局限期小细胞肺癌预防性全脑照射的临床意义

目的探讨预防性全脑照射对局限期小细胞肺癌脑转移率和生存率的影响.方法 46例经化疗加胸部放射治疗后完全缓解的局限期小细胞肺癌被随机分为脑照射组(23例)和对照组(23例).全脑照射在完全缓解后第10～62天进行,采用双侧野对穿照射,常规分割照射,5次/周,2 Gy/次,中平面剂量为30 Gy.结果脑照射组脑转移率为13.0%,低于对照组的47.8%(χ2=5.03,P=0.025).脑照射组1,3,5年生存率分别为82.6%、47.8%和39.1%,对照组分别为73.9%、30.4%和13.0%,两组比较差异有显著性(χ2=4.07,P=0.044).PCI开始时间对生存率无影响,但对脑转移的发生有影响.生存期超过5年以上的脑照射组患者无严重的脑损伤后遗症.结论完全缓解的局限期小细胞肺癌行预防性全脑照射能减少脑转移发生率,提高生存率.PCI开始越早越好.     

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。     

局限期小细胞肺癌胸部放疗及放射损伤的研究现状

目的:总结国内外局限期小细胞肺癌(LSCLC)胸部放疗研究的现状。方法:应用PubMed和CHKD期刊全文数据库检索系统,以"局限期小细胞肺癌、胸部放疗和放射损伤"为关键词,检索1986-01-2008-04相关LSCLC胸部放疗的文献,共检索到英文文献430篇和中文文献187篇。纳入标准:1)LSCLC胸部放疗的疗效评价;2)LSCLC胸部放疗的方法;3)LSCLC胸部放疗与化疗结合的研究;4)LSCLC胸部放疗损伤的研究。根据纳入标准,精选82篇,最后纳入分析29篇。结果:配合胸部放疗可以提高LSCLC生存期,虽然胸部放疗的剂量、照射范围、分割方式、放化疗的顺序和最佳时机的选择等一直存有争议,但多数专家认为胸部放疗更为合理的方式为早期配合化疗(3个周期内)常规的累及野照射,剂量45～55Gy为宜。这几个热点问题也是引起胸部放疗损伤的重要因素。结论:胸部放疗在LSCLC的治疗中占重要地位,应选择适宜的放疗时机、合理的照射靶区和剂量,给予个体化治疗,以最小的放疗损伤获得最佳的治疗效果。     

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.     

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。     

三维适形后程逐步递量加速放疗局部晚期NSCLC的近期疗效观察

目的:观察三维适形后程逐步递量加速放射治疗局部晚期非小细胞肺癌的近期疗效和早期放射反应.方法:对31例局部晚期NSCLC放疗患者均采用6 MV X线照射,全程常规三维适形放疗,2.0 Gy/次,5次/周,于 40 Gy 后行CT扫描重新设计计划,后程改为2.3 Gy/次,2.6 Gy/次,3.0 Gy/次分别照射3次,5次/周,总剂量至 63.7 Gy.照射野包括胸部CT可见的原发灶以及纵隔≥1.0 cm单个或成束淋巴结.结果:放疗结束后1个月和3个月CT评价疗效,完全缓解(CR)4例,部分缓解(PR)14例,稳定(SD)3例,进展(PD)4例,总有效率为72%.急性放射性食管炎发生率Ⅰ、Ⅱ级68.0%(17/25),Ⅲ级4.0%(1/25),急性放射性肺炎发生率Ⅰ、Ⅱ级64.0%(16/25),Ⅲ级4.0%(1/25).结论:后程逐步递量加速放射治疗非小细胞肺癌是对放射治疗非小细胞肺癌的有益尝试,近期疗效满意且早期放射反应可以接受.     

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.     

