Clinical study on simultaneous modulated accelerated radiotherapy and concurrent chemotherapy for locally advanced nasopharyngeal carcinoma

OBJECTIVE To evaluate the clinical efficacy and toxicities of simultaneous modulated accelerated radiotherapy （SMART） and concurrent chemotherapy for locally advanced nasopharyngeal carcinoma. METHODS Eightyseven patients with nasopharyngeal carcinoma received SMART from April 2002 to September 2006. According to the UICC staging system, 30 patients were diagnosed as stage IIb, 42 patients stage III, 13 patients stage IVa and 2 patients stage IVb. The intensitymodulated radiotherapy was delivered with the ＂step and shoot＂ SMART technique with the prescribed dose of 66-76 Gy （2.2-2.4 Gy/day） to the gross tumor volume （GTV） and positive neck lymph nodes （GTVLN）, with 60 Gy （2.0 Gy/day） to the highrisk clinical target volume （CTV1）, encompassing the area around the nasopharynx and the upper neck, and with 54 Gy （1.8 Gy/day） to the lowrisk clinical target volume （CTV2）, including the lower neck and supraclavicular area. Among all the patients, 31 received 2 cycles of SMART concurrently with 5 fluorouracil （5-Fu） and cisplatin （the FP group） and 56 received 2 cycles of concurrent cisplatin. All the patients received 3 to 4 cycles of adjuvant combination chemotherapy of cisplatin and 5fluorouracil starting from the 1st month after completion of SMART. RESULTS With a median follow up of 59 months （ranging from 19 to 85 months）, the 1, 2 and 3year overall survival rates were 100%, 94.6% and 91.3% respectively. Acute mucositis and pharyngitis were more frequently observed in the FP group than in the cisplatin group. CONCLUSION SMART technique provides an excellent opportunity to spare normal tissue and is probably more biologically effective. Combination of single cisplatin was more tolerable.     

Concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: Treatment outcomes of a prospective,multicentric clinical study

Background and purpose

To evaluate long-term outcome in locoregionally advanced nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy.

Material and methods

Between January 2006 and August 2008, 249 patients with stage III–IVb NPC were treated by IMRT plus concurrent chemotherapy in this multicenter prospective study.

Results

With a mean follow-up of 54.1 months, the 5-year actuarial rates of overall survival (OS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), and distant metastasis-free survival (DMFS) were 78.4%, 86.8%, 88.4%, 78.0%, respectively. There were 29 local recurrences, 25 regional recurrences and 52 distant metastases, respectively. Distant metastasis is the main cause of treatment failure. N-stage was an independent prognostic factor for LRFS, RRFS, DMFS and OS. Acute toxicity ?grade III mainly consisted of mucositis (34.9%), neutropenia (11.2%), xerostomia (5.6%), and dermatitis (5.2%). The main documented late toxicity was xerostomia, and the severity of xerostomia decreased over time. At 24 months after treatment, 13.2% of patients had grade 2 xerostomia, and none had grade 3 or 4 xerostomia.

Conclusions

IMRT with concurrent cisplatin chemotherapy resulted in encouraging rates of local and distant control and overall survival with acceptable rates of acute and limited rates of late toxicity in patients with locoregionally advanced NPC. Distant metastasis remained the main cause of failure. More effective systemic therapy should be explored for patients with advanced N-stage.     

Partially hyperfractionated accelerated radiotherapy and concurrent chemotherapy for advanced nasopharyngeal carcinoma

A newly designed concomitant chemoradiotherapy was undertaken to assess the feasibility and efficacy for advanced nasopharyngeal carcinoma (NPC).

Sixty-three patients with biopsy-proven NPC were entered in this Phase II trial from March 1992 to November 1993. Most patients present with Stage IV disease (93.4%) and poorly differentiated epidermoid carcinoma or undifferentiated carcinoma were the major pathologic type. Radiotherapy was delivered using a telecobalt unit and 10 MV x-rays and by altered fractionation (72–74 Gy/45 fractions/6 weeks). Chemotherapy with cisplatin 75 mg/mm², 2 h infusion at day 1, followed by 5-FU 400 mg/m²/day, continuosly infused for 4 days was given concurrently during the first and fifth weeks of radiotheraphy.

The major toxicity was mucositis (61% belong to Grade 3, 31% to Grade 2). Weight loss, leucopenia, and skin reaction were frequently encountered. Three patients withdrew from treatment at 15, 25, and 55.5 Gy, three patients interrupted the radiotherapy for 1–4.5 weeks, and two patients refused the second cycle of concomitant chemotherapy due to toxicities. The initial tumor response showed 100% overall response rate, with 90.5% complete response. After a median follow-up tiem of 38 months, five patients failed at the primary and/or neck (four recurrent and one persistent), and 14 patients developed distant metastases alone. The 3-year primary disease-free, regional disease-free, distant disease-free, and overall survival rates are 89.1, 92.8, 74.3, and 73.6%, respectively. The late complication rate is acceptable so far.

