Preradiation chemotherapy in primary high-risk brainstem tumors: phase II study CCG-9941 of the Children's Cancer Group.

PURPOSE: This Children's Cancer Group group-wide phase II trial evaluated the efficacy and toxicity of two chemotherapy arms administered before hyperfractionated external-beam radiotherapy (HFEBRT). PATIENTS AND METHODS: Thirty-two patients with newly diagnosed brainstem gliomas were randomly assigned to regimen A and 31 to regimen B. Regimen A comprised three courses of carboplatin, etoposide, and vincristine; regimen B comprised cisplatin, etoposide, cyclophosphamide, and vincristine. Both arms included granulocyte colony-stimulating factor. Patients were evaluated by magnetic resonance imaging after induction chemotherapy and HFEBRT at a dose of 72 Gy. RESULTS: Ten percent +/- 5% of regimen A patients objectively responded to chemotherapy. For combined induction and radiotherapy, 27% +/- 9% of patients improved. The neuroradiographic response rate for regimen B was 19% +/- 8% for chemotherapy and 23% +/- 9% after HFEBRT. Response rates were not statistically significant between regimens after induction or chemotherapy/HFEBRT. Event-free survival was 17% +/- 5% (estimate +/- SE) at 1 year and 6% +/- 3% at 2 years. Survival was significantly longer among patients who responded to chemotherapy (P <.05). Among patients who received regimen A induction, grades 3 and 4 leukopenia were observed in 50% to 65%, with one toxicity-related death. For regimen B, severe leukopenia occurred in 86% to 100%, with febrile neutropenia in 48% to 60% per course. CONCLUSION: Neither chemotherapy regimen meaningfully improved response rate, event-free survival, or overall survival relative to previous series of patients with brainstem gliomas who received radiotherapy with or without chemotherapy.     

肺腺癌多发脑转移全脑放疗结合化疗的时机与疗效

目的:比较全脑放疗同步化疗与全脑放疗至30Gy时再联合化疗的近期疗效及生存率,以探讨全脑放疗后结合化疗的时机。方法:收集肺腺癌多发脑转移（转移灶>3个）的患者共47例,根据RTOG独立递归分级指数(RPA）先把47例患者分成3层,然后按放化疗的顺序把每层的患者随机分成A、B两组。放射治疗均采取全脑放疗至（40~50）Gy/（20~25）次。化疗方案采用NP方案（培美曲塞二钠+奈达铂）。A组患者全脑放疗并同步给予化疗,B组患者全脑放疗至30Gy再给予化疗。统计学方法用Pearson χ2检验,Fischer's确切概率法检验两组资料入组病例的特征,比较两组的近期疗效、生存率统计及生存曲线绘制采用Kaplain-Meier法,用Log-rank法检测生存率的差异并对各层进行分层分析。结果:A、B两组患者的近期有效率分别为50%与60%(P＞0.05)。A、B两组半年生存率为53.7%与82.2%,1年生存率为10.8%与27.4%,中位生存期分别为7个月与8个月,两组生存率经Log-rank检验, 有统计学差异（P=0.000<0.05）;进一步进行分层分析:第一分层A、B两组的半年生存率为80.2%与100.0%,1年生存率为16.2%与43.6%,中位生存期分别为9个月与11个月,经Log-rank检验,有统计学差异（P=0.000<0.05）;第二分层A、B两组的半年生存率为0与67.3%,1年生存率均为0,中位生存期分别为4个月与7个月,经Log-rank检验,有统计学差异（P=0.000<0.05）;第三分层A、B两组的半年生存率均为0,中位生存期分别为3个月与5个月,经Log-rank检验,有统计学差异（P=0.009<0.05）。结论:全脑放疗至30Gy时再联合化疗较同步放化疗有提高近期疗效的趋势并可延长生存期,对临床治疗具有一定的指导意义。     

Postoperative chemotherapy vs chemoradiotherapy for thoracic esophageal cancer: a prospective randomized clinical trial.

