局部晚期下咽癌综合治疗进展

下咽癌是头颈部预后较差的恶性肿瘤,总体5年生存率仅为25%~35%。由于下咽重要的位置与功能,器官功能的保全与生存的提高同样重要,综合治疗的地位越来越突出。手术、放疗、化疗以及分子靶向治疗等手段的综合治疗模式不断更新,患者生存以及器官功能保全率逐渐升高。近年随着免疫治疗的兴起,免疫治疗联合放化疗在下咽癌治疗中的研究成为热点。本文主要介绍综合治疗的进展以及最近的临床研究热点。     

290例下咽癌疗效分析

目的：探讨提高下咽癌５年生存率及生存质量。方法：回顾性分析采用放射治疗、化疗、手术治疗及综合治疗２９０例下咽癌远期疗效。其中Ⅰ期３例,Ⅱ期１２例,Ⅲ期９６例,Ⅳ期１７９例;梨状窝癌２１０例,环后癌４２例,咽后壁癌３８例。单纯放射治疗１５例,放射治疗＋化疗２１例,诱导化疗＋手术４０例,单纯手术５３例,综合治疗（手术＋放射治疗＋化疗）１６１例。保留喉功能手术１６３例,不保留喉功能９１例。结果：５年生存     

局部晚期下咽癌综合治疗进展

由于下咽独特的位置与功能,器官功能的保全与生存的提高同样重要,对于下咽癌的最佳保喉策略在持续探索中。手术、放疗、化疗、分子靶向治疗以及免疫治疗等手段的不断进步,新的保喉治疗策略不断涌现。本文主要介绍下咽癌保喉治疗策略的确立、发展以及对未来的展望。     

保留喉功能下咽癌手术体会

[目的]探讨下咽癌保留喉功能的手术要点。[方法]22例下咽癌患者均行手术治疗,手术方式采用咽部分及垂直半喉切除、下咽＋喉1/4切除、颈侧进路单侧梨状窝切除、颈侧进路下咽局部切除、环后板部分＋披裂切除。切除范围距肿瘤1~2cm,切缘常规送快速冰冻检查。所有病人都行颈淋巴结清扫。部分病人辅以术后放疗。[结果]22例下咽癌病人术后出现轻至中度误咽7例,重度误咽2例。气管套管拔管21例,1例因气道狭窄而留管,拔管率95.5%。所有患者全部恢复发音功能。1例并发咽瘘。死亡率41%,T3、T4死亡6例,T1、T2死亡3例;局部复发4例、颈淋巴转移2例、肝转移1例、肺转移2例;3年生存率77.3%。[结论]下咽癌治疗应以手术为主,放疗为辅。不要为追求彻底而过于扩大正常组织切除范围,因切除过多喉的正常部分并不能改变其预后。对肿瘤基底部的安全切缘要引起我们注意,这是局部肿瘤复发关键。     

喉近全切除术治疗晚期唯癌,下咽癌疗效分析

目的：探讨晚期喉癌、下咽癌保留喉功能的方法,降低全喉切除率。方法：对喉癌Ｔ３、Ｔ４病变和下咽癌Ｔ３病变行喉近全切除术１５例。其中喉癌１３例,梨状窝癌２例。年龄４１￣７６岁,平均５６．３岁。临床分期：Ⅲ期９例,Ⅳ期６例。结果：除１例不能发音外,其余１４例（９３．３％）获得了较好的发音和无呛咳吞咽功能。２年生存率７５．０％（９／１２）。结论：该方法在保存发声功能,降低全喉切除率方面有积极作用。     

局部晚期下咽癌调强放疗剂量分割模式改变对急性放疗反应的影响*

目的：评价改变剂量分割模式的调强放疗同步联合化疗治疗局部晚期下咽鳞癌的安全性。方法：对解放军总医院调强放疗（IMRT）联合含顺铂方案化疗的下咽鳞癌患者进行改变分割剂量的研究。以pGTV 的处方剂量分为2 组：常规剂量组（组1）自2008年8 月至2013年2 月,为回顾性分析,pGTV 处方剂量70Gy,2.12Gy/f ,共33次,5 次/ 周;试验剂量组（组2）自2013年2 月开始,为前瞻性分析,pGTV 处方剂量69Gy,2.30Gy/f ,共30次,5 次/ 周。比较两种剂量分割模式对急性不良反应的影响。结果：自2008年8 月1 日至2014年12月1 日共76例符合入组条件的患者完成放疗,其中组1 含35例,组2 含41例。全组患者无3 级口干症,3 级皮肤损伤、口腔黏膜炎及吞咽困难的发生率较低,无≥ 4 级不良反应。两组的急性皮肤损伤、口干症、口腔黏膜炎、吞咽困难比较差异无统计学意义（P > 0.05）。IMRT 技术差异对急性不良反应无明显影响。诱导化疗（ICT ）为急性口干症的独立性影响因子（P = 0.002）。结论：初步结果显示,69Gy/30f 剂量分割模式 IMRT 在下咽癌安全有效,远期不良反应及疗效仍需进一步观察。     

