154例广泛期小细胞肺癌治疗结果预后因素分析

目的 探讨影响广泛期小细胞肺癌预后的临床因素和治疗因素.方法 回顾分析2003-2006年在本院接受首程治疗(化疗±放疗)并有明确细胞学或病理诊断的广泛期小细胞肺癌患者154例,其中化放疗组89例,单化疗组65例.用Kaplan-Meier法进行生存分析,Logrank法对性别、年龄、卡氏评分、吸烟、体重减轻、远处转移、脑转移等临床因素和化疗周期数目、是否放疗等治疗因素进行单因素预后分析,Cox回归模型进行多因素预后分析.结果 中位随访时间40.5个月,随访率为92.2%.单因素分析结果显示吸烟和不吸烟的中位生存时间、3年生存率分别为13个月、11.8%和17个月、22.8%(χ2=3.40,P=0.064),化放疗和单化疗的分别为17.2个月、17.9%和9.3个月、13.9%(χ2=10.47,P=0.001),化疗周期数≥4和＜4的分别为16个月、20.1%和9.3个月、2.9%(χ2=17.79,P=0.000).多因素分析结果显示吸烟与否、化疗周期数≥4与＜4个和治疗模式(化疗+化放疗)对预后影响的危险比分别为1.462(χ2=4.40,P=0.036)、0.420(χ2=17.17,P=0.000)和0.634(χ2=6.20,P=0.013).结论 吸烟、胸部放疗及化疗周期数目是影响广泛期小细胞肺癌预后的独立因素.

Abstract：

Objective To investigate independent prognostic factors for overall survival (OS) in extensive disease small cell lung cancer (EDSCLC). Methods Between January 2003 and December 2006, 154 patients diagnosed with extensive stage small cell lung cancer were enrolled in this study.Prognostic factors such as gender, age, performance status, smoking history, weight loss, distant metastasis, the number of matastasis, brain metastasis, the cycle of chemotherapy and thoracic radiation therapy (TRT) for EDSCLC patients were evaluated by univariate and multivariate analysis. Results The median following-up time was 40. 5 months. The rate of follow-up was 92. 2%. The MST and overall survival rates at 3-year in smoking group and no-smoking group were 13 months, 11.8% and 17 months,22. 8%,respectively (χ2=3.40,P =0. 064);in ChT/TRT group and ChT group, they were 17. 2 months, 17.9%and 9.3 months,13.9%, respectively(χ2=10.47,P=0.001);and in the cycle of chemotherapy ≥4 group and ＜ 4 group, they were 16 months, 20. 1% and 9.3 months, 2. 9%, respectively (χ2=17.79,P=0. 000). By multivariate analysis, smoking history was a statistically significant unfavorable factor for OS in EDSCLC patients (versus no-smoking, hazard ratio (HR)=1.462, χ2=4.40, P=0.036). In addition, ≥4 cycles of chemotherapy and TRT were favorable prognostic factors ( ≥4 cycles vs ＜4 cycles, HR =0. 420,χ2 = 17. 17, P = 0. 000; ChT/TRT vs ChT, HR = 0. 634, χ2 = 6. 20, P = 0. 013). Conclusions Smoking is a independent unfavorable prognostic factor and ≥ 4 cycles of chemotherapy And TRT are independent favorable prognostic factors for OS in EDSCLC.     

局限期小细胞肺癌的放射治疗现状和展望

目的:通过复习局限期小细胞肺癌(SCLC)放射治疗的文献,探讨局限期SCLC最佳放射治疗策略.方法:应用计算机检索PubMed和CHKD数据库有关SCLC放射治疗的70篇研究文章,纳入分析39篇,检索词为小细胞肺癌、局限期、放射治疗和预防性脑照射.结果:试验表明放射治疗优于手术治疗,中位总生存期手术组为6个月,放疗组为10个月,差异有统计学意义;Meta分析显示,联合化疗+放疗较单纯联合化疗方法改善了生存期,单纯联合化疗组患者3年生存率为8.9%,联合化疗+放疗组3年生存率为14.3%,P=0.001.预防性脑照射(PCI)的作用已肯定.但是,胸部照射(thoracic radiation therapy, TRT)的剂量、时机和靶体积等问题未完全解决.结论:局限期SCLC的治疗策略为化疗和同步TRT以及预防性脑照射(PCI).胸部照射应该在化疗早期(化疗第1或2个周期)进行,不赞同根据化疗前肿瘤体积来确定照射靶区. PCI应尽可能在化疗完成后就开始.     