BACKGROUND: Neither postoperative radiotherapy nor chemotherapy alone provided a survival benefit after curative esophagectomy for esophageal squamous carcinoma. MATERIAL AND METHODS: Of 103 consecutive patients who underwent potentially curative esophagectomy for esophageal squamous carcinoma, 45 patients with advanced cancers without preoperative adjuvant treatments were prospectively randomized to two groups; postoperative chemotherapy alone (Group A, n=23) and postoperative radio/chemotherapy (Group B, n=22). In Group A, cisplatin (CDDP) (50 mg/m(2)) was given by intravenous infusion on days 1 and 15, and 5-fluorouracil (5-FU) (300 mg/m(2)) was given daily by continuous intravenous infusion for 5 weeks. In Group B, in addition to the same chemotherapeutic regimen of Group A, 50 Gy of radiotherapy was given to the mediastinum over 5 weeks. The immunohistochemical staining of tumoral p53 and microvessel density was undertaken to correlate to the radio/chemosensitivity. RESULTS: There were no significant differences in the clinicopathologic characteristics between the two groups. The median dose of 5-FU and CDDP administered were not significantly different between the two groups. The mean (SD) dose of radiotherapy in Group B was 42+10 Gy. The 1-, 3- and 5-year survival rates in Group A were 100, 63 and 38% and those in Group B were 80, 58 and 50%, respectively (P=0.97). In each group, four patients succumbed to locoregional recurrences.Tumoral p53 was immunohistochemically negative in 43% in Group A and 77% in Group B (P=0.03), indicating that many patients in Group B might be potentially sensitive to radiochemotherapy. The 3- and 5-year survival rates (75 and 64%) of patients with p53 negative expression (n=18) were significantly (P=0.03) better than those with p53 positive expression (n=27, 44 and 26%). The long-term survival was better for patients with p53 negative tumours than those with p53 positive tumours in Group B (P=0.06 by long-rank test, P<0.05 by Generalized-Wilcoxon test). However, the long-term survival was not different between the patients who had p53 negative and positive tumours in Group A (P=0.19). These data suggest that there were no survival advantage for patients receiving radiotherapy in Group B, instead p53 negative tumours appeared to have a favorable prognosis. CONCLUSION: Postoperative radiotherapy administered concurrently with chemotherapy does not provide a survival benefit compared with chemotherapy alone. Tumoral p53 expression has a predictive value for survival in patients treated with postoperative radio/chemotherapy.     

基于GELOX方案诱导化疗的Ⅰ—Ⅱ期结外鼻型K/T细胞淋巴瘤根治性放疗的预后分析

目的 探讨早期结外鼻型NK/T细胞淋巴瘤(ENKTL)接受GELOX (吉西他滨、奥沙利铂、左旋门冬酰胺酶)方案化疗和放疗疗效及影响因素。方法 回顾分析2007—2013年间收治的74例Ⅰ_E—Ⅱ_E期ENKTL患者,根据化疗方案及有无放疗分为3个组,A组47例为首选GELOX化疗后根治性放疗,B组10例为其他方案化疗改用GELOX挽救后放疗,C组17例为接受GELOX方案化疗后未放疗。全组化疗中位3周期,放疗中位剂量54.6 Gy分20~30次。结果 全组化疗后CR率33.8%(其中放疗后为90%),2年OS和PFS分别为88%和79%。A+C组的疗后CR率、2年OS和PFS分别为73%、92%和84%。A组的2年OS和PFS (96%和84%)均高于B组(50%和45%)和C组(47%和40%,P均<0.05)。单因素分析显示疗前LDH水平升高和化疗后无缓解是OS和PFS的不良预后因素,局部广泛侵犯也是OS的不良预后因素;多因素分析显示化疗后无缓解是OS及PFS的不良预后因素。结论 早期ENKTL患者接受GELOX诱导化疗结合根治性放疗可获得良好疗效,但该方案用于单纯化疗和挽救化疗的疗效仍不理想。     