下咽癌的治疗

目的 总结中国医学科学院肿瘤医院30余年下咽癌治疗的经验。方法 初程以根治性治疗为收治的下咽癌病例262例，术前放射治疗加手术146例（55.7%），单纯放射治疗80例（30.5%），手术加术后放射治疗17例（6.5%），单纯手术治疗19例（7.3%）。全组分为60－70年代、80年代和90年代3个治疗时期，分析各时期病例的特点、治疗方法、放射治疗技术和预后。结果 随着治疗方法和技术的改进，5年总生存率和无瘤生存率分别由60－70年代的14.3%和23.8%提高到90年代的62.2%和53.7%。结论 疾病分期、原发灶部位、治疗方法和照射技术影响预后。     

下咽癌的手术治疗及预后分析

目的：探讨下咽癌的手术疗效及影响预后的因素。方法：回顾性收集本院1990年1月份－2009年12月份行手术治疗的249例下咽鳞癌患者的临床资料。其中男236例,女13例,男女比例为18∶1;年龄40～84岁,中位数59岁;梨状窝型217例,下咽后壁型27例,环后型5例;全组患者病理诊断均为鳞状细胞癌;将全组资料按时间分为两组,即1999年12月31日之前行手术治疗的为前10年组,2000年1月1日之后的为后10年组,两组分别按照 UICC1997TNM分级分期标准,Ⅰ期2例,Ⅱ期22例,Ⅲ期50例,Ⅳ期175例。44例作了喉功能保留手术,205例未保留喉功能。所有患者均行颈淋巴清扫术,其中双侧颈清扫术143例,单侧颈清扫术106例。患者术后均给予放射治疗,剂量50～60Gy。累积生存率计算采用 Kaplan －Meier 法,生存率差异比较采用 Log －rank 检验。结果：随访率91．4％,总的3年生存率为54．6％,5年生存率为36．5％;前10年的3年、5年生存率为47．6％、33．5％,后10年的3年、5年生存率为56．8％、41．5％;喉功能保留组的3年、5年生存率分别为59．1％、45．5％,喉功能未保留组3年、5年生存率分别为50．2％、24．9％;无颈淋巴结转移组的3年、5年生存率分别为74．0％和56．0％,有淋巴结转移组的3年、5年生存率分别为46．2％、21．6％。前10年咽瘘的发生率为17．8％,后10年咽瘘的发生率为5．8％。结论：保留喉功能的下咽癌手术是可行的,根据具体情况合理选用咽喉功能重建方法是提高患者生存质量的重要保证。颈部淋巴结转移率较高,有无颈淋巴结转移直接影响预后,初诊时对其进行准确评估并行及时有效的颈淋巴结清扫可能有助于改善预后。     

新辅助化疗在局部晚期下咽癌综合治疗中功能保存作用的研究

目的探讨新辅助化疗(TPF方案)在局部晚期下咽癌综合治疗中的作用,观察患者的喉功能保存差异。方法以2006年12月至2013年2月46例经病理确诊为鳞癌的晚期下咽癌患者为研究对象,分别采用手术+放疗(手术组)和TPF方案化疗+手术+放疗(实验组)的治疗方案。对两组患者的手术情况、术后喉发音功能、进食吞咽等情况进行比较并评估疗效。结果 13例入手术组,33例入实验组。所有病例均获得完整切除并达到切缘阴性。实验组喉功能保全24例,器官功能保全率72.7%(24/33例);手术组喉功能保全2例,器官功能保全率15.4%(2/13例)。实验组喉功能保全率显著高于手术组(P<0.01)。两组患者术后的进食、吞咽MTF评分没有显著差异(P>0.05)。结论采用TPF方案新辅助化疗联合手术、放疗治疗中晚期下咽癌,可提高患者的喉功能保全率,改善生存质量,是局部晚期下咽癌有效的治疗方法。     

