小细胞肺癌放射治疗进展

目的 放射治疗是小细胞肺癌治疗的主要方式,其实施过程涉及到小细胞肺癌的诸多环节,总结国内外关于小细胞肺癌放射治疗的研究现状,探讨胸部放射治疗和全脑预防性照射在小细胞肺癌治疗中的价值.方法 应用PubMed、西文生物医学期刊文献数据库、中国知网及万方期刊全文数据库检索系统,以"小细胞肺癌,放疗,全脑预防性照射"为中文关键词,以"small cell lung cancer,radiotherapy,prophylactic cranial irradiation"为英文关键词,联合检索1996-01-2016-12的相关文献.共检索到英文文献377篇,中文文献4篇.纳入标准:(1)小细胞肺癌;(2)放疗;(3)全脑预防性照射.排除标准:(1)非小细胞肺癌;(2)手术;(3)化疗.根据剔除标准剔除中文文献2条,英文文献326条,最后纳入分析37篇文献.结果局限期小细胞肺癌的胸部放疗的分割剂量和模式为45 Gy/30次,超分割放疗或60~70 Gy/30~35次,常规分割放疗.胸部放疗参与的最佳时间为于化疗第1个周期或第2个周期参与.胸部同步放化疗结束以后行全脑预防性照射,放疗期间可给予药物盐酸美金刚以保护神经认知功能或海马保护的调强放射治疗;广泛期小细胞肺癌的胸部放疗的分割剂量和模式为30 Gy/10次或45 Gy/15次.全脑预防性照射存在争议.结论胸部放射治疗和全脑预防性照射在小细胞肺癌治疗中起着非常重要的作用.     

局限期小细胞肺癌胸部放疗剂量和分割方式研究进展

目前手术、全身化疗、胸部放疗及预防性脑照射的综合治疗已成为局限期小细胞肺癌的治疗共识。近几十年,药物治疗没有明显突破。在放疗方面,放疗加入的时机、靶区范围、剂量分割方式,以及预防性脑照射等是研究的热点问题。本文对局限期小细胞肺癌胸部放疗剂量和分割方式的研究进展展开简要分析。     

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.     

放疗时间选择对局限期小细胞肺癌预后影响的meta分析

背景与目的研究结果显示序贯化放疗是小细胞肺癌主要的治疗手段,它可以提高患者的生存率,但是何时开始实施放疗仍然存在争议.本研究旨在探讨放疗实施时间埘局限期小细胞肺癌预后的影响.方法通过计算机检索Medline、CENTRAL(the Cochrane central register of controlled trials)、中国生物医学文献数据库系统(CBM)、中国期刊全文数据库(CNKI)等收集国内外公开发表的关于早期放疗(化疗开始后30天内开始放疗)对比后期放疗(化疗开始30天以后开始放疗)治疗局限期小细胞肺癌的随机对照研究.应用统计软件Stata 11.0进行数据分析.研究人群为局限期小细胞肺癌;干预措施为胸部放疗+化疗;结局指标为2/3年死亡率和放疗相关副反应.以优势比(odds ratio,OR)及相应的95%置信区间(confidence interval,CI)作为效应指标对结局进行比较.Q统计量的I2检验米检测各研究间的统计学异质性.双侧P<0.05认为各研究间存在明显的异质性.采用Begg法对发表偏倚进行量化检测.结果最终纳入分析的文章6篇,共1189例患者,其中早期放疗组587例,后期放疗组602例.接受早期放疗与接受后期放疗相比,两者2/3年生存优势差别无统计学意义(OR=0.78,95%CI:0.55-1.05,P=0.093);单独分析放疗性肺炎(OR=1.93,95%CI:0.97-3.86,P=0.797)疗性食管炎(OR=1.43,95%CI:0.95-2.13,P=0.572)相关血小板减少(OR=1.23,95%CI:0.88-1.77,P=0.746)差别均无统计学意义.结论接受早期放疗与接受后期放疗相比,2/3年生存优势、放疗相关副反应无明显区别.     

