Nasopharyngectomy for recurrent nasopharyngeal carcinoma: a review of 31 patients and prognostic factors

OBJECTIVES/HYPOTHESIS: Nasopharyngectomy is a well-established treatment option for recurrent nasopharyngeal carcinoma. Over a period of 4 years and 3 months, in a total of 43 patients, 45 nasopharyngectomies were performed. Thirty-one patients with follow-up ranging from 12 to 58 months were studied. Twenty-two patients (58%) survived; of these, 18 patients (82%) remained disease free. All patients who developed repeat recurrence or died (n = 12) had a high recurrent T-stage tumor, skull base involvement, multiple recurrences, positive surgical margins, or concurrent neck node metastasis. These factors are poor prognostic parameters and might mitigate the indications for aggressive salvage surgery. However, low recurrent T-stage tumor without neck metastasis carries a good prognosis. Modern minimally invasive surgery carries minimal morbidity.STUDY DESIGN A retrospective study was made to determine prognostic indicators in patients treated with salvage surgery for recurrent nasopharyngeal carcinoma. METHODS: Medical records were analyzed for all patients who had received nasopharyngectomy for recurrent nasopharyngeal carcinoma from March 1997 to June 2001. They were followed up from March 1997 to January 2002. Recurrent T stage, nodal metastasis, surgical approach, surgical margins, and pathological nodal status, together with surgical mortality, morbidity, and the delivery of postoperative irradiation, were compared with survival. RESULTS: In all, 43 patients underwent 45 nasopharyngectomies over a period of 4 years and 3 months. Patients with less than 1 year of follow-up were excluded. Four patients with residual disease, who represent a more favorable group, and five patients with planned debulking, nasopharyngectomy, and postoperative stereotactic irradiation were also excluded. The study group comprised 25 men and 6 women (ratio of 4:1) with age ranging from 26 to 69 years (mean age, 49.5 y). In 28 patients (90.3%), the recurrence of nasopharyngeal carcinoma was their first recurrence; in 3 patients (9.7%), the recurrences were second recurrences. Twenty-two patients (71%) survived, achieving a mean survival of 28.5 months. Nine patients died with a mean interval of 7.8 months (range, 1-14 mo). Of the nine patients who died, six (67%) had T3 or T4 tumor, four (44.4%) had concurrent recurrent neck disease, and five (55.5%) had positive surgical margins. Two patients died of perioperative meningitis. Fifteen (83.3%) of the 18 disease-free survivors had a low recurrent T-stage tumor. Mean intervals for development of repeat recurrence or distant metastasis were 16 and 7.9 months, respectively. CONCLUSIONS: High recurrent T stage, skull base involvement, repeated recurrence before surgery, nodal metastasis, and positive surgical margins carry a poor prognosis. This is particularly evident with high T stage and concurrent nodal metastasis. However, patients with low T stage have a survival advantage and benefit most from surgical treatment.     

Nasopharyngectomy for recurrent nasopharyngeal cancer: a 2- to 17-year follow-up

OBJECTIVE: To review the 2- to 17-year outcome of nasopharyngectomy following local recurrence of nasopharyngeal carcinoma. DESIGN: Retrospective review. SETTING: University medical center. PATIENTS: Thirty-seven patients with biopsy-proven recurrent nasopharyngeal cancer followed up for a minimum of 2 years after transpalatal, transmaxillary, and/or transcervical resection with and without neck dissection. OUTCOME: Clinical examination, magnetic resonance imaging, chest x-ray examination, and liver function tests to determine re-recurrence; unlimited follow-up. RESULTS: With a mean follow-up of 5.4 years, the crude, 5-year, overall, free-of-disease survival rate was 52%, local control at 5 years was 67%, and the 5-year actuarial survival rate was 60%. Survival by recurrent T stage (rT) was as follows: rT1, 73%; rT2, 40%; rT3, 14%; and rT4, 0%. Complications occurred in 54% and included 1 death from carotid artery injury and 1 patient with permanent pharyngeal plexus paralysis with resultant dysphagia. The remaining patients had transitory complications that spontaneously resolved, required further surgery (closure of palate fistula, debridement, and reapplication of skin graft), or required further medical therapy. CONCLUSIONS: The results of this study are better than most published reports of additional irradiation for rT1 and rT2 lesions. More recent radiation studies that use radiosurgery or implants suggest promising early results. A randomized prospective study comparing surgery with additional irradiation for recurrent disease at the primary site is warranted.     