适形调强放疗联合PF方案同步治疗中晚期食管癌

目的 探讨适形调强放疗（IMRT）联合PF方案同步治疗中晚期食管癌的临床价值。方法 将77例中晚期食管癌患者随机分两组研究。A组采用适形调强放疗＋PF方案化疗,共37例。B组采用常规放疗＋PF方案化疗,共40例。A、B两组均采用PF方案化疗,在放疗第1、5周使用DDP每天30 mg/m²,5-Fu 每天0.5 g/m²,静脉滴注3天,放疗不间断。两组放射剂量均为DT 66Gy,6～7周完成。结果 A组有效率（CR＋PR）89.2%,B组有效率65.0%;A组的1、2、3年生存率为83%、65%、51%,B组的1、2、3年生存率为72%、53%、32%,A、B两组差异均存在明显的统计学意义。χ²分别为7.18和5.53,P均＜0.05。两组的急性放射性食管炎等不良反应基本相同,差异无统计学意义（χ²＝0.08,P>0.05）。但两组的急性放射性肺炎差异有明显统计学意义（χ²＝8.99,P<0.01）。结论 在中晚期食管癌的治疗中,调强放疗联合化疗与常规放化疗联合相比较,具有疗效好、不良反应轻,患者容易耐受等特点,调强放疗在不增加放疗不良反应的同时,能提高靶区的剂量及局控率,降低局部复发率,对总生存率的提高亦有益处。     

化疗和放疗联合治疗中晚期宫颈癌疗效分析

目的对比化疗配合放射治疗与单纯放疗治疗宫颈癌的疗效,探讨综合治疗在中晚期宫颈癌中的疗效及安全性。方法100例Ⅱ～Ⅲ中晚期宫颈癌患者分成两组,放疗同步化疗（A组）50例,在放疗同时给予PVB或PF方案化疗2～4周期,化疗第1天开始行放射治疗。单纯放疗组（B组）50例,两组放射治疗均用15MV—X线盆腔大野前后对穿体外照射,DT：45～50Gy;并加坶。IrHDR腔内后装照射,A点DT：20-25Gy。结果A组和B组近期有效率分别为94．0％和74．0％,两组的差异有显著性意义（P〈0．01）。A组和B组的3年生存率分别为76．0％和48．0％,差异有显著性意义（P〈0．05）。毒性反应方面,同步化放疗组高于单纯放疗组,尤以造血系统和消化道反应为主,但大部分能够耐受。结论中晚期宫颈癌患者PVB或PF方案同步放化疗可提高局部控制率和提高生存率。     

老年Ⅲ期非小细胞肺癌同步放化疗的临床对照研究

目的:探讨不同方案同步放化疗和单纯放疗对老年Ⅲ期非小细胞肺癌(NSCLC)的疗效和安全性.方法:老年Ⅲ期NSCLC患者193例,根据患者入组顺序,采用随机数字表法,按不同治疗方案分为4组(A、B、C和D组),均接受三维适形放疗,照射剂量60～66.6 Gy,常规分割剂量1.8～2.0 Gy/次,6～8周内完成放疗.A组仅行单纯放疗;B组接受同步榄香烯乳治疗;C组联合吉西他滨(GEM)加顺铂(DDP)化疗,放疗期间同步化疗1～2个周期,放疗结束后巩固化疗2～3个周期;D组联合紫杉醇脂质体(PL)加DDP化疗,同步化疗1～2个周期,放疗结束2～4周后巩固化疗2～3个周期.定期复查并观察疗效及不良反应,主要研究终点为疾病无进展时间(PFS)及总生存时间(OS).结果:全组中位随访21个月,中位PFS 13个月,中位OS 19个月.各组治疗有效率(CR+PR)依次为43.6％、54.3％、70.8％和75.0％.有效率组间比较,C组较A、B两组高,差异有统计学意义,P值均＜0.05.D组亦较A、B两组高,差异有统计学意义,P值均＜0.05.各组的1、3和5年生存率比较,C组最高,依次为72.9％、39.6％和16.4％,A组最低,依次为46.2％、15.4％和0.C组较A、B组均显著延长PFS和OS,差异均有统计学意义,P值均＜0.05.D组也较A组显著延长了PFS和OS,且差异有统计学意义,P值均＜0.05.D组对B组也有生存优势,但仅OS的差异有统计学意义,P值均＜0.05.在放射性肺炎、放射性食管炎、骨髓抑制和胃肠道反应方面,同步放化疗组不良反应发生率高于单纯放疗组,差异有统计学意义,P值均＜0.05.结论:对于老年Ⅲ期NSCLC患者,同步放化疗可显著提高有效率,延长PFS和OS.     

Induction chemotherapy for advanced head and neck cancer: modification of response to chemotherapy by antiemetics.

