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.     

Whole Brain Radiotherapy Combined with Stereotactic Radiotherapy Versus Stereotactic Radiotherapy Alone for Brain Metastases: a Meta-analysis

Aim: This study was to evaluate the effect of whole brain radiation (WBRT) combined with stereotacticradiotherapy (SRS) versus stereotactic radiotherapy alone for patients with brain metastases using a metaanalysis.Materials and Methods: We searched PubMed, EMBASE, Cochrane Library from their inceptionup to October 2013. Randomized controlled trials involving whole brain radiation combined with stereotacticradiotherapy versus stereotactic radiotherapy alone for brain metastases were included. Statistical analyseswere performed using RevMan5.2 software. Results: Four randomized controlled trials including 903 patientswere included. The meta-analysis showed statistically significant lowering of the local recurrence rate (OR=0.29,95%CI: 0.17~0.49), new brain metastasis rate (OR=0.45, 95%CI: 0.28~0.71) and symptomatic late neurologicradiation toxicity rate (OR=3.92, 95%CI: 1.37~11.20) in the combined group. No statistically significant differenceexisted in the 1-year survival rate (OR=0.78, 95%CI: 0.60~1.03). Conclusions: The results indicate that wholebrain radiotherapy combined with stereotactic radiotherapy has advantages in local recurrence and new brainmetastasis rates, but stereotactic radiotherapy alone is associated with better neurological function. However, asthe samples included were not large, more high-quality, large-sample size studies are necessary for confirmation.     

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.     

肺癌脑转移的立体定向放疗

脑转移是癌症患者的主要转移部位,而肺癌是最常见的脑转移的原发病。对于脑转移患者,仅给予最佳支持治疗或内科治疗,中位生存期只有1~2个月,使用全脑放疗、立体定向放疗和手术后,患者生存期明显延长,但对于寡转移和多发转移患者,其治疗策略不同,同样对于如何选择不同的治疗方法,有必要进一步探讨。在延长患者生存期的基础上,尽量保存认知功能同样重要。     

Combined Razoxane and Radiotherapy for Melanoma Brain Metastases. A Retrospective Analysis

Summary We retrospectively compared the efficacy of razoxane and radiotherapy with radiotherapy alone or in combination with a non-razoxane based medication in patients with melanoma brain metastases. From 19 assessable patients receiving whole brain irradiation with or without a boost (mean total dose 40.5 Gy) for measurable brain metastases, 8 patients underwent an additional razoxane therapy with 125 mg per os twice daily started 5 days before radiotherapy and given throughout the whole radiation period. The median razoxane dose was 6.25 g (range 3.2–8.0 g). Endpoints included radiation response rates, median survival time and 1-year survival rates. To generate reliable prognostic parameters for this non-randomized study population, the Score Index for Stereotactic Radiosurgery and the Radiation Therapy Oncology Group Recursive Partitioning Analysis score were applied. Radiotherapy with razoxane led to higher response rates (62% vs. 27%) and a lower percentage of progressive disease (12.5% vs. 36%) if compared with radiotherapy alone or with a non-razoxane based medication. This combination was associated with a longer median survival (5 months vs. 2.2 months; P=0.052) and a 1-year survival rate of 37.5% vs. 0% (P=0.027). Both treatment groups belonged to similar prognosis subsets. The treatment was well tolerated. Taken together our data support the therapeutic concept of a combined razoxane radiation therapy in melanoma patients with brain metastases. The favorable treatment effects are probably due to the radiosensitizing and the cytorallentaric mode of action of razoxane. Since the patient numbers are low, confirmatory studies are certainly necessary.     

A Phase II Trial of Temozolomide for Patients with Recurrent or Progressive Brain Metastases

Background: Treatment options for patients with recurrent brain metastases are extremely limited. This study was designed to determine the safety and efficacy of temozolomide in the treatment of recurrent or progressive brain metastases. Patients and methods: Forty-one patients (11 men, 30 women) with a median KPS of 80 were treated with temozolomide 150mg/m²/day (200mg/m²/day if no prior chemotherapy) for 5 days; treatment cycles were repeated every 28 days. Primary tumor types included 22 non-small cell lung, 10 breast, three melanoma, two small cell lung, two rectal, one ovarian and one endometrial cancer. Results: There were five episodes of grade 3 thrombocytopenia and one grade 4 leukopenia. Significant non-hematologic toxicity possibly related to temozolomide included pneumonitis [2], constipation [1], and elevated liver enzymes [2]. Thirty-four patients were assessed for radiographic response; two had a partial response, 15 stable disease and 17 progressed. Both objective responses were seen in patients with non-small cell lung cancer. Overall median survival was 6.6 months. Conclusions: Single agent temozolomide achieved disease control (PR or SD) in 41% of patients with recurrent brain metastases from a variety of primary malignancies with minimal toxicity. Therefore, temozolomide may be a reasonable treatment option for some patients with recurrent brain metastases.     