154例广泛期小细胞肺癌治疗结果预后因素分析

Objective To investigate independent prognostic factors for overall survival (OS) in extensive disease small cell lung cancer (EDSCLC). Methods Between January 2003 and December 2006, 154 patients diagnosed with extensive stage small cell lung cancer were enrolled in this study.Prognostic factors such as gender, age, performance status, smoking history, weight loss, distant metastasis, the number of matastasis, brain metastasis, the cycle of chemotherapy and thoracic radiation therapy (TRT) for EDSCLC patients were evaluated by univariate and multivariate analysis. Results The median following-up time was 40. 5 months. The rate of follow-up was 92. 2%. The MST and overall survival rates at 3-year in smoking group and no-smoking group were 13 months, 11.8% and 17 months,22. 8%,respectively (χ2=3.40,P =0. 064);in ChT/TRT group and ChT group, they were 17. 2 months, 17.9%and 9.3 months,13.9%, respectively(χ2=10.47,P=0.001);and in the cycle of chemotherapy ≥4 group and ＜ 4 group, they were 16 months, 20. 1% and 9.3 months, 2. 9%, respectively (χ2=17.79,P=0. 000). By multivariate analysis, smoking history was a statistically significant unfavorable factor for OS in EDSCLC patients (versus no-smoking, hazard ratio (HR)=1.462, χ2=4.40, P=0.036). In addition, ≥4 cycles of chemotherapy and TRT were favorable prognostic factors ( ≥4 cycles vs ＜4 cycles, HR =0. 420,χ2 = 17. 17, P = 0. 000; ChT/TRT vs ChT, HR = 0. 634, χ2 = 6. 20, P = 0. 013). Conclusions Smoking is a independent unfavorable prognostic factor and ≥ 4 cycles of chemotherapy And TRT are independent favorable prognostic factors for OS in EDSCLC.     

早期非小细胞肺癌的放射治疗

在早期非小细胞肺癌(NSCLC)中,有部分患者因各种原因采用单纯放射治疗.多数学者认为,其照射剂量应不低于60Gy.靶区范围的制定,要结合肿瘤的生物学规律和患者的具体情况,体现治疗的个体化.超分割和大剂量分割放射治疗在一定程度上提高了NSCLC的疗效.立体定向放射治疗为早期NSCLC的治疗提供了一种新的治疗手段,初步的临床实践表明是安全、可行的.     

放射治疗非小细胞肺癌的预后因素分析

目的回顾性分析根治性放射治疗的非小细胞肺癌（ＮＳＣＬＣ）病例,探讨影响放射治疗非小细胞肺癌预后的因素。方法选择１９９０年１月～１９９６年１２月间根治性放射治疗并经病理确诊的Ⅰ～Ⅲｂ期ＮＳＣＬＣ患者２５６例,生存统计采用ＫａｐｌａｎＭｅｉｅｒ法及Ｌｏｇｒａｎｋ检验,多因素分析采用Ｃｏｘ逐步回归模型。以多因素分析时各因素的变异系数乘以分组值计算预后指数。结果全组中位生存时间１４．５个月,１,３,５年生存率分别为６０％,２１％和７％。单因素和多因素分析均显示临床分期早;在较短的总疗程时间内接受较高剂量的照射;病理类型为鳞癌和放射治疗前细胞免疫状态较好的患者预后较好。综合以上４种因素的预后指数模型能够较好地区分不同的预后亚组。结论临床分期、放射治疗方法、病理类型和放射治疗前细胞免疫状态是放射治疗ＮＳＣＬＣ的独立预后因素。预后指数模型能够比ＴＮＭ分期等单个因素更好地反映预后。     