Forty Stage IV head and neck cancer patients were entered on a multimodality trial of induction chemotherapy (cisplatin + infusional 5-fluorouracil), surgery, and radiation. During chemotherapy, the patients of Group A (the first 19 patients) were medicated with metoclopramide. The patients of Group B (the next 21 patients) were medicated with droperidol. The groups were comparable. The response rate (complete + partial) was 32% for Group A and 52% for Group B (p = 0.16). Primary site (p = 0.08) and surgical margin (p = 0.005) clearance of tumor were better in Group B. Nodal disease responded poorly to chemotherapy in both groups. Tumor necrosis (p = 0.006) and granulation tissue (p = 0.07) were reduced in surgical specimens after chemotherapy in Group B. The drugs were well tolerated with reversible toxicity; nausea/vomiting (p = 0.01) and weight loss (p = 0.07) after chemotherapy, were increased in Group B. The 2-year survival was 26% for Group A and 62% for Group B (p = 0.027). The median survival was 15 months for Group A and 33 months for Group B (p = 0.05). Progression-free survival improved in Group B (p greater than 0.17). These improvements in response and survival did not appear to reflect changes in surgical or radiotherapy management, but may have reflected an uninhibited effect of cisplatin in Group B. It is theorized that the metabisulfite formulated with metoclopramide altered the pharmacokinetics or pharmacodynamics of cisplatin. This resulted in the poor response to chemotherapy and poor survival in Group A. An analysis of a randomized trial comparing metoclopramide (formulated with metabisulfite) versus a control antiemetic can confirm the data presented in this pilot study. Overall, our patients survived as well as others in comparable multimodality studies in Europe and the United States.     

同步加量放疗技术在非小细胞肺癌脑转移患者中的应用

目的:评估同步加量放疗技术在非小细胞肺癌（non-small cell lung cancer,NSCLC）脑转移应用中的临床疗效、不良反应、生存时间,探索该技术的可行性。方法:76例NSCLC脑转移患者以不同分割模式分为A组（42例）和B组（34例）。A组患者全脑放疗DT 40Gy/（20f·4周）后局部推量DT 20Gy/（10f·2周）,B组患者全脑放疗DT 36Gy/（20f·4周）全程同步加量适形放疗DT 24Gy/（20f·4周）。比较两组放疗疗效、不良反应、半年、1年总生存率。结果:采用 RECIST 1.1标准,A组放疗有效率为95.2%(40/42),B组有效率为97.1%（33/34）,两组疗效未见统计学差异。A、B两组患者在血液毒性、神经系统受损、消化道反应、脱发等方面均未见明显异常。A组中位生存时间为8.94个月,患者半年、1年生存率为71.4%、35.7%;B组患者中位生存时间为9.47个月,半年、1年生存率为82.4%、38.2%,两组无统计学差异。结论:两种分割模式在临床疗效、不良反应、生存时间方面疗效相当。全脑照射全程同步加量治疗脑转移近期疗效确切,患者耐受性很好,可缩短放疗时间。     

中晚期鼻咽癌新辅助化疗联合放疗的临床研究

目的:探讨新辅助化疗联合放疗治疗中晚期鼻咽癌的疗效。方法:自1998年1月至2002年11月,92例中晚期鼻咽癌患者分别采用新辅助化疗联合放疗(化放组)及单纯放疗(单放组)。新辅助化疗组在放疗前给予DDP 5-Fu化疗2周期,二组放疗相同。鼻咽DT(68~72)Gy/(7~7.5)W,颈部50Gy~76Gy/(5~8)W,比较二组疗效及不良反应。结果:放疗结束时鼻咽肿瘤完全退缩率二组分别为60.4%,38.6%(P<0.05),颈部淋巴结完全退缩66.7%,36.4%(P<0.05),急性反应化放组的胃肠道反应,白细胞下降等副反应增加。1年生存率化放组及单放组分别为81.3%,81.8%(P>0.05),3年生存率分别为58.3%,61.3%(P>0.05)。结论:新辅助化疗联合放疗治疗中晚期鼻咽癌能提高近期鼻咽病灶及颈淋巴结完全消退率,未能提高中晚期病人的生存率,未能降低远处转移的几率。     