全脑放疗联合替莫唑胺同期化疗在脑转移瘤治疗中的疗效观察

目的 探讨联合使用全脑放疗和替莫唑胺治疗脑转移瘤的疗效.方法 将160例脑转移瘤患者随机分为对照组和观察组,每组各80例.对照组使用全脑放疗进行治疗.使用6mV-X线全脑放射治疗,全脑两侧对穿野等中心放射治疗,DT 30 Gy/10次,5次/周.观察组在全脑放射治疗的基础上使用替莫唑胺75 mg/m2/d进行治疗,连续口服14 d进行.观察2组患者治疗后的近远期疗效以及治疗过程中出现的副作用.结果 观察组总有效率为87.50%,显著高于对照组中的53.75%.对照组和观察组在3个月的生存期上没有统计学差异(P>0.05);在6个月生存率和1年生存率上,观察组显著高于对照组(P<0.05).中位生存期的比较上,观察组显著优于对照组(11.8 v.s.6.4,P<0.05).2组患者治疗过程中均没有出现无法耐受的严重副作用(Ⅳ级);在白细胞、血红蛋白和血小板等骨髓抑制的指标中,观察组出现副作用的发生率显著高于对照组,但是经过对症治疗后,患者均可以耐受;在恶心呕吐和头疼的副作用发生率和等级分布上,2组患者没有统计学差异(P>0.05).结论 全脑放疗联合使用替莫唑胺治疗脑转移瘤,可以显著提高患者总的缓解率,并能够显著延长患者的生存期和提高生存率,且副作用均可耐受,值得临床推荐使用.     

Fractionated Stereotactic Radiotherapy using CyberKnife for the Treatment of Large Brain Metastases: A Dose Escalation Study

AimsTo evaluate the toxicity and efficacy of fractionated stereotactic radiotherapy (FSRT) with doses of 18–30 Gy in three fractions and 21–35 Gy in five fractions against large brain metastases.Materials and methodsBetween 2005 and 2012, 61 large brain metastases (≥2.5 cm in maximum diameter) of a total of 102 in 54 patients were treated with FSRT as a first-line therapy. Neurological symptoms were observed in 47 of the 54 patients before FSRT. Three fractions were applied to tumours with a maximum diameter ≥2.5 cm and <4 cm, and five fractions were used for brain metastases ≥4 cm. After ensuring that the toxicities were acceptable (≤grade 2), doses were escalated in steps. Doses to the large brain metastases were as follows: level I, 18–22 Gy/three fractions or 21–25 Gy/five fractions; level II, 22–27 Gy/three fractions or 25–31 Gy/five fractions; level III, 27–30 Gy/three fractions or 31–35 Gy/five fractions. Level III was the target dose level.ResultsOverall survival rates were 52 and 31% at 6 and 12 months, respectively. Local tumour control rates of the 102 total brain metastases were 84 and 78% at 6 and 12 months, respectively. Local tumour control rates of the 61 large brain metastases were 77 and 69% at 6 and 12 months, respectively. Grade 3 or higher toxicities were not observed.ConclusionsThe highest dose levels of 27–30 Gy/three fractions and 31–35 Gy/five fractions seemed to be tolerable and effective in controlling large brain metastases. These doses can be used in future studies on FSRT for large brain metastases.     

98例脑转移癌放疗疗效分析

目的 探讨全脑放疗在脑转移癌姑息性治疗中的疗效.方法 98例脑转移癌姑息性全脑放疗患者根据放疗分割方式的不同分为3组,均选用6 MV-X线全脑照射,每天1次,每周5次.A组45例:DT40Gy/20次/4周;B组20例:DT 30 Gy/15次/3周;C组23例:DT 30 Gy/10次/2周.分析不同分割方式全脑放疗后患者的生存情况.结果 A组、B组、C组的总有效率分别为97.8％、95.0％、95.7％ (P ＞0.05).A组、B组、C组的中位生存期分别为11.5、11.0、10.8个月;1a生存率分别为40.0％、30.0％、34.8％(P＞0.05);2 a生存率分别为11.1％、10.0％、8.7％(P＞0.05).3组患者的KPS评分比较差异无统计学意义(P＞0.05).结论 全脑放疗对脑转移癌患者疗效较好,毒副反应轻,其中DT30 Gy/10次/2周的分割方式较其他2种方式具有节约医用资源的优势.     

