【作者】 李飞；

【导师】 朱国培；

【作者基本信息】 复旦大学 ， 肿瘤学（专业学位）， 2014， 硕士

【摘要】 目的：分析我院大唾液腺癌综合治疗的疗效、预后相关因素以及对治疗失败模式的探索,其基础治疗为手术联合术后放疗,部分患者接受化疗。材料和方法：回顾性分析2005年至2011年复旦大学肿瘤医院收治的经过手术联合术后放疗±化疗的205例患者。计划靶区包括原发肿瘤和阳性淋巴结手术床,给予60Gy/30次(范围56-66Gy)照射,同侧淋巴结有涉及时,靶区包括同侧淋巴结引流区,选择性颈部放疗应用于高危的、颈部淋巴结阴性的患者。对于临床和病理证实淋巴结阴性,但伴有不良预后因素的患者,预防性照射同侧颈部淋巴结引流区,剂量50-56Gy。根据肿瘤病理类型和高危因素判断化疗的应用指征。主要研究终点是无进展生存率(progression-free survival, PFS)、总生存率(overall survival, OS)、不良预后因素,治疗失败模式。使用单因素和多因素分析来预测生存相关的因素。结果：所有患者的中位随访时间是51月(范围5-109月)。168例患者位于腮腺,36例位于颌下腺,1例位于舌下腺。组织病理学分类,淋巴上皮癌49例,粘液表皮样癌38例,腺样囊性癌33例,涎腺导管癌22例,腺癌非特异类型20例,腺泡细胞癌16例,其他类型共27例。所有患者均经手术联合术后放疗,中位剂量60Gy。中位手术放疗间隔时间为5周。病程中29例患者接受了化疗,化疗组患者中不良预后因素更常见,包括T3-T4分期,淋巴结阳性,切缘阳性,神经侵犯等。最常见的化疗方案为铂类为基础的化疗方案。共发生39例治疗失败事件,33例远处转移,13例局部区域复发,其中7例患者同时发生远处转移和局部区域复发。3年、5年无进展生存率及总生存率分别为82.1%、79.8%和85.7%、85.1%。总生存率的独立预后因素为淋巴结转移和神经侵犯；无进展生存率的独立预后因素为性别、年龄、淋巴结转移、神经侵犯。结论：经手术联合术后放疗治疗原发性大唾液腺恶性肿瘤获得较好的预后和总生存,全组患者中经过手术联合术后放疗取得良好的生存结果而且不良反应较小。男性、大龄、伴神经侵犯及淋巴结转移患者预后较差。通过观察本研究中的失败模式发现治疗后2年内为复发转移的高发时期,远处转移为治疗失败的主要原因。辅助全身治疗以及靶向治疗需要在前瞻性试验中验证。目的：本研究通过评价分析大唾液腺淋巴上皮癌的诊断策略、综合治疗的疗效、治疗失败模式以及预后相关因素,探寻控制该病的最优策略。方法：纳入2005.01月至2011.12月经病理证实的原发性大唾液腺淋巴上皮癌患者。所有患者均经手术联合术后辅助放疗,部分患者辅以化疗。大唾液腺癌目前的标准术式为肿瘤根治性切除加同侧Ⅱ区及Ⅰb区淋巴结清扫。临床淋巴结转移患者需行根治性颈清。术后分别给予肿瘤以及阳性淋巴结手术床60Gy/30Fx,同侧淋巴结引流区56Gy/28Fx术后放疗。应用Kaplan-Meier法计算无进展生存(progression-free survival, PFS)总生存(overall survival, OS)以及相关的预后因素。结果：共有49例患者纳入该研究,全组中位年龄为44岁(15-77岁)。本组患者中男性28例,女性21例,Ⅰ-Ⅱ期21例,Ⅲ-Ⅳ期28例。中位随访46月(12-109月)。3年、5年无进展生存率以及总生存率分别为89.8%、82.0%和91.3%、91.3%。随访过程中共有4人死亡,其中2人同时局部复发和远处转移,另外2例局部复发。单、多因素分析显示,肿瘤原发部位为PFS的独立预后因素,患者年龄较大、伴淋巴结转移倾向预后较差。晚期患者即使应用化疗,疗效仍较差。结论：手术切除联合术后辅助放疗可获得良好的生存期,化疗的应用未带来明显的生存获益,手术联合放疗是大唾液腺淋巴上皮癌合理有效的治疗策略。更多还原

