复发鼻咽癌的治疗

目前放疗是鼻咽癌首选治疗手段且疗效令人满意,但仍有部分患者经积极治疗后出现复发,对这些患者的治疗有一定困难.近年来主要通过现代放疗、化疗和手术治疗等对复发鼻咽癌患者进行挽救治疗,临床效果得到认同.     

Management of locally recurrent nasopharyngeal carcinoma

As a consequence of the current excellent loco-regional control rates attained using the generally accepted treatment paradigms involving intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC), only 10–20% of patients will suffer from local and/or nodal recurrence after primary treatment. Early detection of recurrence is important as localized recurrent disease is still potentially salvageable, but this treatment often incurs a high risk of major toxicities. Due to the possibility of radio-resistance of tumors which persist or recur despite adequate prior irradiation and the limited tolerance of adjacent normal tissues to sustain further additional treatment, the management of local failures remains one of the greatest challenges in this disease. Both surgical approaches for radical resection and specialized re-irradiation modalities have been explored. Unfortunately, available data are based on retrospective studies, and the majority of them are based on a small number of patients or relatively short follow-up. In this article, we will review the different salvage treatment options and associated prognostic factors for each of them. We will also propose a treatment algorithm based on the latest available evidence and discuss the future directions of treatment for locally recurrent NPC.     

Meningeal infiltration in recurrent nasopharyngeal carcinoma

Permeative infiltration of the meninges appears to be a distinct form of recurrent nasopharyngeal carcinoma (NPC). The present report of eight patients with recurrent NPC illustrates meningeal infiltration following basal foramina extension. Seven of the eight patients (88%) showed jugular foramen involvement. Three patients had concomitant infiltration of the foramen magnum. There was one patient showing spread through the foramen lacerum. Only four (50%) of these patients had clinically detectable tumour in the nasopharynx, while the other half showed deep submucosal recurrence with endoscopically unremarkable findings. Permeative meningeal infiltration appears to be a distinct form of NPC recurrence. It is important to recognize this phenomenon so as to optimize the treatment options.     

Concurrent chemoradiotherapy in locoregionally recurrent nasopharyngeal carcinoma

PURPOSE: To analyze the results of concurrent chemoradiotherapy in patients with locoregional recurrent nasopharyngeal carcinoma. METHODS AND MATERIALS: We performed a retrospective analysis of 35 patients with locoregional recurrent nasopharyngeal carcinoma referred to our department between March 1994 and November 2002. Most patients were male (77%), Chinese (97%), and had undifferentiated carcinoma (89%). Most had extensive locally recurrent Stage rT3-T4 disease (66%) with a median age at recurrence of 49 years (range, 35-69 years). A repeat course of radiotherapy was given concurrently with cisplatin, with cisplatin/5-fluorouracil as consolidation treatment. Significant morbidities were present, including cranial nerve palsies due to extensive recurrent local disease before treatment of the recurrence. RESULTS: The response rate to concurrent chemoradiotherapy was 58% (29% complete response and 29% partial response). The 5-year progression-free and overall survival rate, calculated using the Kaplan-Meier method, was 15% and 26%, respectively. Only 3 patients developed systemic metastases. Grade 3-4 acute toxicities included emesis (9%) and neutropenia (14%), and Grade 3-4 late toxicities consisted of temporal lobe necrosis (3%), cranial neuropathy (6%), and endocrine abnormalities (14%). CONCLUSION: Concurrent chemoradiotherapy is feasible in a selected group of patients with locoregional recurrent NPC, but the risk of major late toxicities is significant.     

Locally advanced nasopharyngeal carcinoma: Current and emerging treatment strategies

Although nasopharyngeal carcinoma (NPC) is a widespread malignant tumor, it is particularly frequent in Southeast Asia. Although T1 tumors can be effectively controlled with exclusive radiotherapy, this treatment modality is insufficient for most NPC patients, who present with locally advanced disease at diagnosis. In fact, for stages ranging from T2b N0 to T4 N3, definitive scientific evidence supports the use of concurrent platinum-based chemotherapy with standard external beam radiotherapy. This treatment approach has shown a statistically significant advantage in terms of overall survival, with respect to radiotherapy alone. Several trials have also investigated the use of neoadjuvant and adjuvant chemotherapy in combination with radiotherapy or chemo-radiotherapy. Platinum compounds, anthracyclines and taxanes are among the chemotherapy agents employed. This review focuses on the clinical results obtained in the field of adjuvant/concurrent/neoadjuvant chemotherapy for locally advanced NPC, for which exclusive concurrent chemo-radiotherapy currently represents the standard treatment approach.     

