Xerostomia and quality of life after intensity-modulated radiotherapy vs. conventional radiotherapy for early-stage nasopharyngeal carcinoma: initial report on a randomized controlled clinical trial

PURPOSE: To compare directly the effect of intensity-modulated radiotherapy (IMRT) vs. conventional radiotherapy (CRT) on salivary flow and quality of life (QoL) in patients with early-stage nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Fifty-one patients with T2, N0/N1, M0 NPC took part in a randomized controlled clinical study and received IMRT or CRT. Stimulated whole (SWS) and parotid (SPS) saliva flow were measured and Medical Outcomes Short Form 36 (SF-36), European Organization for Research and Treatment of Cancer (EORTC) core quetionnaire, and EORTC head-and-neck module (QLQ-H&N35) were completed at baseline and 2, 6, and 12 months after radiotherapy. RESULTS: Forty-six patients (88%) were in disease remission 12 months after radiotherapy. At 12 months postradiotherapy, 12 (50.0%) and 20 patients (83.3%) in the IMRT group had recovered at least 25% of preradiotherapy SWS and SPS flow respectively, compared with 1 (4.8%) and 2 patients (9.5%), respectively, in the CRT group. Global health scores showed continuous improvement in QoL after both treatments (p < 0.001). However, after 12 months subscale scores for role-physical, bodily pain, and physical function were significantly higher in the IMRT group, indicating a better condition (p < 0.05). Dry mouth and sticky saliva were problems in both groups 2 months after treatment. In the IMRT group, there was consistent improvement over time with xerostomia-related symptoms significantly less common than in the CRT group at 12 months postradiotherapy. CONCLUSIONS: IMRT was significantly better than CRT in terms of parotid sparing and improved QoL for early-stage disease. The findings support the case for assessment of health-related QoL in relation to head-and-neck cancer using a site-specific approach.     

Parotid-sparing intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma: preserved parotid function after IMRT on quantitative salivary scintigraphy, and comparison with historical data after conventional radiotherapy

PURPOSE: To evaluate the parotid function after parotid-sparing intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: From March 2003 to May 2004, 16 patients with nonmetastatic NPC underwent parotid-sparing IMRT. Eight of these patients had Stage III or IV NPC based on the 1997 American Joint Committee on Cancer staging system. The post-IMRT parotid function was evaluated by quantitative salivary scintigraphy and represented by the maximal excretion ratio (MER) of the parotid gland after sialogogue stimulation. The parotid function of 16 NPC patients who were previously treated with conventional radiotherapy was reviewed as the historical control. RESULTS: In the parotid-sparing IMRT group, all 16 patients were alive and without cancer at the end of follow-up period (median, 24.2 months). The mean parotid MER was 53.5% before radiotherapy, 10.7% at 1 month post-IMRT, and 23.3% at 9 months post-IMRT. In the conventional radiotherapy group, the mean parotid MER was 0.6% at 6 to 12 months postradiotherapy. The difference was statistically significant (23.3% vs. 0.6%, p<0.001, Mann-Whitney test). In the IMRT group, the mean parotid doses ranged from 33.2 Gy to 58.8 Gy (average, 43.9 Gy). The correlation between the mean parotid dose and the percentage decrease of parotid MER at 9 months post-IMRT (dMER) was statically significant (p=0.008, Pearson correlation). CONCLUSIONS: Although the mean parotid doses are relatively high, the significant preservation of parotid function is achieved with IMRT for NPC patients. The significant correlation between mean parotid dose and parotid dMER demonstrates the dose-function relationship of the parotid gland.     

