肺癌脑转移诊治策略进展

正随着肺部原发病灶治疗手段的日趋完善,脑转移病灶的治疗成为临床研究的热点。目前对脑转移瘤治疗仍存在着一些争议,尚未形成标准的诊治规范。主要是几个关键因素缺乏可比性,如系统疾病的病程阶段、神经损害症状的程度、转移灶数目和     

脑转移瘤的放射治疗进展

脑转移瘤是成人最常见的颅内肿瘤。患者一经发现存在脑转移,其生存期及生活质量都会明显下降。现如今,在全球医学领域针对脑转移瘤的治疗手段主要包括外科手术、化疗、放疗及综合治疗等,随着放疗技术的不断更新,放射治疗对脑转移瘤的治疗也得到新发展,治疗方式也趋于个体化。本文主要就脑转移瘤的放疗技术进展作一综述。     

大分割立体定向放射治疗对非小细胞肺癌脑转移瘤的疗效评估

背景与目的：立体定向放疗（stereotacticradiotherapv,SRT）与全脑放疗（wholebrainradiationtherapy’WBRT）是治疗脑转移瘤的主要手段。本文旨在探讨伽玛射线大分割SRT加或不加WBRT对肺癌有限脑转移瘤治疗的疗效。方法：回顾性分析非小细胞肺癌多发脑转移瘤（1～4枚）患者66例,其中单纯SRT30例,SRT＋WBRT36例。分析两组患者的临床特征并应用Kaplan-Meier法计算生存率．用Logrank法对各因素进行预后分析。结果：两组患者的临床特点无明显区别：SRT组与WBRT＋SRT组的中位生存期（MST）分别为12．1与1313个月,二者无显著性差异（P=0．216）。Logrank分析显示卡氏评分（P=0．017）和颅外病变的控制情况（P=0．032）是影响预后的主要因素。结论：SRT是非小细胞肺癌有限脑转移瘤患者有效治疗手段．单纯SRT可取得与WBRT＋SRT相似的生存期．     

立体定向放射治疗肺癌脑转移的疗效观察及护理

背景与目的肺癌脑转移发生率高,放射治疗是此类患者的主要治疗方法。本研究的目的是观察立体定向放射治疗对肺癌脑转移的疗效,并探讨积极有效的护理的价值。方法2002年6月~2006年12月43例肺癌脑转移患者接受了立体定向放射治疗,放疗期间根据病情采取针对性护理。结果全部患者顺利完成放疗,无严重副反应和并发症发生。放疗后颅内病灶控制率为81.4%,神经系统症状缓解率为76.7%,KPS评分显著上升。生存时间2~34个月,中位生存时间8.5个月,半年、1年、2年生存率分别为58.9%、26.2%、6.0%。结论对肺癌脑转移患者给予立体定向放射治疗,配合积极有效的护理,患者可顺利完成放疗,并达到缓解症状、延长生存期和提高生活质量的预期目的。     

立体定向外科联合全脑放射治疗脑转移瘤疗效分析

肿瘤发生脑转移后，如果不进行有效地治疗，中位生存期仅为1个月。长期以来，尽管临床上给予了积极治疗，生存期有明显延长，但预后仍非常差。目前何种治疗方法最佳尚无明确定论。1975年Leksell教授采用通过高能射线聚焦一次性大剂量定向照射靶区治疗病灶并取得了成功，此即立体定向外科治疗（stereotatic radiosurgery，SRS）。近年来这一方法得到越来遗多地应用。但如何正确、合理地应用立体定向外科治疗，     

肺癌脑转移全脑放射治疗的护理

肺癌脑转移发生率在50％以上,多因神经系统症状而就诊。肺癌脑转移最常见症状为头痛,其次为定位功能失常、精神异常及颅内压升高,另有5％～10％的患者有急性脑卒中表现。全脑放疗（wholebrain radiation therapy,WBRT）为肺癌脑转移者的常规放疗方式。做好全脑放疗的护理工作,对改善此类疾病患者的生存质量起关键作用。现总结我院2011年2月至2013年2月68例肺癌脑转移WBRT患者的护理经验如下。     

