奈达铂或顺铂联合紫杉醇同步放化疗局部晚期食管癌的近期疗效比较

目的探讨奈达铂替代顺铂与紫杉醇化疗联合同步放疗局部颈段食管癌的疗效及耐受性。方法实验组（TN组）30例,采用紫杉醇135 mg/m2,静脉滴注,第1天,奈达铂100 mg/m2静脉滴注,第1天,诱导化疗,每3周为1个化疗周期,共2个疗程,同期行根治性放疗。对照组（TP组）30例,采用顺铂（30 mg/m2第1～3天）代替奈达铂,其余治疗方法同实验组。结果有效率实验组和对照组分别是66.7%和64.0%,P〉0.05,差异无统计学意义;不良反应显示实验组和对照组白细胞减少的发生率分别为53.3%（16/30）和48.0%（12/25）,贫血发生率分别为26.7%（8/30）和36.0%（9/25）,血小板下降的发生率分别为40.0%（12/30）和32.0%（8/25）,肝功损害发生率分别是6.7%（2/30）和12.0%（3/25）,实验组和对照组比较,P〉0.05,差异均无统计学意义。由于对照组将顺铂分为3日小剂量连续使用,故2组肾毒性发生率都很低,差异无统计学意义。恶心呕吐发生率实验组明显低于对照组,差异有统计学意义。结论奈达铂联合紫杉醇结合同步放疗治疗局部颈段食管癌疗效确切,且患者耐受性良好。     

Phase II Study of Chemoradiotherapy for Advanced Squamous Cell Carcinoma of the Thoracic Esophagus: Nine Japanese Institutions Trial

A phase II study of chemoradiotherapy for advanced squamouscell carcinoma of the thoracic esophagus was carried out cooperativelyby nine Japanese institutions. Forty-five patients with thoracicadvanced squamous cell carcinoma, who had T4 tumor or distantlymph node metastasis (M1_(LYM)), were enrolled in the studyfor treatment with cisplatin (70 mg/m²) on days 1 and 36, and5-fluorouracil infusion (700 mg/m²) on days 1–4 and 36–39sandwiched around external beam irradiation (60 Gy over 6 weeks).Of the 45 evaluable patients, 37 (84.1%) completed the treatment.The overall response rate was 64.4%, and the complete responserate 8.9%. The median duration of response was 125.0 days forpatients who achieved complete and partial response. The 50%median survival time was 215 days. There was one toxicity-relateddeath due to radiation pneumonitis. The major form of toxicityexceeding grade 2 was myelosuppression and anorexia, but grade4 toxicity was also observed (2 pulmonary, 1 severe hypoxemia,1 severe cardiac failure and 1 mental disturbance). The resultsshowed that this form of chemoradiotherapy had a satisfactoryeffect and might be useful for treatment of inoperable advancedesophageal cancer.     

同步放化疗后联合化疗对局部晚期宫颈癌患者预后的研究

目的 探讨同步放化疗后巩固化疗对局部晚期宫颈癌患者预后的影响.方法 选择拟行宫颈癌同步放化疗的患者200例,随机分为观察组和对照组,观察组采用同步放化疗后巩固化疗治疗,对照组采用单纯同步放化疗治疗,比较两组患者近期疗效、不良反应发生率、2年生存率和局部无进展生存率.结果 观察组近期疗效总有效率、胃肠道反应、骨髓抑制发生率(92.0％,90.0％,98.％)与对照组(88.0％,84.0％,96.0％)比较差异无显著统计学意义(P＞0.05);但观察组2年生存率和局部无进展生存率(92.0％,88.0％)显著高于对照组(78.0％,65.0％),具有统计学意义(P＜0.01).结论 局部晚期宫颈癌患者同步放化疗后巩固化疗可有效改善患者预后,有望成为局部晚期宫颈癌患者的有效治疗手段.     

