早期非小细胞肺癌局部治疗研究进展

【摘要】 对于早期非小细胞肺癌（non-small cell lung cancer,NSCLC）采用局部治疗具有损伤相对较小、安全、有效等优点,其治疗价值引起广泛关注。本文主要回顾亚肺叶切除、立体定向放射治疗和热消融在早期NSCLC中的应用,比较不同局部治疗方法的疗效及安全性,并对其进一步应用做出展望。     

由SABR再论放射敏感性

随着现代放射治疗技术进步,放疗已由过去二维时代进入三维和四维时代,治疗精度大幅度提高,分割模式也发生了深刻变革。从传统放射治疗发展到以三维适形放射治疗（3D-CRT）和调强放射治疗（IMRT）为代表的聚焦照射,提高了肿瘤靶区剂量,减少了正常组织的损伤。同时随着影像引导技术进步,治疗机与影像引导结合,每次治疗前通过影像扫描技术获得肿瘤靶区位置信息,或用4D影像引导技术精确地将射线投射到目标靶点,达到立体定向体部放射治疗（stereotactic body radiation therapy,SBRT）/立体定向消融放疗（stereotactic ablative radiotherapy,SABR）的目的,放射治疗完全进入精准、高效和低毒时代。高剂量、大分割照射已经取得令人信服和可喜的疗效,传统放射生物学理论已无法解释这种照射模式抗肿瘤细胞作用机制。传统放疗认为,肿瘤有敏感与不敏感之分,但是,进入SABR时代,肿瘤对其治疗均反应良好,放射治疗学迫切需要建立新的放射生物学学说和体系,在传统放射生物学理论基础上,更好地阐明新技术原理、作用机制,并建立与传统放射生物学内在联系,为临床普及和推广消融放疗技术奠定理论基础。     

体部γ刀治疗非小细胞肺癌的经验探讨

体部立体定向放射治疗（stereotactic body radiation therapy,SBRT）已有20多年历史,在早期非小细胞肺癌（non-small cell lung cancer, NSCLC）和肺转移瘤方面取得了良好的疗效。解放军空军总医院采用自主研发的体部γ刀技术,较早开展SBRT技术,治疗早期NSCLC和肺转移瘤,不良反应更轻,价格低廉,适合我国国情,值得推广应用。     

立体定向放射治疗在鼻咽癌初治中的推量应用效果观察

目的探讨立体定向放射治疗在鼻咽癌初治患者放射治疗中的推量应用对局控率和近期疗效的影响。方法常规放射治疗＋立体定向放射治疗鼻咽癌36例。肿瘤体积3～76cm3,应用BJ-6B6MV-X射线进行常规放射治疗,剂量达60～70GY后,应用SGI-TPS拟制立体定向放射治疗计划,BEV方向4～8个非共面照射野,计划靶区体积（PTV）一次治疗量4～5GY,3/周,总剂量12～20GY。结果本组患者1、2、3年的鼻咽局部控制率分别达到97.2%、91.6%和86.1%。除1例患者在治疗后13个月死于远处广泛转移外,无其他特殊并发症发生。结论鼻咽癌初治患者在常规外照射后给予立体定向加量照射,能够取得较好的局部控制。     

立体定向放射治疗非小细胞肺癌研究进展

立体定向放射非小细胞肺癌近年研究较多,主要研究内容包括呼吸动度对立体定向放射治疗的影响。对原发性肺癌、早期肺癌、老年性肺癌、转移性肺癌,及肺癌局部复发者的治疗方法及其疗效进行了观察和评价;对治疗禁忌证、并发症也进行了分析。总之,立体定向放射治疗对原发性肺癌、转移性肺癌、复发性肺癌、不能手术的早期肺癌、老年性肺癌都有积极的治疗作用,而且副作用小,但仍有许多问题有待深入研究。     

立体定向放射治疗胰腺癌

目的 对立体定向放射治疗胰腺癌的临床意义进行评价。方法 对16例胰腺癌患者行立体定向放射治疗,病变体积26.5~116.5cm3,肿瘤边缘单次剂量为3~5Gy,治疗10~20次,每日1次,每周治疗5次,治疗后临床和影像手段随访。结果 治疗有效率(完全缓解+部分缓解)为81.2%,合并疼痛患者均有不同程度缓解,6/7患者黄疸消除,生存质量明显改善,中位生存期11个月,死亡原因多为远处转移;治疗副作用根据RTOG标准评价,68.7%患者有轻度早期反应,1例重度晚期反应。结论 立体定向放射治疗胰腺癌是有效的局部控制手段,可明显的缓解症状,改善患者生存质量,并且治疗的并发症可以被临床接受,但肿瘤的远处转移是影响患者生存的主要问题。     