Adhesion molecules as prognostic factors in nasopharyngeal carcinoma.

OBJECTIVE/HYPOTHESIS: To identify the significance of molecular markers in determining the risk of recurrence and distant metastases in nasopharyngeal carcinoma. STUDY DESIGN: In this retrospective case study, we evaluated archival nasopharyngeal carcinoma specimens for patterns of expression of E-cadherin, beta-catenin, c-erb-B2, and Ki-67, which have been demonstrated to be important in other tumors. METHODS: Fifty-four cases of nasopharyngeal carcinoma were identified, with a maximum follow-up of 13 years. The histopathological sections were stained using an automated immunohistochemical stainer (NexES, Ventana Medical Systems, Tucson, AZ) for E-cadherin (Zymed Laboratories [San Francisco, CA] and Transduction Laboratories [Lexington, KY] clones), beta-catenin (Zymed), c-erb-B2 (Ventana Medical Systems), and Ki-67 (Novocastra, Burlingame, CA). The numbers of positively staining cells were scored as follows: 0%, 1% to 33%, 34% to 66%, or greater than 67%. RESULTS: E-cadherin (Zymed) stained positively in only one case. The Transduction Laboratories clone demonstrated a spectrum of staining in all cases, from complete to disrupted to no identifiable membranous staining. The staining was consistently absent at the advancing tumor border, regardless of stage. The loss of beta-catenin expression did not correlate with that of E-cadherin or with clinical outcomes. No staining was identified for c-erb-B2. Ki-67 staining was variable and did not correlate with clinical outcomes. CONCLUSIONS: Altered expression or loss of E-cadherin, or both, may result in loss of function, particularly at the infiltrating edge, with resultant loss of cell polarity, cell migration, and eventual metastasis. The interpretation of E-cadherin staining depends on antibody source. In contrast to recent studies, beta-catenin expression is not altered and c-erb-B2 expression not identified, suggesting that these markers are not important in the prognosis of nasopharyngeal carcinoma.     

Salvage surgery for recurrent nasopharyngeal carcinoma

OBJECTIVE: To evaluate the efficacy of salvage surgery in the treatment of recurrent nasopharyngeal carcinoma (NPC) at the primary site. STUDY DESIGN: A retrospective investigation of the outcome of salvage surgery for 28 patients with recurrent NPC after definite radiation therapy. METHODS: The nasopharynx was approached anteroposteriorly by the transmaxillary approach (maxillary swing, maxillectomy) or inferior approach (midline mandibulotomy or median labiomandibular glossotomy), or laterally by modified facial translocation or transpterygoid approach; intentional ligation of the internal carotid artery was performed after establishment of extracranial-intracranial (EC-IC) bypass in one patient; postoperative irradiation was given to the patients with positive pathological margins. RESULTS: Nine patients lived without disease for 20 to 93 months (mean interval, 52 mo) after surgery; among them, eight patients had T1 tumors that were resected totally by surgery via anteroposterior approaches and the other patient had postoperative irradiation to control the disease. Seven patients had local recurrence 8 to 21 months after treatment. Four patients developed distant metastases, including one patient with a T2b tumor that was totally resected through modified facial translocation approach with ligation of internal carotid artery. Eight patients died of other causes; internal carotid artery blowout was the cause of death in four of these eight patients. CONCLUSIONS: In most cases of recurrence, T1 nasopharyngeal tumors can be resected totally by anteroposterior approaches; for T2 or larger tumors, postoperative irradiation is usually necessary. Otherwise, facial translocation offers a better chance to completely resect the tumors. Internal carotid artery is better ligated if patients have received greater than 70 Gy irradiation or if the artery must be exposed during the surgery. We suggest that EC-IC bypass be used to avoid the possible complications (or cerebral ischemic stroke) caused by ligation of internal carotid artery. The transmaxillary approach is favored in the management of nasopharyngeal tumor recurrence with nasal cavity extension, and midline mandibulotomy is more suitable for resection of posterior margin of nasopharyngeal tumor recurrence. Facial translocation offers the widest operative field and is the most versatile approach for radical resection of nasopharyngeal tumor recurrence, but the surgeon should be skilled in the management of the facial nerves to reduce morbidity.     