全脑放疗与联合立体定向外科治疗非小细胞肺癌脑转移60例

[目的]探讨全脑放疗加立体定向放射外科(SRS)补量对非小细胞肺癌(NSCLC)脑转移的疗效。[方法]60例非小细胞肺癌脑转移病例,34例接受了单纯全脑放疗(30Gy/10次～39Gy/13次),26例采用全脑放疗(30Gy/10次)加SRS,周边剂量10Gy～24Gy。[结果]非小细胞肺癌脑转移患者采用全脑放疗加SRS治疗与仅单纯全脑放疗,中位生存时间分别为8.0个月和6.0个月(P=0.041)。多发脑转移患者两种治疗方法,中位生存时间分别为8.0个月和5.6个月(P=0.021)。年龄<65岁患者两种治疗方法中位生存时间分别为9.6个月和5.8个月(P=0.033)。确诊NSCLC治疗后发生脑转移者两种治疗患者中位生存时间分别为10个月和6.9个月(P=0.007)。[结论]非小细胞肺癌脑转移患者采用全脑放疗加SRS可以延长生存时间。     

SRS、WBRT 及 WBRT ＋SRS 治疗1～4个脑转移瘤的 Meta 分析

目的：探讨立体定向放射外科（SRS）、全脑放疗（WBRT）及全脑放疗联合立体定向治疗1～4个脑转移瘤,并为进一步研究提供循证医学依据。方法：根据设定的纳入、排除标准,在 PubMed、Springer －link、Cancer list 数据库、中国生物医学文献数据库（CBM）、万方数据库、CNKI 知识网络服务平台及其他期刊进行相关随机对照试验检索。单变量计数资料的效应量用优势比（OR）和95％可信区间（95％CI）表示,用 Rev-man 5．2软件对数据进行异质性检验后采用固定效应模型或随机效应模型对数据进行分析。结果：共检索出1985－2014年间发表的126篇相关文献,最终得到8篇包含1213例脑转移瘤患者的随机对照试验符合所纳入的标准。SRS 与 WBRT ＋SRS 比较：WBRT ＋SRS 虽能提高脑转移瘤1年局部控制率及远处肿瘤控制率（OR ＝0．43,95％CI：0．29～0．63,P ＜0．0001;OR ＝0．42,95％CI：0．30～0．57,P ＜0．00001）;但不能提高1年生存率且不良反应及神经认知异常发生率高（OR ＝1．27,95％CI：0．93～1．73,P ＝0．14;OR ＝0．50,95％CI：0．28～0．89,P ＝0．02;OR ＝0．41,95％CI：0．21～0．78,P ＝0．006）。SRS 与 WBRT 比较：SRS 治疗脑转移瘤可明显提高患者1年生存率及1年局部肿瘤控制率,但远处肿瘤控制率与WBRT相当（OR＝2．78,95％CI：1．57～4．92,P ＝0．0004;OR ＝4．8,95％CI：2．69～8．57,P ＜0．00001;OR ＝0．52,95％CI：0．15～1．83,P ＝0．31）。WBRT ＋SRS 与单独 WRBT 比较：1年局部肿瘤控制率及1年生存率无明显差别（OR ＝1．23,95％CI：0．81～1．86,P ＝0．32;OR ＝1．21,95％CI：0．76～1．93,P ＝0．42）。结论：1～4个脑转移瘤患者,单独 SRS 是理想治疗方法。     