新辅助化疗联合同步放化疗对局部晚期鼻咽癌预后影响的Meta分析

目的： 评价新辅助化疗联合同步放化疗对比同步放化疗治疗局部晚期鼻咽癌的远期疗效。方法: 计算机检索The Cochrane Library（2016年2期）、Pubmed、Embase、中国生物医学文献数据库（CBM）、中国期刊全文数据库(CNKI)、维普中文科技期刊全文数据库(VIP)和万方数据库,对符合纳入标准的研究进行方法学质量评价,采用RevMan5.3进行Meta分析。结果: 共纳入11个研究1 521名患者,结果显示,新辅助化疗联合同步放化疗在5年无远处转移生存率,优于同步放化疗［OR=1.70,95%CI（1.14,2.55）,P=0.009］,两组的3年生存率,3年无远处转移生存率、3年无进展生存率、3年复发生存率、5年生存率、5年无进展生存率和5年复发生存率无差别（P＞0.05）。结论: 现有证据表明,与同步放化疗相比,新辅助化疗联合同步放化疗提高了局部晚期鼻咽癌患者的无远处转移生存率,但未提高患者的总生存率。     

Association of p53 Protein Expression with Responses and Survival of Patients with Locally Advanced Esophageal Carcinoma Treated with Chemoradiotherapy

Immunohistochemical analysis was performed to determine theclinical role of p53 mutations in patients with locally advancedesophageal carcinomas treated with concurrent chemoradiotherapy.The subjects of this study were 20 patients with previouslyuntreated esophageal carcinomas with evidence of T4 diseaseand/or distant node metastases. Treatment comprised protracted5-fluorouracil and 2-h cisplatinum infusions along with radiationtreatment with a total radiation dose of 60 Gy. Tumor specimensfrom 18 of the 20 patients were analyzed immunohistochemically.Mutant p53 protein expression in the biopsy materials from theprimary tumors was analyzed by immunohistochemical stainingusing a polyclonal antibody, RSP53. Expression of p53 was detectedimmunohistochemically in 10 (56%) of the 18 esophageal tumors,the cancer cell nuclei of which were diffusely stained. Therewere no significant differences between the patient backgroundsof the p53-"positive" and "negative" groups. Four (40%) of the10 patients with p53 expression achieved overall complete remissions(CRs) and 7 (70%) of these 10 achieved CRs of their primarytumors. In contrast, none of the 8 p53-negative patients achievedoverall CRs and two (25%) achieved CRs of their primary tumors.The CR rates overall and of primary tumors tended to be higherin the p53-positive than negative group, but the differenceswere not significant. The survival rate for the 10 patientswith p53 expression was better than that for the 8 negativeones (P > 0.01): their median survival times were 12 and4.5 months, respectively. Expression of p53 protein may be anindicator of a favorable prognosis in patients with locallyadvanced esophageal carcinomas treated with concurrent chemoradiotherapy.     

Simultaneous Modulated Accelerated Radiation Therapy and Concurrent Weekly Paclitaxel in the Treatment of Locally Advanced Nasopharyngeal Carcinoma

Objectives: To evaluate the feasibility and efficacy of simultaneous accelerated radiation therapy (SMART) andconcurrent weekly paclitaxel in the treatment of locally advanced nasopharyngeal carcinoma. Methods: Fortyonepatients with pathologically confirmed nasopharyngeal carcinoma were treated by SMART with concurrentweekly paclitaxel. Daily fraction doses of 2.5 Gy and 2.0 Gy were prescribed to the gross tumor volume (GTV)and clinical target volume (CTV) to a total dose of 70 Gy and 56 Gy, respectively. Paclitaxel of 45 mg/m2 wasadministered concurrently with radiation therapy every week. Adjuvant chemotherapy was given four weeksafter the completion of the radiotherapy (RT) if the tumor demonstrated only a partial response (PR). Results:All patients completed the radiotherapy (RT) course. Adjuvant chemotherapy was administered to 12 patientsdue to PR. The CR (complete remission) rate was 82.9% three months after RT. Thirty-nine (95.1%) patientscompleted the concurrent weekly chemotherapy with paclitaxel, and two patients skipped their sixth course.Seven patients had a 15% dosage reduction at the fifth and sixth course due to grade 3 mucositis. The medianfollow-up was 30 (range, 14-42) months. The three-year overall survival (OS), metastases-free survival (MFS),and local control rates were 77.0%, 64.4%, and 97.6%, respectively. No correlation between survival rate and Tor N stage was observed. Grade 3 acute mucositis and xerostomia were present in 17.1% and 7.1%, respectively.Conclusion: SMART with concurrent weekly paclitaxel is a potentially effective and toxicity tolerable approachin the treatment of locally advanced NPC.     