局限期小细胞肺癌放射治疗研究进展

摘 要：手术、全身化疗、胸部放疗及预防性脑照射的综合治疗已成为局限期小细胞肺癌的治疗共识。近几十年,药物治疗没有明显突破。在放射治疗方面,放射治疗加入的时机、靶区范围、剂量分割方式以及预防性脑照射等是研究热点问题。全文对局限期小细胞肺癌放疗方面的相关争议及研究进展作一分析。     

局限期小细胞肺癌放疗现状及研究进展

小细胞肺癌中大约30％～40％属于局限期.大量研究已经证明胸部放疗联合同步化疗可以改善局部控制率及总生存率,是目前局限期小细胞肺癌的标准治疗模式,预防性脑照射也被证实可以改善小细胞肺癌的预后.目前认为放疗应在化疗早期加入,个体化制定合适的放疗靶区,放疗方案推荐超分割方式或常规分割方式.     

小细胞肺癌的综合治疗进展

基于铂类的化疗方案联合胸部放疗已成为局限期小细胞肺癌的标准治疗方案,放疗的尽早参与能够提高患者的生存期.对于治疗后达到或接近CR者应行预防性脑照射.广泛期小细胞肺癌化疗仍然是主要治疗方法,而胸部放疗也逐步体现出其在综合治疗中的价值.     

放射治疗对小细胞肺癌预后的影响

目的:综述胸部放疗以及脑预防照射在小细胞肺癌(SCLC)治疗的作用以及对预后的影响.方法:以"小细胞肺癌和放疗"为关键词,检索1992-2009年PubMed以及CNKI期刊全文数据库,共检索到相关文献614篇,以近5年Ⅲ期临床研究和Meta分析为主要入组标准,以符合分析条件的30篇文献进行综述.结果:胸部放疗联合化疗降低局限期SCLC胸部复发率,改善生存,与晚期同步放化疗以及序贯放化疗相比,早期同步放化疗明显提高SCLC的生存率;胸部放疗能减少广泛期SCLC胸部进展的发生,改善生存;脑预防照射减少放化疗有效的SCLC脑转移事件的发生,提高生存率.结论:胸部放疗以及脑预防照射是提高SCLC生存率的治疗手段,是影响预后的重要治疗因素.     

放射治疗在小细胞未分化肺癌治疗中的作用

小细胞未分化肺癌(简称SCLC)对放化疗的敏感性与其它类型肺癌不同。通常采用3～4种化疗药物联合应用并加胸部放疗,对局限期病例可提高生存率,广泛期病例可有较好的姑息作用。近年来,国内外很多学者对局限期和广泛期Sclc治疗中胸部照射的作用,预防性全脑照射,大面积照射是否必要进行了探讨,期望能够提高疗效。     

局限期小细胞肺癌胸部放疗剂量分割现状

胸部放疗是局限期小细胞肺癌的重要治疗手段,与之相关的剂量分割存在一定争议。超分割放疗方案(2 次/d)作为前瞻性研究确立的标准方案,由于不良反应的发生和治疗的不便利,在临床实践中常常被其他治疗策略代替。另外在不可手术的淋巴结阴性的Ⅰ期小细胞肺癌中,立体定向消融放疗为部分高龄且预计难以耐受长疗程放疗的患者提供了新的选择。合适的剂量分割方案既可以保证治疗疗效,也能降低放疗相关急性及晚期损伤。本文将对目前局限期小细胞肺癌剂量分割研究现状进行阐述。     