Impact of Treatment Time on Chemoradiotherapy in Locally Advanced Cervical Carcinoma

Background: Adverse effects of treatment prolongation beyond 8 weeks with radiotherapy for cervicalcancer have been established. Clinical data also show that cisplatin increases the biologically effective dose ofradiotherapy. However, there are no data on the effect of overall treatment time in patients with locally advancedcervical cancer treated with concomitant chemo-radiotherapy (CCRT) in an Indian population. The presentstudy concerned the feasibility of concurrent chemotherapy and interspacing brachytherapy during the courseof external radiotherapy to reduce the overall treatment time and compare the normal tissue toxicity and locoregionalcontrol with a conventional schedule. Materials and Methods: Between January 2009 and March 2012fifty patients registered in the Gynaecologic Oncology Clinic of Institute Rotary Cancer Hospital with locallyadvanced cervical cancer (FIGO stage IIB-IIIB) were enrolled. The patients were randomly allocated to treatmentarms based on a computer generated random number. Arm I (n=25) treatment consisted of irradiation of thewhole pelvis to a dose of 50 Gy in 27 fractions, and weekly cisplatin 40mg/m2. High dose rate intra-cavitarybrachytherapy (HDR-ICBT) was performed after one week of completion of external beam radiotherapy (EBRT).The prescribed dose for each session was 7Gy to point A for three insertions at one week intervals. Arm II (n=25)treatment consisted of irradiation of the whole pelvis to a dose of 50 Gy in 27 fractions. Mention HDR-ICBTICRT was performed after 40Gy and 7Gy was delivered to point A for three insertions (days 23, 30, 37) at oneweek intervals. Cisplatin 20 mg/m2/day was administered from D1-5 and D24-28. Overall treatment time wastaken from first day of EBRT to last day of HDR brachytherapy. The overall loco-regional response rate (ORR)was determined at 3 and 6 months. Results: A total of 46 patients completed the planned treatment. The overalltreatment times in arm I and arm II were 65±12 and 48±4 days, respectively (p=0.001). At three and six monthsof follow-up the ORR for arm I was 96% while that for arm II was 88%. No statistically significant differencewas apparent between the two arms. The overall rate of grade ≥3 toxicity was numerically higher in arm I(n=7) than in arm II (n=4) though statistical significance was not reached. None of the predefined prognosticfactors like age, performance status, baseline haemoglobin level, tumour size, lymph node involvement, stageor histopathological subtype showed any impact on outcome. Conclusions: In the setting of concurrent chemoradiotherapya shorter treatment schedule of 48 days may be feasible by interspacing brachytherapy duringexternal irradiation. The response rates and toxicities were comparable.     

局部晚期鼻咽癌同期调强放化疗联合辅助化疗的临床疗效

目的观察同期调强放射治疗联合辅助化疗对局部晚期鼻咽癌的临床疗效和不良反应。方法初治局部晚期鼻咽癌患者49例,按92福州分期Ⅲ期30例,ⅣA期19例。鼻咽和上颈部靶体积采用IMRT技术照射,下颈部和锁骨上靶体积采用下颈前切野常规照射。调强放疗设鼻咽大体肿瘤为GTVnx、颈部阳性淋巴结GTVnd、高危临床靶体积CTV1和低危临床靶体积CTV2。处方剂量分别为GTVnx 73.9Gy/33次、GTVnd及CTV166Gy/33次、CTV2(504~594)Gy/(28~33)次。按EORTC或RTOG标准评价急性反应。全组患者均给与同期化疗,放疗结束予3周期辅助化疗。结果中位随访28月,1、2年局部控制率100％,97．96％,1、2年总生存率(OS) 均为97．96％,1、2年无远处转移生存率95.92％、93.89％。结论局部晚期鼻咽癌同期调强放化疗联合辅助化疗可获得较理想的局部区域控率和总生存率。3~4级急性黏膜炎和3～4级血液系统不良反应是化疗的剂量限制性因素。     

