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，     

肝细胞癌脑转移瘤的立体定向放射治疗

目的探讨立体定向放射治疗加或不加全脑放疗对肝细胞癌有限数目脑转移瘤治疗的疗效.方法回顾性分析2008年8月-2018年7月武警部队上海肿瘤放射诊疗中心及海军军医大学附属东方肝胆外科医院肿瘤放疗中心收治的肝细胞癌脑转移瘤(1~4枚)患者75例,其中行立体定向放射治疗的患者45例,立体定向放射治疗加全脑放疗的患者30例.分析两组患者治疗的肿瘤客观缓解率、总生存期、放射治疗后的不良反应情况并行多因素分析.结果立体定向放射治疗组与立体定向放射治疗加全脑放疗组的客观缓解率分别为88.9%和80.0%,未见统计学差异(P=0.537);全组患者的中位总生存期为5.7个月,其中立体定向放射治疗组为6.2个月,立体定向放射治疗加全脑放疗组为5.4个月,未见统计学差异(P=0.380);多因素分析显示病灶数目(P=0.041)、病灶总体积(P=0.012)及肝内病灶的控制情况(P=0.006)是影响脑转移瘤患者总生存期的主要因素;两种治疗方式均未见严重不良反应.结论立体定向放射治疗是肝细胞癌有限数目脑转移瘤患者安全有效的治疗方式,单纯立体定向放射治疗可取得与立体定向放射治疗加全脑放疗相似的疗效.     

X射线立体定向放射治疗多发脑转移瘤的价值

目的　探讨X射线立体定向放射治疗多发脑转移瘤的疗效。方法　在 4种预后因素(年龄、治疗前卡氏评分、有无其他部位转移及转移灶数目 )相同或相似的条件下 ,配对选择两组病例。X射线立体定向放射治疗加常规放射治疗组 (研究组 )和常规放射治疗组 (对照组 )各 53例。在研究组中 ,X射线立体定向放射治疗采用单次照射 40例 ,分次照射 1 3例 ;单次靶区平均周边剂量为 2 0Gy,分次照射剂量为 4～ 1 2Gy/次 ,2次 /周 ,总剂量为 1 5～ 30Gy。X射线立体定向放射治疗结束后即开始全脑放射治疗。对照组采用全脑照射 30～ 40Gy,3～ 4周。结果　研究组和对照组中位生存期分别为1 1 .6、6 .7个月 (P <0 .0 5) ;1年生存率分别为 44 .3 %、1 7.1 % (P <0 .0 1 ) ;1年局部控制率分别为50 .9%、1 3 .2 % (P <0 .0 5) ;治疗后 1个月卡氏评分增加者分别占 69.8%、30 .2 % (P <0 .0 1 ) ;治疗后 3个月影像学上的有效率分别为 82 .0 %、55 .0 % (P <0 .0 1 )。在死因分析中 ,研究组死于脑转移的占2 3 .3 % ,比对照组的 51 .0 %低 (P <0 .0 5)。两组病例放射并发症的发生率相似。结论　对于多发脑转移瘤 ,X射线立体定向放射治疗加常规放射疗在提高局部控制率、延长生存期和提高生存质量方面均优于单纯放射治疗。     

肺癌脑转移瘤的立体定向放射外科治疗

肺癌脑转移发生率较高 ,约 2 0 %～5 0 %。Ｅｒｉｃｓ等[1] 报道了 72 9例脑转移瘤患者 ,原发灶为肺癌者占 39% ,其中非小细胞肺癌为 2 4% ,小细胞肺癌为 15 % ,明显多于其他肿瘤。肺癌脑转移患者如未经治疗 ,其中位生存期仅 1个月。采用皮质激素治疗和全脑放疗 ,中位生存期可提高到 3～ 6个月[2 ] 。有报道称手术切除加全脑放疗与单用全脑放疗相比可显著提高中位生存期并改善功能情况[3] 。但近来的随机试验显示两者无显著差异[4 ] 。肺癌远处转移治愈的可能性很小。尽管采取了一些新的外科技术和方法 ,但单纯外科手术仍很难取得令人满意的…     