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。     

三维适形放射治疗局部晚期非小细胞肺癌的临床观察

目的评价放弃选择性区域淋巴结照射的低分割三维适形放射治疗局部晚期非小细胞肺癌的毒性和近期疗效.方法 45例经病理组织学和(或)细胞学确诊的局部晚期非小细胞肺癌患者接受三维适形放射治疗,分割剂量2.5～3 Gy/次,5次/周,放疗总量DT 63～72.5 Gy.靶区仅包括肿瘤原发灶和转移淋巴结,放疗前MVP或CAP方案化疗不超过两个周期.结果总有效率为84.5%.1,2年的局部控制率分别为48.9%和37.8%;1,2年生存率分别为65.4%和42.8%.中位生存期13.1个月.未出现Ⅲ级以上的放射性肺炎和放射性食管炎.7例(15.6%)患者在随访期间出现选择性淋巴结失败.结论三维适形放射治疗局部晚期非小细胞肺癌提高了局部控制率和近期疗效,减轻了放疗的毒副反应.放弃选择性区域淋巴结照射并没有明显增加区域淋巴结的复发率,是实现剂量提升的重要途径.     

替莫唑胺联合放疗治疗非小细胞肺癌脑转移的疗效观察

目的：观察替莫唑胺联合全脑照射治疗非小细胞肺癌脑转移的疗效.方法：收集非小细胞肺癌脑转移患者40例,随机分成2组,A组接受6MV-X全脑照射DT 40Gy/20f,常规分割DT 2Gy/f;B组接受6MV-X全脑照射DT 40Gy/20f,常规分割DT 2Gy/f,同时口服替莫唑胺胶囊行同步化疗.结果：A、B两组近期疗效（CR＋ PR）及复发中位时间有显著性差异.结论：同步放化疗能提高非小细胞肺癌脑转移患者的疗效,并延长复发中位时间.     

Phase I study of hypofractionated dose-escalated thoracic radiotherapy for limited-stage small-cell lung cancer

PURPOSE: To determine the maximal tolerated dose of hypofractionated thoracic radiotherapy with concurrent chemotherapy for limited-stage small-cell lung cancer patients. METHODS AND MATERIALS: Three radiotherapy regimens were used. Radiotherapy was given in two phases: patients initially received 20 Gy in 10 fractions to gross tumor plus uninvolved mediastinal nodes, followed by a boost to gross disease of 30, 38, or 42 Gy in 15 fractions. Radiotherapy was planned with conformal techniques. All patients received four cycles of cisplatin (25 mg/m2) and etoposide (100 mg/m2) chemotherapy. Radiotherapy commenced with Day 1 of Cycle 2 of chemotherapy. All complete/near-complete responders were offered prophylactic cranial irradiation. The maximal tolerated dose of radiotherapy was based on the dose that caused unacceptably high rates of radiotherapy-related toxicity. RESULTS: Thirteen patients were accrued. All patients who commenced radiotherapy received all prescribed chemo- and radiotherapy. There were no treatment-related deaths. There was one Grade 3 acute nonhematologic toxicity in the 50-Gy group. Of the 6 patients given 58 Gy, 3 experienced acute Grade 3 esophagitis. With a median follow-up of 7 months, median overall survival was 9.5 months. CONCLUSIONS: The maximal tolerated dose of thoracic radiotherapy with concurrent chemotherapy on this trial was 50 Gy in 25 daily fractions.     