评估诱导化疗在局部晚期鼻咽癌放射治疗中的作用

[目的]通过对配对研究患者进行长期随访,重新评价诱导化疗在局部晚期鼻咽癌放射治疗中的作用。[方法]1999年全年放疗前进行诱导化疗的Ⅲ期、Ⅳa期患者127例(ICT/RT组),按照T分期、N分期、性别、年龄和病理类型的匹配条件,与来自同年接受单纯放疗的127例(RT组)相匹配。两组采用的放疗剂量和技术基本一致,化疗采用以顺铂为基础的联合方案,接受1、2和3个疗程化疗的患者分别为71例(56%)、50例(39%)和6例(5%)。生存患者的中位随访83个月(11～101个月)。[结果]ICT/RT组和RT组的5年总生存率分别为64.6%和52.2%(P=0.045),5年无远处转移生存率分别为86.7%和71.7%(P=0.003)。ICT/RT组生存受益来自于远处转移率的降低。无复发生存率两组比较无显著性差异,其原因可能与ICT/RT组患者接受1个疗程化疗的比例高达56%有关。[结论]配对研究结果显示以顺铂为基础的诱导化疗加放疗能改善局部晚期鼻咽癌患者的无远处转移生存率和总生存率,为临床选择该项治疗提供一个佐证。     

诱导化疗联合同期放化疗治疗47例局部晚期鼻咽癌

[目的]评价诱导化疗联合同期放化疗治疗局部晚期鼻咽癌的近期疗效。[方法]2005年3月至2006年11月局部晚期鼻咽癌患者93例随机分成两组。治疗组47例行紫杉醇+顺铂诱导化疗1个周期后行根治性放疗,同期予紫杉醇每周方案治疗;对照组46例行单纯根治性放疗。[结果]治疗组和对照组在治疗结束时及结束后3个月的鼻咽肿瘤完全消退率分别为74.5%、47.8%和85.1%、65.2%,淋巴结完全消退率分别为78.7%、52.2%和89.4%、69.6%,治疗组病灶消退率优于对照组(P<0.05)。治疗组和对照组2年总生存率分别为80.9%、69.6%,差异无统计学意义。治疗组的急性毒副反应增加,以骨髓抑制和口腔黏膜炎为主,但均可耐受。[结论]诱导化疗+同期放化疗可提高局部晚期鼻咽癌的病灶完全消退率,急性毒副反应可耐受,但能否提高远期生存率有待进一步观察。     

联合放化疗与单纯放疗治疗65例局部中晚期鼻咽癌比较研究

[目的]探讨诱导化疗联合放疗和辅助化疗治疗中晚期鼻咽癌的疗效。[方法]65例中晚期鼻咽癌分为治疗组45例,采用放疗前诱导化疗1次＋根治性放疗＋辅助化疗3～5次;对照组20例,行单纯行根治性放疗。化疗方案为氟尿嘧啶（5-Fu）0.5g/m^2,d1～3;表柔比星（EPI）60mg/m^2,d1;顺铂（DDP）30mg/m^2,d1～3;静脉滴注。两组放疗方法、时间和剂量分割均相同。[结果]治疗组与对照组3年无瘤生存率分别为71.0%、35.0%（P〈0.05）,远处转移率分别为46.7%、75.0%（P〈0.05）。无不可耐受的毒副反应发生。[结论]诱导化疗联合放疗和辅助化疗治疗局部中晚期鼻咽癌能提高生存率,降低远处转移率。     

Radiation Treatment in Pathologic N0-N1 Patients Treated with Neoadjuvant Chemotherapy Followed by Surgery for Locally Advanced Breast Cancer

Purpose

This study evaluated the treatment results and the necessity to irradiate the supraclavicular lymph node (SCN) region in pathological N0-N1 (pN0-N1) patients with locally advanced breast cancer treated with neoadjuvant chemotherapy (NAC) followed by surgery and radiotherapy (RT).

Methods

Between 1996 and 2008, 184 patients with initial tumor size >5 cm or clinically positive lymph nodes were treated with NAC followed by surgery and RT. Among these patients, we retrospectively reviewed 98 patients with pN0-N1. Mastectomy was performed in 55%. The pathological lymph node stage was N0 in 49% and N1 in 51%. All patients received adjuvant RT to chest wall or breast and 56 patients (57%) also received RT to the SCN region (SCNRT).

Results

At 5 years, locoregional recurrence (LRR)-free survival, distant metastasis-free survival, disease-free survival (DFS), and overall survival rates were 93%, 83%, 81%, and 91%, respectively. In pN0 patients, LRR was 7% in SCNRT- group and 5% in SCNRT+ group. In pN1 patients, LRR was 7% in SCNRT- group and 6% in SCNRT+ group. There was no significant difference of LRR, regardless of SCNRT. However, in pN1 patients, there were more patients with poor prognostic factors in the SCNRT+ group compared to SCNRT- group. These factors might be associated with worse DFS in the SCNRT+ group, even though RT was administered to the SCN region.