Long-term parotid gland function after radiotherapy

PURPOSE: Irradiation of the parotid glands causes salivary dysfunction, resulting in reduced salivary flow. Recovery can be seen with time; however, long-term prospective data are lacking. The objective of this study was to analyze the long-term parotid gland function after irradiation for head-and-neck cancer. METHODS AND MATERIALS: A total of 52 patients with head-and-neck cancer and treated with radiotherapy (RT) were prospectively evaluated. Stimulated bilateral parotid salivary flow rates were measured before RT and 6 weeks, 6 months, 12 months, and at least 3.5 years after RT completion. A complication was defined as a stimulated parotid flow rate of <25% of the pre-RT flow rate. The normal tissue complication probability model proposed by Lyman was fit to the data. Multilevel techniques were used to model the patterns of flow rates with time. RESULTS: The mean stimulated flow rate of the parotid glands before RT was 0.31 mL/min (standard deviation [SD], 0.21). This was reduced to 0.14 mL/min (SD, 0.15) at 6 weeks after RT and recovered to 0.20 mL/min (SD, 0.22) at 6 months and 0.19 mL/min (SD, 0.21) at 12 months after RT. The mean stimulated flow rate was 0.25 mL/min (SD, 0.28) 5 years after RT. The mean dose to the parotid gland resulting in a 50% complication probability increased from 34 Gy at 6 weeks to 40 Gy at 6 months, 42 Gy at 12 months, and 46 Gy at 5 years after RT. Multilevel modeling indicated that both dose and time were significantly associated with the flow ratio. CONCLUSION: Salivary output can still recover many years after RT. At 5 years after RT, we found an increase in the salivary flow rate of approximately 32% compared with at 12 months after RT.     

Intensity-modulated radiotherapy significantly reduces xerostomia compared with conventional radiotherapy

PURPOSE: Xerostomia is a severe complication after radiotherapy for oropharyngeal cancer, as the salivary glands are in close proximity with the primary tumor. Intensity-modulated radiotherapy (IMRT) offers theoretical advantages for normal tissue sparing. A Phase II study was conducted to determine the value of IMRT for salivary output preservation compared with conventional radiotherapy (CRT). METHODS AND MATERIALS: A total of 56 patients with oropharyngeal cancer were prospectively evaluated. Of these, 30 patients were treated with IMRT and 26 with CRT. Stimulated parotid salivary flow was measured before, 6 weeks, and 6 months after treatment. A complication was defined as a stimulated parotid flow rate <25% of the preradiotherapy flow rate. RESULTS: The mean dose to the parotid glands was 48.1 Gy (SD 14 Gy) for CRT and 33.7 Gy (SD 10 Gy) for IMRT (p < 0.005). The mean parotid flow ratio 6 weeks and 6 months after treatment was respectively 41% and 64% for IMRT and respectively 11% and 18% for CRT. As a result, 6 weeks after treatment, the number of parotid flow complications was significantly lower after IMRT (55%) than after CRT (87%) (p = 0.002). The number of complications 6 months after treatment was 56% for IMRT and 81% for CRT (p = 0.04). CONCLUSIONS: IMRT significantly reduces the number of parotid flow complications for patients with oropharyngeal cancer.     

Intensity modulated radiotherapy for head and neck cancer: evidence for preserved salivary gland function.

BACKGROUND AND PURPOSE: To investigate the salivary gland function following intensity modulated radiotherapy (IMRT) for head and neck cancer. PATIENTS AND METHODS: Seventeen patients with oropharyngeal (n=11) or nasopharyngeal (n=6) carcinoma located adjacent to the major salivary glands were treated with IMRT with an emphasis to spare the salivary glands from high-dose irradiation and to reduce the risk of postirradiation xerostomy. Three patients had stage 2, 4 stage III, and 10 stage IVA cancer. The total basal and stimulated saliva flow rates were measured before the treatment, and 6 and 12 months after radiotherapy. RESULTS: The median basal saliva flow rate measured before radiation treatment was 0.13 mL/min, and at 6 and 12 months after the completion of IMRT 0.04 mL/min and 0.07 mL/min, respectively. The corresponding median stimulated saliva flow rates were 0.49 mL/min, 0.33 mL/min, and 0.45 mL, respectively. The D50 for an impaired stimulated parotid gland saliva flow rate was 25.5 Gy. Only two (12%) patients developed grade 3 and none grade 4 xerostomia during a median follow-up of 24 months (range, 12-40 months). No patients had locoregional cancer recurrence following IMRT. CONCLUSIONS: The results suggest that much of the salivary gland function can be maintained with IMRT without jeopardizing the local control rate in the treatment of locally advanced oropharynx or nasopharynx carcinoma.     