Practice guideline on prophylactic cranial irradiation in small-cell lung cancer

PURPOSE: To develop an evidence-based clinical practice guideline that would address the following questions: (a) What is the role of prophylactic cranial irradiation (PCI) in patients with limited or extensive stage small-cell lung cancer (SCLC) who have achieved complete remission in response to induction therapy (chemotherapy or chemoradiotherapy)? (b) What dose and fractionation schedules of PCI are optimal? (c) Does the use of PCI in patients with SCLC in complete remission affect quality of life? Survival, disease-free survival, quality of life, and adverse effects were the outcomes of interest. METHODS AND MATERIALS: A systematic review of the published literature was undertaken to provide the data for an evidence-based practice guideline. RESULTS: Six randomized controlled trials and one fully published individual patient data meta-analysis were included in the systematic review of the evidence. For patients who have achieved complete response after induction therapy, there is evidence of a disease-free survival benefit (4 of 6 trials) and an overall survival benefit (meta-analysis). There is insufficient evidence to make a definitive recommendation with respect to dose. There is some indication that 30-36 Gy in 2-3 Gy per fraction, or a biologically equivalent dose, may produce a better outcome than a lower dose or less aggressive fractionation regimen. The schedule commonly used in Canada is 25 Gy in 10 fractions over 2 weeks. Data from further research, including a trial currently ongoing that compares 25 Gy in 10 fractions with 36 Gy in 18 fractions, will be required to determine optimal dose of PCI. There is insufficient evidence to make recommendations concerning the optimal timing of PCI in relation to the administration of chemotherapy. Lung DSG members generally felt that it should be given as soon as possible after completion of chemotherapy. There is evidence from trials with data for up to 2 years of follow-up that prophylactic cranial irradiation does not produce significant late neurotoxicity. There is evidence from one trial that prophylactic cranial irradiation does not have a detrimental effect on quality of life in the first 12 months following the completion of therapy. There is insufficient evidence to comment on the long-term effects of prophylactic cranial irradiation on quality of life. CONCLUSION: For adult patients with limited or extensive SCLC who achieve a complete remission with induction therapy, PCI is recommended.     

Can surgery improve local control in small cell lung cancer?

Current therapy for small cell lung cancer (SCLC) consists of chemotherapy with or without radiotherapy. Radiotherapy is generally accepted as an essential treatment component of limited stage disease. However, the local failure rate after chemo- and radiotherapy is still high and ranges from 30 to 70%. Furthermore, despite having obtained a complete radiographic response, up to 75% of these patients will have residual disease in the tumor specimen, if resection is performed. Therefore, more effective means are needed to eradicate the primary tumor and to obtain an improved local disease control. Recent phase two trials of multimodal regimens for stage I-IIIA SCLC demonstrate that in selected patients with early stage SCLC the combination of surgery and chemotherapy with or without radiotherapy is feasible with low morbidity and mortality rates. The combination therapy results in satisfying long term outcome depending on the pathological tumor stage and a local disease control is achieved in almost all patients. It is remarkable that the pneumonectomy rate has decreased over the past decades from almost 100 to 27-39%. In order to confirm these promising results, a German multicenter prospective randomized phase III trial has been designed for patients with stage I-IIIA SCLC consisting of induction chemotherapy, followed by surgery, adjuvant thoracic radiotherapy and prophylactic cranial radiation compared to thoracic radiotherapy and prophylactic cranial radiation.     

An Overview of the Role of Radiotherapy in the Treatment of Small Cell Lung Cancer – A Mainstay of Treatment or a Modality in Decline?

AimsSmall cell lung cancer (SCLC) accounts for about 15% of all lung cancers. Chemotherapy, immunotherapy and radiotherapy all play important roles in the management of SCLC. The aim of this study was to provide a comprehensive overview of the role and evidence of radiotherapy in the cure and palliation of SCLC.Materials and methodsThe search strategy included a search of the PubMed database, hand searches, reference lists of relevant review articles and relevant published abstracts. ClinicalTrials.gov was also queried for relevant trials.ResultsThoracic radiotherapy improves overall survival in limited stage SCLC, but the timing and dose remain controversial. The role of thoracic radiotherapy in extensive stage SCLC with immunotherapy is the subject of several ongoing trials. Current evidence supports the use of prophylactic cranial irradiation (PCI) for limited stage SCLC but the evidence is equivocal in extensive stage SCLC. Whole brain radiotherapy is well established for the treatment of brain metastases but evidence is rapidly accumulating for the use of stereotactic radiosurgery. Further studies will define the role of PCI, whole brain radiotherapy and hippocampal avoidant PCI in the immunotherapy era.ConclusionRadiotherapy is an essential component in the multimodality management of SCLC. Technological advances have allowed safer delivery of radiotherapy with reduced toxicities. Discussion at multidisciplinary team meetings is important to ensure radiotherapy is considered and offered in appropriate patients.     