鼻咽癌颅底骨质破坏放射治疗后预后因素分析

目的评价分析鼻咽癌颅底骨质破坏在首程放射治疗后远期疗效及预后因素.方法1985～1986年100例经病理证实为鼻咽癌,均为鳞状细胞癌,其中低分化96例,高分化4例.所有病例经CT扫描证实颅底骨质被破坏,胸部X线摄片及腹部B型超声检查未见异常.采用60Co或直加单纯外照射,总剂量66～80 Gy/6～8周,2 Gy/次.所有患者均定期随访,平均随访22.3个月(2～174个月).采用Kaplan-Meier统计生存率,Cox模型分析各种预后因素,包括侵犯海绵窦、蝶窦、筛窦、上颌窦,咽旁间隙侵犯、头痛、颅神经损害,治疗后头痛缓解及颅神经损害的修复等.结果 1、3、5、10年生存率分别为78.8%、38.0%、26.9%、13.0%,但伴有前组颅神经(Ⅰ～Ⅷ)和后组颅神经(Ⅸ～Ⅻ)同时侵犯者5年生存率仅为7.7%.死亡原因包括局部复发59例,远处转移21例,局部复发加远处转移1例,非肿瘤原因死亡5例.经多因素分析影响预后的独立因素为颅神经损害、放射治疗后颅神经修复及头痛缓解.结论鼻咽癌颅底骨质侵犯患者的长期随访结果分析,发现颅神经损害、放射治疗后颅神经修复及头痛症状的缓解对预后有重要意义.     

鼻咽癌放疗后局部复发挽救性手术入路的探讨

目的探讨鼻咽癌放疗后鼻咽部复发挽救性手术入路的方法和效果。方法1998年1月—2003年1月对13例鼻咽癌放疗后鼻咽部复发进行挽救性手术治疗。手术采用经口腔硬腭入路2例，鼻锥内翻入路2例，上颌骨外旋入路5例，经颞下窝入路4例，术后随访2～5年。回顾性分析4种不同的手术路径与方法、适应证以及治疗效果。结果T1和T2a各2例患者经硬腭入路和鼻锥内翻入路，随访生存均达3年以上。3例T2b和2例13上颌骨外旋入路，分别在术后2个月、2年死亡，1例术后复发光敏治疗后带瘤生存13个月死亡；2例健在，随访分别达2年和4年。T44例经颞下窝入路，术后咬殆）功能均有影响，术后1年内死亡3例，1例随访2年健在。13例均无术中并发症，术后发生鼻咽部颅底骨坏死、脑脊液漏并发颅内感染、上消化道大出血各1例，2年生存率54％（7／13）。结论根据鼻咽复发肿瘤的部位、侵犯范围，以尽可能小的创伤获得足够的显露的原则选择手术入路。T1和他病变可外科手术根治，手术效果良好。肿瘤侵犯咽旁组织和中耳者，预后较差，手术可以减轻患者痛苦，延长生命。     

Salvage surgery for recurrent nasopharyngeal carcinoma.

OBJECTIVE: To evaluate the results of salvage surgery for patients with primary recurrence of nasopharyngeal carcinoma after radiotherapy. DESIGN: Cohort study. SETTING: Academic tertiary referral center. PATIENTS: Eighteen consecutive patients with primary recurrence of nasopharyngeal carcinoma after radiation failure underwent nasopharyngectomy for cure via a facial translocation approach from July 1, 1993, to December 31, 1999. Follow-up ranged from 3 to 71 months. Five patients with skull base invasion required a combined neurosurgical approach to treatment. Seven patients had additional postoperative radiotherapy. RESULTS: The actuarial 3-year survival was 57%, while the local control was 78%. Four of 5 patients who had skull base invasion achieved local control. There was no surgical mortality, and the morbidity was 22%. CONCLUSION: Advances in skull base surgery make possible the effective control of primary recurrence of nasopharyngeal carcinoma, with acceptable mortality and morbidity.     