Ⅲ期非小细胞肺癌同步放化疗的临床研究

目的比较两种同步放化疗方案对不能手术的Ⅲ期非小细胞肺癌（NSCLC）的疗效及不良反应。方法52例不能手术的Ⅲ期NSCLC患者,随机分成两组,A组每周紫杉醇方案,B组三周紫杉醇＋顺铂（DDP）方案。两组的放疔方法相同,均采用常规分割放疗,每次2．0Gy,每周5次,原发肿瘤灶总剂量60～64Gy。A组在放疗同时给予紫杉醇每周45mg／m^2;B组给予紫杉醇135mg／m^2第1、22天＋DDP30mg／m^2第2天至第4天,第23天至第25天。结果两组的有效率（CR＋PR）分别为78％和74％（P〉0．05）,而两组CR率分别为22％和14％（P〈0．05）。两组1、2、3、5年局部控制率分别为78％、57％、32％、8％和59％、26％、18％、5％,差异有统计学意义（P=0．0493）;1、2、3和5年生存率分别为82％、62％、37％、12％和64％、43％、18％和9％,差异接近具有统计学意义（P=0．0532）。两组重度不良反应差异无统计学意义（P〉0．05）。结论每周小剂量同步放化疗方案可提高NSCLC的局部控制率,并有望延长患者生存时间。     

Phase III study of the Eastern Cooperative Oncology Group (ECOG 2597): induction chemotherapy followed by either standard thoracic radiotherapy or hyperfractionated accelerated radiotherapy for patients with unresectable stage IIIA and B non-small-cell lung cancer.

PURPOSE: To compare once-daily radiation therapy (qdRT) with hyperfractionated accelerated radiation therapy (HART) after two cycles of induction chemotherapy. PATIENTS AND METHODS: Eligible patients were treatment naive, and had stage IIIA and B unresectable non-small-cell lung cancer, Eastern Cooperative Oncology Group performance status 0/1, and normal organ function. Induction chemotherapy consisted of two cycles of carboplatin area under time-concentration curve 6 mg/mL . min plus paclitaxel 225 mg/m2 on day 1. RT consisted of arm 1 (qdRT), 64 Gy (2 Gy/d), versus arm 2 (HART), 57.6 Gy (1.5 Gy tid for 2.5 weeks). A total of 388 patients were needed to detect a 50% increase in median survival from 14 months of qdRT to 21 months of HART; accrual was not achieved and the study closed prematurely. RESULTS: Of 141 patients enrolled, 83% were randomly assigned after chemotherapy to qdRT (n = 59) or HART (n = 60). Median survival was 20.3 and 14.9 months for HART and qdRT, respectively (P = .28). Overall response was 25% and 22% for HART and qdRT, respectively (P = .69). Two- and 3-year survival was 44% and 34% for HART, and 24% and 14% for qdRT, respectively. Grade > or = 3 toxicities included esophagitis in 14 v nine patients, and pneumonitis in 0 v 6 patients for HART and qdRT, respectively. Any subsequent trials of the HART regimen must address the issues that led to early closure, including slow accrual, logistics of HART, mucosal toxicity, and the fact that concurrent chemoradiotherapy now seems more effective than sequential treatment. CONCLUSION: After two cycles of induction chemotherapy with carboplatin-paclitaxel, HART is feasible with an acceptable toxicity profile. Although statistical significance was not achieved and the study closed early, there was a positive statistical trend suggesting a survival advantage with the HART regimen.     

Neoadjuvant chemotherapy and radiation for inoperable carcinoma of the maxillary antrum: a matched-control study

A matched-control study comparing standard radiotherapy versus neoadjuvant chemotherapy and radiation was undertaken to clarify the effects of neoadjuvant systemic chemotherapy for locally advanced squamous cell carcinoma of the maxillary antrum. Thirty-four patients with inoperable maxillary cancer were treated with neoadjuvant chemotherapy and radiotherapy (Group II). Before starting radiotherapy, all patients in Group II received two or three cycles of neoadjuvant chemotherapy consisting of cisplatin and a 5-day continuous infusion of 5-fluorouracil with or without intravenous injection of vinblastine. Radiation doses ranged from 66 Gy to 75 Gy (median, 70 Gy). The response rate, patterns of failure, toxicity, and survival for Group II were compared with those for 34 stage-matched patients treated with radiation alone (Group I). Despite a higher response rate to neoadjuvant chemotherapy, the recurrence rate and patterns of treatment failure were not influenced by the addition of neoadjuvant chemotherapy. In most cases, neoadjuvant chemotherapy did not interfere with subsequent radiotherapy, and radiation-induced late complications occurred equally in both treatment groups. After a median follow-up of 48 months, there was no significant difference in 5-year actuarial survival or disease-free survival between the two treatment groups. Radiation alone for inoperable maxillary cancer was clearly suboptimal for improving local control and survival rate, but neoadjuvant chemotherapy in addition to standard radiotherapy failed to demonstrate any therapeutic advantage over radiation alone.     

