Advances and Challenges in Intensity-Modulated Radiotherapy for Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma is an endemic disease within specific regions in the world. Radiotherapy is themain treatment. In recent decades, intensity-modulated radiation therapy has undergone a rapid evolution.Compared with two-dimensional radiotherapy and/or three-dimensional conformal radiotherapy, evidence hasshown it may improve quality of life and prognosis for patients with nasopharyngeal carcinoma. In addition,helical tomotherapy is an emerging technology of intensity-modulated radiation therapy. Its superiority indosimetric and clinical outcomes has been demonstrated when compared to traditional intensity-modulatedradiation therapy. However, many challenges need to be overcome for intensity-modulated radiation therapyof nasopharyngeal carcinoma in the future. Issues such as the status of concurrent chemotherapy, updatingof target delineation, the role of replanning during IMRT, the causes of the main local failure pattern requiresettlement. The present study reviews traditional intensity-modulated radiation therapy, helical tomotherapy,and new challenges in the management of nasopharyngeal carcinoma.     

Intensity-Modulated Radiotherapy for Nasopharyngeal Carcinoma: Penang General Hospital Experience

Purpose: To study the overall treatment time (OTT) and acute toxicity of intensity-modulated radiotherapy(IMRT) treatment for nasopharyngeal carcinoma (NPC). Methods: This retrospective study covered all NPCpatients who underwent radical IMRT treatment at the Penang General Hospital from June 2011 to February2012. Patients of any age and stage of disease with histologically proven diagnosis were included. Informationwas collected on patient demographics, clinical stage, treatment received, including any neoadjuvant and/orconcurrent chemotherapy, acute toxity and completion of IMRT within the OTT. Results: A total of 26 NPCpatients were treated with IMRT during the study period; 88.5% had stage III/IV disease. 45.2% receivedneo-adjuvant chemotherapy while 50.0% were given concurrent chemo-irradiation. All patients completed thetreatment and 92.3% within the 7 weeks OTT. Xerostomia was present in all patients with 92.3% having grade2. Severe grade III/IV acute toxicity occurred in 73.1% of patients, the commonest of which was oral mucositis(57.6%). This was followed by dysphagia which occurred in 53.8%, skin reactions in 42.3% and weight loss in19.2%. However, haematological toxicity was mild with only one patient having leucopaenia. Conclusion: IMRTtreatment for NPC is feasible in our center. More importantly, it can be delivered within the 7 weeks OTT inthe majority of patients. Severe grade 3/4 toxicity is very common (73.1%) and thus maximal nutritional andanalgesic support is required throughout the treatment.     

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。     

鼻咽癌患者调强放疗过程中体重变化及影响因素分析

目的 研究鼻咽癌(nasopharyngeal carcinoma,NPC)患者调强放疗(intensity-modulated radiotherapy, IMRT)过程中的体重变化规律及影响因素。方法 回顾性分析57例鼻咽癌患者调强放疗过程中体重及身体质量指数(body mass index, BMI)变化,探讨鼻咽癌调强放疗患者体重和BMI变化规律及影响因素。结果 57例患者放疗前后平均体重分别为（60.4±9.4）kg和（55.1±8.7）kg（P=0.0025）,变化范围为17 kg~-0.5 kg;放疗前后BMI分别为（22.8±3.5）kg/m²和（20.8±3.1）kg/m²（P=0.0017）,变化范围为6.0 kg/m²~-0.2 kg/m²。约93.0%患者调强放疗中出现不同程度体重和BMI减轻,平均体重减轻8.4%,35.1%患者体重减轻超过10.0%,68.4%体重减轻超过5.0%,体重减轻百分比范围23.4%~-0.7%。单变量多因素方差分析显示,患者性别、WHO病理分级、AJCC6th分期、身体状况评分（performance status,PS）、是否同期化疗及后程加速超分割放疗(late course accelerated hyperfractionated radiotherapy, LCAFR)）对体重和BMI无明显影响（P＞0.05）, 而年龄≥50岁或BMI＞25 kg/m²或体重＞60 kg者体重减轻更明显（P＜0.05）。线性回归分析每周平均放疗剂量和每周平均体重呈明显负相关（R2=-0.996,P＜0.001）。结论 鼻咽癌患者调强放疗过程中体重减轻现象非常普遍,性别、WHO病理分级、AJCC6th分期、身体状况评分、是否同期化疗及后程加速超分割放疗对患者体重和BMI变化影响可能较小,而年龄、放疗前体重和BMI、放疗剂量对患者体重和BMI影响更明显。     

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.     