肺癌脑转移不同放射治疗方式临床分析

目的:探讨不同放射治疗方法对肺癌脑转移瘤的疗效,并结合文献分析.方法:130例肺癌脑转移患者行放射治疗,分全脑照射组(Whole brain radiotherapy WBRT),立体定向放射治疗外科组(Stereotactic radiosurgery SRS),全脑照射 立体定向放射外科治疗外科组(WBRT SRS).全脑照射1.8Gy-2Gy/次,总剂量30-40/15-20天,立体定向放射治疗外科边缘剂量8Gy-22Gy,单次或分次完成;全脑照射 立体定向放射治疗外科治疗组,先WBRT2Gy-2.2Gy/次,总剂量30Gy-44Cy/3-4周,之后SRS治疗,单次靶区边缘剂量8Gy-12Gy.结果:三组病例局部控制率分别为49.9%,81.6%和85%,中位生存期分别为5个月,11个月及12.3个月.结论:对于肺癌脑转移,SRS及WBRT SRS治疗在局部控制率和生存率上明显优于WBRT.     

肺癌脑转移不同放射治疗方法的疗效分析

［目的］探讨不同放射治疗方法对肺癌脑转移的疗效。［方法］１７６例有病理学证实的肺癌脑转移患者分为４组：单纯全脑放疗组(WBRT)、全脑放疗加立体定向放射外科(WBRT＋SRS)，单纯立体定向放射治疗(SRT)，全脑放疗加立体定向放射治疗(WBRT＋SRT)。SRS治疗组，单次靶区平均周边剂量８Gy～２０Gy，总剂量２０Gy～３２Gy；SRT治疗组，单次靶区平均周边剂量２Gy～５Gy，总剂量２５Gy～６０Gy；WBRT组，１．８Gy～２Gy／次，总剂量３０Gy～４０Gy。［结果］４组的局部控制率分别为４７．１％、８７．７％、８６．５％、７８％；中位生存期分别为５．０、１１．０、１１．５、１０．０个月；局部无进展生存期分别为３．３３、８．３３、９．３３、７．６７个月；颅脑无新病灶生存期分别为４．１１、８．５７、９．０３、６．１２个月。单纯全脑放疗组死于脑转移的占５７．６％，较其他３组高。而全脑放疗加立体定向放射外科组的晚期放射反应的发生率为１２．２％，较其它组高。［结论］肺癌单发脑转移瘤患者的最佳治疗方式是单纯立体定向放射治疗。多发脑转移，全脑放疗加立体定向放射治疗(WBRT＋SRT)在提高生存率以及减少并发症方面优于其他治疗方法。     

Radiotherapy and chemotherapy of brain metastases

Summary The authors have reviewed the results, the indications and the controversies regarding radiotherapy and chemotherapy of patients with newly diagnosed and recurrent brain metastases. Whole-brain radiotherapy, radiosurgery, hypofractionated stereotactic radiotherapy, brachytherapy and chemotherapy are the available options. New radiosensitizers and cytotoxic or cytostatic agents are being investigated. Adjuvant whole brain radiotherapy, either after surgery or radiosurgery, and prophylactic cranial irradiation in small-cell lung cancer are discussed, taking into account local control, survival, and risk of late neurotoxicity. Increasingly, the different treatments are tailored to the different prognostic subgroups, as defined by Radiation Therapy Oncology Group RPA Classes.     

Prospective study of stereotactic radiosurgery without whole brain radiotherapy in patients with four or less brain metastases: incidence of intracranial progression and salvage radiotherapy

This prospective study was conducted to evaluate the treatment outcome after stereotactic radiosurgery (SRS) alone with special attention to its influence on intracranial freedom from progression (FFP), local control, time to whole brain radiotherapy (WBRT), and survival. Forty-one patients with brain metastases who met the inclusion criteria were enrolled in this prospective cohort and treated by SRS alone between January 1998 and September 2001. The overall local control rate was 76%. The one year actuarial intracranial FFP was 33%. Ten patients (24%) had relapse at treated site. Twenty-three patients (56%) had intracranial progression with a median time of 4.25 months (1–24.6). Salvage radiotherapy was given in 21 patients (51%). Only 12 (29%) patients required WBRT with the median time to WBRT after SRS of 4.85 months. Nine patients (22%) underwent additional SRS at the median time of 5 months after the first procedure. The median survival was 10 months. At the time of follow up, 16 patients (39%) were still alive with a range of 6–31 months. This prospective study suggests that the omission of WBRT in the initial treatment of patients with SRS for four or less brain metastases may allow up to 70% of patients to avoid WBRT.     

