeal carcinoma (NPC) is prevalent in southeast China and Taiwan.1 Radiotherapy is the mainstay of treatment for NPC.2 However, conventional radiotherapy results in significant side effects such as
1 Department
of Otolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan; 2 School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 3 Faculty of Medicine, National Yang-Ming Medical University, Taipei, Taiwan; 4 Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan
Correspondence to: Rong-San Jiang, MD, PhD, Department of Otolaryngology, Taichung Veterans General Hospital, 1650, Sec. 4, Taiwan Boulevard, Taichung, Taiwan 40705; e-mail: [email protected] Potential conflict of interest: None provided. Presented at the 13th Asia-Oceania ORL-HNS Congress, March 19-22, 2015, in Taipei, Taiwan. Received: 18 March 2015; Revised: 8 May 2015; Accepted: 14 May 2015 DOI: 10.1002/alr.21575 View this article online at wileyonlinelibrary.com.
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(CT) scores were 1.7 before IMRT and 3.2 aer IMRT, and the mean ethmoid CT scores were 0.5 before IMRT and 1.2 aer IMRT. The increase in total CT and ethmoid CT scores was both significant (p = 0.004 and 0.002). The decrease in UPSIT-TC scores was moderately negatively correlated with the increase in total CT and ethmoid CT scores (r = −0.348 and −0.423). Conclusion: Our results showed that the olfactory function of NPC patients was mildly impaired aer IMRT, which can C 2015 ARS-AAOA, LLC. cause rhinosinusitis.
Key Words: imaging; intensity-modulated radiotherapy; nasopharyngeal carcinoma; olfactory function; questionnaire; rhinosinusitis; University of Pennsylvania Smell Identification Test How to Cite this Article: Wang JJ, Liang KL, Twu CW, Lin JC, Jiang RS. Olfactory change aer intensity-modulated radiotherapy for nasopharyngeal carcinoma. Int Forum Allergy Rhinol. 2015;5:1059–1062.
xerostomia.3 Because the irradiated fields encompass the posterior nasal cavity, ethmoid sinuses, and sphenoid sinuses,4 the nasal epithelium is often damaged by radiotherapy, resulting in rhinosinusitis.5 The olfactory epithelium is located in the upper nasal vault and is thus included in the irradiated field. This might be a reason why NPC patients experience olfactory loss postirradiation.6 Over the past 20 years, advances in modern radiotherapy techniques for treating NPC have emerged with the development of 3-dimensional conformal radiotherapy.7 Threedimensional conformal radiotherapy relies on computed tomography (CT) or magnetic resonance imaging–guided 3-dimensional planning, which allows better delineation of tumor tissue. Intensity-modulated radiotherapy (IMRT) represents an advanced form of 3-dimensional conformal radiotherapy. It employs inverse planning algorithms and iterative computer-driven optimization to generate treatment fields with varying beam intensity.7 Therefore, the
Wang et al.
TABLE 1. Patient characteristics
radiation doses to the nasal cavity and normal tissue surrounding the nasopharyngeal tumor tissue are expected to be lower.5 It has been reported that IMRT is superior to conventional radiotherapy in preserving parotid function and results in less severe delayed xerostomia.8 However, the influence of IMRT on the olfactory function in NPC patients has not been reported. In this study we investigated the change in olfactory function in NPC patients receiving IMRT treatment.
Characteristic
Gender Male
31 (76)
Female
10 (24)
Age (years)
Patients and methods
Median
45
Range
29–77
T stage
Seventy patients with histologically proven NPC who received IMRT for treatment at our hospital from April 2010 to October 2013 were recruited in the study. They all underwent a detailed nasoendoscopic examination before having a nasopharyngeal specimen taken for histological analysis. Before receiving IMRT, they were asked about their olfactory function and filled out a Taiwanese version of the 22-item Sino-Nasal Outcome Test (TWSNOT-22).9 No patient had a history of loss of olfactory function caused by congenital olfactory dysfunction, head trauma, upper respiratory infection, or psychiatric or neurological disorders. The olfactory function was evaluated by a traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC).10 A head and neck CT scan was arranged to examine tumor extent and sinusitis severity before IMRT. One year after IMRT, 41 patients returned to retake the TWSNOT-22 questionnaire and their olfactory function was evaluated again by the UPSIT-TC. A head and neck CT scan was also arranged to examine tumor status and sinusitis severity. This study was approved by the Ethics Committee of Taichung Veterans General Hospital. Written consent was obtained from each patient.