Current and evolving treatment options for limited stage small cell lung cancer

PURPOSE OF REVIEW: About one-third of small cell lung cancer cases are classified as limited stage. Trials have attempted to establish the most effective, least toxic regimen of combined modality treatment. Recently, issues like the role of the positron emission tomography scan, elderly patient management and the timing and delivery of radiotherapy have been addressed. Several targeted agents have also been evaluated. This review will highlight the data that have greatly impacted on the standard of limited stage small cell lung cancer care. RECENT FINDINGS: Trials have concluded that small cell lung cancer is fluorodeoxy-D-glucose avid and that positron emission tomography has potential for utility in staging and radiation therapy planning, though it is not recommended. Recent trials confirm no benefit to adding chemotherapeutic agents to standard cisplatin and etoposide. To date, all targeted therapies have failed to show impressive results. Two analyses of outcomes in elderly patients argue that combined modality therapy should be considered, with patients carefully monitored. Two meta-analyses demonstrate thoracic radiotherapy should be delivered, with increased dose and schedule intensity. SUMMARY: Current data demonstrate that combined modality therapy with early administration of thoracic radiotherapy remains the care standard in limited stage small cell lung cancer care. Cisplatin and etoposide continue to be the chosen cytotoxic agents. Targeted therapies and advances in the radiotherapy technological aspects represent opportunities for improved outcomes in the future management of this aggressive disease.     

化疗和放射治疗应用时机和顺序与肺癌疗效(附94例局限期小细胞肺癌临床观察)

目的　评价局限期小细胞肺癌应用化疗和放射治疗时机和顺序的重要性。方法　94例局限期小细胞肺癌按化疗和放射治疗使用的时间和顺序随机分为先化疗后放射治疗组( 简称序贯组,46 例) 和化疗、放射治疗交替组(简称交替组,48 例) 。化疗方案用顺铂(Cisplatin,PDD) 依托泊甙(Etoposide,VP16)(EP方案) ,顺铂20 mg/m2 ,1～5 天,依托泊甙100 mg/m2 ,1 ～3 天,每3 ～4 周1疗程,共6 疗程。60Co 放射治疗:每次2 Gy,5 周,50 Gy;交替组在第1 个疗程化疗后第3 天开始,序贯组则在6 个疗程化疗结束后。结果　交替组完全缓解率高于序贯组(66 .7 % 对58.7% ),但差异无显著意义(P> 0.05) 。交替组2 年生存率高于序贯组(43.7 % 对23 .9 %) ,差异有显著意义( P<0 .05) 。结论　交替组疗效优于序贯组,提示尽早放射治疗可提高小细胞肺癌生存率;EP方案可作为与放射治疗交替使用的首选化疗方案     

PET方案化疗联合胸部放疗治疗局限期小细胞肺癌的疗效观察

回顾性分析PET(Paclitaxel135mg/m2,d1,Vp-1675mg/m2d1~d3,DDP80mg/m2,d1~d3使用)方案化疗联合胸部放疗治疗局限期小细胞肺癌的临床疗效。24例局限期小细胞肺癌接受PET化疗,每3周重复1次,共4~6个周期,胸部放疗于化疗2个周期后开始进行,2Gy/(5次·周),DT50~60Gy/25~30次,治疗达完全缓解者予以全脑预防性放疗DT30Gy/(15次·3周)。结果显示,24例局限期小细胞肺癌患者完全缓解(CR)19例,部分缓解(PR)4例,总缓解率95·8%(CR79·2%,PR16·7%),中位生存期25个月,2、3年生存率分别为50·0%和41·7%,局部复发率29·2%,远处转移率54·2%。PET方案化疗联合胸部放疗治疗局限期小细胞肺癌有较好的缓解率和近期疗效,毒性反应可耐受。     

非小细胞肺癌再程放疗联合化疗的临床疗效观察

目的:比较三维适形放射治疗联合化疗和单纯三维适形放射治疗治疗复发的非小细胞肺癌的近期疗效及不良反应。方法:回顾性收集2011年6月至2017年10月入住我院的52例复发的非小细胞肺癌患者。治疗组:三维适形放射治疗+TP方案。对照组:三维适形放射治疗。结果:治疗组患者总有效率为50.00%（14/28）,对照组患者总有效率为20.83%（5/24）,两组患者近期总有效率比较差异有统计学意义（P＜0.05）。治疗组不良反应的发生率消化道反应最为明显,达到85.71%（24/28）,与对照组比较差异有显著统计学差异（P＜0.01）。骨髓抑制的发生率为53.57%（15/28）,与对照组比较差异有统计学意义（P＜0.05）。放射性肺炎、肝功能损害、放射性食管炎,皮肤反应两组均无明显差异（P＞0.05）。 结论:小细胞肺癌复发后,在身体条件允许的情况下,再程放疗联合化疗疗效比单纯放疗疗效高,不良反应可接受,值得临床进一步研究和推广。     