【Abstract】 Purpose:To report our experience in treating patients with major salivary gland malignancies who had undergone surgical resection (primary tumors resection ± neck dissection) followed by postoperative adjuvant radiotherapy (PORT) with or without chemotherapy.Methods and materials:Between 2005 and 2011,205 patients with major salivary gland cancer treated at Department of Radiation Oncology, Cancer Hospital, Fudan University with surgical resection and postoperative radiotherapy (PORT) ± chemotherapy were analyzed. In the postoperative setting, the primary tumor and involved lymph node bed constitute the planning target volume and are generally treated to 60Gy in 30 fractions (R 56-66Gy). Ipsilateral cervical lymph nodes are routinely targeted when involved and elective nodal irradiation (ENI) was applied to high-risk, node-negative disease. For patients without clinical or pathologic lymph node involvement, elective nodal irradiation to a dose of 50-56Gy is usually reserved for patients with adverse prognostic factors. Chemotherapy was administered at the discretion of the treating medical oncologist based on tumor histology and high-risk features. The primary endpoints were progression-free survival(PFS), overall survival (OS) and adverse prognostic factors. Univariate and multivariable regression analyses were performed to identify factors associated with improved survival.Results:The median follow-up for all patients was 51 months (R 5-109 months). The tumor was located in the parotid gland in 168 cases, submandibular gland in 36 cases and sublingual gland in one case. The histologic types included lymphoepithelial carcinoma in 49, mucoepidermoid carcinoma in 38, adenoid cystic carcinoma in 33, salivary duct carcinoma in 22, adenocarcinoma NOS in 20, acinic cell carcinoma in 16 and other in 27. Surgery and radiotherapy were applied to all patients, with a median dose of 60Gy. Median delay between surgery and radiotherapy was 5 weeks.29 patients undergone chemotherapy in the disease course and more adverse prognostic factors prevailed in the chemotherapy group, including stage T3-T4 disease, nodal positivity and positive margins and perineural invasion. The most common chemotherapy regimen was platinum-based regimen.39 failure events were reported:33 distant metastases and 13 local-regional recurrent.7 distant metastases and local-regional recurrent simultaneously. PFS and OS at 3,5 years were 82.1%, 79.8% and 85.7%,85.1%, respectively. On multivariate analysis, LN involvement and presence of perineural/neural invasion correlated significantly with OS. Age, sex, LN involvement and presence of perineural/neural invasion correlated with PFS.Conclusions:Surgical resection and postoperative radiotherapy for major salivary malignancies result in promising locoregional control and overall survival. Of the entire group, surgery and postoperative radiotherapy resulted in excellent outcomes with minimal side effects.Patients with male sex, old age, LN involvement and presence of perineural/neural invasion had a bad prognosis. However, in view of the pattern of failures observed in this study, mostly occurred in the first 2 years after treatment, distance metastasis is the main cause of treatment failure. The role of adjuvant systemic or targeted therapy in patients at high risk of DM should be investigated in prospective trials.Purpose:The present study was undertaken to evaluate the diagnostic approaches, treatment results and failure patterns of lymphoepithelial carcinoma of the major salivary glands (LECSG) who were treated by comprehensive therapy modalities in an attempt to identify the proper strategies for the management of this disease.Material and Methods:Patients with a histologic diagnosis of primary lymphoepithelial carcinoma in the major salivary gland that were treated at our institution between January 2005 and December 2011 were comprehensively analyzed. All patients undergone surgery and adjuvant radiotherapy, some patients received chemotherapy simultaneously. An en bloc radical excision, which generally removes the primary gland with level II and I b lymph nodes, followed by adjuvant radiotherapy was the standard treatment for this group of patients. Radical neck dissection was only performed in patients with metastatic lymphadenopathy. Postoperative irradiation was delivered to the surgical bed of the tumor and involved nodes at a dose of 60Gy and to the ipsilateral cervical lymph nodes at a dose of 56Gy. Clinical and pathological factors correlated with progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier.Results:A total of 49 patients with a median age of 44 years were enrolled in this study. The study population consisted of 28 males and 21 females. There were twenty-one patients with stage Ⅰ-Ⅱ disease, and 28 patients with stage Ⅲ-Ⅳ disease. With a median follow-up of 46 months (range,12 to 109 months), the 3-year、5-year estimated progression-free survival (PFS) and overall survival (OS) were 89.8%、 82.0% and 91.3%、91.3%, respectively. During follow-up, only four patients died.Two of them died of local-regional recurrence and distant metastases. The other two died of local-regional recurrence. Univariate and multiple factor analysis showed that the primary tumor site was an independent prognostic factor for PFS, patients with older age or with lymph node metastasis tended to have a poor prognosis. Even add chemotherapy into patients with late stage, the curative effect is still poor.Conclusions:Surgical resection with adjuvant radiotherapy is a reasonable and proper treatment approach in the definitive management of LECSG and results in a favorable prognosis for a significant proportion of patients. Patients achieved good survival in our study.更多还原