A prospective study of salivary function sparing in patients with head-and-neck cancers receiving intensity-modulated or three-dimensional radiation therapy: initial results

OBJECTIVES: In a prospective clinical study, we tested the hypothesis that sparing the parotid glands may result in significant objective and subjective improvement of xerostomia in patients with head-and-neck cancers. The functional outcome 6 months after the completion of radiation therapy is presented. METHODS AND MATERIALS: From February 1997 to February 1999, 41 patients with head-and-neck cancers were enrolled in a prospective salivary function study. Inverse-planning intensity-modulated radiation therapy (IMRT) was used to treat 27 patients, and forward-planning three-dimensional radiation therapy in 14. To avoid potential bias in data interpretation, only patients whose submandibular glands received greater than 50 Gy were eligible. Attempts were made to spare the superficial lobe of the parotid glands to avoid underdosing tumor targets in the parapharyngeal space; however, the entire parotid volume was used to compute dose-volume histograms (DVHs) for this analysis. DVHs were computed for each gland separately. Parotid function was assessed objectively by measuring stimulated and unstimulated saliva flow before and 6 months after the completion of radiation therapy. Measurements were converted to flow rate (mL/min) and normalized relative to that before treatment. The corresponding quality-of-life (QOL) outcome was assessed by five questions regarding the patient's oral discomfort and eating/speaking problems. RESULTS: We observed a correlation between parotid mean dose and the fractional reduction of stimulated saliva output at 6 months after the completion of radiation therapy. We further examined whether the functional outcome could be modeled as a function of dose. Two models were found to describe the dose-response data well. The first model assumed that each parotid gland is comprised of multiple independent parallel functional subunits (corresponding to computed tomography voxels) and that each gland contributes equally to overall flow, and that saliva output decreases exponentially as a quadratic function of irradiation dose to each voxel. The second approach uses the equivalent uniform dose (EUD) metrics, which assumes loss of salivary function with increase in EUD for each parotid gland independently. The analysis suggested that the mean dose to each parotid gland is a reasonable indicator for the functional outcome of each gland. The corresponding exponential coefficient was 0.0428/Gy (95% confidence interval: 0.01, 0.09). The QOL questions on eating/speaking function were significantly correlated with stimulated and unstimulated saliva flow at 6 months. In a multivariate analysis, a toxicity score derived from the model based on radiation dose to the parotid gland was found to be the sole significant predictive factor for xerostomia. Neither radiation technique (IMRT vs. non-IMRT) nor chemotherapy (yes or no) independently influenced the functional outcome of the salivary glands. CONCLUSION: Sparing of the parotid glands translates into objective and subjective improvement of both xerostomia and QOL scores in patients with head-and-neck cancers receiving radiation therapy. Modeling results suggest an exponential relationship between saliva flow reduction and mean parotid dose for each gland. We found that the stimulated saliva flow at 6 months after treatment is reduced exponentially, for each gland independently, at a rate of approximately 4% per Gy of mean parotid dose.     

鼻咽癌调强放疗对腮腺功能的影响

目的 评价调强放疗对鼻咽癌患者腮腺功能的影响.方法 搜集2003年前2年内83例初治患者放疗前、放疗结束时、放疗后6个月和1、2、3、4、5年的口干变化情况的资料,通过分析其与腮腺受照剂量关系来评价调强放疗对腮腺功能影响.结果 共入组83例,其中Ⅰ期4例,Ⅱ期31例,Ⅲ期31例,ⅣA期17例;16例接受放化综合治疗.中位随访时间65个月,5年局部和区域控制率为96%和95%,总生存率为80%.放疗后7个时间段轻和中度口干发生率分别为42%、51%、71%、77%、58%、38%、26%和52%、53%、21%、8%、3%、2%、2%,无重度口干.双侧腮腺受照射平均剂量为34.34 Gy.放疗后6个月口干分级与腮腺平均受照剂量呈正相关,双侧腮腺50%体积受照剂量是放疗后6个月时口干分级的独立影响因素.当腮腺平均剂量≤33 Gy和D50≤29 Gy时,腮腺功能可得到较好地保护.结论 调强放疗在提高鼻咽癌局部和区域控制率的同时,降低了腮腺的受照剂量,减少了腮腺功能的损伤.     