大分割放疗联合替莫唑胺治疗大体积脑转移瘤的效果观察

目的 观察大分割放疗联合替莫唑胺治疗大体积脑转移瘤的临床疗效.方法 选取90例大体积脑转移瘤患者为研究对象,随机将患者分为对照组和实验组,每组45例.对照组患者给予大分割放疗治疗,实验组患者在大分割放疗的基础上每日加服1次替莫唑胺150 mg/m2,连续口服28天即1个放疗周期结束后,每个放疗周期的前5天给予每天1次口服替莫唑胺200 mg/m2辅助治疗.治疗6个疗程后观察2组的临床疗效及不良反应,并分析患者1年随访记录.结果 实验组患者的临床治疗有效率为75.56%,明显高于对照组的48.89%(P<0.05).实验组患者半年及1年生存率高于对照组,复发率低于对照组(P<0.05).2组患者均有放射性脑水肿、放射性脑坏死、脑神经损伤、恶心呕吐及发热等不良反应,实验组患者临床还表现出骨髓抑制及贫血等不良反应,但均可耐受.结论 大分割放疗联合替莫唑胺对临床治疗大体积脑转移瘤安全有效,患者临床症状可得到明显改善,临床不良反应较轻,值得推广应用.     

152例肺癌脑转移立体定向放疗预后分析

目的 分析肺癌脑转移的立体定向放疗(SRT)疗效和预后因素。方法 回顾分析行SRT的 152例肺癌脑转移病例。单纯SRT组 59例,SRT加全脑放疗(WBRT)组 40例,WBRT失败后SRT挽救组 53例。Logrank法单因素分析,Cox模型多因素分析。结果 全组随访率为97.4%。单纯SRT组,SRT加WBRT组和SRT挽救组6个月、l年局部控制率分别为96.0%、93.4%,94.2%、90.8%和81.7%、77.5%(χ²=5.39,P=0.068),1、2、5年生存率分别为47.4%、23.7%、8.5%,55.0%、20.0%、0%和41.5%、7.5%、1.9%(χ²=4.08,P=0.130)。单因素分析显示诊断肺癌到脑转移时间、卡氏评分、肺癌切除、GPA分级、RPA分级、颅外病变是影响生存的因素(χ²=11.97、5.91、15.48、14.48、15.86、17.36,P=0.001、0.015、0.000、0.000、0.000、0.000)。多因素分析显示RPA分级、肺癌切除与总生存有关(χ²=21.02、8.18,P=0.000、0.004)。全组患者SRT前和后3个月卡氏评分≤70、80、90的比例分别为48.7%、33.6%、17.8%和27.0%、46.7%、26.3%(t=7.16,P=0.000)。     

Whole Brain Radiotherapy Plus Chemotherapy in the Treatment of Brain Metastases from Lung Cancer: A Metaanalysis of 19 Randomized Controlled Trails

Objective: To evaluate the efficacy and safety of whole brain radiotherapy (WBRT) plus chemotherapyversus WBRT alone for treating brain metastases (BM) from lung cancer by performing a meta-analysis basedon randomized controlled trials (RCTs). Methods: The PubMed, Embase, CENTRAL, ASCO, ESMO, CBM,CNKI, and VIP databases were searched for relevant RCTs performed between January 2000 and March 2012.After quality assessment and data extraction, the meta-analysis was performed using the RevMan 5.1 software,with funnel plot evaluation of publication bias. Results: 19 RCTs involving 1,343 patients were included. Themeta-analyses demonstrated that compared to WBRT alone, WBRT plus chemotherapy was more effective withregard to the objective response rate (OR = 2.30, 95% CI = 1.79 – 2.98; P < 0.001); however, the incidences ofgastrointestinal reactions (RR = 3.82, 95% CI = 2.33 - 6.28, P <0.001), bone marrow suppression (RR = 5.49,95% CI = 3.65 - 8.25, P < 0.001), thrombocytopenia (RR = 5.83, 95% CI = 0.39 - 86.59; P = 0.20), leukopenia(RR = 3.13, 95% CI = 1.77 – 5.51; P < 0.001), and neutropenia (RR = 2.75, 95% CI = 1.61 - 4.68; P < 0.001) inpatients treated with WBRT plus chemotherapy were higher than with WBRT alone. There was no obviouspublication bias detected. Conclusion: WBRT plus chemotherapy can obviously improve total efficacy rate,butalso increases the incidence of adverse reactions compared to WBRT alone. From the limitations of thisstudy, more large-scale, high-quality RCTs are suggested for further verification.     