小细胞肺癌放射治疗新进展——东西方的探索

小细胞肺癌(SCLC)是我国肺癌常见类型之一,90年代后,SCLC的全身治疗方面没有令人兴奋的进展,但是放疗在SCLC中的应用研究取得了部分进展,为SCLC治疗疗效的提高提供了可能,这些进展主要包括广泛期SCLC的胸部放疗及脑预防照射、局限期SCLC胸部放疗剂量及放疗技术的研究、早期SCLC脑预防照射的价值研究等。笔者就其内容在东西方研究的进展加以综述,希望能带给读者一些帮助和借鉴。     

Chemotherapy with concurrent brain and thoracic radiotherapy in brain-only metastases of treatment naive small-cell lung cancer: a phase II study

To study the treatment outcomes of brain-only metastases from small-cell lung cancer (SCLC) at initial diagnose treated by chemotherapy with concurrent brain and thoracic radiotherapy (RT). From Jan 2004 to Jan 2009, 36 treatment-na?ve SCLC patients with brain-only metastases in Sun yat-sen University were enrolled. Treatment contained initial EP chemotherapy with concurrent whole-brain radiotherapy (WBRT). EP regimen consisted of etoposide 100 mg/m(2) IV d1-3, cisplatin 80 mg/m(2) IV d1, repeated every 3 weeks. WBRT with total dose of 30 Gy in 10 fractions was started within 1 week from the beginning of chemotherapy followed by thoracic RT including 2 Gy once daily to a total dose of 60 Gy. Treatment responses were evaluated after 3 cycles of chemotherapy. EP regimen was given totally 6 cycles for no tumor progression. Thirty-four patients were evaluable. All of the 20 CNS symptomatic patients experienced symptoms relief. Objective responses in the brain and primary thoracic lesions were observed in 26 (76.5%, 16CR + 10PR) and 29 (85.3%, 23CR + 6PR) patients, respectively. The median survival time (MST) was 19.2 months, and the 1-and 2-year overall survival rates (OS) were 70.6 and 29.4%, respectively, in all patients. Patients with CR response had the longest MST of 21.9 months and 1-and 2-year OS of 93.8 and 43.8%, respectively. Treatment toxicity profiles were acceptable. The treatment strategy of concurrent chemotherapy with brain and thoracic RT might achieve promising survival outcomes comparable to limited-stage SCLC in initially diagnosed SCLC with brain-only metastases.     

局限期SCLC超分割或大分割放疗同步化疗预后比较

目的 比较超分割或大分割放疗同步化疗对局限期SCLC的生存影响。方法 超分割和大分割组分别入组患者92、96例。超分割组采用45 Gy分30次,2 次/d。大分割组采用55 Gy分22次,1 次/d。采用Kaplan-Meier法计算生存率,Cox模型多因素预后分析。结果 超分割和大分割组患者1、2、5年PFS率分别为82%、61%、59%和85%、69%、69%(P=0.27),OS率分别为85%、41%、27%和77%、34%、27%(P=0.37)。多因素分析显示化疗开始到放疗开始时间≤43 d是PFS的有利因素(P=0.005),化疗开始到放疗结束时间≤63 d、PCI是OS有利因素(P=0.044、0.000)。超分割组和大分割组2、3级急性放射性食管炎发生率分别为28%、9%和16%、2%(P=0.009)。结论 采用加速超分割或大分割方案联合同步化疗的PFS及OS均显著提高。控制化疗开始至放疗开始、结束时间≤43 d、≤63 d有利于提高PFS和OS。但2、3级急性放射性食管炎的发生率超分割组显著高于大分割组。     

广泛期小细胞肺癌放射治疗进展

广泛期小细胞肺癌（extensive-stage small cell lung cancer，ES-SCLC）约占小细胞肺癌（（small cell lung cancer，SCLC）的2/3，治疗以化疗为主，辅以放疗等综合治疗。虽然SCLC对放化疗反应敏感、初治缓解率高，但几乎所有ES-SCLC都会发生复发及进展，迫切需要新的治疗策略以提高疗效。近年来，放疗在ES-SCLC中进展主要包括脑预防照射（prophylactic cranial irradiation，PCI）和胸部放疗（thoracic radiotherapy，TRT）。此外，免疫检查点抑制剂展现了良好的抗肿瘤活性，有望成为该领域治疗的重要突破口。本文将对ES-SCLC在放疗和免疫治疗以及其他治疗的临床研究进展方面进行综述。      