颅内转移瘤放射治疗方案的优化

目的:探讨颅内转移瘤放射治疗的优化方案。方法:回顾性分析2005年7月-2008年7月收治的50例颅内转移瘤患者。原发灶均得到控制,30例采用全脑放疗+立体定向放射外科(联合组),20例采用单纯立体定向放射外科(单一组)。立体定向放射外科处方剂量均采用45%-75%等剂量线包绕计划靶区,边缘剂量15-20Gy,中心剂量30-45Gy,一次完成。全脑放疗每次分割剂量为2Gy,1次/d,5次/w,总剂量40Gy/4w。结果:联合组的有效率明显高于单一组(P<0.05)。两组1年、2年生存率比较无差异(P>0.05)。两组均无生存3年以上患者。按病灶数进行分层研究:1年生存率单发病灶两组差异无显著性(P=0.212),1年生存率多发病灶联合组明显优于单一组(P=0.001),2年生存率两组差异无显著性。结论:对于多发颅内转移瘤患者,全脑放疗联合立体定向放射外科是比较优化的选择方案,而对于单发的颅内转移瘤患者,则可以先全脑放疗加立体定向放射外科或者直接立体定向放射外科治疗。     

Outcome of small cell lung cancer (SCLC) patients with brain metastases in a routine clinical setting

Background

Small cell lung cancer (SCLC) represents approximately 13 to 18% of all lung cancers. It is the most aggressive among lung cancers, mostly presented at an advanced stage, with median survival rates of 10 to12 months in patients treated with standard chemotherapy and radiotherapy. In approximately 15-20% of patients brain metastases are present already at the time of primary diagnosis; however, it is unclear how much it influences the outcome of disease according the other metastatic localisation. The objective of this analysis was to evaluate the median survival of SCLC patients treated by specific therapy (chemotherapy and/or radiotherapy) with regard to the presence or absence of brain metastases at the time of diagnosis.

Patients and methods

All SCLC patients have been treated in a routine clinical practice and followed up at the University Clinic Golnik in Slovenia. In the retrospective study the medical files from 2002 to 2007 were review. All patients with cytological or histological confirmed disease and eligible for specific oncological treatment were included in the study. They have been treated according to the guidelines valid at the time. Chemotherapy and regular followed-up were carried out at the University Clinic Golnik and radiotherapy at the Institute of Oncology Ljubljana.

Results

We found 251 patients eligible for the study. The median age of them was 65 years, majority were male (67%), smokers or ex-smokers (98%), with performance status 0 to 1 (83%). At the time of diagnosis no metastases were found in 64 patients (25.5%) and metastases outside the brain were presented in 153 (61.0%). Brain metastases, confirmed by a CT scan, were present in 34 patients (13.5%), most of them had also metastases at other localisations. All patients received chemotherapy and all patients with confirmed brain metastases received whole brain irradiation (WBRT). The radiotherapy with radical dose at primary tumour was delivered to 27 patients with limited disease and they got 4–6 cycles of chemotherapy. Median overall survival (OS) of 34 patients with brain metastases was 9 months (95% CI 6–12) while OS of 153 patients with metastases in other locations was 11 months (95% CI 10–12); the difference did not reach the level of significance (p = 0.62). As expected, the OS of patients without metastases at the time of primary diagnosis turned out to be significantly better compared to the survival of patients with either brain or other location metastases at the primary diagnosis (15 months vs 9 and 11 months, respectively, p < 0.001).