Temozolomide in advanced malignant melanoma with small brain metastases

BACKGROUND: The efficacy of radiotherapy (RT) in patients who have brain metastases from melanoma is limited. In this study, the authors evaluated the efficacy of treatment with temozolomide in patients with metastatic melanoma, including small brain metastases, who did not require immediate RT and investigated the feasibility of deferring RT. METHODS: Patients with brain metastasis were identified from 3 prospective studies of temozolomide (with or without immunotherapy) for metastatic melanoma. Patients with brain metastasis that measured >2 cm, extensive edema, and localization in the brain stem were excluded from the study. For the current analysis, patients with leptomeningeal metastasis and patients who received previous stereotactic RT were excluded. In patients who achieved a systemic response or stabilization to temozolomide, the response of brain metastasis and the necessity for palliative cranial RT were evaluated. RESULTS: Among 179 patients who received temozolomide for advanced melanoma, 52 patients with brain metastasis were evaluable. Stabilization of systemic metastasis was noted in 7 of 52 patients (13%), and there were 6 responses (5 partial responses and 1 complete response; 11%); thus, in those 13 patients, 6 had stabilization of brain metastasis (11%) and 5 had a response (2 partial responses and 3 complete responses; 9%). Immunotherapy did not influence the neurologic response. The median time to neurologic progression was 7 months (range 2-15, months). RT for cerebral recurrence was required in 2 patients. The median survival of patients with brain metastases was 5.6 months (95% confidence interval, 4.4-6.8 months). Intracranial hemorrhagic complications were not observed. CONCLUSIONS: The current results indicated that it is feasible to treat patients who have advanced melanoma and small brain metastasis with temozolomide as the single treatment. The small subset of patients with systemic response usually showed durable stabilization or a response of brain metastasis. With this approach, neurologic disease can be controlled, and cranial irradiation may be deferred and even withheld in most of patients.     

立体定向放射治疗脊柱转移瘤疗效分析

目的观察立体定向放射治疗脊柱转移瘤的疗效与不良反应。方法应用全身伽玛刀治疗脊柱转移瘤24例,肿瘤组织照射剂量38.2~46.8 Gy,10~13分次,13~17天完成。结果放疗后疼痛完全缓解(CR)7例,部分缓解(PR)12例,轻微疗效(MR)2例,止痛有效率90.5%。骨转移灶完全消失3例,明显缩小13例,治疗后生活质量评分较治疗前明显改善,消化道反应和骨髓抑制等不良反应轻微。结论立体定向放射治疗脊柱转移瘤止痛效果迅速持久,能明显改善患者的生活质量,控制肿瘤效果满意,值得推广。     

立体定向放射治疗脊柱转移瘤疗效分析

目的观察立体定向放射治疗脊柱转移瘤的疗效与不良反应。方法应用全身伽玛刀治疗脊柱转移瘤24例，肿瘤组织照射剂量38．2～46．8Gy，10～13分次，13～17天完成。结果放疗后疼痛完全缓解（CR）7例，部分缓解（PR）12例，轻微疗效（MR）2例，止痛有效率90．5％。骨转移灶完全消失3例，明显缩小13例，治疗后生活质量评分较治疗前明显改善，消化道反应和骨髓抑制等不良反应轻微。结论立体定向放射治疗脊柱转移瘤止痛效果迅速持久，能明显改善患者的生活质量，控制肿瘤效果满意，值得推广。     

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.     

Radiotherapy Plus Temozolomide With or Without Nimotuzumab Against the Newly Diagnosed EGFR-Positive Glioblastoma: A Retrospective Cohort Study

BackgroundGlioblastoma (GBM) has a poor prognosis, and patients with epidermal growth factor receptor (EGFR) amplification have an even worse prognosis. Nimotuzumab is an EGFR monoclonal antibody thought to play a significant role in the treatment of GBM. This paper presents a retrospective cohort study that evaluates the clinical efficacy and safety of nimotuzumab in GBM.Materials and MethodsA total of 56 newly diagnosed patients with EGFR-positive GBM were included in our study. The patients were divided into radiotherapy (RT) + temozolomide (TMZ) + nimotuzumab (39 patients) and RT + TMZ (17 patients) groups based on whether or not nimotuzumab was added during RT. Progression-free survival (PFS), overall survival (OS), and toxicities were assessed.ResultsThe median follow-up time was 27.9 months (95% confidence interval [CI], 25.1-30.8). The median PFS was 12.4 months (95% CI, 7.8-17.0) and 8.2 months (95% CI, 6.1-10.3) in the 2 groups, respectively, P = .052. The median OS was 27.3 months (95% CI, 19.0-35.6) and 16.7 months (95% CI, 11.1-22.2), respectively, P = .018. In patients with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter, the PFS and OS were significantly better in patients treated with nimotuzumab than in those without nimotuzumab (median PFS: 19.3 vs 6.7 months, P = .001; median OS: 20.2 vs 13.8 months, P = .026). During the treatment period, no statistically significant difference in toxicity was noted between the 2 groups.ConclusionOur retrospective cohort study suggests the efficacy of Nimotuzumab combined with concurrent RT with TMZ in patients with newly diagnosed EGFR-positive GBM, and specifically those with unmethylated MGMT promoter. Further prospective studies are warranted to validate our findings. Besides, nimotuzumab demonstrated good safety and tolerability.