局限期小细胞肺癌的放射治疗进展

文章主要对局限期小细胞肺癌放射治疗参与的时机、化疗与放疗联合的方式、放射治疗的剂量和分割方式、照射靶区、预防性脑照射等问题进行探讨，并回顾这些方面的进展。     

局限期小细胞肺癌的放射治疗

局限期小细胞肺癌治疗的主要进展来自于放射治疗,涉及放射治疗实施过程中的诸多细节,如放射治疗加入的时机,放射治疗的靶区、剂量和分割方式,预防性脑照射及老年患者的放射治疗等。     

贫血对非小细胞肺癌预后的影响

目的：评估非小细胞肺癌患者的血红蛋白水平与预后的关系。方法：回顾性分析上海市胸科医院2003年11月—2005年3月接受住院治疗的500例初次诊断的非小细胞肺癌患者的病历资料。两样本率的比较采用χ^2验,生存分析采用Kaplan-Meier乘积法和log-rank检验,多因素分析采用COX逐步回归模型。血红蛋白水平以初次诊断时的所得值为准,男性血红蛋白〈120g/L,女性血红蛋白〈110g/L定义为贫血。结果：500例患者的中位生存期为27.17个月,1年生存率为73.4%。贫血患者有147例（29.4%）,无贫血者为353例（70.6%）。贫血的发生率随着化疗周期数的增加而升高,第4周期化疗后贫血发生率为84.3%。贫血组患者的中位生存期为21.38个月,1年生存率为64.3%,而无贫血组则分别为30.82个月和76.8%（P=0.028）。男性患者中贫血对生存期的影响具有统计学意义（P=0.049）。Ⅲ期患者中贫血与无贫血组的生存期差异有统计学意义（P=0.035）,而Ⅰ、Ⅱ、Ⅳ期患者中贫血对生存期的影响无统计学意义。COX回归模型显示贫血、性别、病理类型、临床分期、功能状态评分和是否手术切除是非小细胞肺癌患者的独立预后因素。结论：初次诊断时血红蛋白水平与非小细胞肺癌患者的生存相关,是影响非小细胞肺癌患者的独立预后因素之一。     

288例非小细胞肺癌脑转移全脑放射治疗的预后因素分析

[目的]分析影响接受全脑放射治疗的非小细胞肺癌脑转移患者的预后因素;对比评估RPA和GPA两种预后指数对临床及研究的指导意义。[方法]回顾性分析2006年1月～2008年8月在我科接受全脑放射治疗的288例非小细胞肺癌脑转移患者的临床资料,以Kaplan—Meier法计算生存率．采用多因素Cox回归法分析影响生存预后的各种因素。根据RPA和GPA两种预后指数分别建立预后模型,并分析模型中各亚组生存曲线的差异,各亚组生存率差异的比较采用Log-Rank检验。[结果]各组患者随访时间为1-33个月,其中接受全脑放射治疗后的中位生存期为8个月（95％CI：7．07～8．92个月）。多因素分析显示放射治疗前的KPS评分、原发肿瘤控制情况、年龄、脑转移灶数目、颅外转移情况、分子靶向药物治疗情况是影响生存率的独立预后因素。根据RPA和GPA指数建立的预后模型,各亚组生存曲线的差异均有统计学意义（P〈0．001）。[结论]KPS评分、原发肿瘤控制情况、年龄、脑转移灶数目、颅外转移情况、分子靶向药物治疗情况是影响非小细胞肺癌脑转移全脑放射治疗生存率的独立预后因素．RPA和GPA两种预后指数模型均能较好地反映预后。     

