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 » Introduction
 »  Materials and Me...
 » Results
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  Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 52  |  Issue : 3  |  Page : 398-401
 

Evaluation of salivary function by sialoscintigraphy in locally advanced nasopharyngeal cancer patients after intensity modulated radiotherapy


1 Department of Nuclear Medicine, Buddhist Dalin Tzu Chi Hospital, Chiayi, Taiwan
2 Department of Nuclear Medicine, Buddhist Dalin Tzu Chi Hospital, Chiayi; School of Medicine, Tzu Chi University, Hualian, Taiwan
3 Department of Industrial Engineering and Management, National Yunlin University of Science and Technology, Yunlin, Taiwan
4 Department of Industrial Engineering and Management; Department of Health Industry Management, National Yunlin University of Science and Technology, Yunlin, Taiwan
5 School of Medicine, Tzu Chi University, Hualian; Department of Radiation Oncology, Buddhist Dalin Tzu Chi Hospital, Chiayi, Taiwan
6 Department of Radiation Oncology, Buddhist Dalin Tzu Chi Hospital, Chiayi, Taiwan

Date of Web Publication18-Feb-2016

Correspondence Address:
S K Hung
School of Medicine, Tzu Chi University, Hualian; Department of Radiation Oncology, Buddhist Dalin Tzu Chi Hospital, Chiayi
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.176733

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 » Abstract 

Purpose: This study aimed to evaluate the salivary gland function changes by sialoscintigraphy in locally advanced nasopharyngeal cancer (NPC) after intensity modulated radiotherapy (IMRT). Materials And Methods: Salivary function was assessed by sialoscintigraphy. Quantitative sialoscintigraphy was performed in 24 NPC patients prior to and after IMRT. Results were categorized in four groups according to the duration of treatment. The sialoscintigraphy parameters were examined. Results: Sialoscintigraphy showed a significant difference in the secretion of each interval groups. The parameters of scintigraphy, except maximum accumulation (MA) of submandibular glands, decreased first after radiotherapy, and then recovered. However, the MA of submandibular glands was continuously downhill after radiation. Conclusions: The sialoscintigraphy parameters of each gland changed with the different radiation dose and follow-up intervals. The salivary function was influenced after radiotherapy in locally advanced NPC, especially, in the submandibular gland. Strategies to improve the salivary function should be assessed.


Keywords: Intensity modulated radiotherapy, nasopharyngeal cancer, salivary function, sialoscintigraphy


How to cite this article:
Chuang T L, Wang Y F, Tsai C H, Chiu J E, Lee M S, Chiou W Y, Lin H Y, Tsai W T, Hung S K. Evaluation of salivary function by sialoscintigraphy in locally advanced nasopharyngeal cancer patients after intensity modulated radiotherapy. Indian J Cancer 2015;52:398-401

How to cite this URL:
Chuang T L, Wang Y F, Tsai C H, Chiu J E, Lee M S, Chiou W Y, Lin H Y, Tsai W T, Hung S K. Evaluation of salivary function by sialoscintigraphy in locally advanced nasopharyngeal cancer patients after intensity modulated radiotherapy. Indian J Cancer [serial online] 2015 [cited 2019 Jun 19];52:398-401. Available from: http://www.indianjcancer.com/text.asp?2015/52/3/398/176733



 » Introduction Top


Saliva plays an important role in the maintenance of oral health. It exhibits multiple host defense functions.[1] However, head and neck radiotherapy can impair salivary gland function, leading to mouth dryness, difficulty swallowing, loss of taste and appetite, dental caries, and mucositis.[2] Nasopharyngeal carcinoma (NPC) is unique and distinct from other malignant head and neck tumors.[3] Radiotherapy has long been the standard treatment because of its anatomic location and relative radiosensitivity. However, xerostomia is still a challenge in the long-term survival NPC patients.

Salivary scintigraphy can evaluate the secretory function of salivary glands. Sialoscintigraphy measured significant rank-order correlations in the NPC of follow-up between late effects normal tissue/subjective objective management analytical (LENT/SOMA) scales grading scores.[4] It is very convenient for post-radiation follow-up. In our study, we aimed to use quantitative sialoscintigraphy to evaluate the salivary gland function after intensity modulated radiotherapy (IMRT) in locally advanced NPC patients.


 » Materials and Methods Top


Twenty-four patients with locally advanced NPC from February 2008 to January 2010 inan institution were recorded. Sialoscintigraphy was used to evaluate the salivary function, including pre-therapeutic condition and post-therapy follow-up of several intervals. For post-therapy follow-up interval, patients were assessed at 3, 6, and 12 months, and then every 6-12 months thereafter, we also calculated the radiotherapy dose of each gland to compare the salivary function changes. Each patient signed consent and received an explanation of study protocols. This study was approved by our Institutional Review Board.