Salvage radiation therapy for locally recurrent nasopharyngeal carcinoma

Purpose: To study the treatment outcome in patients with locally recurrent nasopharyngeal carcinoma (NPC) and to explore whether a combination of high-dose-rate (HDR) intracavitary brachytherapy and external beam radiation therapy (ERT) could improve the therapeutic ratio.

Methods and Materials: Ninety-one patients with nonmetastatic locally recurrent NPC who were treated with curative intent during the years 1990–1999 were retrospectively analyzed. Eighty-two patients had histologically proven carcinoma. The remaining 9 had clinical and imaging features suggestive of local recurrence. The Ho’s T-stage distribution at recurrence (rT) was as follows: rT1–37, rT2–14, rT3–40. Total equivalent dose (TED) was calculated by the linear–quadratic formula without a time factor correction. For those treated by combined-modality treatment (CMT), the TED was taken as the summation of the equivalent dose by ERT and the absolute dose delivered to floor of the sphenoid by brachytherapy. Eight patients were treated solely with brachytherapy, all receiving 24–45 Gy in 3–10 sessions. Forty-one patients were treated with ERT alone receiving a median TED of 57.3 Gy (range, 49.8–62.5 Gy). Forty-two patients were treated by CMT with a median equivalent dose of 50 Gy (range, 40–60 Gy) given by ERT and 14.8 Gy by brachytherapy (range, 3–29.6 Gy). Multivariate analyses were performed using the Cox regression proportional hazards model.

Results: The 5-year actuarial overall survival rate, disease specific survival rate and local failure-free survival (LFFS) rate for the whole group were 30%, 33.3% and 37.8%, respectively. The 3-year LFFS rates of rT1, rT2, and rT3 diseases were 64%, 61.5%, and 18.4%, respectively (p = 0.001).

Of the 8 patients treated with brachytherapy alone, 4 failed locally. Further analyses were concentrated on the ERT (41 patients) and CMT (42 patients) groups. The 3-year LFFS rates of rT1, rT2, and rT3 diseases were 66.7%, 66.7%, and 18.4%, respectively (p = 0.0008). Better local control for patients who received a TED of 60 Gy or greater was shown. The corresponding 3-year LFFS rates were 29% and 60% (p = 0.0004). Subgroup analysis on the ERT and CMT groups showed a 3-year LFFS rate of 33.5% and 57% (p = 0.003). ERT group had an excess of patients with rT3 disease. Further analysis was performed on the rT1–2 patients showing a trend toward improvement in local control in favor of the CMT group (3-year LFFS rates: CMT, 71.7%; ERT, 54%; p = 0.13). Multivariate analyses showed that rT stage (p = 0.002) and TED (p = 0.01; HR, 0.93; 95% confidence interval, 0.88–0.98) remained significant.

The 5-year major and central nervous system (CNS) complication-free rates were 26.7% and 47.8%. The following factors were found to be significant on univariate analyses for both complications in the ERT and CMT groups: (1) Modality of treatment: more complications with ERT group; and (2) rT stage. Multivariate analyses showed that the rT stage was significant for predicting the occurrence of major (p = 0.004) and CNS complications (p = 0.04).

Conclusion: For rT1–2 local recurrences, CMT with at least 60 Gy TED is recommended. The high incidence of major late complications is of serious concern. Ways of improving the local control of Ho’s rT3 disease and reducing the risk of late complications should be explored.     

Combined chemotherapy for recurrent and metastatic nasopharyngeal carcinoma

Thirty-two patients (24 males, 8 females; median age 54 yrs) with recurrent and/or metastatic undifferentiated carcinoma of the nasopharyngeal type were treated with chemotherapy. Remissions were observed in 17 of 32 (53.2%) with 5 complete (CR) (15.6%) and 12 partial responses (PR) (37.6%). A combination of cisplatin and 5-fluorouracil was the most effective regimen (CR + PR = 83.3%). Objective responses. (CR + PR) were 47% (CR = 11.7%) in schemes without cisplatin and 60% (CR = 20%) in cisplatin-based combinations. The median overall duration of response was 7.2 months. The median overall survival time was 10.3 months: 15.1 months for responders and 5.2 for non-responders. No important toxicity was observed.     