同步放化疗治疗老年局部晚期非小细胞肺癌的临床研究

目的：探讨长春瑞滨、吉西他滨分别联合三维适形放疗治疗老年局部晚期非小细胞肺癌（ＮＳＣＬＣ）的疗效和毒性反应。方法：８１例患者分为两组,长春瑞滨组：三维适形放疗同步化疗,长春瑞滨２５ｍｇ／ｍ^２,静滴,第１、８天。吉西他滨组：三维适形放疗同步化疗,吉西他滨１０００ｍｇ／ｍ^２,静滴第１、８天。均２１天为１周期。两组均治疗２～４周期。结果：长春瑞滨组ＣＲ率１７.５％,ＰＲ率５０.０％,总有效率（ＣＲ＋ＰＲ）为６７.５％;吉西他滨组ＣＲ率１９.５％,ＰＲ率４６.３％,总有效率（ＣＲ＋ＰＲ）为６５.８％,两组差异无显著性（Ｐ＞０.０５）。长春瑞滨组和吉西他滨组的１、２年生存率分别为６９３％、３６.４％和６８.７％和１８.６％,中位生存时间分别为１７个月和１６.２个月,差异无显著性（Ｐ＞０.０５）。长春瑞滨３～４级血液毒性高于吉西他滨组（Ｐ＜０.０５）。结论：长春瑞滨或吉西他滨联合三维适形放疗同步治疗老年局部晚期ＮＳＣＬＣ安全、有效。     

Induction Chemotherapy in Advanced Head and Neck Cancer Preliminary results of a randomized study

From March 1983 to June 1986, 100 patients with locally advanced squamous cell carcinoma of the head and neck were randomized to receive either two courses of chemotherapy prior to local therapy (group A), or local therapy alone (group B). Local treatment consisted of primary radiotherapy in all patients. When a poor response was observed after 55 Gy, surgery was performed. The chemotherapy regimen was a combination of cisplatinum, bleomycin, vindesine, and mitomycin C. The response rate to induction chemotherapy (group A) was 50% for the primary tumor (CR: 10% and PR: 40%). At the end of radiotherapy, the overall tumor response rates in the two groups A and B, were 77% and 79% respectively. Complete disappearance of the primary tumor occurred more often than that of the lymph node metastases. The response rate to induction chemotherapy for lymph node metastases was 27.1 % (CR: 9% and PR: 18.1 %). An initial major response to chemotherapy predicted subsequent efficacy of irradiation on 90% of the cases, while a failure of chemotherapy had no predictive value in this respect. The survival rates in groups A and B were 66.5% vs. 65.1% at 1 year and 35% vs. 46.2% at 2 years. Local disease-free and disease-free intervals were similar in both groups. A Cox's multi-step regression analysis revealed two significant independant prognostic factors: size of primary tumor and nodal status. After adjustment for these factors, the chemotherapy did not seem to improve the effectiveness of the local treatment in terms of loco-regional control and survival.     