立体定向放疗在非小细胞肺癌治疗中的应用

体部立体定向放疗（stereotactic body radiation therapy,SBRT）是指应用单次或少数多次给予靶区高剂量照射的治疗方式。和常规放疗相比,具有分割剂量大、精度高等特点。其在肺部肿瘤中的应用可归纳为以下3点：①对于因高龄或合并严重心肺等内科疾病不能手术或不愿接受手术的早期（T_1-2N₀M₀）非小细胞肺癌（non-small cell lung cancer,NSCLC）,SBRT已确立标准治疗的地位。②对于可手术的早期NSCLC,SBRT初步应用的结果并不逊于手术。③对于肺内孤立转移灶（1~3个）,在全身治疗的基础上给与SBRT已逐步被接受。本文对此作一综述。     

立体定向放射治疗在结直肠癌肝肺寡转移中的应用进展

结直肠癌是全球范围内最常见的恶性肿瘤之一,远处转移是导致结直肠癌患者死亡的主要原因。不同于广泛性转移,寡转移是肿瘤转移过程中的一种中间状态,积极治疗预后较好。随着放疗技术的进步,立体定向放射治疗在肿瘤局部治疗中发挥着越来越大的作用。本文就结直肠癌肝肺寡转移立体定向放射治疗现状进行综述。     

超级伽玛刀治疗肿瘤536例近期疗效分析

γ射线立体定向全身放射治疗系统(简称:全身γ刀)是由我国首创,具有完全自主知识产权,国际领先的立体定向放射治疗设备,通过近10年的临床应用,目前我国已有近100台不同类型的γ刀治疗了各类癌症患者10万余例,已成为我国重要的立体定向放射治疗手段之一[1].我院自2007年3月～2008年5月应用超级γ刀(SGS-I型)治疗肿瘤患者536例,效果良好.     

立体定向放射治疗在妇科肿瘤中的应用进展

立体定向放射治疗（SBRT）是近年来兴起的放疗新技术,该技术的优点在于它能够在控制正常组织剂量的前提下提高肿瘤组织的剂量。SBRT在妇科肿瘤中的应用主要集中在盆腔复发灶、腹主动脉旁转移淋巴结、远处转移灶的局部治疗,可获得良好的局部控制,甚至一些患者有长期无病生存的可能。尽管SBRT有严格的剂量限制,但放疗后野内复发灶治疗后出现严重不良反应的概率较高。SBRT可以作为局部晚期宫颈癌体外放疗结束后,因某些因素而无法实施后装治疗的替代治疗。     

Treatment of metastatic liver tumors using stereotactic ablative radiotherapy Nair VJ,Pantarotto JP简

The prognosis of patients with metastatic liver disease remains dismal with a median survival of only 6-12 mo. As 80%-90% of patients are not candidates for surgical therapy, there is a need for effective non-surgical therapies that would improve outcomes in these patients. The body of evidence related to the use of stereotactic ablative radiotherapy (SABR) in metastatic liver disease has substantially grown and evolved over the past decade. This review summarizes the current evidence supporting liver SABR with particular attention given to patient selection, target delineation, organ at risk dose volume constraints, response evaluation imaging and the various SABR techniques for delivering ablative radiotherapy to the liver. Even though it is unclear what dose-fractionation scheme, delivery system, concomitant therapy or patient selection strategy yields the optimum liver SABR outcomes, clear and growing evidence is available that SABR is a safe and effective therapy for the treatment of oligometastatic liver disease.     

基于容积旋转弧形调强放疗技术的肝癌立体定向放疗方案评估与位置误差分析

目的 基于容积旋转弧形调强放疗（VMAT）技术,对肝癌立体定向放疗（SABR）方案进行评估,并结合图像引导技术及呼吸管理技术,分析执行中患者位置误差。方法 回顾性分析接受基于VMAT技术的SABR治疗并配合自主深呼气末屏气技术（vDEBH）进行呼吸管理的15例肝癌患者。VMAT计划采用2个部分弧,对治疗方案评估剂量参数,比较VMAT与调强放疗技术（IMRT）的计划质量差异。所有优化方案均经质量保证（QA）验证,包括点剂量和面剂量验证、机器跳数（MU）和出束时间记录。每次治疗时,锥形束CT（CBCT）影像采集2次,包括治疗前1次评估两次治疗间误差和治疗结束后1次评估当次治疗内位移。结果 VMAT和IMRT优化方案的各剂量学参数均满足临床治疗要求,差异无统计学意义（P>0.05）;相比IMRT,VMAT方案的平均MU降低了28.1%（t=3.064,P<0.05）,且治疗时间缩短了31.6%（t=2.278,P<0.05）。CBCT图像引导结果显示,采用vDEBH技术可有效减少当次治疗内的位置误差,各方向上的偏移均控制在可容许范围内（<3 mm）。结论 基于VMAT技术的肝癌SABR治疗计划在靶区体积剂量分布和正常组织受量等剂量学表现与IMRT技术相当,可行性良好且在治疗效率方面优势明显。     