鼻咽癌放疗后局部复发的CT分析

目的：研究鼻咽癌（ＮＰＣ）放疗后局部复发（ｌｏｃａｌ ｒｅｌａｐｓｅ－ＬＲ）的ＣＴ表现及其诊断价值,并从中探索ＬＲ的可能原因。方法：收集１０４例ＮＰＣ患者ＬＲ的ＣＴ片,按其主要ＣＴ表现分为两组：１．单纯鼻咽腔内ＬＲ;２．中同时伴有鼻咽ＬＲ）。并对比二组ＬＲ的中位复发时间及活检阳性率。结果：二组中位复发时间分别为４０个月、１５．６个月。总活检阳性率为５６．７％。两组活检阳性率分别为１００％、３９．２     

鼻咽癌放疗后复发的CT表现

目的分析鼻咽癌放疗后复发的CT表现，探讨鼻咽癌放疗后复发的特点。方法分析有完整临床及CT资料且经病理及随诊证实的鼻咽癌复发患者103例，其中男78例，女25例，年龄18～76岁，中位年龄49岁。由2位有经验的影像诊断科医生对CT资料进行分析。结果放疗后复发103例中鼻咽壁复发79例，CT表现为鼻咽壁均不同程度增厚，其中71例有明显软组织肿物，侵及咽旁间隙58例，茎突后软组织肿物41例，侵及颅底结构23例，侵及海绵窦9例。肿物边缘均不规则，密度不均匀。73例与放疗后CT对比，病变均不同程度增大。放疗后淋巴结转移36例，其中咽后淋巴结转移9例，颈深组淋巴结转移30例，锁骨上区淋巴结转移3例，颌下及腮腺淋巴结转移各1例。边缘规则6例，边缘不规则30例，其中明显侵犯周围结构6例。31例有放疗后CT对比，淋巴结较前均不同程度增大。结论CT扫描能准确评价鼻咽癌放疗后复发，放疗结束后3个月内作基线影像学检查及定期随诊复查，对及时早期发现肿瘤复发十分重要。     

复发鼻咽癌的治疗进展

鼻咽癌是我国南方地区的高发肿瘤,尽管首次根治性放疗后生存率较高,但是仍有约10%的患者出现局部或(和)区域复发.复发鼻咽癌的治疗是一个临床难题,传统的手术及二维放疗因有限的局部控制率及严重的并发症,现已较少使用.近年来随着一些新型治疗方法的出现,使部分鼻咽癌复发患者可取得较好的疗效.然而,由于缺乏足够的循证学证据,使临床医师使用这些新技术时存在一定的困难.本文主要就复发鼻咽癌相关治疗手段及研究进展进行综述.     

Locally advanced nasopharyngeal cancer

Opinion statement The Head and Neck Cancer Intergroup phase III clinical trial (Int 0099) for patients with locally advanced, squamous cell carcinomas (SCC) of the nasopharynx (or NPC) has been recently completed in the United States. The results of this study have defined the new standard of treatment for the group of patients studied. Patients with untreated, locally advanced stages III and IV NPC were randomized to a conven-tional course of radiation, or to radiation given concurrently with chemotherapy followed by three courses of combination chemotherapy. The 3-year progression-free survival (PFS) and overall survival (OS) were 24% versus 69% (P < 0.001) and 46% versus 76% (P < 0.001) for the control and experimental groups, respectively. Recent updates of these survival figures show that they have not changed appreciably. The considerable improvement in OS versus PFS for the patient group receiving radiation alone is accounted for primarily by re-treatment with concurrent radiation-chemo-therapy, combination chemotherapy, and isolated salvage neck dissections. Highly significant differences in local control (41% vs 14%) and distant metastases (35% vs 13%) were demonstrated in favor of the chemoradiation treatment arm. The median age for these patients was 51 years, with a 2:1 male to female ratio. Although many patients had a significant history of tobacco exposure with or without alcohol use or abuse, only 24% had keratinizing or well-differentiated squamous (World Health Organization [WHO] I) type tumors. Whether these results can be extrapolated to the more common Asian variety (WHO II and III) of advanced NPC must be addressed in future clinical trials.     

337例复发鼻咽癌患者的临床特征

背景与目的:目前,原发鼻咽癌即使经过合理的放射治疗和规范的综合治疗后,仍难以避免部分患者出现鼻咽局部和/或颈淋巴结引流区域的肿瘤复发。本文以首次复发鼻咽癌患者临床表现、病理及影像诊断为依据,总结分析复发鼻咽癌的临床特征,为临床医生跟踪鼻咽癌患者治疗后复发的规律提供依据。方法:收集1999年1月至2004年12月间在中山大学肿瘤防治中心治疗和治疗前有病理和/或影像诊断依据的337例首次复发鼻咽癌患者的病例资料,按照复发就诊时的临床表现,影像学显示肿瘤侵犯部位,病理特点,EB病毒血清学检验及临床再分期等特征的相关资料进行统计分析。结果:复发后经2002'UICC/AJCC再分期,Ⅰ/Ⅱ期患者为25.2%,Ⅲ/Ⅳ期为74.8%,中位复发时间为25个月,单纯鼻咽复发为69.4%,单纯颈淋巴结复发为4.5%,鼻咽+颈淋巴结复发为26.1%,最常见的症状为涕血和头痛,最常见的体征是颅神经损害所致的外展障碍与面麻。与鼻咽毗邻的解剖结构如口咽、茎突前间隙及颈动脉鞘区在复发时受侵的概率明显较原发时为低,相反,距离鼻咽部较远的颅底、副鼻窦、颅神经、海绵窦、颅内、翼腭窝、颞下窝、眶尖及软腭在复发时受侵的概率则明显较原发时为高。结论...     