Conclusions

In our investigated population, the prognosis of patients with extensive SCLS with brain metastases at the primary diagnosis treated with chemotherapy and WBRT was not significantly worse compared to the prognosis of patients with extensive SCLC and metastases outside the brain. In extensive SCLC brain metastases were not a negative prognostic factor per se if the patients were able to be treated appropriately. However, the survival rates of extensive SCLC with or without brain metastases remained poor and novel treatment approaches are needed. The major strength of this study is that it has been done on a population of patients treated in a routine clinical setting.     

Immunotherapy in association with stereotactic radiotherapy for non-small cell lung cancer brain metastases: results from a multicentric retrospective study on behalf of AIRO

BackgroundTo define efficacy and toxicity of Immunotherapy (IT) with stereotactic radiotherapy (SRT) including radiosurgery (RS) or hypofractionated SRT (HFSRT) for brain metastases (BM) from non-small cell lung cancer (NSCLC) in a multicentric retrospective study from AIRO (Italian Association of Radiotherapy and Clinical Oncology).MethodsNSCLC patients with BM receiving SRT + IT and treated in 19 Italian centers were analyzed and compared with a control group of patients treated with exclusive SRT.ResultsOne hundred patients treated with SRT + IT and 50 patients treated with SRT-alone were included. Patients receiving SRT + IT had a longer intracranial Local Progression-Free Survival (iLPFS) (propensity score-adjusted P = .007). Among patients who, at the diagnosis of BM, received IT and had also extracranial progression (n = 24), IT administration after SRT was shown to be related to a better overall survival (OS) (P = .037). A multivariate analysis, non-adenocarcinoma histology, KPS = 70 and use of HFSRT were associated with a significantly worse survival (P = .019, P = .017 and P = .007 respectively). Time interval between SRT and IT ≤7 days (n = 90) was shown to be related to a longer OS if compared to SRT-IT interval >7 days (n = 10) (propensity score-adjusted P = .008). The combined treatment was well tolerated. No significant difference in terms of radionecrosis between SRT + IT patients and SRT-alone patients was observed. The time interval between SRT and IT had no impact on the toxicity rate.ConclusionsCombined SRT + IT was a safe approach, associated with a better iLPFS if compared to exclusive SRT.     

立体定向放射治疗肺癌脑转移的疗效观察及护理

Objective:To observe the efficacy of stereotactic radiotherapy (SRT) in lung cancer patients with brain metastases and explore the nursing for those patients.Methods:From June 2002 to December 2006,43 patients of lung cancer with brain metastases were treated with SRT,8 of them were treated with the association of whole-brain radiotherapy (WBRT) and 6 of them were treated with combination of chemotherapy.During the period of SRT,the patients were applied with active psychological nursing and diet nursing.We also tried to prevent patients from epicranium injury,and meanwhile,patients were asked to took active convalesce exercise.Results:All patients finished SRT without serious reaction and complication.Local control rate was 81.4%,nervous system symptoms relief rate was 76.7% and KPS score was raised significantly.Survival time ranged from 2 to 34 months,median survival time was 8.5 months,and 6-month,1-and 2-year survival rates were 58.9%,26.2%,and 6.0% respectively.Conclusion:SRT was one of the effective palliation treatments for the lung cancer patients with brain metastases,and with the assistance of effective nursing,which would prolong their survival time and improved quality of life.     

Hypofractionated stereotactic radiotherapy for the treatment of brain metastases

BACKGROUND:

This retrospective review evaluated the efficacy and toxicity profiles of various dose fractionations using hypofractionated stereotactic radiotherapy (HSRT) in the treatment of brain metastases.

