| Summary: | 博士 === 中山醫學大學 === 醫學研究所 === 95 === The crude incidence of nasopharyngeal cancer (NPC) in Taiwan is 283 cases per 100 thousands people per year. This disease occupies 10th place in incidence of cancer in men and eighteenth in women. As for the death rate position, NPC is 9th in men and eleventh in women. Though the incidence of this disease is not very high compared to other cancers in Taiwan, the incidence is about 25 to 50 times higher than the general incidence of the world. Hence, we must depend on our own efforts to study this disease. Compared to other sites of head and neck cancer, NPC has a totally different epidemiology and etiology. External beam radiotherapy has remained the major treatment method for this disease. Although we could get about 70 - 80 % five-year survival by radiotherapy alone for early stage patients, the long-term survival would be as low as 40 % for stage four disease. There have been two major improvements in the treatment of NPC. First, many researches proved that concurrent chemo-radiotherapy (CCRT) could increase the survival, and disease-free survival, in locally advanced disease. Second, using intensity-modulated radiotherapy (IMRT) could increase the local regional control rate in both early and advanced stage patients. Apart from the improvement of treatment method, many researchers have tried to find prognostic factors other than the clinical stage. For example, Dr. Lin found that EBV DNA copies numbers could be a ‘stand-alone’ prognostic factor for this disease. How to control the side effects becomes a most important issue when more and more patients could become survivors. The xerostomia is the most frequent late sequel after the treatment of NPC. This symptom could impair the life quality of the survivors. Xerostomia impairs chewing, swallowing and speech functions. IMRT could protect the parotid glands in the dosimetric study; however, whether this dosimetric benefit could translate to clinical benefit is the question. Which factor could affect the success of parotid gland protection? Is subjective sensation compatible with the objective findings of parotid gland impairment? All these questions became our motivation for further studying.
From August 2000 to July 2003, 45 patients with histological proven, non-metastatic nasopharyngeal carcinoma were included in this study. There were 34 males and 11 females. For the maximum benefit of both physics and biology, we adopt the simultaneous integrated boost (SIB) method in planning the treatment for these patients. The dose to the gross target volume (GTV), PTV and GTV-LN were as least 70 Gy, 55-60 Gy, 66-70 Gy, respectively. Hence, the fraction-size of the above targets was: 2.12 Gy, 1.7-1.8 Gy, and 2.0-2.12 Gy, respectively. The dose constraint to parotid glands was 33 – 35 Gy. There were thirty-one patients in this series that received CCRT. The regimen of chemotherapy was cisplatin (60mg/m2) on Day 1 and Day 28 and 5-FU (600mg/m2) on Day 1-4 and Day 28-31. We used SOMA/LENT scale for recording both subjective and objective dry mouth grading. The sialoscintigraphy was used as an objective method for the evaluation of the function of parotid glands in this study. The pre-irradiation sialoscintigraphy was performed in all patients, and the tests were repeated at intervals of one (43 cases), six (37 cases), twelve (39 cases), and eighteen (36 cases) months after the completion of radiotherapy. The Wilcoxon signed-rank pair test was used to compare the difference in the SR of salivary glands before and after radiotherapy. The Mann-Whitney rank-sum test was used to compare the difference of SR between parotid and submandibular glands. Spearman rank-order correlation tests were used to evaluate correlations between LENT/SOMA subjective and objective scoring. The mean dose administered to the GTV and PTV was 71.8 Gy and 65.9 Gy, respectively. The dose to the metastatic neck LN was 72.7 Gy. The median dose administered to the parotid glands was 34.6 Gy. The mean SR of the parotid gland was 0.3 (ranged from 0.0 to 0.67). The SR of the right and left parotid gland was 0.36 and 0.22, respectively. There was no significant difference between them. The mean SR after treatment in one, six, twelve, and eighteen months were: 0.01, 0.08, 0.20, and 0.18, respectively. There were significant differences between the pre- and post-irradiation parotid gland SR after one and six months. However, there was no significant difference between pre- and post-irradiation after twelve and eighteen months (Figure 5). As for the group use for studying the correlation between subjective and objective xerostomia grading patients (34 cases), there were no significant differences between ipsilateral and contralateral parotid glands. There were significant difference between pre- (SR=0.3) and one month (SR=0.01, p=0.000), and six months (SR=0.08, p=0.002). However, there were no significant differences compared to the pre-irradiation data up to twelve (SR=0.22, p=0.734), and eighteen (SR=0.16, p=0.885) months. The function of submandibular glands had significant impairment after one to eighteen months following treatments. Based on the SOMA/LENT scale, the numbers of subjective grading of pre-irradiation were: 30 patients belonging to Grade 0 and 4 patients belonging to Grade 1. Up to six months after radiotherapy, most of our patients belonged to Grade 2 (67.6% and 76.5%). However, the most frequent grading became Grade 1 (47.1% and 52.9%), after one year of radiotherapy. After 1 month of radiotherapy, there was no significant correlation between LENT/SOMA subjective and objective xerostomia grading scores (r=0.393, p=0.063). However, there was a significant correlation between scores at 6 months (r=0.657, p=0.000), 12 months (r=0.480, p=0.013), and 18 months (r=0.591, p=0.002). The factor impacting the preservation of parotid function was a mean dose of parotid gland greater than 38.0 Gy (p<0.05). The mean follow-up time was 42.0 months (range, 27-50 months). No patient had local recurrence at the primary site. There were two patients who had regional lymph node recurrences. A total of six patients developed distant metastases. Four-year loco-regional progression–free and disease–free survival rates were 94.1 % and 82.4 %, respectively. Four-year overall survival was 91.2 %.
Even though patients with NPC received a median dose of 34.6 Gy (mean 38.2 Gy) to the bilateral parotid glands, gland function recovered significantly by 12 months after radiotherapy. But there was no further recovery from 12 months to 18 months after radiotherapy. Based on sialoscintigraphy examination, there were significant rank-order correlations between LENT/SOMA subjective and objective (analytic) grading scores measured by SR per sialoscintigraphy after 6 to 18 months of follow-up. The mean dose over 38 Gy was the only factor that affected the function of the parotid gland after treatment.
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