Chemotherapy and Cyclic Radiation Therapy in Locally Advanced Non-Small Cell Lung Carcinoma

Nine patients with non-small cell lung carcinoma (4 squamous, 4 adenocarcinoma, 1 large cell) were treated with a combination of radiation therapy and cyclic chemotherapy with 5-fluorouracil, methotrexate and platinum. Four previously untreated patients had stage III, 2 having distant metastases, 5 previously treated patients were restaged as stage III with distant metastasis in one. Moderate hematologic toxicity was noted. Objective responses occurred in 67 per cent, regardless of previous treatment or performance status. Responders survived for a median of 11 months with one complete response patient surviving at 14 months while 5 partial response patients survived for a median of 10 months. This regimen is feasible and its utility as the initial treatment of locally advanced disease should be further investigated.     

放疗,放化疗结合治疗中晚期食管癌

为了观察在放疗的同期追加化疗能否提高对中晚期食管癌的疗效,将１５６ 例中晚期食管癌随机分成Ａ、Ｂ２ 组,每组７８ 例。Ａ组：每周放疗６ 次,每次２ Ｇｙ;Ｂ组：放疗方式同Ａ 组,另于周末（ 放疗休息日）化疗,ＰＤＤ２０ ｍｇ 、５Ｆｕ ０．５ ｇ／ｍ ２ ,静脉滴注共５ 次。各组照射总肿瘤量为６４ ～７０ Ｇｙ 。随访结果：１、２、３ ａ 生存率,Ａ组分别为６９ ．２ ％（５４／７８） 、２３．１ ％ （１８／７８）和１２ ．８ ％ （１０／７８） ;Ｂ 组分别为７９ ．５％ （６２／７８）、４８ ．７％ （３８／７８）和２０．５ ％（１６／７８）。Ｂ 组２ ａ 生存率明显高于Ａ 组（Ｐ＜ ０．０１）,１、３ ａ 生存率２ 组无显著性差异（Ｐ＞ ０．０５）。结果显示,采用每周６ 次、每次２ Ｇｙ 放疗＋ 周末化疗方式治疗中晚期食管癌,近期疗效优于单纯放疗组,无明显毒副作用。     

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。     

Accelerated Hyperfractionated Radiation Therapy and Concurrent 5-Fluorouracil/Cisplatin Chemotherapy for Locoregional Squamous Cell Carcinoma of the Thoracic Esophagus: A Phase II Study

Purpose: To improve the poor prognosis of patients with locoregional esophageal squamous cell cancer, we used concurrent accelerated hyperfractionated radiation therapy (ACC HFX RT) and chemotherapy (CHT).

Material and Methods: Between January 1988 and June 1993, 28 patients were treated with ACC HFX RT with 1.5 Gy twice daily, to a total dose of 54 Gy concurrently with 5-fluorouracil (5-FU) (300 mg/m², days 1–5) and cisplatin (CDDP) (10 mg/m², days 1–5), both given during weeks 1 and 4 of the ACC HFX RT course. Following the ACC HFX RT/CHT, two additional courses of 5-FU (500 mg/m², days 1–5) and CDDP (20 mg/m², days 1–5) were both given during weeks 7 and 10. The median age and Eastern Cooperative Oncology Group performance status were 62 and 1, respectively. The American Joint Committee on Cancer (AJCC) stage was I in 12 patients, II in 10, and III in 6.

Results: The median survival time was 26 months, and the 5-year survival rate was 29%. The rates at 5 years for freedom from relapse, locoregional recurrence, and distant metastasis were 29%, 61%, and 45%, respectively. Univariate analysis revealed that performance status, stage, weight loss, tumor length, and tumor location influenced survival, while age and sex did not. The most frequent acute high-grade (3 or 4) toxicities were esophagitis and leukopenia, seen in 50% and 39% of patients, respectively. Late high-grade toxicity was infrequent. There were no treatment-related deaths.