放射治疗同时化疗治疗晚期非小细胞肺癌的疗效观察

目的评价放疗同时化疗治疗Ⅲ期非小细胞肺癌(NSCLC)的疗效以及并发症.方法68例Ⅲ期NSCLC患者随机分为放疗+化疗组(A组)和单纯放疗组(B组).放疗采用累及野照射,2.0 Gy/次,1次/d,5 d/周.总DT(66～68)Gy/(6.6～7.0)周.化疗方案为鳞癌采用EP方案,腺癌采用MVP方案.结果总有效率化放组为76.5%,单放组为52.9%两组差异有显著意义,χ2=4.121,P=0.044.两组1、2、3年生存率分别化放组为70.6%、50.1%、35.3%,单放组为52.9%、26.5%、14.7%两组间差异有显著意义,P＜0.05.两组毒副反应相似,患者均能耐受.结论以顺铂为主联合化疗加放疗同时治疗晚期NSCLC可以增加局控率,减少远处转移率,从而提高远期生存率.     

广泛期小细胞肺癌放射治疗研究进展

胸部放疗和预防性脑照射在局限期小细胞肺癌治疗中占有重要的地位和作用,使总生存有大幅度提高。本文回顾近几年国内外关于其在广泛期小细胞肺癌治疗中的作用,对其作一综述,以便为临床实际工作提供借鉴和下一步研究提供参考。     

Concurrent chemotherapy and thoracic radiation therapy for limited-stage small cell lung cancer

We conducted a phase II study of therapy for limited-stage small cell lung cancer (LD-SCLC). The chemotherapy regimen consisted of a three-week cycle of cisplatin (80 mg/m(2), given intravenously on day 1) and etoposide (100 mg/m(2), given intravenously on days 1, 3 and 5), given three to four times. Fifty Cy thoracic irradiation was administered in standard fractions simultaneously without a treatment break. A total of 19 patients with SCLC were entered into the study, and 18 were eligible. This concurrent treatment produced 39% complete-response and 89% overall-response rates in the eligible patients. The median response duration was 36 weeks, and the median survival time was 67 weeks. A local relapse within the irradiation field was observed in 28% of the eligible patients. Brain metastasis as the first relapse was seen in 33% of the eligible patients. Myelosuppression represented by grade 3 and 4 leukopenia was experienced in 79% of the entered patients. We conclude that the concurrent modality with cisplatin and etoposide (PE) chemotherapy and early thoracic radiation therapy without split is a feasible and beneficial therapy.     

Vaccine therapy for small cell lung cancer

One novel approach to the treatment of lethal residual disease in patients with small cell lung cancer (SCLC) relies on the induction of a host-immune response to attack chemoresistant tumor cells. Because of its neuroectodermal origin, SCLC has a number of specific antigens that could be capitalized on as immune targets. This article reviews two vaccine strategies currently in clinical study. The anti-idiotype vaccine to the GD3 ganglioside, BEC-2, has recently been tested in a phase III trial. In this trial, patients with SCLC who had completed initial chemotherapy were randomized to observation or vaccination with BEC-2 plus bacillus Calmette-Guerin adjuvant. A series of other trials have established the immunogenicity of several keyhole limpet hemocyanin conjugate vaccines relevant to SCLC, including GM2, Globo H, fucosyl GM1, and polysialic acid. To optimize an immune response against a broad range of tumor phenotypes, these components will be combined into a polyvalent vaccine. A randomized phase II trial of this polyvalent vaccine is planned to start in 2004.     

小细胞肺癌的靶向治疗

小细胞肺癌（SCLC）靶向治疗药物包括血管生成抑制剂、酪氨酸激酶抑制剂和信号通路抑制剂等。研究表明血管生成抑制剂如贝伐珠单抗疗效并不显著;酪氨酸激酶抑制剂如舒尼替尼等可能更适合单药治疗;信号通路抑制剂如 Amuvatinib、LDE225等正在进行Ⅰ、Ⅱ期临床试验。目前认为 SCLC对于靶向治疗不敏感,或更具有选择性和针对性,有待于进一步研究。     

Targeted therapy for small cell lung cancer

Small cell lung cancer (SCLC) is very aggressive clinically, and current cytotoxic therapy has only a limited impact on survival. The development of targeted therapy for SCLC has lagged behind that of non-small cell lung cancer. Current drugs under investigation include those targeting the angiogenetic, apoptotic, sonic hedgehog, and mammalian target of rapamycin (mTOR) pathways. Vaccines seem to be promising adjunctive therapies. This review will present the available data on these agents. Common genetic abnormalities seen in SCLC, which could serve as potential future targets are also discussed.     