T1
15 (37)
T2
11 (27)
T3
7 (17)
T4
8 (20)
N stage N0
4 (10)
N1
4 (10)
N2
25 (61)
N3 Stage
8 (20) a
I
1 (2)
II
5 (12)
III
17 (41)
IVA
10 (24)
IVB
8 (20)
*
Values are n (%) except where indicated otherwise. Staging based on the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 7th edition (2010). a
Patient characteristics The TNM classification system of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 7th edition (2010), was used to stage our patients. None of the patients had distant metastatic disease at presentation. Local radiotherapy was administered to the primary tumor and neck region via an IMRT technique. The total dose to the primary tumor was 70 Gy/35 fractions/7 weeks for T1 to T3 lesions, and 76.8 Gy by a hyperfractionated (1.2 Gy twice per day [bid] × 64 fractions) schedule for T4 tumors. Thirty-seven patients received induction chemotherapy before IMRT, 2 received concurrent chemoradiotherapy, and 2 received IMRT alone (Table 1).
Evaluation of rhinosinusitis severity
from 0 to 5 (0 for no problem, 5 for the problem as bad as it can be). The total score is the sum of the scores of all the items (range, 0-110).11 The sinus CT scan findings were quantified according to the staging method described by Lund and Mackay.12 The CT findings of maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal sinus were graded as 0, 1, or 2 (0 = clear sinus, 1 = partial opacification, and 2 = total opacification) and the osteomeatal complex was scored as 0 or 2 (0 = not obstructed and 2 = obstructed). The total CT score is the sum of the all the scores of the bilateral sinuses (range, 0-24), and the ethmoid CT score is the sum of the all the scores of the bilateral anterior and posterior ethmoids (range, 0-8).
The severity of rhinosinusitis in these patients was rated by scores on a TWSNOT-22 questionnaire and sinus CT. TWSNOT-22 is a 22-item questionnaire that has been used as a tool in assessing the degree and effect of treating patients with rhinitis and rhinosinusitis.9 Based on the frequency and severity of symptoms, each question is graded
The olfactory function was subjectively evaluated by the score for the 5th item of the TWSNOT-22 (loss of smell or taste). The olfactory function was objectively measured by the UPSIT-TC, which is a modified version of the
Evaluation of olfactory function
International Forum of Allergy & Rhinology, Vol. 5, No. 11, November 2015
1060
Olfactory change after IMRT for NPC
TABLE 2. Comparison of scores pre-IMRT, and 1 year
post-IMRT Pre-IMRT (mean ± SD) Post-IMRT (mean ± SD)
p
32.1 ± 15.3
28.8 ± 19.9
0.27
Total CT score
1.7 ± 2.3
3.2 ± 3.7
0.004
Ethmoid CT score
0.5 ± 0.9
1.2 ± 1.4
0.002
Loss of smell/taste
1.1 ± 1.4
1.7 ± 1.4
0.035
30.6 ± 5.2
28.0 ± 6.0
0.001
TWSNOT-22
UPSIT-TC
CT = computed tomography; Ethmoid CT score = bilateral ethmoid score by Lund-Mackay staging method; IMRT = intensity-modulated radiotherapy; Total CT score = total CT score by Lund-Mackay staging method; TWSNOT-22 = Taiwanese version of the 22-item Sino-Nasal Outcome Test; UPSIT-TC = traditional Chinese version of the University of Pennsylvania Smell Identification Test.
UPSIT for Taiwanese patients.13 The test is comprised of four 10-odorant booklets. Each of the 40 “scratch and sniff” odorants is embedded in 10 to 50 μm of ureaformaldehyde polymer microcapsules fixed in a propriety binder and positioned on brown strips located at the bottom of the pages of each test booklet. When the examinee takes the UPSIT-TC, he/she releases each of the 40 odorants by scratching the strip with a pencil tip in a standardized manner. The identity of the released odorant is signified by choosing a name from a set of 4 odor descriptors. The test is scored as the number of odors identified correctly. The normative data were 29 for males aged 20 to 49 years and 22 for males aged 50 to 79 years; 29 for females aged 20 to 49 years and 21 for females aged 50 to 79 years.14
Statistical analysis All data are presented as mean ± standard deviation. The pre-IMRT and post-IMRT scores of the TWSNOT-22, the fifth item of the TWSNOT-22 (loss of smell or taste), total CT score, ethmoid CT score, and UPSIT-TC were compared by Wilcoxon signed-rank test. The correlation between the change of UPSIT-C scores after IMRT and the T stage, and the correlation between the change of UPSIT-C scores after IMRT and the change of total CT scores as well as ethmoid CT scores after IMRT were evaluated by Spearman’s correlation coefficient. All computations were performed using SPSS version 17.0 (SPSS, Inc., Chicago, IL). Two-tailed p values < 0.05 were considered statistically significant.
