Intensity-modulated radiotherapy for nasopharyngeal carcinoma: clinical correlation of dose to the pharyngo-esophageal axis and dysphagia

PURPOSE: The aim of this study was to quantify the dose delivered to the pharyngo-esophageal axis using different intensity-modulated radiation therapy (IMRT) techniques for treatment of nasopharyngeal carcinoma and to correlate this with acute swallowing toxicity. METHODS AND MATERIALS: The study population consisted of 28 patients treated with IMRT between February 2002 and August 2005: 20 with whole field IMRT (WF-IMRT) and 8 with IMRT fields junctioned with an anterior neck field with central shielding (j-IMRT). Dose to the pharyngo-esophageal axis was measured using dose-volume histograms. Acute swallowing toxicity was assessed by review of dysphagia grade during treatment and enteral feeding requirements. RESULTS: The mean pharyngo-esophageal dose was 55.2 Gy in the WF-IMRT group and 27.2 Gy in the j-IMRT group, p < 0.001. Ninety-five percent (19/20) of the WF-IMRT group developed Grade 3 dysphagia compared with 62.5% (5/8) of the j-IMRT group, p = 0.06. Feeding tube duration was a median of 38 days for the WF-IMRT group compared with 6 days for the j-IMRT group, p = 0.04. CONCLUSIONS: Clinical vigilance must be maintained when introducing new technology to ensure that unanticipated adverse effects do not result. Although newer planning systems can reduce the dose to the pharyngo-esophageal axis with WF-IMRT, the j-IMRT technique is preferred at least in patients with no gross disease in the lower neck.     

关于鼻咽癌临床靶区剂量学规定的分析

目的分析鼻咽癌调强放疗中临床靶区（CTV）处方剂量与实际剂量间存在的差异,探讨是否有必要对CTV剂量报告、甚至剂量学规定进行必要的修改。方法 2009年10月至2010年5月收治经病理检查确诊为低分化鳞癌的初治鼻咽癌患者,共46例,行调强放疗,靶区设置为PTV70、PTV60和PTV54,统一靶区勾画方法,并按照RTOG0615试验中有关靶区剂量学规定来制定调强放疗计划,分别统计PTV60-70（PTV60 s-PTV70 s）和PTV54-60（PTV54 s-PTV60s）的D95%、Dm ean、V110%处方、V115处方、V95%处方。结果在统一靶区勾画方法并满足RTOG0615靶区剂量学规定的前提下,PTV60-70的D95%、Dm ean、V66、V69、V57的变化范围和中位值分别为：5 980~6 400 cGy,6 175 cGy;6391~7003 cGy,6652 cGy;12.8%~89.5%,50.5%;4.9%~68.3%,24.6%;97.3%~100%,99.4%。PTV54-60的D95%、Dm ean、V59.4、V62、V51的变化范围和中位值分别为：5230~5 560 cGy,5 410 cGy;5648~6322 cGy,5 919 cGy;9.9%~80.8%,47.5%;1.9%~63.1%,20.3%;96%~99.7%,98%。均存在较大差异。结论调强放疗的计划系统有着强大的计算能力,在满足一定限定条件的基础上,能提供相当多的治疗计划,而目前关于CTV的剂量学规定,约束力较弱,造成CTV内实际剂量差异较大,不利于对CTV勾画的研究。     

Preliminary results of a phase I/II study of simultaneous modulated accelerated radiotherapy for nondisseminated nasopharyngeal carcinoma