Conclusion: The results of this study compare favorably with those of previous studies, albeit of relatively high incidence of acute high-grade toxicity. Further studies are warranted to compare its efficacy with other approaches.     

诱导化疗加放疗与同期放化疗治疗局部晚期鼻咽癌的疗效比较

[目的]比较诱导化疗加放疗与同期放化疗治疗局部晚期鼻咽癌的疗效.[方法]收集2007年1月至2009年12月中山大学附属肿瘤医院收治的经病理证实的局部晚期鼻咽癌258例,其中采用顺铂+5-Fu诱导化疗加调强放疗(诱导组)128例,采用顺铂同期放化疗(同期组)130例.应用Kaplan-Meier和Log-rank方法计算和比较两组患者的生存率,应用COX风险回归模型进行预后多因素分析.[结果]诱导组和同期组5年总生存率(83.1％ vs 83.0％)、无瘤生存率(80.9％ vs 79.1％)、无转移生存率(84.9％ vs 83.6％)、无复发生存率(95.0％ vs 92.8％)比较差异均无统计学意义(P＞0.05).同期组3、4级恶心呕吐的发生率明显高于诱导组(10％ vs 1.6％,P=0.004),体重下降的平均数也明显大于诱导组(P＜0.001).多因素分析结果显示N分期是影响局部晚期鼻咽癌总生存的独立因素.[结论]诱导化疗加调强放疗治疗局部晚期鼻咽癌的疗效与同期放化疗相近,但同期放化疗的消化道反应较重.远处转移是局部晚期鼻咽癌治疗失败的主要原因.     

紫杉醇同步放化疗治疗老年局部晚期鼻咽癌45例

[目的]评价小剂量紫杉醇每周给药同步放疗对老年局部晚期鼻咽癌患者的疗效及毒副作用。[方法]88例老年局部晚期鼻咽癌患者,分为单纯放疗（对照组）43例,紫杉醇同步放疗（研究组）45例。[结果]研究组和对照组鼻咽全消率分别为95．6％、83．7％（／％0．05）,颈淋巴结残留率分别为6．7％、23_3％（／9〈0．05）;2年生存率分别为80．0％、60．5％（／9〈0．05）,3、5年生存率分别为60．O％、51．2％和31．1％、23-3％,差异均无统计学意义。5年远处转移率分别为28．9％、34．9％,差异无统计学意义。毒副反应主要表现为白细胞减少和Ⅲ度口腔黏膜反应。[结论]小剂量紫杉醇每周化疗同步放疗可提高局部晚期鼻咽癌颈淋巴消除率,但未能明显提高远期生存率。     

累及野调强放疗联合同步化疗治疗局部晚期非小细胞肺癌的疗效观察

目的比较累及野照射（IFI）和选择性淋巴结照射（ENI）调强放射治疗联合同步化疗治疗局部晚期非小细胞肺癌（LA-NSCLC）的不良反应和疗效。方法49例LA-NSCLC患者前瞻性随机分为IFI组和ENI组,同步化疗两周期,行根治性调强放射治疗。结果IFI组和ENI组≥2级放射性肺炎发生率分别为8.0％和37.5％（P=0.01）;GTV平均剂量分别是（66.2±6.5）Gy和（61.3±6.3）Gy,（P=0.01）;总有效率为92.0％和66.7％（P=0.03）;预防照射区内淋巴结复发率为4.2％和4.0％,（P=0.49）;1年局部失败率分别为8.0％和16.7％（P=0.62）;1年生存率为72.0％和62.5％（P=0.48）。结论IFI同步放化疗治疗LA-NSCLC可降低正常组织并发症的概率,提高靶区照射剂量和肿瘤控制率,预防照射区内淋巴结复发率无增加,有望延长患者生存期。     

Single-Agent Versus Double-Agent Chemotherapy in Concurrent Chemoradiotherapy for Esophageal Squamous Cell Carcinoma: Prospective,Randomized, Multicenter Phase II Clinical Trial

Lessons Learned

• The efficacy of single‐agent chemotherapy was not significantly different from that of double‐agent chemotherapy in concurrent chemoradiotherapy for inoperable esophageal squamous cell carcinoma.
• Single‐agent concurrent chemoradiotherapy had lower gastrointestinal and hematologic toxicity.
• Overall survival and progression‐free survival were not significantly different between single‐ and double‐agent concurrent chemoradiotherapy.