Results Table 2 shows the comparison of the scores of the TWSNOT-22, the 5th item of the TWSNOT-22 (loss of smell or taste), total CT score, ethmoid CT score, and UPSIT-TC before IMRT and 1 year after IMRT. The TWSNOT-22 scores ranged from 3 to 61 with a mean of 32.1 before IMRT and from 0 to 75 with a mean of 28.8 after IMRT. The total CT scores ranged from 0 to 11 with a mean of 1.7 before IMRT and from 0 to 16 with a mean of 3.2 after IMRT, and the ethmoid CT scores ranged from
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International Forum of Allergy & Rhinology, Vol. 5, No. 11, November 2015
0 to 3 with a mean of 0.5 before IMRT and from 0 to 5 with a mean of 1.2 after IMRT. The total CT scores and ethmoid CT score increased significantly after IMRT. The scores for the 5th item of the TWSNOT-22 ranged from 0 to 5 with a mean of 1.1 before IMRT and from 0 to 5 with a mean of 1.7 after IMRT. The scores for the 5th item of the TWSNOT-22 increased significantly after IMRT. The UPSIT-TC scores ranged from 11 to 37 with a mean of 30.6 before IMRT and from 13 to 35 with a mean of 28 after IMRT. The UPSIT-TC scores decreased significantly after IMRT. According to our normative data, 34 (82.9%) patients were classified as normosmic before IMRT, and 31 (75.6%) were normosmic after IMRT. When the change of UPSIT-C scores after IMRT was correlated with the T stage, the correlation was not significant (r = −0.169, p = 0.29). When the change of UPSIT-TC scores after IMRT was correlated with the change of CT scores after IMRT, there was a moderately negative correlation for total CT scores (r = −0.348, p = 0.026) as well as ethmoid CT scores (r = −0.423, p = 0.006).
Discussion Conventional radiotherapy results in significant side effects in NPC patients postirradiation. The incidence of sinus mucosal abnormality was approximately doubled after radiotherapy.15 Therefore, chronic rhinosinusitis has become 1 of the most common side effects of radiotherapy.16 Because the olfactory epithelium and some of the brain structure such as olfactory bulbs are included in the irradiated field, olfactory dysfunction and diminished volume of olfactory bulbs have been reported following radiotherapy.2, 17 The olfactory loss was considered to be most likely sensorineural.6 IMRT is an advanced form of 3-dimensional conformal radiotherapy. The radiation doses to the nasal cavity and normal tissue surrounding the nasopharyngeal tumor are expected to decrease. Our results showed that the TWSNOT-22 scores did not increase after IMRT. This implied that overall sinonasal symptoms did not worsen after IMRT, and a mean score of 28.8 indicated a very mildto-mild sinonasal problem. On the other hand, CT scores increased after IMRT, which meant that rhinosinusitis became worse after IMRT. However, a mean score of 3.2 indicated mild rhinosinusitis. In summary, our results suggested IMRT might lessen rhinosinusitis side effects. One year after IMRT, our patients considered their olfactory function was worse, but a mean score of 1.7 for the 5th item of the TWSNOT-22 (loss of smell or taste) indicated a very mild-to-mild problem. UPSIT-TC scores decreased after IMRT, which meant that olfactory function was impaired after IMRT. Nevertheless, 75.6% of patients still had normal olfactory function, and this showed that the olfactory function of most NPC patients was not affected by IMRT. When the change of UPSIT-TC scores after IMRT was correlated with the change of total CT scores and ethmoid
Wang et al.
CT scores after IMRT, the correlation was moderately negative. This implied that olfactory change after IMRT might result from rhinosinusitis caused by IMRT. Ho et al.6 considered that the olfactory dysfunction in NPC patients after radiotherapy was most likely sensorineural and not conductive, but their patients received conventional radiotherapy. Veyseller et al.2 reported diminished volume of olfactory bulbs following radiotherapy, but all of their patients except 2 also received conventional radiotherapy. In this study, we did not measure the volume of olfactory bulbs. Therefore, we did not evaluate the influence of IMRT on olfactory bulbs, and were not able to exclude the
possibility of sensorineural olfactory dysfunction caused by IMRT.
Conclusion Our results showed that IMRT caused rhinosinusitis side effects but the severity might not be as serious as that with conventional radiotherapy. IMRT also mildly impaired the olfactory function of NPC patients and this might result from the rhinosinusitis side effects caused by IMRT, but we were not able to exclude the possibility of sensorineural olfactory dysfunction caused by IMRT.
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