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.     

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。     

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。     

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。     

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.     

鼻咽癌患者调强放射治疗后颞颌关节损伤及其影响因素

背景与目的:放射性颞颌关节损伤是鼻咽癌患者放射治疗后常见的并发症,主要表现为张口时门齿距缩小.严重的张口困难可影响进食,影响患者生活质量.本研究通过量化鼻咽癌患者调强放疗后张口困难的情况,探讨颞颌关节放射损伤的影响因素.方法:2001年2月至2003年2月,148例初治鼻咽癌患者接受调强放疗,放疗总剂量63～77 Gy,分次剂量为每次2.27～2.80 Gy,总疗程时间31～86 天.放疗前及放疗后6个月、1年、2年和3年分别用直尺测量患者门齿距.结果:全组1、2、3年累积生存率为97.26%、94.83%、92.04%.颞颌关节平均剂量17.99～51.36 Gy.Ⅰ～Ⅱ级张口困难发生率4.73%,未观察到Ⅲ级和Ⅳ级颞颌关节损伤.结论:调强放疗技术使颞颌关节受照剂量显著下降,放疗后发生严重张口困难的风险较低.     

初治鼻咽癌调强适形放疗的疗效分析

目的 探讨根治性调强适形放疗（IMRT）治疗初治鼻咽癌的临床疗效及毒副反应。方法 74例鼻咽癌患者均接受全程IMRT照射,给予鼻咽大体肿瘤体积（GTVnx）处方剂量69.9Gy／30f,颈部转移淋巴结（GTVnd）69.9Gy／30f,临床靶体积1（CTV1）60Gy／30f,临床靶体积2（CTV2）54Gy／30f。按照RTOG/EORTC标准评价急性反应和晚期放射损伤;采用Kaplan-Meier法进行生存分析。结果 中位随访时间为39个月（13～80个月）。全组1、2、3、5年生存率分别为97.3％、93.8％、88.2％和77.2％,无远处转移生存率分别为93.2％、91.1％、91.1％和84.1％,局部区域控制率分别为98.6％、91.0％、86.8％和80.6％。不同临床分期和T分期患者的生存率差异均无统计学意义（P＞0.05）,而不同N分期患者的生存率差异有统计学意义（P=0.02）。在治疗失败的12例患者中,局部和区域失败分别占治疗失败病例的50.0％和16.7％,远处转移占58.3％。74例患者中3例出现3级口干,1例出现放射性颞叶损伤,4例出现3级张口困难,全组未发现颅神经损伤病例。结论 采用GTV照射剂量69.9Gy/30f IMRT治疗初诊时无远处转移的鼻咽癌远期疗效较好,毒副反应少,N分期是其预后的影响因素。     

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.     

Prognostic value and predictive threshold of tumor volume for patients with locally advanced nasopharyngeal carcinoma receiving intensity-modulated radiotherapy

Background:Gross target volume of primary tumor (GTV?P) is very important for the prognosis prediction of patients with nasopharyngeal carcinoma (NPC), but it is unknown whether the same is true for locally advanced NPC patients treated with intensity?modulated radiotherapy (IMRT). This study aimed to clarify the prognostic value of tumor volume for patient with locally advanced NPC receiving IMRT and to ifnd a suitable cut?off value of GTV?P for prognosis prediction. Methods:Clinical data of 358 patients with locally advanced NPC who received IMRT were reviewed. Receiver oper?ating characteristic (ROC) curves were used to identify the cut?off values of GTV?P for the prediction of different end?points [overall survival (OS), local relapse?free survival (LRFS), distant metastasis?free survival (DMFS), and disease?free survival (DFS)] and to test the prognostic value of GTV?P when compared with that of the American Joint Committee on Cancer T staging system. Results:The 358 patients with locally advanced NPC were divided into two groups by the cut?off value of GTV?P as determined using ROC curves: 219 (61.2%) patients with GTV?P≤46.4mL and 139 (38.8%) with GTV?P>46.4mL. The 3?year OS, LRFS, DMFS, and DFS rates were all higher in patients with GTV?P≤46.4mL than in those with GTV?P>46.4mL (allP<0.05). Multivariate analysis indicated that GTV?P>46.4mL was an independent unfavorable prognostic factor for patient survival. The ROC curve veriifed that the predictive ability of GTV?P was superior to that of T category (P<0.001). The cut?off values of GTV?P for the prediction of OS, LRFS, DMFS, and DFS were 46.4, 57.9, 75.4 and 46.4mL, respectively. Conclusion:In patients with locally advanced NPC, GTV?P>46.4mL is an independent unfavorable prognostic indi?cator for survival after IMRT, with a prognostic value superior to that of T category.     