BackgroundThis multicenter, randomized, phase II trial aimed to compare the efficacy and safety of single‐agent concurrent chemoradiotherapy using the oral fluoropyrimidine S‐1 with those of double‐agent concurrent chemoradiotherapy using S‐1 and cisplatin in patients with inoperable esophageal squamous cell carcinoma.MethodsPatients with inoperable esophageal squamous cell carcinoma (clinical stages I to III) were randomly allocated to the single‐agent group (S‐1) or the double‐agent group (S‐1/cisplatin). The concurrent intensity‐modulated radiation therapy plan was similar for both groups: planning target volume 1.8 Gy/f*30–33f and planning gross target volume of 2 Gy/f*30–33f. The primary outcome measure was the endoscopic complete response rate.ResultsOf the 105 patients randomized, 89 were assessable. The endoscopic complete response rate was 46.9% (23/49) in the single‐agent group and 52.5% (21/40) in double‐agent group. The median progression‐free survival within a median follow‐up of 23 months was 20 and 21 months, respectively. The median overall survival was 26 months and not reached, respectively. Grade 3 hematological toxicities occurred in 4.1% and 27.5% of the patients in the single‐ and the double‐agent group, respectively.ConclusionSingle‐agent chemotherapy in concurrent chemoradiotherapy for inoperable esophageal squamous cell carcinoma has good efficacy and safety, thus warranting a phase III trial.     

西妥昔单抗联合同步放化疗用于局部晚期全喉鳞癌术后的疗效

目的探究西妥昔单抗联合同步放化疗用于局部晚期全喉鳞癌术后的治疗效果。方法选取局部晚期全喉鳞癌患者共86例,随机分为实验组(n=43)与对照组(n=43)。患者均接受全喉切除术,术后4周伤口愈合后,实验组给予西妥昔单抗联合同步放化疗治疗,对照组给予单纯同步放化疗。2组患者均治疗6周。治疗结束后,比较2组患者的卡氏(Karnofsky,KPS)评分、治疗期间死亡率、毒副作用发生率等。依据患者纳入本研究的时间,依次对患者进行60个月的随访,统计随访期间的死亡人数及对应的死亡时间及复发率,采用Kaplan-Meier法和对数秩检验(log-rank test)进行生存分析。结果与对照组相比,实验组患者的KPS评分显著提高(P<0.05)、复发率显著降低(P<0.05)。而2组治疗期间死亡率差异无统计学意义(P>0.05)。对照组与观察组患者血液学反应、消化系统反应、肝肾功能损害与总不良反应的发生率均无明显差异(P>0.05)。生存分析结果表明,相比于对照组,实验组患者的5年总生存率与生存时间均显著提高,差异具有统计学意义(χ^2=6.129,P=0.013)。结论相比于单纯同步放化疗,联合西妥昔单抗可提高治疗效果,并提高患者生存率,在临床上具有推广使用价值。     

局部晚期鼻咽癌新辅助化疗研究进展

鼻咽癌的治疗手段是以放射治疗为主的综合治疗,随着调强放疗等精确放疗技术和放化综合治疗的广泛应用,初治鼻咽的局部控制率已经提高到90%以上。为了提高局部晚期鼻咽癌的治愈率、降低复发或远处转移,放疗与化疗的结合一直是学者们研究热点。由于同步放化疗已成为局部晚期鼻咽的标准治疗,新辅助化疗是鼻咽癌综合治疗研究的热点,新辅助联合同步放化疗是否获益一直存在争议。同时调强放疗的大量应用,同步化疗的地位受到怀疑,新辅助化疗在调强时代能否替代同步化疗及新辅助化疗后靶区应如何勾画值得进一步研究。因此,本文就新辅助化疗治疗局部晚期鼻咽癌的进展进行综述。