分次立体定向放射治疗全脑放疗后肺癌脑转移瘤52例疗效分析

[目的]分析分次立体定向放射治疗全脑放疗后肺癌脑转移瘤的疗效及不良反应.[方法]2007年12月至2010年12月对KPS＞60分的52例全脑放疗后的肺癌脑转移(病灶数目少于4个)患者给予分次立体放射治疗,单次靶区周边剂量为3～5Gy,总剂量为15～25Gy,分3～5次完成,50％等剂量曲线包绕PTV.[结果]截至2011年12月,46例患者死亡.自再次放疗开始算起,全组中位生存期为10.7个月(95％CI为8.5～12.9),1年及2年生存率分别为28.4％和7.2％.全组临床症状缓解率为73.1％,肿瘤局部控制率为90.4％.仅1例患者出现放射性脑坏死.[结论]分次立体定向放射治疗用于全脑放疗后疾病进展的肺癌脑转移患者,可以提高生存质量、延长患者生存期,安全性较好,但需严格掌握适应证.     

脊柱转移瘤立体定向放射治疗研究进展

脊柱是恶性肿瘤发生骨转移的最常见部位之一。多年来,放疗在脊柱转移瘤患者中发挥重要作用。近年来,立体定向放射治疗（SBRT）成为治疗脊柱转移瘤的有效方法之一,分割方式分单次与多次分割。本文就已发表文献中脊柱转移瘤立体定向放射治疗单次与多次分割的适应证与禁忌证、治疗技术、剂量及疗效、脊髓安全剂量分析、局部失败模式分析等方面做一综述。     

23例脑转移瘤的立体定向放射治疗疗效观察

我院于 2 0 0 0年 10月～ 2 0 0 2年 4月采有X刀立体定向放射外科 (stereotacticradiotherapytreatment,SRT)治疗 2 3例脑转移瘤 ,共 5 9个病灶 ,取得了较好的临床疗效 ,现报道如下。1　材料与方法1 1　一般资料　本组 2 3例脑转移瘤病人 ,其中男性 10例 ,女性 13例。年龄 30～ 73岁 ,平均 5 6岁。 7例为单发 ,16例为多发 ,最多者 5个病灶 ,共 5 9个病灶。1 2　治疗方法　治疗系统应用医科达 6MSli-precise直线加速器和STAR - 10 0 0三维治疗计划系统 (大恒公司产品 )。治疗前采用胶片曝光法进行检验 ,机械误差在± 0 5mm以内。对脑转…     

脑转移瘤X线立体定向放射治疗的疗效及影响因素

背景与目的:X线立体定向放射治疗(X-ray stereotactic radiotherapy,SRT)是治疗脑转移瘤的有效方法之一,该研究意在评价脑转移瘤患者SRT的疗效以及影响预后的因素。方法:自1999年7月至2004年12月止,78例脑转移瘤患者在本中心接受SRT方式治疗。其中,49例为单发病灶,29例为多发(2～6个)病灶,总病灶数为122个。38个病灶采用SRT单次治疗,中位处方剂量为15Gy(11～24Gy)。84个病灶采用SRT分次(2～6次)治疗,中位处方剂量为24Gy(11～40Gy)。39例SRT联合全脑放疗30～40Gy。无进展生存率(progression-free survival,PFS)和总生存率(overall survival,OS)分析采用Kaplan-Meier法,单因素和多因素分析分别采用log-rank法和Cox模型。结果:中位生存时间12.9(1.7～77.4)个月。1年颅内PFS为87.4%,1和2年OS分别为53.9%和25.8%。单因素分析显示治疗前KPS(karnofsky performance state)≥70、颅外肿瘤获控制和SRT联合全脑放疗的...     