Dose Planning Study of Target Volume Coverage with Intensity-Modulated Radiotherapy for Nasopharyngeal Carcinoma: Penang General Hospital Experience

Background: To compare the dosimetric coverage of target volumes and organs at risk in the radicaltreatment of nasopharyngeal carcinoma (NPC) between intensity-modulated radiotherapy (IMRT) and threedimensionalconformal radiotherapy (3DCRT). Materials and Methods: Data from 10 consecutive patientstreated with IMRT from June-October 2011 in Penang General Hospital were collected retrospectively foranalysis. For each patient, dose volume histograms were generated for both the IMRT and 3DCRT plans usinga total dose of 70Gy. Comparison of the plans was accomplished by comparing the target volume coverage (5measures) and sparing of organs at risk (17 organs) for each patient using both IMRT and 3DCRT. The meansof each comparison target volume coverage measures and organs at risk measures were obtained and testedfor statistical significance using the paired Student t-test. Results: All 5 measures for target volume coverageshowed marked dosimetric superiority of IMRT over 3DCRT. V70 and V66.5 for PTV70 showed an absoluteimprovement of 39.3% and 24.1% respectively. V59.4 and V56.4 for PTV59.4 showed advantages of 18.4% and16.4%. Moreover, the mean PTV70 dose revealed a 5.1 Gy higher dose with IMRT. Only 4 out of 17 organsat risk showed statistically significant difference in their means which were clinically meaningful between theIMRT and 3DCRT techniques. IMRT was superior in sparing the spinal cord (less 5.8Gy), V30 of right parotid(less 14.3%) and V30 of the left parotid (less 13.1%). The V55 of the left cochlea was lower with 3DCRT (less44.3%). Conclusions: IMRT is superior to 3DCRT due to its dosimetric advantage in target volume coveragewhile delivering acceptable doses to organs at risk. A total dose of 70Gy with IMRT should be considered as astandard of care for radical treatment of NPC.     

Concurrent Chemoradiotherapy Versus Radiotherapy Alone for Locoregionally Advanced Nasopharyngeal Carcinoma

Objective: To compare the clinical effects of concurrent radiochemotherapy with those of radiotherapy intreating locally advanced nasopharyngeal carcinoma (Stage III~IVa). Methods: A total of 95 patients sufferingfrom nasopharyngeal carcinoma (Stage III~IVa) were divided into two groups: concurrent radiochemotherapy(Group CCRT, n=49) and radiotherapy (Group RT, n=46). The two groups were both delivered conventionalfractionated radiotherapy, while Group CCRT also received three cycles of PF (DDP+5-Fu) or PLF (DDP+5-Fu+CF) chemotherapy. Results: The complete remission rate and total remission rate of Group CCRT werehigher than those of Group RT (Ⅹ2=4.72~7.19, P<0.05). The one-year overall survival (OS) rate calculated bythe life table method, was also higher than that of Group RT (Ⅹ2=4.24, P<0.05) as well as the 3-year OS rate,nasopharyngeal control rate and cervical lymph nodes’ control rate (Ⅹ2=4.28~4.40, P<0.05). In addition, the5-year OS and metastasis-free rates of Group CCRT were higher than those of Group RT and the differenceswere of statistical importance (Ⅹ2=3.96~8.26, P﹤0.05). However, acute toxicity was also obviously higher, thedifference in gastrointestinal reactions being statistically significant (Ⅹ2=11.70, P<0.05). Conclusion: This studydemonstrated that concurrent radiochemotherapy could improve the remission rate, overall survival rate andlocally control rate. The toxicity of concurrent radiochemotherapy could be tolerated by the patients.     

放射合并西咪替丁治疗鼻咽癌的远期疗效

目的 :探讨组胺 2受体拮抗剂西咪替丁 (CMD)在鼻咽癌综合治疗中的应用价值。方法 :6 5例无远处转移的鼻咽癌患者 ,随机分为两组。放射治疗组 ,放疗 DT:70～ 76 Gy/7～ 8周。放疗 CMD组 ,放疗同上 ,CMD:16 0 0～ 2 0 0 0 mg,d1,分 4次口服 ,疗程为 4～ 6个月。结果 :5年生存率 ,放射治疗组为 5 9.38% (19/32 ) ,放射 CMD组为 6 6 .6 7% (2 2 /33) ,P>0 .0 5。 5年无瘤生存率分别为 43.75 % (14/32 )和 6 3.6 4% (2 1/33) ,P>0 .0 5。 5年内复发和转移发生率 ,放射治疗组为 5 0 % (16 /32 ) ,放射 CMD组为 2 4.2 4% (8/33) ,P<0 .0 5。差异有显著性。提示放射合并西咪替丁治疗可减少鼻咽癌的复发和转移。结论 :西咪替丁是一种经济、安全、有效的免疫调节剂 ,可能具有肿瘤治疗的应用价值。     