After an intravenous injection of 370 MBq Tc-99m pertechnetate, dynamic salivary gland scintigraphy was performed with a dual-head gamma camera and data analysis system (DST-XLi, General Electric Medical Systems, Buc, France) using a low-energy, high-resolution collimator set for the 140-keV photo energy peak with a 20% photo-peak energy window. Anterior sequential salivary gland images and dynamic acquisition started with 20-s frames for 50 min using a 128 × 128 matrix with a zoom factor of 1.6. At the 40th min, we added three full drops of solution with 0.6 g citrate in 50 ml water as an oral salivary stimulant. Data analysiswas performed according to the previous study calculations.[5] The following functional parameterswere calculated for each salivary gland: Uptake ratio (UR), Tmax, Tmin, maximum accumulation, and maximum secretion (MS).

An IMRT technique and inverse planning system (PLATO, Nucletron Inc., Veenendaal, Netherlands) were used for the treatment delivery. The radiation field encompassed the primary tumor bed and neck lymph nodes. The prescribed dose of external beam treatment was 70-72 Gy to the gross tumor and positive neck nodes, 60-64 Gy to the clinical target volume, and 50-60 Gy to the clinically negative neck. Doses were delivered at 1.8-2.0 Gy/day for five consecutive days by a linear accelerator with patients lying supine with a mask.

Sialoscintigraphy used four parameters for analysis, including maximum accumulation of upper parotid glands (MAU), maximum accumulation of lower submandibular glands (MAL), maximum secretion of upper parotid glands (MSU), and maximum secretion of lower submandibular glands (MSL). According to the exam date, the results of sialoscintigraphy were divided in to four groups, including Group 1: Before radiotherapy; Group 2: 1-180 days post-radiotherapy; Group 3: 181-360 days post-radiotherapy, and Group 4: >360 days post-radiotherapy. The data were analyzed by one-way ANOVA (SPSS, version 16), and P < 0.05 was considered statistically significant.


 » Results Top


A Total of 24 patients with 19 men and 5 women (range: 28-78 years old) were collected. Patient baseline characteristics are presented in [Table 1]. Median patient follow-up at the commencement of the analysis was 36 months (range 15-49). All patients received the planned doses of radiation. Median radiation dose delivered to the primary tumor over the study duration was 7200 cGy (range 6120-8100 cGy). The full planned dose of radiotherapy was given to 23 patients. The other one patient did not complete the course because of treatment-induced complications with confluent mucositis and weakness. The average mean dose to the parotid gland was 4413 cGy (range 3767-6657 cGy). The average mean dose to submandibular gland was 6410 cGy (range 6202-7756 cGy).
Table 1: Baseline patient characteristics

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[Table 2] showed the results of sialoscintigraphy at different groups. Except for the MAL, the other three parameter values (MAU, MSU, MSL) decreased from before radiotherapy (Group 1) to 1-180 days post-radiotherapy (Group 2), and then increased 181-360 days post-radiotherapy (Group 3). However, the MAL parameter value decreased progressively even after 12 months follow-up [Figure 1]. Scatterplot drew a trend that showed decreased MSU as an increment of target mean dose [Figure 2] and a trend that showed increased MSU through time post-IMRT [Figure 3].
Table 2: The results of sialoscintigraphy (N: The number of glands)

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Figure 1: The plots of the four sialoscintigraphy parameters according to the four groups. The red line showed a statistically significant differences of the paired groups (P < 0.05) in the post hoc analysis

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Figure 2: Scatterplot of maximum secretion of upper parotid glands (Y-axis) and mean dose (X-axis). There was a trend that showed decreased MSU as an increment of mean dose

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Figure 3: Scatterplot of maximum secretion of upper parotid glands (MSU) (Y-axis) and time (X-axis, 1~360 days post-intensity modulated radiotherapy). There was a trend that showed increased MSU through time

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 » Discussion Top


Radiotherapy is the major treatment for NPC. Because radiotherapy covers the regions of the salivary glands, radiotherapy will induce salivary parenchymal damage and lead impairment. This impairment will decrease saliva production and induce xerostomia.[6] These xerostomia patients often have oral disease and poor quality of life.[7] To establish the tolerance of salivary gland for clinic used is important. Many methods have been used to determine the post-radiation salivary function, including questionnaires, visual analog scales, and salivary scintigraphy. Each has its advantages and disadvantages. The first two methods are subject to significant variation. However, salivary scintigraphy is a convenient method for post-radiation follow-up. It can semiquantitatively evaluate the secretory function of salivary glands.[8] Tc-99m pertechnetate could be used to evaluate changes in excretion and uptake functions of the major salivary glands where the late irradiation effects are associated with gland parenchyma damage and decreased Tc-99m pertechnetate trapping ability.[2] The MS and URs were found to be sufficiently sensitive enough to distinguish the severity of the damage.[9] In this study, we aimed to evaluate salivary gland function changes by sialoscintigraphy in NPC after IMRT.