Reirradiation of recurrent node-positive non-small cell lung cancer after previous stereotactic radiotherapy for stage I disease

Background

Practice guidelines have been developed for early-stage and locally advanced non-small cell lung cancer (NSCLC). However, many common clinical scenarios still require individualized decision making. This is true for locoregional relapse after initial stereotactic radiotherapy (stereotactic body radiation therapy or stereotactic ablative radiotherapy; SBRT or SABR), an increasingly utilized curative treatment option for stage I NSCLC.

Methods

A consortium of expert radiation oncologists was established with the aim of providing treatment recommendations. In this scenario, a case was distributed to six radiation oncologists who provided their institutions’ treatment recommendations. In this case, a patient developed local and mediastinal relapse after SABR (45?Gy, 3 fractions), comparable to the tumor burden in de novo stage IIIA NSCLC. Treatment recommendations were tabulated and a consensus conclusion was developed.

Results

Three institutions recommended evaluation for surgery. If the patient was not a surgical candidate, and/or refused surgery, definitive chemoradiation was recommended, including retreating the primary to full dose. European participants were more in favor of a non-surgical approach. None of the participants were reluctant to prescribe reirradiation, but two institutions prescribed doses lower than 60?Gy. Platinum-based doublets together with intensity-modulated radiotherapy were preferred.

Conclusion

The institutional recommendations reflect the questions and uncertainties discussed in current stage III guidelines. All institutions agreed that previous SABR is not a contraindication for salvage chemoradiation. In the absence of high-quality prospective trials for recurrent NSCLC, all treatment options recommended in current guidelines for stage III disease can be considered in clinical scenarios such as this.

     

Stereotactic ablative radiotherapy in the UK: current status and developments

Stereotactic ablative radiotherapy (SABR) has developed from the principles and techniques used in the stereotactic radiosurgery treatment of brain metastases. Advances in computer technology, imaging, planning and treatment delivery and evidence from retrospective analysis of single- and multi-institutional early-phase studies have established SABR in the treatment of medically inoperable early lung cancer. Effective multidisciplinary team working is crucial to safe delivery of SABR. The variation in patient selection, radiotherapy planning and delivery techniques has led to a collective approach to SABR implementation across the UK. Centres developing the technique are represented in the UK SABR Consortium, which is supported by the relevant UK professional bodies and represents a platform to develop extracranial SABR across the UK. The uptake of SABR in the UK has been slowed by workforce issues, but at least 15 centres are currently delivering treatment with over 500 patients treated using UK SABR Consortium guidance. A mentoring program is being piloted helping new centres to develop their programs, and over 30 UK centres are expected to be offering SABR treatment by the end of 2014. The use of consistent guidance for patient selection, treatment planning and delivery in the UK gives the opportunity to collect and audit toxicity and outcome across the centres, contributing to the internationally reported SABR experience. Having established this service in the UK, the development of SABR through clinical research is a priority, and with input from the Radiotherapy Trials Quality Assurance Group, the UK is developing a national study program that includes participation in international trials.Stereotactic ablative radiotherapy (SABR), also described as stereotactic body radiotherapy (SBRT), takes the principles of intracranial stereotactic radiosurgery and applies them to extracranial sites. SABR aims to deliver an ablative radiation dose in 3–8 fractions, typically >7.5 Gy over 2–3 weeks, with high precision and accuracy of 2–3 mm. The radiobiological rationale for SABR is that in delivering a few large fractions over a short overall treatment time, a more potent biological effect is achieved [1]. However, using a high dose per fraction to treat extracranial lesions poses significant challenges owing to both the inter- and the intrafractional motion of the tumour and the organ at risk (OAR) [2].Despite lacking modern radiotherapy planning and delivery techniques, early studies of efficacy and toxicity from SABR regimens reported local control rates comparable to surgery [3]. Modern lung SABR is characterised by use of advanced planning algorithms, with improved modelling of the heterogeneity of the lung tissue [4], and image-guided radiotherapy (IGRT) techniques that incorporate patient-specific tumour motion and ensure accurate set-up [5].The advantage of the SABR technique has been demonstrated for early-stage lung cancer patients, who are unfit for radical surgery, with improved local control and disease-specific survival compared with conventional radiotherapy [6–8] and reported rates of serious toxicity (≥Grade 3) below 5% [9]. Despite a lack of phase III trial evidence, SABR has now become an internationally established treatment for early lung cancer based on several centres reporting large case series with consistent outcomes [10]. The strongest evidence may come from the Netherlands, where the introduction of SABR has led to an increase in radiotherapy treatments in the over-75-years population with improved survival from early lung cancer without adversely affecting surgical resection rates [11].Within this evidence for early-stage non-small-cell lung cancer (NSCLC), where there is significant variation in patient selection and dose/fractionation, a few principles are well established: (i) a biologically equivalent dose of ≥100 Gy is needed to achieve high local control rates; (ii) increased toxicity is seen when central tumours, in close proximity to proximal airways, are treated with three fractions of 20 Gy [12]; and (iii) there does not appear to be an absolute contradiction of SABR with poor lung function.The implementation and practice of SABR is a multidisciplinary team process that requires a high level of accuracy throughout the entire planning and treatment delivery process, for which clear clinical pathways need to be defined. This article aims to use results from the recent UK SABR Consortium survey to give an overview of the current status of SABR in the UK and discusses the impact of this technique on radiotherapy delivery at a national level.     