立体定向放射外科对脑转移瘤的治疗现状

脑转移瘤在肿瘤临床中是常见的.恶性肿瘤脑转移的发生率约为5%～30%.未经治疗的脑转移患者中位生存期仅为1个月,经传统全脑放射治疗后中位生存期达3～4个月.近来发展起来的立体定向放射外科(SRS)技术能更有效的控制脑转移瘤,把中位生存期提高到8～12个月.SRS是采用电离辐射、单次、大剂量集中照射颅内病灶,使病灶产生不同程度的放射损伤和其它放射性改变,避免常规开颅手术而达到治疗的目的,这种技术最早是由瑞典的著名神经外科医生Lesksell提出的.随着各种影像技术及电子计算机三维治疗计划系统的发展,使SRS技术更加完善.目前SRS主要有以广3种方法:(1)γ—刀:以~(60)Co为辐射源,通过球形准直器聚焦201个~(60)Co源射线于靶区.(2)X-刀:以电子直线加速器产生的高能X线为辐射源,通过若干(5～10个)非共面的等中心放射弧,聚焦X线于靶区.(3)质子刀:利用质子Bragg峰的特性,使质子的能量集中释放于靶区.质子刀的设备昂贵,难以广泛应用于临床,目前国内外常用X-刀及γ-刀实现SRS.     

Whole Brain Radiotherapy Combined with Stereotactic Radiosurgery versus Stereotactic Radiosurgery Alone for Brain Metastases

Background: The aim of this study was to evaluate the effect of whole brain radiotherapy (WBRT) combined with streotactic radiosurgery versus stereotactic radiosurgery (SRS) alone for patients with brain metastases. Materials and Methods: This was a retrospective study that evaluated the results of 46 patients treated for brain metastases at Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Radiation Oncology Department, between January 2012 and January 2015. Twenty-four patients were treated with WBRT+SRS while 22 patients were treated with only SRS. Results: Time to local recurrence was 9.7 months in the WBRT+SRS arm and 8.3 months in SRS arm, the difference not being statistically significant (p= 0.7). Local recurrence rate was higher in the SRS alone arm but again without significance (p=0,06). Conclusions: In selected patient group with limited number (one to four) of brain metastases SRS alone can be considered as a treatment option and WBRT may be omitted in the initial treatment.     

放射治疗脑转移癌54例疗效分析

 目的　探讨放射治疗对脑转移癌的疗效。方法　 1996年 9月～ 2 0 0 0年 9月对我科 5 4例脑转移癌患者行放射治疗。全脑放射剂量达 30Gy后追加照射 2 0～ 2 4Gy或 16～ 18Gy。 结果　全脑照射剂量达 30Gy后未作追加照射的 8例 1年内全部死亡 ,作追加照射的 4 6例 ,1年存活率达5 8.7% ,2年存活率达 2 1.7%。 5 4例病人经全脑放射治疗后总缓解率为 77.5 %。结论　脑转移癌采用放射治疗可以改善患者的症状 ,延长生存时间 ,是一种安全有效的姑息性治疗手段。     

Recursive Partitioning Analysis for the Prediction of Stereotactic Radiosurgery Brain Metastases Lesion Control

Purpose.

The objective of this investigation was to identify independent pretreatment factors that predict for control of local brain metastases (BM) in a large single-institution series of patients receiving stereotactic radiosurgery (SRS). Recursive partitioning analysis was used to potentially identify a class of patients with durable lesion control characteristics.

Methods.

A retrospective SRS database containing baseline characteristics, treatment details, and follow-up data of newly diagnosed patients with 1–3 BM (on magnetic resonance imaging) treated with linear accelerator-based SRS was created. Three study endpoints were used: time to progression (primary endpoint, individual lesion progression; n = 536), time to first progression (secondary endpoint, first lesion progression on an individual patient basis; n = 380), and overall survival (secondary endpoint; n = 380). Recursive partitioning analysis (RPA) was performed to identify predictors of time to progression.

Results.

Multivariable analysis demonstrated that lesion aspect/phenotype and radiotherapy schedule were independent factors associated with both progression outcomes. Presence of tumor necrosis was found to be associated with a significant hazard of progression (hazard ratio >3), whereas use of the most intense radiotherapy fractionation schedule (21 Gy in one fraction) was associated with significant reductions in progression (hazard ratio <0.3). RPA using SRS dose and lesion aspect/phenotype was created and described three distinct prognostic groups.