Conclusion

Our study showed the similar LRR, regardless of SCNRT in pN0-pN1 breast cancer patients after NAC followed by surgery. Prospective randomized trial is called for to validate the role of SCNRT.     

复发鼻咽癌的挽救治疗

鼻咽癌局部复发的处理是一个棘手的问题。放疗仍是复发鼻咽癌治疗的主要手段,手术和化疗的有效临床资料十分缺乏。全文就近年来有关复发鼻咽癌治疗的文献描述进行复习,对其临床处理状况作一简单综述。     

顺铂或紫杉醇联合放射治疗中晚期鼻咽癌临床研究

[目的]比较顺铂和紫杉醇在中晚期鼻咽癌放射治疗中的作用。[方法]在放疗全程中,低剂量每周1次分别应用顺铂或紫杉醇,观察顺铂组和紫杉醇组放疗半量和全量疗效、肿瘤消退时剂量分布以及毒副反应,并与对照组(单纯放疗)比较。[结果]两药在提高放射疗效、肿瘤消退时放射剂量分布和毒副反应方面差异无显著性(P>0.05)。[结论]顺铂或紫杉醇联合放射治疗中晚期鼻咽癌,在提高疗效、放射增敏以及毒副反应方面相近,但顺铂更经济,使用更方便。     

立体定向放疗联合吉西他滨治疗局部晚期胰腺癌

目的：观察立体定向放疗联合吉西他滨治疗局部晚期胰腺癌的临床疗效。方法40例晚期胰腺癌患者根据治疗方案分为观察组和对照组,观察组23例行立体定向放疗序贯吉西他滨化疗,对照组17例行吉西他滨化疗。比较观察2组患治疗结束后的疗效。结果观察组疾病控制率为65.22%,明显高于对照组的29.41%,差异有统计学意义（P ﹤0.05）。肿瘤直径治疗后均有所减小,而观察组减少更为明显,差异有统计学意义（P ﹤0.05）。观察组患者1 a 生存率及死亡患者存活时间均明显高于对照组,差异均有统计学意义（P 均﹤0.05）。结论立体定向放疗联合吉西他滨化疗能够有效控制晚期胰腺癌患者的病情,并延长其生存时间。     

The Impact of Radiotherapy Dose in Patients with Locally Advanced Esophageal Squamous Cell Carcinoma Receiving Preoperative Chemoradiotherapy

Objective: For patients with esophageal squamous cell carcinoma, preoperative chemoradiotherapy followed by planned esophagectomy is used as a curative treatment modality. However, the impact of radiotherapy dose remains undefined. Method: A total of 141 patients with stage III esophageal squamous cell carcinoma (ESCC; as defined by the 7th American Joint Committee on Cancer), receiving preoperative chemoradiotherapy followed by esophagectomy between 2000 and 2015 at Kaohsiung Chang Gung Memorial Hospital, Taiwan, were retrospectively reviewed. The radiotherapy dose of preoperative chemoradiotherapy (36 Gy before 2009 and 50–50.4 Gy after 2009) and other clinicopathological parameters were collected and correlated with the response to chemoradiotherapy and treatment outcome. Result: Of these 141 patients, the radiotherapy dose was 36 Gy in 59 (42%) patients and 50 Gy in 82 (58%) patients. A complete pathological response was noted in 12 (20%) of 59 patients receiving 36 Gy radiotherapy, and 37 (45%) of 82 patients receiving 50 Gy radiotherapy (p = 0.002). The three-year overall survival and disease-free survival rates were 31% and 25% in patients receiving 36 Gy radiotherapy, and 54% and 46% in patients receiving 50–50.4 Gy radiotherapy, respectively (p = 0.023 for overall survival; p = 0.047 for disease-free survival). Multivariate analysis showed that a higher radiotherapy dose was associated with increased pathological complete response (p = 0.003, hazard ratio: 3.215), better overall survival (p = 0.024, hazard ratio: 1.585), and superior disease-free survival (p = 0.049, hazard ratio: 1.493). However, higher radiotherapy doses revealed more surgical complications, including acute respiratory distress syndrome (p = 0.048) and anastomosis leaks (p = 0.004). Conclusion: For patients with locally advanced ESCC, preoperative chemoradiotherapy with higher radiotherapy doses led to increased pathologic complete response rates and improved survival.