Our data indicates that concurrent chemoradiotherapy for advanced NPC is both feasible and effective, with acceptable toxicities. Distant metastases are the major site of treatment failure. Postradition adjuvant chemotherapy to eradicate subclinical distant metastasis should be further studied.     

Long-term outcomes of a phase II randomized controlled trial comparing intensity-modulated radiotherapy with or without weekly cisplatin for the treatment of locally recurrent nasopharyngeal carcinoma

Background: Salvage treatment for locally recurrent nasopharyngeal carcinoma (NPC) is complicated and relatively limited. Radiotherapy, combined with effective concomitant chemotherapy, may improve clinical treatment out?comes. We conducted a phase II randomized controlled trial to evaluate the efcacy of intensity?modulated radio?therapy with concomitant weekly cisplatin on locally recurrent NPC. Methods: Between April 2002 and January 2008, 69 patients diagnosed with non?metastatic locally recurrent NPC were randomly assigned to either concomitant chemoradiotherapy group (n = 34) or radiotherapy alone group(n= 35). All patients received intensity?modulated radiotherapy. The radiotherapy dose for both groups was 60 Gy in 27 fractions for 37 days (range 23–53 days). The concomitant chemotherapy schedule was cisplatin 30 mg/m2 by intravenous infusion weekly during radiotherapy. Results: The median follow?up period of all patients was 35 months (range 2–112 months). Between concomitant chemoradiotherapy and radiotherapy groups, there was only significant difference in the 3?year and 5?year overall survival (OS) rates (68.7% vs. 42.2%, P = 0.016 and 41.8% vs. 27.5%, P = 0.049, respectively). Subgroup analysis showedthat concomitant chemoradiotherapy significantly improved the 5?year OS rate especially for patients in stage rT3–4 (33.0% vs. 13.2%, P = 0.009), stages III–IV (34.3% vs. 13.2%, P = 0.006), recurrence interval >30 months (49.0% vs. 20.6%,P= 0.017), and tumor volume >26 cm3 (37.6% vs. 0%, P = 0.006). Conclusion: Compared with radiotherapy alone, concomitant chemoradiotherapy can improve OS of the patients with locally recurrent NPC, especially those with advanced T category (rT3–4) and stage (III–IV) diseases, recurrence intervals >30 months, and tumor volume >26 cm3.     

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。     

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.     

后程加速超分割放射治疗鼻咽癌的远期疗效分析

目的　观察后程加速超分割治疗鼻咽癌的远期疗效及毒副反应。方法　 136例鼻咽癌患者分为后程加速超分割 (LCAF)治疗组和常规分割 (CF)治疗组 ,其中LCAF组 6 6例 ,先用常规分割照射 36～ 4 0Gy ,18～ 2 0分次 ,2 4～ 2 8d完成 ,再用LCAF照射 35 .1～ 4 0 .5Gy,2 6～ 30分次 ,17～ 2 1d ,2次/d ,1.35Gy/次 ,间隔 6h以上 ,总量 75 .1～ 76 .5Gy ,4 6～ 4 8分次 ,4 5～ 4 7d完成。CF组 70例 ,总量 70Gy,35分次 ,4 7～ 4 9d完成。结果　鼻咽部肿瘤完全缓解率 (CR)LCAF组和CF组分别为 97%、90 % ;1、3、5年肿瘤局部控制率LCAF组分别为 97.0 %、95 .4 %、89.8% ,CF组分别为 92 .8%、77.1%、70 .1% ,2个组差异有显著性意义 (χ2 =7.0 6 ,P <0 .0 1)。 1、3、5年的生存率LCAF组分别为 98.5 %、77.3%、6 8.2 % ,CF组分别为 95 .7%、72 .7%、5 9.6 % ,2个组差异无显著性意义 (χ2 =0 .81,P >0 .0 5 )。2个组放射治疗急性毒副反应 ,LCAF组口腔黏膜反应与CF组差异无显著性意义 (χ2 =0 .5 0 ,P >0 .0 5 )。 2个组远期毒副反应差异也无显著性意义 (χ2 =0 .0 7,P >0 .0 5 )。结论　鼻咽癌LCAF的局部控制率明显高于CF的 ,但长期生存率无差别 ,患者能耐受LCAF治疗 ,不增加远期毒副反应。     

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.     