鼻咽癌颅底骨质破坏放射治疗后预后因素分析

目的 评价分析鼻咽癌颅底骨破坏在首程放射治疗后无期疗效及预后因素。方法 1985-1986年100例经病理证实为鼻咽癌,均为鳞状细胞癌,其中低分化96例,高分化4例。所有病例经CT扫描证实颅底骨质被破坏,胸部X线摄片及腹部B型超声检查未见异常。采用^60Co或直加单纯外照射,总剂量66-80Gy/6-8周,2Gy/次。所有患者均定期随访,平均随访22.3个月（2-174个月）。采用Kaplan-Meier统计生存率,Cox模型分析各种预后因素,包括侵犯海绵窦、蝶窦、筛窦、上颌窦,咽旁间隙侵犯、头痛、颅神经损害,治疗后头痛缓解入颅神经损害的修复等。结果 1、3、5、10年生存率分别为78.8%、38.0%、26.9%、13.0%,但伴有前组颅神经（Ⅰ-Ⅷ）和后级颅神经（Ⅸ-Ⅻ）同时侵犯者5年生存率仅为7.7%。死亡原因包抱局部复发59例,远处转移21例,局部复发加远处转移1例,非肿瘤原因死亡5例。经多因素分析：影响预后的独立因素为颅神经损害、放射治疗后颅神经修复及头痛缓解。结论 鼻咽癌颅底骨质侵犯患者的长期访结果分析,发现颅神经损害、放射治疗后颅神经修复及头痛缓解。结论 鼻咽癌颅底骨质侵犯患者的长期随访结果分析,发现颅神经损害、放射治疗后颅神经修复及头痛症状的缓解对预后有重要意义。     

复发鼻咽癌手术治疗地位的思考

外科治疗在复发鼻咽癌的治疗中越来越受到重视。随着手术技术的不断提高,特别是经鼻内镜外科挽救手术的开展,对于经过选择的复发鼻咽癌患者,其标准治疗逐渐从再程放疗向手术治疗转换。检索收集近年发表的重要文献,介绍了复发鼻咽癌的各种手术方式,分析各种手术方式的优劣势,并对疗效及不良反应等进行阐述。     

Stereotactic radiotherapy for locally recurrent nasopharyngeal carcinoma.

OBJECTIVE: To determine the efficacy of stereotactic radiotherapy (SRT) in the treatment of recurrent nasopharyngeal carcinoma. STUDY DESIGN: A retrospective review of the outcome of SRT for patients with recurrent nasopharyngeal carcinomas following definitive conventional radiation therapy. METHODS: Five patients were treated with daily static multiportal irradiation. Two Gy was administered with eight isocentric portals in a single plane 5 days a week, and the plane was changed for every 20 to 30 Gy. Of these patients, three had poorly differentiated squamous cell carcinoma. Tumor sizes ranged from 1 to 15 cm3, with a median size 3.2 cm3. Median follow-up time from SRT was 34 months (range, 4-61 mo). RESULTS: Four of five recurrent tumors responded well and achieved complete regression. Three patients have survived without evidence of local recurrence with a median follow-up time of 34 months. Marginal recurrence was observed at the posterosuperior wall in a patient with adenoid cystic carcinoma at 30 months after SRT. One patient who received SRT after the two complete courses of radiation therapy died 6 months after SRT as a result of rupture of a branch of the left carotid artery, but autopsy revealed no local residual tumor. CONCLUSIONS: Stereotactic radiotherapy with isocentric multiportals in one plane, which is changed at every 20 to 30 Gy, can provide local control with acceptable toxicity in patients with recurrent nasopharyngeal carcinoma, but increased clinical experience and longer follow-up will be necessary to evaluate the overall role of this technique in nasopharyngeal carcinoma.     

Prognostic factors and outcome for nasopharyngeal carcinoma

BACKGROUND: Nasopharyngeal cancer (NPC) is a distinct form of cancer of the upper respiratory or digestive tract in which the epidemiologic features, origin, histopathologic types, treatment, and prognosis are different from those associated with other malignant neoplasms of this anatomical area. Recent publications have demonstrated the advantage of aggressive multimodality treatment for advanced NPC. OBJECTIVES: To evaluate the results of standardized treatment of NPC during 11 years and to identify pertinent factors for clinical outcome. METHODS: Between January 1, 1989, and December 31, 2000, 173 patients with newly diagnosed NPC were treated at Instituto Nacional de Cancer. Clinical records and radiographic studies of the patients were retrospectively reviewed. Documented data of the initial presenting symptoms, head and neck examination, radiotherapy protocols, chemotherapy regimens, and surgical technique were analyzed. To determine important prognostic factors, we correlated survival rates with age, clinical stage, tumor extent, histopathological type, and therapeutic approach. The major end point used for assessment was relapse-free survival. Survival curves were estimated by the Kaplan-Meier product-limit method. Multivariate analysis was performed using the Wilcoxon signed rank and Cox proportional hazards regression tests. RESULTS: Most patients (88.5%) had locoregional advanced disease, mostly (53.4%) of the nonkeratinizing subtype. Forty-seven percent of patients had clinical cervical nodal metastases at first consultation. Gross extension of the primary tumor involving the facial bones and skull base was observed in 39.3% and 20.8%, respectively. Just under 75% of patients were treated with radiotherapy (median dose, 6600 cGy), and 25.4% underwent concomitant chemoradiotherapy with adjuvant chemotherapy (cisplatin plus 5-fluorouracil) (median dose, 6800 cGy). The 5-year disease-specific survival for the 173 patients was 32.3%. The disease-specific survival for the radiotherapy group was 22.5%, compared with 61.4% for the chemoradiotherapy plus adjuvant chemotherapy group (P =.004). Factors associated with adverse outcomes were age older than 40 years at treatment (P =.001), advanced TNM stage (P =.002), skull base invasion (P =.004), and facial bone invasion (P<.001). CONCLUSIONS: Compared with radiotherapy alone, concomitant chemoradiotherapy with adjuvant chemotherapy improved the treatment outcome of patients with NPC treated in our institution. Advanced age, local extension, and stage of the disease adversely affected the prognosis in our patients. Compared with reirradiation, salvage brachytherapy and radical neck dissection for local and regional residual or recurrent NPC were associated with increased rates of locoregional control and survival.     