直肠癌术后三维适形/调强放疗联合化疗与单纯辅助化疗的疗效比较

目的 比较直肠癌术后三维适形/调强放疗联合化疗与术后单纯化疗的疗效及不良反应。方法 回顾性分析直肠癌根治术患者226例,其中辅助化疗组116例,辅助放化疗组110例。辅助放化疗组采用三维适形放疗88例,调强放疗22例。剂量范围45～54 Gy,中位剂量50 Gy。全组患者化疗周期数为2～8周期,中位4周期。观察患者不良反应,比较三维适形/调强放疗联合化疗与单纯术后化疗两组不同辅助治疗模式对局部复发率、总生存率（OS）及无病生存率（DFS）的影响。结果 术后放化组1、2、3年局部复发率分别为3.8%、10.5%、10.5%,明显低于术后化疗组的15.5%、29.7%、33.2%（P=0.001）,术后放化组与术后化疗组1、2、3年OS分别为94.2%、76%、70.7%和95.6%、68.4%、53.5%,组间差异接近统计学意义（P=0.059）,1、2、3年DFS组间差异无统计学意义（P=0.608）。术后放化组的胃肠道、血液学不良反应发生率分别为78.2%和64.5%,高于术后化疗组的41.4%和30.2%（P=0.000;P=0.000）。亚组分析显示Ⅱ期患者术后放化组和术后化疗组1、2、3年OS、DFS差异均无统计学意义（P=0.810;P=0.067）。Ⅲ期患者术后放化组的1、2、3年OS高于术后化疗组,差异有统计学意义（P=0.047）,DFS与术后化疗组比较差异无统计学意义（P=0.201）。术后放化组中20.9%患者出现放射性肠炎;10%患者出现放射性膀胱炎。无3级以上不良反应发生。结论 直肠癌术后三维适形/调强放疗联合化疗可显著降低局部复发率,提高Ⅲ期直肠癌患者总生存率。放化联合治疗组血液学及胃肠道不良反应高于术后单纯化疗,但患者耐受性较好。盆腔照射采用三维适形或调强放疗技术,在提高局控率的同时可较常规放疗显著降低放射性膀胱炎和放射性肠炎的发生率和发生程度。     

Induction chemotherapy followed by concurrent standard radiotherapy and daily low-dose cisplatin in locally advanced non-small-cell lung cancer.

Both induction chemotherapy and concurrent low-dose cisplatin have been shown to improve results of thoracic irradiation in the treatment of locally advanced non-small-cell lung cancer (NSCLC). This phase II study was designed to investigate activity and feasibility of a novel chemoradiation regimen consisting of induction chemotherapy followed by standard radiotherapy and concurrent daily low-dose cisplatin. Previously untreated patients with histologically/cytologically proven unresectable stage IIIA/B NSCLC were eligible. Induction chemotherapy consisted of vinblastine 5 mg m(-2) intravenously (i.v.) on days 1, 8, 15, 22 and 29, and cisplatin 100 mg m(-2) i.v. on days 1 and 22 followed by continuous radiotherapy (60 Gy in 30 fractions) given concurrently with daily cisplatin at a dose of 5 mg m(-2) i.v. Thirty-two patients were enrolled. Major toxicity during induction chemotherapy was haematological: grade III-IV leukopenia was observed in 31% and grade II anaemia in 16% of the patients. The most common severe toxicity during concurrent chemoradiation consisted of grade III leukopenia (21% of the patients); grade III oesophagitis occurred in only two patients and pulmonary toxicity in one patient who died of this complication. Eighteen of 32 patients (56%, 95% CI 38-73%) had a major response (11 partial response, seven complete response). With a median follow-up of 38.4 months, the median survival was 12.5 months and the actuarial survival rates at 1, 2 and 3 years were 52%, 26% and 19% respectively. The median event-free survival was 8.3 months with a probability of 40%, 23% and 20% at 1, 2 and 3 years respectively. Induction chemotherapy followed by concurrent daily low-dose cisplatin and thoracic irradiation, in patients with locally advanced NSCLC, is active and feasible with minimal non-haematological toxicity. Long-term survival results are promising and appear to be similar to those of more toxic chemoradiation regimens, warranting further testing of this novel chemoradiation strategy.     

化放疗序贯治疗局部晚期非小细胞肺癌疗效观察

目的探讨局部晚期非小细胞肺癌的有效治疗方案.方法 105例局部晚期非小细胞肺癌随机分为化、放序贯治疗组(A组)与单纯放疗组(B组).A组采用MVP或NP方案全身化疗2周期,休息1至2周胸部放疗;B组不做化疗,胸部放疗同A组.观察近期疗效,生存期,1、2年生存率及主要毒副反应、并发症.结果 A组有效率高于B组(92.0%对65.5%),中位生存期A组长于B组(15.5个月对11.4个月),A组和B组1,2年生存率分别为68.0%、39.5%和60.0%、17.5%.2年生存率差异有显著性(χ2=4.65,P＜0.05).两组在Ⅲ～Ⅳ级血液学毒性、放射性食管炎、放射性肺炎发生率方面差异无显著性(P＞0.05).结论序贯化、放疗可提高局部晚期非小细胞肺癌局部控制率,延长生存期,毒副反应可以耐受,不增加并发症.     