Radiation induced salivary gland dysfunction and the impairment was increased worse with the total dose.[9] Hakim et al. revealed marked redistribution of reduced acinar cells correlated with the manifested functional impairment.[10] Sagowski et al. showed edema developed after radiation and passed over in to lipomatosis (46 Gy) and necrosis (60 Gy) in the parotid and submandibular glands.[11] According to these data, radiation injury could microscopically show in cell level, and irreversible if threshold dose reached. Salivary dysfunction appeared to be not only an acute but also a chronic condition. In our study, we also had similar results. There was a trend that showed decreased secretion as an increment of salivary gland mean dose, and increased secretion through time post-IMRT.

Patients who received heterogeneous radiation dose to the salivary glands, salivary gland function were inversely correlated with the regional radiation dose.[12] Radiotherapy will induce salivary serous secretory cell atrophy.[13] Parotid glands are mainly composed of serous acinar cells and are more easily affected by radiation than other mucous acinar cells.[14] However, the damage in the submandibular glands was serious in our study. The excretion function of both glands and accumulation function of parotid glands decreased first and then gradually recovery. However, the accumulation function of submandibular glands decreased progressively during follow-up. The reason maybe submandibular glands were not spared and received the higher dose in advanced NPC patients.

Xerostomia has been become a troublesome problem in long-term survival NPC patients.[15] How to improve the quality of life in important. Several strategies have been developed. Modern techniques such as IMRT can reduce the parotid glands dose.[16] Dose <26-30 Gy could significantly preserve salivary gland function.[17] However, it is difficulty to spare the submandibular glands in locally advanced NPC. These glands contribute at least 40% of all saliva during the day and >90% under resting conditions.[17],[18] In our study, the function of submandibular glands was difficult to recover in locally advanced NPC. Surgical submandibular gland transfer was reported to spare 30% of pretreatment salivary function.[19] In addition, certain drugs, such as aminofostine or pilocarpine were developed to protect or promote salivary gland function.[20] In a case report, the salivary scintigraphy is a useful technique to objectively assess salivary gland function in patients with Sjögren's Syndrome and to test their response to pilocarpine.[21] Salivary gland scintigraphy showed a tendency, but not significantly, to recover within the pilocarpine group in both the parotids, and the submandibular glands at 12 months after radiotherapy.[22] Quantitative parotid gland scintigraphy showed both amifostine and IMRT can partially preserve the parotid function after radiotherapy, especially at 13-47 months after radiotherapy.[23] Conventional RT plus Amifostine prevents reduced salivary gland function only in the patient group treated with <40.6 Gy.[24] According to these reports, multiple approaches to improve the quality of life should be assessed.


 » Conclusion Top


The sialoscintigraphy parameters of each gland changed with the different radiation dose and follow-up intervals. The salivary function was influenced after radiotherapy in locally advanced NPC, especially, in the submandibular gland. Strategies to improve the quality of life should be assessed.

 
 » References Top

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2.
Liem IH, Olmos RA, Balm AJ, Keus RB, van Tinteren H, Takes RP, et al. Evidence for early and persistent impairment of salivary gland excretion after irradiation of head and neck tumours. Eur J Nucl Med 1996;23:1485-90.  Back to cited text no. 2
    
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Liu MT, Hsieh CY, Chang TH, Lin JP, Huang CC, Wang AY. Prognostic factors affecting the outcome of nasopharyngeal carcinoma. Jpn J Clin Oncol 2003;33:501-8.  Back to cited text no. 3
    
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Liu WS, Kuo HC, Lin JC, Su MC, Lee JK, Chou MJ, et al. Assessment of salivary function change in nasopharyngeal carcinoma treated by parotid-sparing radiotherapy. Cancer J 2006;12:494-500.  Back to cited text no. 4
    
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Umehara I, Yamada I, Murata Y, Takahashi Y, Okada N, Shibuya H. Quantitative evaluation of salivary gland scintigraphy in Sjörgen's syndrome. J Nucl Med 1999;40:64-9.  Back to cited text no. 5
    
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Rhodus NL, Moller K, Colby S, Bereuter J. Dysphagia in patients with three different etiologies of salivary gland dysfunction. Ear Nose Throat J 1995;74:39-42, 45-8.  Back to cited text no. 7
    
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Kohn WG, Ship JA, Atkinson JC, Patton LL, Fox PC. Salivary gland 99mTc-scintigraphy: A grading scale and correlation with major salivary gland flow rates. J Oral Pathol Med 1992;21:70-4.  Back to cited text no. 8
    