鼻咽癌适形调强放疗中涎腺功能的全面保护

  目的  探讨鼻咽癌适形调强放疗(intensity modulate radiation therapy, IMRT)患者各涎腺功能的保护方法。  方法  选取2010年3月至2012年11月101例连续于中山大学肿瘤医院接受IMRT鼻咽癌患者, 勾画危及器官, 包括腮腺、颌下腺、口腔, 于3、6、12、18、24个月复查时采用面对面访谈式问卷调查评分口干程度情况, 并结合剂量体积直方图(dose-volume histograms, DVH)进行分析。  结果  腮腺平均剂量(MD)为37.4 Gy (患侧), 33.8 Gy (健侧); 颌下腺MD为51.6 Gy (患侧), 45.7 Gy (健侧); 口腔MD为38.2 Gy。77.2%(78/101)患者放疗结束后6个月口干症状明显改善, 1年后中度(G3)以上口干患者 < 5.0%(5/101)。  结论  随着时间的推移, 放疗后口干燥症明显改善; 限定至少一侧腮腺V30~35≤50.0%, 至少一侧颌下腺V40~45≤66.7%~50.0%, 口腔MD < 40 Gy可有效保护唾液腺功能。      

唾液腺显像对鼻咽癌放疗后腮腺功能的评价

目的探讨唾液腺显像对鼻咽癌放疗后腮腺功能的评价。方法对40例鼻咽癌行适形调强放疗（30例）及常规放疗（10例）的患者,分别于放疗前、放疗结束时及放疗后5个月作口干程度的比较及唾液腺功能显像榆查。结果放疗结束时患苦出现不同程度口干症状,放疗后5个月,部分患者口千症状有明显改善。唾液腺受损后腮腺显像图像征象及时问放射性曲线均有变化。放疗结束时腮腺定量分析摄取指数（UI）及分泌指数（E1）均比放疗前低（P〈0．05）,但适形调强放疗组的UI及EI均比常规放疗组高（P〈0．05）。结论适形凋强放疗可以有效保护腮腺功能,唾液腺显像可用于监测鼻咽癌放疗后腮腺功能变化。     

不同放射治疗方式致鼻咽癌患者腮腺功能损伤的研究

目的评价不同放射治疗方式对鼻咽癌患者腮腺功能的损伤状况。方法常规分割（CF）组175例,总量70Gy;后程加速超分割放射治疗（LCAF）组63例,先用CF照射36—40Gy,再用LCAF照射35～40Gy,总量75Gy;调强适形放射治疗（IMRT）组142例,处方剂量72Gy。放射治疗期间观察急性放射性腮腺炎发生情况,2年后测定腮腺静止性分泌功能。结果IMRT组的腮腺受照射剂量远远低于其他两组。CF组、LCAF组和IMRT组急性放射性腮腺炎发生率分别为23．4％、41．3％和20．4％,差异有统计学意义（P〈0．05）。2年后,CF组、LCAF组和IMRT组腮腺分泌功能下降率分别为81．7％、81．0％和69．7％,差异有统计学意义（P〈0．05）。结论不同放射治疗方式对鼻咽癌患者的腮腺功能损伤程度不同,IMRT有利于覆盖肿瘤靶区,并使邻近敏感器官获得有效分割,使腮腺功能得到较好保护。     

Preservation of oral health-related quality of life and salivary flow rates after inverse-planned intensity- modulated radiotherapy (IMRT) for head-and-neck cancer