Intensity-modulated radiotherapy prolongs the survival of patients with nasopharyngeal carcinoma compared with conventional two-dimensional radiotherapy: A 10-year experience with a large cohort and long follow-up

BackgroundTo evaluate the survival benefit of intensity-modulated radiotherapy (IMRT) compared with conventional two-dimensional radiotherapy (2D-CRT) in nasopharyngeal carcinoma (NPC) using a large cohort with long follow-up.MethodsWe retrospectively analysed 7081 non-metastatic NPC patients who received curative IMRT or 2D-CRT from February 2002 to December 2011.ResultsOf the 7081 patients, 2245 (31.7%) were administered IMRT, while 4836 (68.3%) were administered 2D-CRT. At 5 years, the patients administered IMRT had significantly higher local relapse-free survival (LRFS), loco-regional relapse-free survival (LRRFS), progression-free survival (PFS) and overall survival (OS) (95.6%, 92.5%, 82.1% and 87.4%, respectively) than those administered 2D-CRT (90.8%, 88.5%, 76.7% and 84.5%, respectively; p < 0.001). The distant metastasis-free survival (DMFS) was higher for IMRT than 2D-CRT, with borderline significance (87.6% and 85.7%, respectively; p = 0.056). However, no difference was observed between IMRT and 2D-CRT in nodal relapse-free survival (NRFS; 96.3% and 97.4%, respectively; p = 0.217). Multivariate analyses showed that IMRT was an independent protective prognostic factor for LRFS, LRRFS and PFS, but not NRFS, DMFS or OS.ConclusionsIMRT provided an improved LRFS, LRRFS and PFS in both the early and advanced T classifications and overall stage for non-disseminated NPC compared with 2D-CRT. However, no significant advantage was observed in NRFS, DMFS or OS when IMRT was used.     

Prognostic value of parapharyngeal extension in nasopharyngeal carcinoma treated with intensity modulated radiotherapy

Background and purpose

The development of improved diagnostic and therapeutic techniques has revolutionized the management of nasopharyngeal carcinoma (NPC). The purpose of this study is to revaluate the prognostic value of parapharyngeal extension in NPC in the IMRT era.

Material and methods

We retrospectively reviewed data from 749 biopsy-proven non-metastatic NPC patients. All patients were examined with magnetic resonance imaging (MRI) and received intensity-modulated radiotherapy (IMRT) as the primary treatment.

Results

The incidence of parapharyngeal extension was 72.1%. A significant difference was observed in the disease-free survival (DFS; 70.3% vs. 89.1%, P < 0.001), distant metastasis-free survival (DMFS; 79.3% vs. 92.0%, P < 0.001), and local relapse-free survival (LRFS; 92.8% vs. 99.0%, P = 0.002) of patients with and without parapharyngeal extension. Parapharyngeal extension was an independent prognostic factor for DFS and DMFS in multivariate analysis (P = 0.001 and P = 0.015, respectively), but not LRFS. The difference between DMFS in patients with or without parapharyngeal space extension was statistically significant in patients with cervical lymph node metastasis (P < 0.001).