PURPOSE: To present preliminary results of intensity-modulated radiotherapy (IMRT) with the simultaneous modulated accelerated radiotherapy (SMART) boost technique in patients with nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Twenty patients who underwent IMRT for nondisseminated NPC at the Asan Medical Center between September 2001 and December 2003 were prospectively evaluated. Intensity-modulated radiotherapy was delivered with the "step and shoot" SMART technique at prescribed doses of 72 Gy (2.4 Gy/day) to the gross tumor volume, 60 Gy (2 Gy/day) to the clinical target volume and metastatic nodal station, and 46 Gy (2 Gy/day) to the clinically negative neck region. Eighteen patients also received cisplatin once per week. RESULTS: The median follow-up period was 27 months. Nineteen patients completed the treatment without interruption; the remaining patient interrupted treatment for 2 weeks owing to severe pharyngitis and malnutrition. Five patients (25%) had Radiation Therapy Oncology Group Grade 3 mucositis, whereas 9 (45%) had Grade 3 pharyngitis. Seven patients (35%) lost more than 10% of their pretreatment weight, whereas 11 (55%) required intravenous fluids and/or tube feeding. There was no Grade 3 or 4 xerostomia. All patients showed complete response. Two patients had distant metastases and locoregional recurrence, respectively. CONCLUSION: Intensity-modulated radiotherapy with the SMART boost technique allows parotid sparing, as shown clinically and by dosimetry, and might also be more effective biologically. A larger population of patients and a longer follow-up period are needed to evaluate ultimate tumor control and late toxicity.     

鼻咽癌调强放疗118例临床观察

目的：观察鼻咽癌调强放疗（ IMRT）的疗效和不良反应。方法鼻咽癌初治患者118例,按2008分期标准,Ⅰ期5例,Ⅱ期29例,Ⅲ期45例,Ⅳ期39例;均予调强放疗,总剂量71．9～74．3Gy,每次2．28～2．34 Gy。结果中位随访时间42个月,1、2、3年总生存率分别为97．5％、93．2％和88．1％。急性不良反应主要是放射性黏膜炎,Ⅰ～Ⅳ级分别为22．9％、41．5％、30．5％、1．7％。晚期不良反应主要是口干,Ⅰ级31．4％,Ⅱ级7．6％,Ⅲ级3．4％。结论鼻咽癌调强放疗虽然肿瘤靶区剂量高,但周围正常组织受量小,故不良反应较轻。     

鼻咽癌放疗后复发再程调强放疗的疗效分析

目的　研究鼻咽癌放疗后复发再程调强放疗的疗效及影响预后的因素。方法　回顾性分析６２例鼻咽癌放疗后复发患者,男性４６例,女性１８例,中位年龄４９岁（３７～６５岁）,中位复发时间为２５个月（１０～５７个月）。全组患者均行调强放疗,肿瘤靶体积ＧＴＶ总剂量为６０～７０Ｇｙ,每次分割剂量１.８～２.３Ｇｙ。结果　全组患者的中位随访时间为１４个月,１、３年生存率分别为６２.２％和４１.８％。至随访截止日期,死亡２８例,再复发３例,再复发同时转移２例,转移５例。单因素分析结果显示,仅化疗（Ｐ＝０.００３）与生存期相关;多因素分析提示,化疗（Ｐ＝０.０００）和ＧＴＶ体积（Ｐ＝０.０１９）是影响复发鼻咽癌的独立预后因素。毒副反应可耐受。结论　鼻咽癌放疗后复发患者再程调强放疗有效、可靠,化疗与ＧＴＶ体积是影响预后的主要因素。     

调强放疗与常规放疗鼻咽癌患者生活质量的比较

目的　通过与常规放疗比较,了解调强放疗对鼻咽癌患者生活质量的影响,并分析鼻咽癌患者总体生活质量和口干的影响因素。方法　以２００５年５月至２００８年５月武汉大学中南医院放化疗科行常规放疗或调强放疗且同意配合调查的初治鼻咽癌患者为研究对象,采用问卷方式调查接受调强放疗和常规放疗鼻咽癌患者的生活质量。调查表包括生活质量核心问卷（ＱＬＱ-３０）中文版及头颈部特殊问卷（ＱＬＱ-Ｈ＆Ｎ３５）。结果　１２０例鼻咽癌患者,其中调强组６１例,常规组５９例。与常规放疗比较,调强放疗改善了总体生活质量、角色功能、口干、口黏等,两者比较差异有统计学意义（Ｐ＜０.０５）。接受调强放疗的患者总体生活质量较高（ＯＲ＝２.６８５;９５％ＣＩ：１.２１２～５.９４８）,接受化疗的患者总体生活质量较低（ＯＲ＝０.３７４;９５％ＣＩ：０.１５０～０.９３３）,接受调强放疗的患者口干症状较轻（ＯＲ＝０.３４７;９５％ＣＩ：０.１２４～０.９６８）。结论　与常规放疗比较,调强放疗改善了患者口干、口黏、疼痛、乏力及总体生活质量等评分。治疗方式和化疗是患者总体生活质量的影响因素。     