Treatment of Stage IV(A-B) nasopharyngeal carcinoma by induction-concurrent chemoradiotherapy and accelerated fractionation: impact of chemotherapy schemes

PURPOSE: The aim of this study was to evaluate the impact of different chemotherapy regimens in patients with advanced nasopharyngeal carcinoma (NPC) treated by induction-concurrent chemoradiotherapy. METHODS AND MATERIALS: Between 1998 and 2003, 75 Stage IV(A-B) NPC patients were treated with 3 cycles of induction chemotherapy with cisplatin plus 5-fluorouracil (PF) (n = 41) or cisplatin plus gemcitabine (PG) (n = 34), followed by accelerated radiotherapy in concurrence with 2 cycles of cisplatin. In 18 (24%) patients, cisplatin was completely replaced by carboplatin in both concurrent cycles, mainly because of borderline renal functions. RESULTS: The median follow-up was 3.6 years. The 3-year locoregional failure-free survival, progression-free survival, and overall survival of the whole group were 80%, 68%, and 80% respectively. No significant difference was found between patients treated with either induction regimens. However, patients with only carboplatin in the 2 concurrent cycles had significantly inferior 3-year locoregional failure-free survival (56% vs. 86%, p = 0.014), progression-free survival (39% vs. 72%, p = 0.001), and overall survival (61% vs. 87%, p = 0.046) when compared with the rest of the group. In multivariate analysis, the complete replacement of cisplatin by carboplatin during concurrent chemoradiotherapy was still an independent adverse factor in locoregional failure-free survival (hazard ratio, 3.662; 95% CI, 1.145-11.765; p = 0.029) and progression-free survival (hazard ratio, 3.390; 95% CI, 1.443-7.937; p = 0.005). CONCLUSIONS: The more convenient PG regimen is as effective as the PF regimen as induction chemotherapy for patients with advanced NPC. Replacing cisplatin with carboplatin in the concurrent phase carries a poor prognosis.     

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。     

图像引导鼻咽癌调强放疗的初步观察

调强放疗(intensity modulated radiotherapy, IMRT)技术使鼻咽癌(nasopharyngeal carcinoma, NPC)放疗的剂量得以优化,但实施过程中存在着靶区运动、摆位误差等不确定因素,影响IMRT的准确性.我们将影像引导放疗(image guided radiotherapy, IGRT)系统应用于NPC的IMRT,以探讨其应用价值.     

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。     

鼻咽癌同步推量同步放化疗与常规分割后缩野同步放化疗的疗效及毒性反应对比分析

目的 对比分析鼻咽癌同步推量同步放化疗与常规分割后缩野同步放化疗的疗效及毒性反应。方法 回顾性分析自2007年1月—2008年12月于我院接受同步放化疗后的90例鼻咽癌患者,其中同步推量组45例,常规分割后缩野组45例。对比分析两组患者的5年总生存率(Overall survival,OS)、无进展生存率(Progression free survival,PFS)、无局部区域复发生存率(Loco-regional recurrence-free survival,LRFS)以及毒性反应。结果 同步推量组5年OS、PFS、LRFS分别为84.4%、75.6%、88.9%,常规分割后缩野组5年OS、PFS、LRFS分别为82.2%、71.1%、86.7%,两组OS、PFS、LRFS差异无统计学意义。常规分割后缩野组脑干、脊髓、腮腺放疗反应要轻于同步推量组。结论 在调强放疗时代,应用同步推量同步放化疗和常规分割后缩野同步放化疗两种方式在预后方面无统计学差异,而常规分割后缩野组放疗毒性较轻。     

Induction chemotherapy forlocoregionally advanced nasopharyngeal carcinoma

The value of adding induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) for the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC) remains unclear. In our recent article entitled “Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial” published in theLancet Oncology, we reported the results of a phase III, multicenter, randomized controlled trial comparing cisplatin, 5?lfuo?rouracil, and docetaxel (TPF) IC plus CCRT versus CCRT alone in patients with T3?4N1/TxN2?3M0 NPC (ClinicalTrials.gov registration number NCT01245959). The IC?plus?CCRT group showed signiifcantly higher 3?year failure?free survival, overall survival, and distant failure?free survival rates than the CCRT?alone group, with an acceptable toxicity proifle. Our study suggests that adding TPF IC to CCRT could increase survival rates and reduce distant failure in patients with locoregionally advanced NPC. However, long?term follow?up is required to assess the eventual effcacy and toxicity of this strategy, and a more accurate method to determine prognosis is needed to enable better tailoring of treatment strategy for individual patients.     

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。     

超分割后程加速放疗鼻咽癌长期结果分析

目的 研究鼻咽癌后程加速超分割放疗对鼻咽局部控制、生存的影响和并发症状况。方法 全组178例鼻咽癌患者于1995年12月至1998年4月行首次单纯放疗，鼻咽原发灶采用^60Co γ线或6MV X线外照射，其中前4周采用超分割1．2Gy/次，2次／d，5d／周，间隔≥6h，剂量为48Gy分40次；后2周采用加速超分割1．5Gy／次，2次／d，间隔≥6h，5d／周，剂量为30Gy分20次，全疗程的总剂量为78Gy分60次6周完成。结果 急性黏膜反应中鼻咽黏膜反应0级仅2例，1级43例，2级78例，3级52例，4级3例。鼻咽5年局部控制率为87．7％，颈部5年局部控制率为85．7％。5年生存率为67．9％。5年远处转移率为26．1％，颅神经损伤占9．0％。结论 该方法患者能耐受，5年局部控制率、生存率比常规分割和超分割有所提高，颅神经等晚期放射性损伤未见明显增加。