PURPOSE: To assess whether comprehensive bilateral neck intensity-modulated radiotherapy (IMRT) for head-and-neck cancer results in preserving of oral health-related quality of life and sparing of salivary flow in the first year after therapy. METHODS AND MATERIALS: Twenty-three patients with head-and-neck cancer (primary sites: nasopharynx [5], oral cavity [12], oropharynx [3], and all others [3]) were accrued to a Phase I-II trial. Inverse planning was carried out with the following treatment goals: at least 1 spared parotid gland (defined as the volume of parotid gland outside the planning target volume [PTV]) to receive a median dose of less than 20 Gy; spinal cord, maximum 45 Gy; PTV(1) to receive a median dose of 50 Gy; PTV(2) to receive a median dose of 60 Gy (postoperative setting, n = 15) or 66-70 Gy (definitive radiotherapy setting, n = 8). Treatment was delivered with 6 and 15 MV photons using a "step-and-shoot" technique on a Varian 2300 EX linac with 120-leaf Millenium MLC. Unstimulated and stimulated whole-mouth salivary flow rates were measured, and patients completed the University of Washington instrument (UWQOL) and a separate xerostomia questionnaire (XQOL) in follow-up. RESULTS: Early functional outcome end point data are available at the 1-, 3-, and 12-month follow-up time points for 22, 22, and 18 patients, respectively. The combined mean parotid dose was 30.0 Gy (95% confidence interval: 26.9-33.1). The differences from baseline in mean overall UWQOL scores at 1, 3, and 12 months postradiotherapy were -0.24, 0.32, and 4.28, not significantly different from zero (p = 0.89, p = 0.87, p = 0.13). None of the UWQOL individual domain scores related to oral health (pain, eating-chewing, eating-swallowing, and speech) at 1, 3, or 12 months were significantly different from baseline. Both unstimulated and stimulated whole-mouth flow was variably preserved. Unstimulated salivary flow at 1 and 12 months was inversely correlated with combined mean parotid dose (p = 0.014, p = 0.0007), whereas stimulated salivary flow rates at 3 and 12 months were also correlated with combined mean parotid dose (p = 0.025, p = 0.0016). Combined maximum parotid dose was correlated with unstimulated flow rate at 12 months (p = 0.02, r = -0.56) and stimulated flow rate at 1 and 12 months (p = 0.036, r = -0.45; p = 0.0042, r = -0.66). The proportion of patients reporting total XQOL scores of 0 or 1 (no or mild xerostomia) did not diminish significantly from baseline at 1, 3, or 12 months (p = 0.72, p = 0.51, p = 1.0). Unstimulated and stimulated flow at 1 month was inversely correlated with total XQOL score at 12 months (p = 0.025, p = 0.029). CONCLUSIONS: Oral health-related quality of life (HRQOL) was highly preserved in the initial 12 months after IMRT, as assessed with separate, validated instruments for xerostomia-specific quality of life and oral HRQOL. In general, patients with better-preserved unstimulated salivary flow rates tended to report lower xerostomia scores. Whole-mouth salivary flow rates post IMRT were inversely correlated with combined mean parotid doses. Longer follow-up is required to assess to what extent HRQOL is favorably maintained.     

30例早期鼻咽癌调强放射治疗疗效分析

目的:探讨调强放射治疗(IMRT)对早期鼻咽癌的近期疗效和不良反应.方法:回顾分析30例早期鼻咽癌患者,鼻咽部和上颈部淋巴引流区采用IMRT技术照射,下颈部淋巴引流区采用颈前野常规照射.鼻咽大体肿瘤体积(GTVnx)处方剂量68Gy-74Gy,颈部淋巴结(GTVnd)处方剂量64Gy-70Gy,临床靶体积(CTV1)处方剂量 60Gy-64Gy,临床靶体积(CTV2)处方剂量 50Gy-54Gy,分30-34次进行照射.对于淋巴结分期为N1的患者,结合淋巴结的情况行诱导化疗和(或)同期化疗2-4周期,N0患者行单纯调强放射治疗.结果:鼻咽大体肿瘤体积(GTVnx)D95平均剂量为74.5Gy,GTVnx V95平均体积99.6%,脊髓D1cc平均剂量41.5Gy,脑干D3平均剂量50.3Gy,左腮腺D50平均剂量32.8Gy,右腮腺D50平均剂量31.4Gy,左颞叶D10平均剂量45.5Gy,右颞叶D10平均剂量45.2Gy,均低于限制剂量.中位随访时间33.5个月(4-45个月).1年、2年、3年的总生存率、无局部复发生存率和无远处转移生存率均为100%.最严重的急性反应是放射性黏膜炎,1-3级分别有 63.3%,30%,和6.7%,晚期不良反应主要表现为口干(Ⅰ度33.3%,Ⅱ度3.7%).结论:IMRT对初治早期鼻咽癌可获得理想的剂量分布,取得较好的近期疗效,正常组织得到很好的保护.     