常规放疗结合后程立体定向放射治疗老年非小细胞肺癌患者的预后分析

目的观察老年非小细胞肺癌立体定向放疗疗效,并探讨其预后因子。方法128例老年非小细胞肺癌患者行常规放疗结合立体定向放疗,定期随访。结果全组患者1年生存率65.72%,单因素分析表明肿瘤体积、肿瘤剂量、卡氏评分影响近期结果,多因素分析仅肿瘤体积和肿瘤剂量为近期疗效预后因子,与生存期有关的预后因素为近期疗效、肿瘤剂量、临床分期。结论立体定向放疗可延长生存时间,对Ⅲ期患者,肿瘤剂量提高至72Gy是安全的。     

Case report of visual biofeedback-driven,magnetic resonance-guided single-fraction SABR in breath hold for early stage non–small-cell lung cancer

Stereotactic ablative body radiation therapy (SABR) is a well-established alternative to surgery for early stage non–small-cell lung cancer (NSCLC). While SABR is typically delivered in 3 to 5 fractions, randomized trials have shown single-fraction SABR to be a reasonable alternative. We present the case of a 66-year-old male with history of cholangiocarcinoma who was subsequently diagnosed with peripheral early stage NSCLC and treated in mid-inspiration breath hold (BH) to 34 Gy in 1 fraction on a magnetic resonance (MR)-guided linear accelerator, with treatment delivery completed in 17 minutes. Visual biofeedback was utilized to maximize patient compliance with appropriate depth of inspiration BH and improve overall treatment delivery time efficiency. The benefits of single- vs multifraction SABR and unique advantages of MR guidance that are particularly well-suited for single-fraction SABR are reviewed.     

立体定向放射治疗体部肿瘤(附96例随访分析)

目的:通过临床随访观察,确定用立体定向分次放射治疗(Fractionted Stereotactic Radiotherapy,FSRT)体部肿瘤的近期疗效。对象与方法:96例体部肿瘤患者,其中38例肺癌、12例肝癌、11例胰腺癌、6例纵隔恶性肿瘤、6例食管癌、5例胃癌、5例胆管癌、6例直肠癌、3例宫颈癌和卵巢癌、4例椎骨转移瘤,继确诊和/或手术后,均经x线立体定向分次放射治疗。全部病例中67例(70％)经术前经皮穿刺针吸活组织检查或术后病理组织学检查证实,其余病例由临床、CT和/或磁共振等影像资料证实。用体箱、负压袋固定患者后CT扫描定位,X线立体定向放射治疗计划系统设计并优化治疗计划,加速器旋转照射。部分病人结合常规放射治疗。结果:X线立体定向放射治疗后1～3周内,90例(近94％)表现出临床症状明显改善,而且在此期间未发现1例严重并发症或死亡。肺癌患者随访CT检查32例,其中29例于FSRT后1～6个月肿瘤消失,2例肿瘤体积缩小50％以上,只有1例肿瘤大小无变化,有效率近97％。FSRT对其他肿瘤也有明显疗效,不仅可使原发癌灶缩小或消失,而且可使有癌转移的淋巴结消失。结论:FSRT是一种安全、无痛苦的、且能保持器官原有形态、结构及功能的治疗体部肿瘤的方法,它不仅适合于早期肿瘤患者,而且尤其适合于那些年老体弱,不能耐受手术的或术后残