METHODS:

Between 2004 and 2007, 36 patients with 66 brain metastases were treated with HSRT. Nine of these subjects were excluded because of the absence of post‐treatment magnetic resonance imaging scans, resulting in 27 patients with a total of 52 lesions. Of these 52 lesions, 45 lesions were treated with whole‐brain radiotherapy plus a HSRT boost and 7 lesions were treated with HSRT as the primary treatment. The median prescribed dose was 25 grays (Gy) (range, 20 Gy‐36 Gy) with a median of 5 fractions (range, 4 fractions‐6 fractions) to a median 85% isodose line (range, 50%‐100%). The median follow‐up interval was 6.6 months (range, 0.9 months‐26.8 months).

RESULTS:

The median overall survival time was 10.8 months, and 66.7% of patients died of disease progression. After HSRT treatment of 52 brain lesions, 13 lesions demonstrated complete responses, 12 lesions demonstrated partial responses, 22 lesions demonstrated stable disease, and 5 lesions demonstrated progressive disease. Actuarial local tumor control rates at 6 months and 1 year were 93.9% and 68.2%, respectively. Maximum tumor dimension, concurrent chemotherapy, and a tumor volume <1 cc were found to be statistically significant factors for local tumor control. One patient had a grade 3 toxicity (according to National Cancer Institute Common Terminology Criteria for Adverse Events).

CONCLUSIONS:

HSRT provides a high level of tumor control with minimal toxicity comparable to single‐fraction stereotactic radiosurgery (SRS). The results of the current study warrant a prospective randomized study comparing single‐fraction SRS with HSRT in this patient population. Cancer 2009. © 2009 American Cancer Society.     

Stereotactic radiosurgery with or without whole-brain radiotherapy for brain metastases: an update

Brain metastases are unfortunately a common occurrence in patients with cancer. Whole-brain radiation therapy (WBRT) is still considered the standard of care in the treatment of brain metastases. Stereotactic radiosurgery (SRS) offers the additional ability to treat tumors with relative sparing of normal brain tissue in a single fraction. While the addition of SRS to WBRT has been shown to improve survival and local tumor control in selected patients, the idea of deferring WBRT in order to avoid its effects on normal tissues and using SRS alone continues to generate significant discussion and interest. Three recent randomized trials from Japan, Europe and the MD Anderson Cancer Center (TX, USA) have attempted to address this issue. In this article, we update a previous review by discussing these trials to compare the outcomes for SRS alone versus SRS plus WBRT for limited metastases. We also discuss recent nonrandomized evidence for the use of SRS alone for oligometastatic disease.     

Prognostic index to identify patients who may not benefit from whole brain radiotherapy for multiple brain metastases from lung cancer

Palliative whole brain radiotherapy (WBRT) is often recommended in the management of multiple brain metastases. Allowing for WBRT waiting time, duration of the WBRT course and time to clinical response, it may take 6 weeks from the point of initial assessment for a benefit from WBRT to manifest. Patients who die within 6 weeks (‘early death’) may not benefit from WBRT and may instead experience a decline in quality of life. This study aimed to develop a prognostic index (PI) that identifies the subset of patients with lung cancer with multiple brain metastases who may not benefit from WBRT because of ‘early death’. The medical records of patients with lung cancer who had WBRT recommended for multiple brain metastases over a 10-year period were retrospectively reviewed. Patients were classified as either having died within 6 weeks or having lived beyond 6 weeks. Potential prognostic indicators were evaluated for correlation with ‘early death’. A PI was constructed by modelling the survival classification to determine the contribution of these factors towards shortened survival. Of the 275 patients recommended WBRT, 64 (23.22%) died within 6 weeks. The main prognostic factor predicting early death was Eastern Cooperative Oncology Group (ECOG) status >2. Patients with a high PI score (>13) were at higher risk of ‘early death’. Twenty-three per cent of patients died prior to benefit from WBRT. ECOG status was the most predictive for ‘early death’. Other factors may also contribute towards a poor outcome. With further refinement and validation, the PI could be a valuable clinical decision tool.