１１６例鼻咽癌一体化照射野调强放疗的疗效分析

目的　探讨初诊时无远处转移的鼻咽癌患者应用一体化照射野调强放疗的远期疗效、安全性及预后相关因素。方法　收集２００５年２月至２００８年１２月共１１６例初诊时无转移鼻咽癌患者,根据福州分期：Ⅰ期４例,Ⅱ期２２例,Ⅲ期４５例,ⅣＡ期４５例。所有患者均接受鼻咽和全颈部一体化照射野调强放疗,具体剂量为：ＧＴＶｎｘ６１.３２～７５Ｇｙ,ＧＴＶｎｄ６５～８０Ｇｙ,中位剂量均为７０Ｇｙ;ＣＴＶ１５６～６０Ｇｙ,ＣＴＶ２５０～５２Ｇｙ。２１例单纯放疗,９５例合并化疗,采用以铂类药物为基础的化疗方案。结果　随访率１００％,中位随访期２８个月（６～６０个月）。３例局部复发,３例颈淋巴结复发,１６例远处转移。１、２、３、４年总生存率及无疾病生存率分别为６％ 、９２％ 、９２％、８４％及９１％、８５％、８０％、８０％。１２例死亡患者中６例死于鼻咽癌远处转移,其余６例死于其他疾病。预后因素分析,临床分期、Ｔ分期与３年无疾病生存率、３年无转移生存率明显相关（Ｐ＜０.０５）。随访满２年的６５例患者中,６例出现３级以上口干（９.２％）,４例出现放射性脑病（３.４％）。全组未发现后组颅神经损伤及张口困难病例。结论　采用一体化照射野调强放疗技术治疗初诊时无转移鼻咽癌远期疗效较好,副反应发生率低,临床分期、Ｔ分期是其预后的相关因素。     

调强放疗对鼻咽癌患者甲状腺功能的影响

目的 探讨鼻咽癌患者调强放射治疗后早期甲状腺功能的变化情况,为甲状腺功能保护提供依据.方法 收集经病理证实、排除基础甲状腺疾病且接受IMRT治疗的鼻咽癌患者.分析对比放疗前后TT3和TT4水平.结果 全组患者治疗前、后TT3水平分别为1.83 IU/L、1.69 IU/L,治疗前、后TT4水平分别为124.66 IU/L、127.23 IU/L.其中150例(59.8％)治疗后TT3水平下降,变化具有统计学差异(P=0.001).N3患者放疗后血清TT3及TT4水平均明显降低(P值分别为0.043、0.032).结论 IMRT模式下,鼻咽癌患者放疗结束时甲状腺激素降低,N3患者尤为明显.N3患者可运用VMAT/Tomotherapy等技术降低甲状腺照射剂量,且应早期监测甲状腺激素水平,发现问题及早干预.     

影像引导调强放射治疗鼻咽癌

目的：探讨调强放疗技术（ＩＭＲＴ）治疗鼻咽癌的近期疗效、毒副反应及技术特点。方法：采用影像引导的ｓｌｉｄｉｎｇｗｉｎｄｏｗｓ动态调强技术对３１例鼻咽癌初治患者进行根治性放疗,分３０～３３次照射。靶区处方剂量ＧＴＶｎｘ、ＧＴＶｎｄ、ＣＴＶ１、ＴＶ２分别为７０～７６Ｇｙ、６８～７０Ｇｙ、６０～６６Ｇｙ和５４Ｇｙ,同时对脑干、腮腺等重要器官给予剂量限制保护。结果：随访３～１８个月,中位随访时间１０个月,患者１年局部区域无进展生存率、无远处转移生存率和总生存率分别为９３.５％、８７.１％和９３.５％。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,未观察到Ⅳ度急性反应。ＤＶＨ分析显示ＩＭＲＴ提高了靶体积照射总剂量和分次剂量,减少了危及器官受照总剂量和分次剂量。结论：调强放射治疗鼻咽癌能够取得良好的近期疗效,明显减轻了急性放射反应,患者生活质量得到改善,值得推广应用和深入研究。     