调强放疗联合化疗治疗局限期小细胞肺癌近期疗效分析

目的:分析化疗联合调强适形放疗治疗局限期小细胞肺癌(SCLC)的近期疗效和放射损伤情况。方法:42例局限期SCLC采用放化疗综合治疗,放疗常规分割,单次剂量2Gy,每周5次,中位总剂量58Gy。化疗采用卡铂或顺铂+VP 16为主的方案,4-6个周期。中位随访32个月。结果:全组患者CR为35.7%(15/42),PR为57.1%(24/42),SD为7.1%(3/42),有效率为92.8%。1年总生存率(OS)为75.8%,2年为37.5%,3年为21.5%,中位生存时间为23个月。2级急性放射性肺损伤为4.8%(2/42),2级晚期放射性肺损伤为7.1%(3/42),2级急性放射性食管损伤11.9%(5/42),2级血液学毒性为11.9%(5/42)。结论:化疗联合IMRT用于局限期SCLC治疗,能获得较好的近期疗效和2年生存率,放射损伤在可接受范围,放疗剂量、照射范围值得进一步研究。     

A phase II study of VP-16-fosfamide-cisplatin combination chemotherapy plus early concurrent thoracic irradiation for previously untreated limited small cell lung cancer

BACKGROUND: At present the addition of thoracic irradiation to combination chemotherapy is a standard treatment for limited staged small cell lung cancer. However, there is still controversy about the optimum timing of chest irradiation. We conducted a phase II study of etoposide (VP-16)-ifosfamide-cisplatin (VIP) combination chemotherapy plus early concurrent thoracic irradiation for the patients with previously untreated limited small cell lung cancer in order to assess if the treatment modality could improve the response rate and the toxicity. METHODS: Forty-four patients with limited small cell lung cancer were treated with etoposide-ifosfamide-cisplatin and concurrent thoracic irradiation. Combination chemotherapy consisted of etoposide 100 mg/m2 (on days 1-3), ifosfamide 1000 mg/m2 (on days 1 and 2) and cisplatin 100 mg/m2 (on day 1). Concurrent thoracic irradiation consisted of a total of 4000 cGy over 4 weeks starting on the first day of the first chemotherapy. All patients who showed a complete response were given prophylactic cranial irradiation for 2.5 weeks. RESULTS: Forty-four of the 49 patients who entered the study from May 1994 to August 1998 were evaluable. The median age was 59 years and 40 patients had a performance status of 0 or 1. The median survival time was 22.5 months. Twenty-eight patients (62%) showed a complete response and 16 (38%) a partial response. Twenty-four patients (54%) developed grade 3 or 4 neutropenia; there was a 9% RTOG score 3 or 4 esophagitis. CONCLUSION: VIP combination chemotherapy and early concurrent thoracic irradiation for patients with limited stage small cell lung cancer revealed excellent antitumor response with tolerable toxicity.     

The role of radiotherapy in lung cancer: where is the evidence?

Radiotherapy is one of the main treatment modalities in lung cancer, contributing to both its cure and palliation. Thoracic irradiation has traditionally been considered the mainstay of treatment in inoperable stage III non-small cell lung cancer. However, despite technical developments and the addition of chemotherapy, the curative potential of radiotherapy in this subset of patients is disappointingly poor. The role of radiotherapy as an adjunct to pulmonary resection (preoperative and postoperative) is questionable, but well-designed and executed phase III studies are lacking. An important application of radiotherapy is palliation of tumor-related symptoms in the chest and in metastatic sites, such as bones and brain. In small cell lung cancer, routine applications of radiotherapy include chest radiotherapy in limited disease and prophylactic cranial irradiation in complete responders to chemotherapy, each increasing survival by about 5%.     