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

PURPOSE: The aim of this study was to compare changes in salivary gland function after intensity-modulated radiotherapy (IMRT) and conventional radiotherapy (RT), with or without Amifostine, for tumors of the head-and-neck region using quantitative salivary gland scintigraphy (QSGS). METHODS AND MATERIALS: A total of 75 patients received pre- and post-therapeutic QSGS to quantify the salivary gland function. In all, 251 salivary glands were independently evaluated. Changes in the maximum uptake (DeltaU) and relative excretion rate (DeltaF) both pre- and post-RT were determined to characterize radiation-induced changes in the salivary gland function. In addition, dose-response curves were calculated. RESULTS: In all groups, maximum uptake and relative excretion rate were reduced after RT (DeltaU 相似文献   

Two-year longitudinal study of parotid salivary flow rates in head and neck cancer patients receiving unilateral neck parotid-sparing radiotherapy treatment

Radiotherapy (RT) is a common treatment for head and neck cancers, and frequently causes permanent salivary dysfunction and xerostomia. This 2-year longitudinal study evaluated unstimulated and stimulated parotid flow rates in 11 patients with head and neck cancers who received unilateral neck parotid-sparing RT. The results demonstrated that treated parotid glands had essentially no output up to 2 years post-RT. Alternatively, spared parotid flow rates were indistinguishable from pre-RT values at 1 and 2 years post-RT, and increased slightly over time. Total unstimulated and stimulated parotid flow rates 2 years after completion of RT were similar to pre-RT values, suggesting that spared parotid function may compensate for lost function from treated parotid glands. These results demonstrate that unilateral neck parotid-sparing techniques are effective in preserving contralateral parotid glands up to 2 years after the completion of RT.     

鼻咽癌调强放疗后近期腮腺功能影响因素分析

[目的]总结鼻咽癌调强放疗后腮腺功能影响因素。[方法]收集2008年7月至2009年8月初治的20例鼻咽癌调强放疗靶区及腮腺剂量学参数,随访其放疗后3个月口干情况,分析腮腺受照剂量与口干分级之间的关系。[结果]20例接受调强放疗鼻咽癌腮腺平均剂量41.25Gy,患侧腮腺V20：96.77%,V30：80.56%,V40：52.43%,健侧腮腺V20：971.47%,V30：69.95%,V40：40.85%。放疗后3个月轻度、中度、重度口干发生率分别为15%、55%、30%,口干分级与腮腺平均剂量、患侧及健侧腮腺V20、V30、V40呈正相关。[结论]鼻咽癌调强放疗后腮腺功能与腮腺受照体积、剂量显著相关。     

Evaluation of salivary gland function after treatment of head-and-neck tumors with intensity-modulated radiotherapy by quantitative pertechnetate scintigraphy

PURPOSE: To evaluate salivary gland function after inversely planned stereotactic intensity-modulated radiotherapy (IMRT) for tumors of the head-and-neck region using quantitative pertechnetate scintigraphy. METHODS AND MATERIALS: Since January 2000, 18 patients undergoing IMRT for cancer of the head and neck underwent pre- and posttherapeutic scintigraphy to examine salivary gland function. The mean dose to the primary planning target volume was 61.5 Gy (range 50.4-73.2), and the median follow-up was 23 months. In all cases, the parotid glands were directly adjacent to the planning target volume. The treatment planning goal was for at least one parotid gland to receive a mean dose of <26 Gy. Two quantitative parameters (change in maximal uptake and change in the relative excretion rate before and after IMRT) characterizing the change in salivary gland function after radiotherapy were determined. These parameters were compared with respect to the dose thresholds of 26 and 30 Gy for the mean dose. In addition, dose-response curves were calculated. RESULTS: Using IMRT, it was possible in 16 patients to reduce the dose for at least one parotid gland to < or =26 Gy. In 7 patients, protection of both parotid glands was possible. No recurrent disease adjacent to the protected parotid glands was observed. Using the Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer scoring system, only 3 patients had Grade 2 xerostomia. No greater toxicity was seen for the salivary glands. The change in the relative excretion rate was significantly greater, if the parotid glands received a mean dose of > or =26 Gy or > or =30 Gy. For the change in maximal uptake, a statistically significant difference was seen only for the parotid glands and a dose threshold of 30 Gy. For the end point of a reduction in the parotid excretion rate of >50% and 75%, the dose-response curves yielded a dose at 50% complication probability of 34.8 +/- 3.6 and 40.8 +/- 5.3 Gy, respectively. CONCLUSION: Using IMRT, it is possible to protect the parotid glands and reduce the incidence and severity of xerostomia in patients. Doses <26-30 Gy significantly preserve salivary gland function. The results support the hypothesis that application of IMRT does not lead to increased local failure rates.     