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。     

三维适形放射治疗鼻咽癌后程大分割的剂量学研究

目的寻求1种较理想的鼻咽癌三维放疗的分割方式,从而提高局部控制率。方法对15例行三维适形放射治疗的鼻咽癌患者进行模拟的剂量学研究,将后程大分割（分次量2.5Gy和3.0Gy）与常规分割（2.0Gy）进行剂量学对比。结果大分割放疗可以较大幅度增加肿瘤区（GTV）的剂量。2.5组脊髓最大剂量、腮腺、颞颌关节、脑干平均剂量提高均不超过1.0Gy,脑干最大剂量增加2.3Gy。3.0组腮腺及颞颌关节的平均剂量增加幅度较大达3.4Gy和1.4Gy,脑干最大剂量增加4.5Gy。结论分次量2.5Gy的后程大分割放疗能够较大幅度地增加GTV剂量,且对正常器官的剂量增加幅度较小,并发症增加较少。     

612例鼻咽癌放射治疗预后因素分析

 目的 1973年1月至1987年12月我院共放射治疗鼻咽癌612例,本文对其结果 及影响预后的因素予以分析。全组总的5年生存率42．2％。性别、年龄对预后无明显影响,病期、原发肿瘤超胜,预淋巴结转移、颅神经受损和照射剂量是主要的预后因素。随着病期变晚,5年生存率逐渐下降,Ⅰ、Ⅱ期的5年生存率明显高于Ⅲ、Ⅳ期（P＜0．01）。肿瘤局限于鼻咽腔者的预后明显好于超腔者（P＜0．01）。前后组颅神经同时受累预后最差。预淋巴结转移的大小、单双侧、部位、活动或固定对预后有不同的影响。放疗剂量应以65－75Gy／6．5－7．5周为宜。本组资料证明,鼻咽癌放疗失败的主要原因是远处转移与局部复发。     

超分割后加速放疗鼻咽癌患者的疗效和安全性研究

目的 研究超分割后加速放疗鼻咽癌患者的疗效和安全性.方法 将48例经CT或MRI确诊的鼻咽癌患者随机分为超分割后加速放疗组(研究组)和常规放疗组(对照组),每组24例,对照组每周5次,每次2 Gy,总量70Gy/7周;研究组1.2 Gy/次,每周5天,每天2次,间隔不小于6h,剂量48 Gy/40次,后2周采用后加速超分割:1.5 Gy/次,每周5天,每天2次,间隔不小于6h,剂量30 Gy/20次,整个疗程总剂量为78 Gy/60次,共6周完成.结果 研究组与对照组治疗后36个月及60个月复发率分别为12.5％、20.8％和25.0％、37.5％,差异有统计学意义(P＜0.05).对照组5年转移率为33.3％,研究组5年转移率为20.8％,差异显著(P＜0.01);对照组5年总生存率为62.5％,研究组5年总生存率为83.3％,差异显著(P＜0.01).研究组与对照组皮肤3级和4级损伤发生率比较有显著差异(P＜0.05),粘膜2～4级损伤发生率比较有显著差异(P＜0.05).两组晚期损伤在耳聋、放射性脑病和颈部纤维化方面比较差异有显著性(P＜0.05).结论 超分割后加速放疗治疗鼻咽癌提高了疗效降低了复发率和转移率,提高了生存率,提高了安全性.     

鼻咽癌自适应放疗的临床应用进展

放射治疗是鼻咽癌首选治疗方法。随着影像导向下放疗技术的发展,自适应放疗（ART）逐渐应用于临床。ART通过动态影像来评判患者解剖和生理变化,或者通过治疗过程中的自反馈信息如肿瘤大小、形态及位置变化,重新优化生成新的放疗计划,以使靶区剂量达到最大并保护周围正常组织。本综述从ART的物理学基础、鼻咽癌ART的临床应用现状和进展以及存在问题等方面进行探讨。