Prognostic factors and failure patterns in non-metastatic nasopharyngeal carcinoma after intensity-modulated radiotherapy

Background:The prognostic values of staging parameters require continual re?assessment amid changes in diag?nostic and therapeutic methods. This study aimed to identify the prognostic factors and failure patterns of non?meta?static nasopharyngeal carcinoma (NPC) in the intensity?modulated radiotherapy (IMRT) era. Methods:We reviewed the data from 749 patients with newly diagnosed, biopsy?proven, non?metastatic NPC in our cancer center (South China, an NPC endemic area) between January 2003 and December 2007. All patients under?went magnetic resonance imaging (MRI) before receiving IMRT. The actuarial survival rates were estimated using the Kaplan–Meier method, and survival curves were compared using the log?rank test. Multivariate analyses with the Cox proportional hazards model were used to test for the independent prognostic factors by backward eliminating insigniifcant explanatory variables. Results:The 5?year occurrence rates of local failure, regional failure, locoregional failure, and distant failure were 5.4, 3.0, 7.4, and 17.4%, respectively. The 5?year survival rates were as follows: local relapse?free survival, 94.6%; nodal relapse?free survival, 97.0%; distant metastasis?free survival, 82.6%; disease?free survival, 75.1%; and overall survival, 82.0%. Multivariate Cox regression analysis revealed that orbit involvement was the only signiifcant prognostic fac?tor for local failure (P=0.011). Parapharyngeal tumor extension, retropharyngeal lymph node involvement, and the laterality, longest diameter, and Ho’s location of the cervical lymph nodes were signiifcant prognostic factors for both distant failure and disease failure (allP<0.05). Intracranial extension had signiifcant prognostic value for distant failure (P=0.040). Conclusions:The key failure pattern for NPC was distant metastasis in the IMRT era. With changes in diagnostic and therapeutic technologies as well as treatment modalities, the signiifcant prognostic parameters for local control have also been altered substantially.     

Radiotherapy with neoadjuvant chemotherapy versus concurrent chemoradiotherapy for ascending?type nasopharyngeal carcinoma: a retrospective comparison of toxicity and prognosis

Background: In the era of intensity-modulated radiotherapy (IMRT), the role of neoadjuvant chemotherapy (NACT) in treating ascending-type nasopharyngeal carcinoma (NPC) is under-evaluated. This study was to compare the efficacy of NACT followed by IMRT (NACT + RT) with the efficacy of concurrent chemoradiotherapy (CCRT) on ascending-type NPC.Methods: Clinical data of 214 patients with ascending-type NPC treated with NACT + RT or CCRT between December 2009 and July 2011 were analyzed. Of the 214 patients, 98 were treated with NACT followed by IMRT, and 116 were treated with CCRT. The survival rates were assessed using Kaplan –Meier analysis, and the survival curves were compared using a log-rank test.Results: The 4-year overall survival, locoregional failure-free survival, distant failure-free survival, and failure-free survivalrates were not significantly different between the two groups (all P > 0.05). However, patients in the CCRT group exhibited more severe acute adverse events than did patients in the NACT + RT group during radiotherapy, including leukopenia (30.2% vs. 15.3%, P = 0.016), neutropenia (25.9% vs. 11.2%, P = 0.011), and mucositis (57.8% vs. 40.8%, P = 0.028). After radiotherapy, patients in the CCRT group exhibited significantly higher rates of xerostomia (21.6% vs.10.2%, P = 0.041) and hearing loss (17.2% vs. 6.1%, P = 0.023).Conclusions: The treatment outcomes of the NACT + RT and CCRT groups were similar; however, CCRT led to higher rates of acute and late toxicities. NACT + RT may therefore be a better treatment strategy for ascending-type NPC.