Combined modality treatment with radiotherapy and chemotherapy

Combined modality treatment with radiotherapy and chemotherapy is used increasingly for the primary management of a variety of human tumours, with the aim of improving both local and distant control. The present paper reviews methodological issues related to the evaluation of combined modality therapy. Reports that patients have superior outcome in single-arm studies as compared to historical controls treated with radiation alone have limited value because of several types of bias including patient selection, stage migration, the tendency to publish positive results, or inadequate follow-up as compared to the historical series. The observation that response to chemotherapy predicts for survival after combined treatment also conveys no proof that combined treatment is superior to radiation alone. Randomized controlled trials provide the only rigorous method for evaluating combined therapy, but are also subject to misinterpretation. The majority of published trials report negative results but are too small to detect clinically important differences in survival. Even large trials may give spurious results if they seek small benefits of treatment in a spectrum of patients with widely differing prognosis. Some randomized trials have demonstrated improved local control and increased toxicity from combined treatment, a result that might have been achieved by increasing the effective radiation dose. Ideally, combined treatment should be compared with radiotherapy alone at equal levels of normal tissue damage. A review of published data for patients with cancers of the head and neck, lung, gastrointestinal tract and bladder reveals very few trials which have adequately evaluated the role of combined modality therapy (with or without surgery). Most of the large randomized trials have demonstrated no benefit from the use of radiation and chemotherapy, although some of them suggest small therapeutic gains from using thoracic radiation with chemotherapy in small-cell-lung cancer of limited extent, or from combined modality treatment after resection of rectal cancer. Possible reasons for the failure of active drugs to lead to easily detected gains in therapeutic index include insufficient reduction in cell survival from chemotherapy, selective killing of radiosensitive subpopulations, stimulation of the proliferation of surviving cells, or enhancement of metastasis. With the possible exception of radiation and concurrent 5-fluorouracil for squamous cancers of the anal canal, there are no convincing data to mandate the routine combined use of radiotherapy and chemotherapy in any of the above sites.     

Chemotherapy response as a prognosticator for survival in patients with limited squamous cell lung cancer treated with combined chemotherapy and radiotherapy

Twenty-two patients with limited unresectable squamous cell lung cancer were treated with 6 courses of combination chemotherapy consisting of cyclophosphamide, adriamycin, cisplatin, and bleomycin (CAP-Bleo) and short-course thoracic irradiation started after the first 4 weeks of chemotherapy. Of 20 patients with visible tumor who were treated with 4 weeks of chemotherapy alone, 10 (50 %) had a tumor regression in that 4 week period and 10 did not. Those patients with tumor regression had significantly better progression free and overall survivals than did patients with no chemotherapy regressions (medians of 258 days vs. 136 days and 356 days vs. 150 days respectively). The original bleomycin dose had to be reduced by 50 % primarily because of excessive radiation esophagitis that has not been reported with use of either the CAP regimen or bleomycin along in conjunction with thoracic irradiation. An initial chemotherapy regression seems to be a good prognosticator for progression-free and overall survival in patients with limited squamous cell lung cancer treated with combined chemotherapy and radiotherapy.     

胸腔镜联合化疗与单纯化疗对晚期非小细胞肺癌患者预后的影响

目的 评价胸腔镜联合化疗与单纯化疗对晚期非小细胞肺癌患者治疗后肺功能、生存率和生活质量的影响.方法 选取晚期非小细胞肺癌患者125例,依据随机原则并结合患者选择意愿将患者分为2组:胸腔镜联合化疗组(n=65),单纯化疗组(n=60).计算随访时患者生存时间或患者死亡时间,并计算3年随访期间的死亡率.患者整个治疗结束后4周行肺功能检测.随访患者KPS评分,取其生存期限内的KPS评分的平均值.结果 随访患者治疗后的中位生存期和生存率,胸腔镜联合化疗组患者优于单纯化疗组的患者,差异有统计学意义(P＜0.05).胸腔镜联合化疗组的肺功能指标均优于单纯化疗组的患者,差异有统计学意义(P＜0.05).患者治疗后KPS评分在55～85分之间,胸腔镜联合化疗组患者优于单纯化疗组的患者,差异有统计学意义(P＜0.05).结论 非小细胞肺癌患者行胸腔镜联合化疗后,其肺功能、生存率和生活质量优于单纯化疗后的患者.