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Raza H, Khan AU, Hameed A, Khan A. Quantitative evaluation of salivary gland dysfunction after radioiodine therapy using salivary gland scintigraphy. Nucl Med Commun 2006;27:495-9.  Back to cited text no. 9
    
10.
Hakim SG, Jacobsen HCh, Hermes D, Kosmehl H, Lauer I, Nadrowitz R, et al. Early immunohistochemical and functional markers indicating radiation damage of the parotid gland. Clin Oral Investig 2004;8:30-5.  Back to cited text no. 10
    
11.
Sagowski C, Wenzel S, Riehle I, Tesche S, Jenicke L, Zywietz F, et al. Histomorphologic and salivary gland scintigraphic findings in radiation-induced sialadenitis due to fractionated irradiation of the head and neck region of rats. A model for evaluating potentially radioprotective substances. HNO 2004;52:25-32.  Back to cited text no. 11
    
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Greenspan JS, Melamed MR, Pearse AG. Early histochemical changes in irradiated salivary glands and lymph-nodes of the rat. J Pathol Bacteriol 1964;88:439-53.  Back to cited text no. 12
    
13.
Buus S, Grau C, Munk OL, Bender D, Jensen K, Keiding S. 11C-methionine PET, a novel method for measuring regional salivary gland function after radiotherapy of head and neck cancer. Radiother Oncol 2004;73:289-96.  Back to cited text no. 13
    
14.
Stephens LC, Schultheiss TE, Price RE, Ang KK, Peters LJ. Radiation apoptosis of serous acinar cells of salivary and lacrimal glands. Cancer 1991;67:1539-43.  Back to cited text no. 14
    
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Dirix P, Nuyts S, Van den Bogaert W. Radiation-induced xerostomia in patients with head and neck cancer: A literature review. Cancer 2006;107:2525-34.  Back to cited text no. 15
    
16.
Eisbruch A, Ship JA, Martel MK, Ten Haken RK, Marsh LH, Wolf GT, et al. Parotid gland sparing in patients undergoing bilateral head and neck irradiation: Techniques and early results. Int J Radiat Oncol Biol Phys 1996;36:469-80.  Back to cited text no. 16
    
17.
Münter MW, Karger CP, Hoffner SG, Hof H, Thilmann C, Rudat V, et al. Evaluation of salivary gland function after treatment of head-and-neck tumors with intensity-modulated radiotherapy by quantitative pertechnetate scintigraphy. Int J Radiat Oncol Biol Phys 2004;58:175-84.  Back to cited text no. 17
    
18.
Dawes C. Rhythms in salivary flow rate and composition. Int J Chronobiol 1974;2:253-79.  Back to cited text no. 18
    
19.
Seikaly H, Jha N, Harris JR, Barnaby P, Liu R, Williams D, et al. Long-term outcomes of submandibular gland transfer for prevention of postradiation xerostomia. Arch Otolaryngol Head Neck Surg 2004;130:956-61.  Back to cited text no. 19
    
20.
Brizel DM, Wasserman TH, Henke M, Strnad V, Rudat V, Monnier A, et al. Phase III randomized trial of amifostine as a radioprotector in head and neck cancer. J Clin Oncol 2000;18:3339-45.  Back to cited text no. 20
    
21.
Santos LAN, Neto FH, Boscolo FN, Campos PS, Martelli Jr H, Laranjeira AL, et al. Scintigraphy of the salivary gland in patients with sjögren' s syndrome treated with pilocarpine. Rev Clín Pesq Odontol, Curitiba 2010;6:101-06.  Back to cited text no. 21
    
22.
Mateos JJ, Setoain X, Ferre J, Rovirosa A, Navalpotro B, Martin F, et al. Salivary scintigraphy for assessing the protective effect of pilocarpine in head and neck irradiated tumours. Nucl Med Commun 2001;22:651-6.  Back to cited text no. 22
    
23.
Rudat V, Münter M, Rades D, Grötz KA, Bajrovic A, Haberkorn U, et al. The effect of amifostine or IMRT to preserve the parotid function after radiotherapy of the head and neck region measured by quantitative salivary gland scintigraphy. Radiother Oncol 2008;89:71-80.  Back to cited text no. 23
    
24.
Münter MW, Hoffner S, Hof H, Herfarth KK, Haberkorn U, Rudat V, et al. Changes in salivary gland function after radiotherapy of head and neck tumors measured by quantitative pertechnetate scintigraphy: Comparison of intensity-modulated radiotherapy and conventional radiation therapy with and without Amifostine. Int J Radiat Oncol Biol Phys 2007;67:651-9.  Back to cited text no. 24
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2]



 

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