Pharyngolaryngectomy for advanced and recurrent cancer: prognostic factors and complications

INTRODUCTION: The aim of this study was to evaluate the results of the initial surgical treatment and salvage treatment for advanced laryngopharyngeal cancer. METHODS: From 1984 to 1997, primary surgical treatment was undertaken in 60 patients. 75 patients underwent surgical salvage following radiotherapy. RESULTS: 55/135 patients (40.7%) experienced local regional relapse. The overall survival at 5 years was 43.9% in the first group of patients treated initially with surgery. In the group of patients treated with salvage surgery, the overall survival at 5 years was 40.2%. A multivariate analysis showed that involved lymph nodes (p = 0.0004), a nutritional score inferior to 5 (p = 0.03), positive resection margins (hazard ratio 2.05; 95% c.i. 1.03 to 4.04 ; p = 0.03), a local-regional relapse (p = 0.04) and appearance of metastasis (p = 0.03) were independent risk factors for overall survival. Survival is dependent from each factor, and each factor is independent from each other Stenosis was rare: 5.1% in the present series. A pharyngocutaneous fistula developed in 49.6% of patients. After a multivariate analysis, the site of the tumor (odds 2.26; 95% c.i. 1.05 to 4.85; p = 0.03) had an influence for apparition of a fistula. CONCLUSION: Initial surgical surgery and salvage surgery of respectively 43.9% and 40.2% overall survival compares favorably with the literature. Despite progress made with reconstruction, morbidity is still elevated in a selected group defined after analysis of pronostic factors.     

纳米脂质体介导p53治疗鼻咽癌的实验研究

目的 探讨纳米脂质体介导p53基因在体外转染鼻咽癌细胞株后细胞的生长变化情况.方法 不同比例的纳米脂质体与p53质粒的混合物转染鼻咽癌细胞,转染效率最高的组用MTT法和流式细胞术检测鼻咽癌细胞的生长和凋亡情况.结果 比例为纳米脂质体/Porf-GFP=2.5/1的转染效率最高,达60%～70%.MTT法测定纳米脂质体包裹p53能明显抑制鼻咽癌细胞株的体外生长,抑制率为67.7%,且转染脂质体/Porf-hp53的鼻咽癌细胞中凋亡细胞占47.8%.结论 纳米脂质体作为一种非病毒载体能有效的将p53基因转导入鼻咽癌细胞中,并抑制肿瘤细胞生长,诱发凋亡.     

Local infiltration of T-lymphocyte subsets as a prognostic indicator in patients with nasopharyngeal carcinoma

We studied tumor-host interactions in 47 patients with NPC. The local infiltration of T-lymphocyte subsets was investigated by an immunoperoxidase technique using monoclonal antibodies. Biopsy specimens of patients without cervical metastasis showed more T-lymphocyte (T11) infiltration. The amount of Leu-3a (helper/inducer) and T8 (cytotoxic/suppressor) cell infiltration did not correlate with the age, sex, clinical stage, and peripheral blood T4 and T8 cells of the patients. A higher incidence of Leu-3a cell infiltration was found in patients with high serum IgA antibody titers to EBV VCA. A trend of better prognosis was revealed in those cases with no or slight stromal T8 cell infiltration. A local immune response was found to exist which may prevent the spread of NPC to the cervical nodes, but this needs further study to evaluate the local infiltration of T-lymphocyte subsets as a prognostic indicator.