Conclusions

In the IMRT era, parapharyngeal extension remains a poor prognosticator for DMFS in NPC, especially in patients with positive lymph node metastasis. Additional therapeutic improvements are required to achieve a favorable distant control in NPC with parapharyngeal extension.     

Long-term outcomes of intensity-modulated radiotherapy for 868 patients with nasopharyngeal carcinoma: An analysis of survival and treatment toxicities

Background and purpose

To evaluate the long-term survival outcomes and toxicity of NPC patients treated with intensity-modulated radiotherapy (IMRT).

Materials and methods

From May 2001 to October 2008, 868 non-metastatic NPC patients treated by IMRT were analyzed retrospectively. The Radiation Therapy Oncology Group (RTOG) criteria were used to assess toxicity.

Results

With a median follow-up of 50 months (range, 5–115 months), the 5-year estimated disease specific survival (DSS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS) and distant metastasis-free survival (DMFS) were 84.7%, 91.8%, 96.4% and 84.6%, respectively. Of the 868 patients, 186 (21.3%) developed failure after treatment. Distant metastasis was the major failure pattern after treatment. The 5-year OS rate in patients with stage I, II, III, and IVa–b were 100.0%, 94.3%, 83.6%, and 70.5%, respectively. The 5-year LRFS rate in patients with stage T1, T2, T3, and T4 disease were 100.0%, 96.0%, 90.4%, and 83.3%, respectively (χ² = 26.32, P < 0.001). The 5-year DMFS for N0, N1, N2, and N3 patients were 96.1%, 85.6%, 73.7%, and 62.1%, respectively (χ² = 65.54, P < 0.001). Concurrent chemotherapy failed to improve survival rates for patients with advanced locoregional disease. The most common acute toxicities were mainly in grade 1 or 2. Compared with IMRT alone, IMRT plus concurrent chemotherapy increased the severity of acute toxicities. The incidence of brain radiation damage was relatively high (5.5%, 48/868 cases), and was not observed in patients with stage T1–2.

Conclusion

IMRT for NPC yielded excellent survival outcomes, and distant metastasis was the most commonly seen failure pattern after treatment. The role of concurrent chemotherapy for advanced locoregional stage NPC patients needs to be further investigated. Treatment-related toxicities were well tolerable. However, the incidence of brain radiation damage was relatively high, especially for patients with advanced T-stage.     

局部复发鼻咽癌再程IMRT远期疗效分析

目的 回顾分析局部复发鼻咽癌再程IMRT远期生存、晚期不良反应及预后影响因素。方法 2001—2010年共335例诊断为局部复发鼻咽癌且接受再程IMRT纳入分析,其中合并有明显放疗并发症的患者占20.6%(69例)。全组中男268例,年龄21~75岁(中位数45岁),T₁、T₂、T₃、T₄期分别为41、36、122、136例,肿瘤体积中位数37.5 cm³,肿瘤靶区处方剂量60~70 Gy (中位数68 Gy)。Kaplan-Meier法计算生存率,Cox模型预后因素分析。结果 5年随访样本数290例。5年OS、LRFFS、DFFS分别为34.7%、64.2%、82.2%。多因素分析预后不良因素包括年龄>45岁(P=0.01)、疗前合并明显放疗并发症(P=0.00)、肿瘤分期(T₂~T₄)(P=0.00)、肿瘤体积>38.0 cm³(P=0.00)以及GTV_nx的D_mean>68.0 Gy (P=0.01)。鼻咽黏膜坏死、鼻咽出血、放射性脑病、颅神经损伤及张口困难发生率分别为28.6%、16.4%、22.4%、15.8%及13.7%。结论 局部复发鼻咽癌再程IMRT能获得较好肿瘤控制,可作为有效补救治疗手段,但其严重不良反应发生率仍较高,如何更好平衡肿瘤控制和正常组织保护仍需进一步探讨。