Role of radiation therapy in the treatment of patients with small cell lung cancer

The paper presents a review of up-to-date literature on the problems of morphological heterogeneity of small cell lung cancer, clinico-morphological parallels, main prognostic factors and rationale for application of radiation therapy in the complex treatment of the disease. The authors also discuss their own findings on 208 cases, with 170 of them having localized tumor. Superfractionated irradiation of a locoregional zone with 1.2 Gy thrice a day was conducted at the initial stage of treatment (total dose--46.8 Gy). As a result, complete regression was obtained in 65.5% and partial regression in 34.5%. All patients with localized tumor survived six months after radiation chemotherapy, 58.5%--12 months, and 57.1%--24 months.     

Late consolidative radiation therapy in the treatment of limited-stage small cell lung cancer.

Two hundred twenty-three patients were enrolled on this randomized Phase III trial testing the value of late consolidative involved-field radiation therapy in the treatment of limited-stage small cell lung cancer (SCLC). Patients were treated with induction chemotherapy consisting of alternating cycles of procarbazine, vincristine, lomustine, and cyclophosphamide (POCC) and etoposide, doxorubicin, and methotrexate (VAM) for 6 to 9 months. Responding patients were then randomized at 6 or 9 months to chemotherapy alone or to involved-field radiation therapy. All partial and complete responders received prophylactic cranial irradiation. Of the 180 eligible and evaluable patients, 80 (44%) achieved a complete response and 39 (22%) achieved a partial response (overall rate of response, 66%). Actuarial median survival time was 11.6 months, with 16% of patients surviving 2 years and 11% surviving 5 years. Forty-eight patients were randomized to chemotherapy alone (24 patients) versus chemotherapy plus involved-field radiation therapy (24 patients). There were no significant differences in time to progression or survival between those patients receiving or not receiving involved-field radiation therapy. The thorax was the site of first relapse in 58% of patients randomized to chemotherapy alone versus 29% in patients randomized to chemotherapy plus involved-field radiation therapy (P equals 0.042). The major acute toxicity was reversible myelosuppression, and the major late toxicity was chronic central nervous system dysfunction. The authors conclude that the addition of late consolidative radiation therapy to induction chemotherapy in the treatment of limited-stage SCLC is well tolerated and improves local control, but does not improve time to progression or rates of survival.     

Five-year results of combined chemotherapy and mediastinal radiation therapy in small cell lung cancer

Eighty-five patients with small cell lung cancer (limited disease = LD in 39, extensive disease = ED in 46) received the combination of cyclophosphamide, methotrexate, vincristine and CCNU, and mediastinal radiotherapy given simultaneously after the third course of chemotherapy. The duration of treatment was approximately 12 months. A complete response was obtained in 41% of LD and in 15% of ED patients, and a partial response in 38 and 22%, respectively. Median survival was 55 weeks for LD and 37 weeks for ED patients. Two patients (5%) with LD have survived free of disease more than 3 years since their diagnosis.     

逐步递量加速超分割照射加化疗非小细胞肺癌

目的 观察逐步递量加速超分割放射治疗（ＥＨＡＲＴ）Ⅲｂ期非小细胞肺癌（ＮＳＣＬＣ）的近期疗效和急性放射反应。方法 ７３例Ⅲｂ期ＮＳＣＬＣ进入ＥＨＡＲＴ组。放射治疗的第１,２周,１．２Ｇｙ２次／ｄ间隔６ｈ以上,第３,４,５周分别为１．３,１．４,１．５Ｇｙ２次／ｄ,均５天／周,照射野仅包括胸部ＣＴ或ＭＲＩ可见的原发灶和淋巴结转移以及周围１．０～１．５ｃｍ的正常组织。肿瘤灶总剂量６６Ｇｙ,５０次,５周