三维适形放疗和化疗同步治疗非小细胞肺癌临床分析

目的比较三维适形放疗和化疗同步与单纯化疗治疗局部晚期非小细胞肺癌(NSCLC)的疗效和耐受性.方法对84例初治的ⅢA～Ⅳ期局部晚期NSCLC进行随机分组,同步放化疗组43例(A组),单纯化疗组41例(B组).A组采用NP方案化疗,同期分别给予原发灶和纵隔转移淋巴结区三维适形放疗(TRT),原发灶DT 64～70 Gy,常规分割32～35次(中位剂量66 Gy);B组采用NP方案化疗.结果 A组有效率(CR PR)为65.9%(27/41),其中有6例(14.6%)手术治疗;B组有效率为48.8%(20/41),手术治疗2例(4.8%).A、B两组治疗有效率和手术切除率相比,差异均有显著性(P＜0.05).A组骨髓抑制、肝肾损伤较B组未见明显增加.A组轻、中度放射性食管炎的发生率为53.7%(22/41).结论三维适形放疗同期化疗较单纯化疗有效率(局部控制率)高,手术切除率提高,治疗时间缩短,且耐受性良好,值得推广.     

The effects of sequential versus concurrent chemotherapy and radiotherapy on survival and toxicity in patients with newly diagnosed high-grade astrocytoma.

PURPOSE: To determine the effects of sequential versus concurrent administration of cranial radiotherapy and cisplatin/carmustine (BCNU) chemotherapy on survival and toxicity in newly diagnosed high-grade astrocytomas. METHODS AND MATERIALS: From 1988 to 1996, 101 patients were treated on 2 therapeutic protocols for malignant glioma that used the identical chemotherapy regimen but differed in the timing of cranial radiotherapy. The eligibility criteria for the 2 protocols were identical. In the first protocol (1988-1991, 52 patients), cisplatin 120 mg/BCNU 120 mg i.v. over 72 h, was given for 3 monthly cycles prior to cranial radiotherapy. After a response rate of 42%, with a median survival of 13 months was achieved with this sequential regimen, a successor protocol (1992-1996, 49 patients) was developed in which cranial radiotherapy began concurrently with the start of the identical chemotherapy regimen. Chemotherapy was delayed but not discontinued if prolonged grade III/IV hematologic toxicity was experienced, but protocol therapy was discontinued if disease progression or thromboembolic events occurred. Survival outcome and hematologic toxicity were compared for the patients treated on these protocols. RESULTS: Seventy-seven percent of sequentially-treated patients and 68% of concurrently-treated patients completed all planned therapy. Kaplan-Meier survival was similar to concurrent or sequential administration of chemotherapy and radiotherapy (median 12.8 months vs. 13.8 months, respectively). Hematologic toxicity was significantly less in sequentially- versus concurrently-treated patients, with median nadir per cycle (2.9 vs. 1.8 x 10(3)/mm3) (p < 0.001), and incidence of grade 3/4 leukopenia 40% versus 77% (p = 0.002). There was also an increase in platelet transfusion requirements in concurrently-treated patients, but no significant worsening of anemia. We postulate that the worsened leukopenia results from the effects of concurrent radiotherapy on circulating stem cells. CONCLUSION: Concurrent radiotherapy with this regimen of cisplatin and BCNU chemotherapy did not improve survival, but did increase hematologic toxicity. Therefore, we do not recommend further testing of the concurrent regimen, whereas the sequential regimen is currently under evaluation in a Phase III trial of the Eastern Cooperative Oncology Group and the Southwest Oncology Group. In addition, these studies demonstrate that relatively small radiotherapy fields can deliver a dose to circulating stem cells sufficient to worsen the hematologic toxicity of concurrent myelosuppressive chemotherapy, a phenomena which should be considered in the design of combined modality protocols for other body sites.