Fractionated stereotactic radiotherapy in residual or recurrent nasopharyngeal carcinoma

The aim of this study was to evaluate results of fractionated stereotactic radiotherapy (FSRT) in patients with residual or recurrent nasopharyngeal carcinoma (NPC) in terms of local progression-free (LPFS) and overall survival (OS) rate and complications after treatment. There were 32 residual or recurrent NPC patients treated with FSRT using linac-based radiosurgery system. Time from the previous radiotherapy to FSRT was 1-165 months (median, 15). Two patients were treated for the second and one for the third recurrence. Thirteen patients (40.6%) also received chemotherapy with FSRT. Tumor volume ranged from 6.2-215 cc (median, 44.4). Average FSRT dose was 17-59.4 Gy (median, 34.6) in 4-25 fractions (median,6) in 1-5.5 weeks (median, 3). Median follow-up time was 25.5(3-67) months. LPFS rate at 1 and 3 years after FSRT was 67.8% and 37.9%. OS rate at 1 and 3 years was 89.7% and 71.2%. If all patients who had tumor progression with no further follow-up were assumed dead, the OS rate at 1 and 3 years would be 75.0% and 37.9%. Univariate analysis showed better local tumor control in patients with tumor volume ≤100 cc (p=0.04) or in those without chemotherapy (p=0.0005). Only chemotherapy retained significance in multivariate analysis (hazard ratio 5.47, 95%CI 1.86-16.04). Eight patients (25%) had complications after FSRT, all grade 2-3 except 1 grade 4 with complete recovery.     

鼻咽癌复发患者的生存质量研究

目的研究鼻咽癌放疗后患者的生存质量。方法从2005年8月1日至2005年9月30日对广西医科大学一附院进行复查的307例鼻咽癌患者进行问卷调查,所用问卷是Washington大学的UW-QOL简体中文第四版,并增加了三项问题:耳部症状、视力、鼻部症状。结果不同年龄和性别的QOL总分差异无显著性(P>0.05)。QOL各项中,得分最低的是唾液、耳部症状、咀嚼及鼻部症状。复发组的总体生存质量显著低于无复发组(P<0.05),但单项只有疼痛、活动及娱乐三项差异有显著性(P<0.001)。结论年龄、性别不影响QOL,QOL得分最低的项目所对应的器官均为在放疗照射野覆盖范围。二程放疗加重了照射区域的正常组织器官功能损害,造成复发组生存质量较差。虽然大部分单项在两组间差异无显著性,但是其叠加结果造成了疼痛、活动及娱乐这三个综合项目显著恶化。     

复发鼻咽癌局部治疗

复发鼻咽癌目前仍以再程放射治疗为主,常规外照射的放疗后遗症发生率较高,适形调强放疗及立体定向放疗在降低靶区周围重要器官和正常组织的照射剂量的同时也提高了局部控制率,近距离放疗和手术治疗在早期病例中也显示出良好疗效.     

内窥镜下微波固化术治疗鼻咽癌放疗后鼻咽腔内复发患者的疗效

背景与目的:局部复发鼻咽癌的治疗是一个临床难题.再程放疗可治愈部分患者,但会带来明显后遗症.本研究旨在评价内窥镜下微波固化术治疗鼻咽癌放疗后鼻咽腔内复发患者的疗效.方法:选取1994年8月至2005年4月中山大学肿瘤防治中心采用内镜下微波同化术治疗的局部复发(rT1)鼻咽癌病例55例,分析其无局部进展生存率及总生存率.结果:本组病例中位随访时间为102.1个月(22.4～153.9个月).放疗后局部复发的中位时间为22.1个月(6.5～125.6个月).微波固化术后鼻咽局部再复发5例.5年无局部进展生存率和总生存率分别为90.7%和93.6%.55例患者均无术中并发症.1例患者术后出现鼻咽溃疡,1个月后愈合.结论:内窥镜下微波同化术治疗选择性的局部复发鼻咽癌(rT1)患者可取得较好的生存率及局控率且并发症少,是目前治疗局部复发鼻咽癌患者的一种操作简便易行、疗效较理想的救援性治疗方法.