Split-course versus continuous thoracic radiation therapy for limited-stage small-cell lung cancer: final report of a randomized phase III trial

The optimal integration of radiation and chemotherapy for limited-stage small-cell lung cancer (SCLC) remains unclear. This phase III trial was conducted to determine whether chemotherapy plus interdigitating split-course thoracic radiation therapy (RT) improved survival compared with standard-dose continuous thoracic RT. One hundred fourteen patients were randomized to receive 50 Gy thoracic RT delivered in 2.0-Gy fractions given continuously (5 weeks) concurrent with the first 2 cycles of chemotherapy (arm A) or 50 Gy delivered via an interdigitating split course in 2.5-Gy fractions (8 weeks) concurrent with the first 3 cycles of chemotherapy (arm B). During the split-course RT, once-daily radiation was delivered on days 8-17 of each of the first two 21-day cycles and days 8-11 of the third 21-day cycle. All patients received the following chemotherapy: cisplatin/etoposide on cycles 1, 2, and 5 and cyclophosphamide/vincristine/doxorubicin on cycles 3, 4, and 6. Prophylactic cranial irradiation was recommended after a complete response to all therapy. One hundred ten eligible patients were randomized. Grade 3/4 esophagitis was reported in 9% of patients receiving continuous thoracic RT versus 4% of patients receiving split-course RT. Grade 3/4 hematologic toxicity was common in both treatment arms. Complete/partial response was observed in 80% of patients on arm A versus 84% on arm B. Overall survival rates at 5 years were 18% and 17% for arms A and B, respectively. Interdigitating split-course thoracic RT delivered in 2.5-Gy fractions was tolerable in patients with limited-stage SCLC but did not provide a survival advantage.     

A Herpes simplex virus-1 fatal encephalitis following chemo-radiotherapy, steroids and prophylactic cranial irradiation in a small cell lung cancer patient

Approximately 20-25% of patients with limited small cell lung cancer (SCLC) can be cured with an aggressive approach (chest radiation concomitant with chemotherapy) followed by prophylactic cranial irradiation (PCI) to a total dose of 30-36Gy with 3-2Gy per fraction, five fractions per week. Steroid prophylactic therapy with dexamethasone is usually prescribed during PCI to minimize acute radiation induced brain oedema. This approach may induce an immunosuppressive condition leading to a reactivation of an endogenous latent Herpes simplex virus and severe or fatal acute encephalitis may occur as our report will show. A 55-year-old man affected by locally advanced SCLC was referred to our institution after four cycles of chemotherapy with a good partial remission. Chest radiation started concomitantly with two cycles of chemotherapy followed by PCI 36Gy total dose and dexamethasone 8mg i.m. daily. Fifteen days after PCI completion the patient developed acute neurological symptoms of confusion, cognitive impairment, fever with shaking requiring severe sedation therapy. Twenty-five days later MRI T1 weighted images showed haemorrhagic streaked lines on cortical convolutions of the right cerebral hemisphere and diffuse oedema suggestive of herpetic encephalitis. The DNA consensus test on cerebrospinal fluid (CSF) was positive for Herpes simplex virus 1 infection (HSV-1). A diagnosis of herpetic encephalitis HSV-1 was made. Antiviral therapy with high doses of acyclovir was prescribed but symptoms did not ameliorate leading to a comatose state. The patient died 55 days after the end of PCI. In eligible SCLC patients, PCI is an important part of an aggressive therapeutic approach that improves overall and disease free survival decreasing the risk of relapse in the brain. A primary infection or a reactivation of an endogenous latent HSV in brain parenchyma under steroid therapy concomitant to brain irradiation may compromise these benefits.