Conclusions.

RPA of a large retrospective database of patients receiving SRS confirmed previous observations regarding the importance of SRS dose and lesion aspect/phenotype in lesion control and overall survival. The SRS lesion analysis may help to stratify future clinical trials and better define patient care options and prognosis.     

Whole Brain Radiotherapy Versus Stereotactic Radiosurgery in Poor-Prognosis Patients with One to 10 Brain Metastases: A Randomised Feasibility Study

AimsA significant proportion of patients with brain metastases have a poor prognosis, with a life expectancy of 3–6 months. To determine the optimal radiotherapeutic strategy for brain metastases in this population, we conducted a randomised feasibility study of whole brain radiotherapy (WBRT) versus stereotactic radiosurgery (SRS).Materials and methodsPatients with a life expectancy of 3–6 months and between one and 10 brain metastases with a diameter ≤4 cm were enrolled at six Canadian cancer centres. Patients were randomly assigned (1:1) to receive either WBRT (20 Gy in five fractions) or SRS (15 Gy in one fraction). The primary end point was the rate of accrual per month. Secondary feasibility and clinical end points included the ratio of accrued subjects to screened subjects. This trial is registered with ClinicalTrials.gov (number NCT02220491).ResultsIn total, 210 patients were screened to enrol 22 patients into the trial; 20 patients were randomised between the two arms. Two patients did not receive treatment because one patient died and another patient withdrew consent after being enrolled. Patients were accrued between January 2015 and November 2017; the accrual rate was 0.63 patients/month. The most common reasons for exclusion were anticipated median survival outside the required range (n = 40), baseline Karnofsky Performance Score below 70 (n = 28) and more than 10 brain metastases (n = 28). The median follow-up was 7.0 months and the median survival was 7.0 months for all patients in the trial. The median intracranial progression-free survival was 1.8 months in the SRS arm and 9.2 months in the WBRT arm. There were five grade 3+ toxicities in the SRS arm and one grade 3+ toxicity in the WBRT arm; no grade 5 toxicities were observed. The cumulative rates of retreatment were 40% in the SRS arm and 40% in the WBRT arm.ConclusionsA randomised trial evaluating WBRT versus SRS in patients with one to 10 metastases and a poor prognosis is feasible. A slower than expected accrual rate and difficulties with accurate prognostication were identified as issues in this feasibility study. A larger phase III randomised trial is planned to determine the optimal treatment in this patient population.     

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．     

The Rationale for Targeted Therapies and Stereotactic Radiosurgery in the Treatment of Brain Metastases

Brain metastases are the most common intracranial malignancy. Many approaches, including radiation therapy, surgery, and cytotoxic chemotherapy, have been used to treat patients with brain metastases depending on the patient’s disease burden and symptoms. However, stereotactic surgery (SRS) has revolutionized local treatment of brain metastases. Likewise, targeted therapies, including small-molecule inhibitors and monoclonal antibodies that target cancer cell metabolism or angiogenesis, have transformed managing systemic disease. Prospective data on combining these treatments for synergistic effect are limited, but early data show favorable safety and efficacy profiles. The combination of SRS and targeted therapy will further individualize treatment, potentially obviating the need for cytotoxic chemotherapy or whole-brain radiation. There is a great need to pursue research into these exciting modalities and novel combinations to further improve the treatment of patients with brain metastases. This article discusses reported and ongoing clinical trials assessing the safety and efficacy of targeted therapy during SRS.

Implications for Practice:

Treatment of patients with brain metastases requires a multidisciplinary approach. Stereotactic radiosurgery is increasingly used in the upfront setting to treat new brain metastasis. Targeted therapies have revolutionized systemic treatment of many malignancies and may sometimes be used as initial treatment in metastatic patients. There is sparse literature regarding safety and efficacy of combining these two treatment modalities. This article summarizes the supporting literature and highlights ongoing clinical trials in combining radiosurgery with targeted therapy.