鼻咽癌调强放疗初步结果

目的:探讨鼻咽癌三维适形调强放射治疗(intensity-modulatedradiotherapy,IMRT)的初步疗效。方法:对91例经病理确诊的鼻咽低分化鳞癌患者进行调强放疗。处方剂量分别为GTV(鼻咽部和颈部淋巴结肿瘤靶区)66~70Gy,CTV1(临床靶区)60~62Gy,CTV2和CTVn(颈部淋巴结区域)54~56Gy。11例患者IMRT结束后有局部残留,1例采用IMRT追量照射10Gy/4次,其余给予鼻咽腔内后装追量照射9~15Gy/3~5次。分析疗效及放射治疗毒性。结果:中位随访时间12个月,1和2年生存率为97·1%和97·1%,局控率为97·1%和92·5%。急性放射反应多为Ⅰ度和Ⅱ度以口干和放射性口腔炎为主,分别占72·5%和58·2%。远期放射反应表现为不同程度的口干和听力下降,占患者的39·6%和17·6%。GTV、CTV1及CTV2的平均剂量分别为70·6、67·9和65·0Gy;5%体积的正常器官受照射剂量的平均值为:脑干41·4Gy,脊髓35·4Gy,左腮腺46·5Gy,右腮腺51·8Gy。结论:调强放疗能使得鼻咽癌各靶区得到很好的剂量分布,提高了初治鼻咽癌的局部控制率,明显减轻了急性放射反应。鼻咽癌IMRT处方剂量70Gy以上,CTV2预防照射的范围有待于进一步探讨。     

Dose, volume, and function relationships in parotid salivary glands following conformal and intensity-modulated irradiation of head and neck cancer.

PURPOSE: To determine the relationships between the three-dimensional dose distributions in parotid glands and their saliva production, and to find the doses and irradiated volumes that permit preservation of the salivary flow following irradiation (RT). METHODS AND MATERIALS: Eighty-eight patients with head and neck cancer irradiated with parotid-sparing conformal and multisegmental intensity modulation techniques between March 1994 and August 1997 participated in the study. The mean dose and the partial volumes receiving specified doses were determined for each gland from dose-volume histograms (DVHs). Nonstimulated and stimulated saliva flow rates were selectively measured from each parotid gland before RT and at 1, 3, 6, and 12 months after the completion of RT. The data were fit using a generalized linear model and the normal tissue complication probability (NTCP) model of Lyman-Kutcher. In the latter model, a "severe complication" was defined as salivary flow rate reduced to < or =25% pre-RT flow at 12 months. RESULTS: Saliva flow rates data were available for 152 parotid glands. Glands receiving a mean dose below or equal to a threshold (24 Gy for the unstimulated and 26 Gy for the stimulated saliva) showed substantial preservation of the flow rates following RT and continued to improve over time (to median 76% and 114% of pre-RT for the unstimulated and stimulated flow rates, respectively, at 12 months). In contrast, most glands receiving a mean dose higher than the threshold produced little saliva with no recovery over time. The output was not found to decrease as mean dose increased, as long as the threshold dose was not reached. Similarly, partial volume thresholds were found: 67%, 45%, and 24% gland volumes receiving more than 15 Gy, 30 Gy, and 45 Gy, respectively. The partial volume thresholds correlated highly with the mean dose and did not add significantly to a model predicting the saliva flow rate from the mean dose and the time since RT. The NTCP model parameters were found to be TD50 (the tolerance dose for 50% complications rate for whole organ irradiated uniformly) = 28.4 Gy, n (volume dependence parameter) = 1, and m (the slope of the dose/response relationship) = 0.18. Clinical factors including age, gender, pre-RT surgery, chemotherapy, and certain medical conditions were not found to be significantly associated with the salivary flow rates. Medications (diuretics, antidepressants, and narcotics) were found to adversely affect the unstimulated but not the stimulated flow rates. CONCLUSIONS: Dose/volume/function relationships in the parotid glands are characterized by dose and volume thresholds, steep dose/response relationships when the thresholds are reached, and a maximal volume dependence parameter in the NTCP model. A parotid gland mean dose of < or =26 Gy should be a planning goal if substantial sparing of the gland function is desired.