Temozolomide With or Without Radiotherapy in Melanoma With Unresectable Brain Metastases

Summary Brain metastases are a common complication in patients suffering from metastatic malignant melanoma. We analyzed efficacy and toxicity of the alkylating agent temozolomide with excellent CNS penetration and known activity in brain metastasis in 35 patients with unresectable melanoma brain metastases. Patients received 200 mg/m² temozolomide on days 1 to 5 every 28 days as first or second-line therapy. This therapy regimen was combined with radiotherapy of the brain metastases in 22/35 patients. Grade III and IV toxicity was observed in 8/35 patients (leukopenia, granulocytopenia, thrombocytopenia, anemia, nausea and obstipation). Complete remission was observed in 1/34, partial remission in 2/34 and stable disease in 9/34 patients. In 5/34 a mixed response was assessed, 17/34 had disease progression and in one patient tumor response was not evaluable. The median progression free time was 5 (0–8) months for all patients, the median survival time for all patients from start of therapy was 8 (0–28) months, 9 (2–28) months in patients with concurrent stereotactic radiotherapy and 7 (3–17) months in patients with concurrent whole brain radiotherapy. Our results demonstrate that temozolomide can be combined with radiotherapy for the treatment of brain metastases in malignant melanoma, and that this combination may prolong survival in this patient group.     

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 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.     

脑转移瘤全脑放疗后前瞻性记忆与回顾性记忆功能损害的研究

[目的]了解脑转移瘤患者全脑放疗后前瞻性记忆(PM)与回顾性记忆(RM)的功能损害情况.[方法]以34例脑转移瘤患者为研究对象,在全脑放疗前1周、放疗后1个月分别进行简易精神状态量表(MMSE)测查及RM和PM问卷调查.[结果]放疗前后MMSE评分(27.26±1.86 vs 26.35±1.76)差异具有统计学意义(P＜0.05).放疗后PM成绩为12.18±2.74,低于放疗前(14.06±4.66)(P＜0.01);RM成绩放疗前后(14.26±4.60 vs 14.18±4.41)差异无统计学意义(P＞0.05).[结论]全脑放疗对脑转移瘤患者的总体认知功能有损害,但可改善患者PM功能,RM功能无明显影响.     

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.     

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。     

全脑放疗联合伽玛刀治疗脑转移瘤

[目的]评价全脑放疗联合伽玛刀治疗脑转移瘤的价值.[方法]将60例脑转移瘤病人随机分为两组:全脑放疗联合伽玛刀治疗组(A组)及单纯伽玛刀治疗组(B组).A组先全脑放疗40Gy/20F/4W后,复查颅脑MRI或CT,如果有残留,则继以伽玛刀治疗,周边剂量8Gy～26Gy,一次照射:B组单纯伽玛刀治疗,肿瘤周边剂量16Gy～32Gy,一次照射.分别对两组不同病灶数患者的近期疗效及生存率进行统计学分析.[结果]两组患者近期疗效及生存率差异无显著性;分层研究显示:单个病灶者两组生存率差异无显著性,而两个以上病灶者全脑放疗联合伽玛刀治疗的生存率高于单纯伽玛刀治疗,差异有显著性.[结论]对于单个病灶的脑转移瘤可单纯行伽玛刀治疗:而多发病灶的脑转移瘤,建议全脑放疗联合伽玛刀治疗.     

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.     

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.     

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.     

厄洛替尼联合全脑放疗治疗NSCLC脑转移的疗效及患者生存分析

目的研究厄洛替尼联合全脑放疗治疗非小细胞肺癌脑转移的疗效以及患者生存效果。方法随机选取非小细胞肺癌患者98例,根据治疗途径分为对照组和实验组,每组49例患者。对照组患者接受全脑放疗;实验组患者接受厄洛替尼联合全脑放疗,即患者在放疗开始应用厄洛替尼片,应用到放疗完成后2个月为止。对全部入组患者定期进行住院或者门诊随访。结果 2组患者经治疗后,实验组患者完全缓解率为12.2%,部分缓解率为28.6%,病灶稳定率为42.9%,病灶进展率为16.3%,而对照组患者完全缓解仅有1例,差异具有统计学意义(χ~2=3.950,P<0.05)。2组对比,对照组患者的疾病控制率远远低于实验组,差异具有统计学意义(χ~2=1.376,P<0.05);此外,实验组患者的生存时间明显长于对照组,差异具有统计学意义(P<0.05)。实验组患者主要的不良反应为皮疹和恶心呕吐。结论厄洛替尼联合全脑放疗治疗非小细胞肺癌脑转移,疗效显著,能够有效地控制脑转移病灶,提高患者客观有效率和生存率。     

Radiotherapy for Brain Metastases in Southern Thailand: Workload,Treatment Pattern and Survival

Purpose: To study the patient load, treatment pattern, survival outcome and its predictors in patients withbrain metastases treated by radiotherapy. Materials and Methods: Data for patients with brain metastasestreated by radiotherapy between 2003 and 2007 were collected from medical records, the hospital informationsystem database, and a population-based tumor registry database until death or at least 5 years after treatmentand retrospectively reviewed. Results: The number of treatments for brain metastases gradually increased from48 in 2003 to 107 in 2007, with more than 70% from lung and breast cancers. The majority were treated withwhole brain radiation of 30 Gy (3 Gy X 10 fractions) by cobalt-60 machine, using radiation alone. The overallmedian survival of the 418 patients was 3.9 months. Cohort analysis of relative survival after radiotherapy wasas follows: 52% at 3 months, 18% at 1 year and 3% at 5 years in males; and 66% at 3 months, 26% at 1 year and7% at 5 years in females. Multivariate analysis demonstrated that the patients treated with combined modalitieshad a better prognosis. Poor prognostic factors included primary cancer from the lung or gastrointestinal tract,emergency or urgent consultation, poor performance status (ECOG 3-4), and a hemoglobin level before treatmentof less than 10 g/dl. Conclusions: This study identified an increasing trend of patient load with brain metastases.Possible over-treatment and under-treatment were demonstrated with a wide range of survival results. Practicalprognostic scoring systems to assist in decision-making for optimal treatment of different patient groups isabsolutely necessary; it is a key strategy for balancing good quality of care and patient load.     

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.     

初诊脑转移癌全脑放射治疗现状与进展

脑转移癌是最常见的成人颅内肿瘤,采用积极治疗措施可以延长生存时间,提高生活质量。不同预后因素患者需选择个体化治疗模式。本文综述目前初诊脑转移癌全脑放射治疗现状与进展。全脑放疗联合手术或立体定向放疗的治疗模式在延长生存期、改善神经认知功能、提高生活质量方面显示出了很大优势,期望多学科综合治疗研究进展能进一步改善疗效。     

多发脑转移瘤放疗方式与预后

 目的 探讨多发脑转移瘤放疗方式与预后的关系。方法 112例多发脑转移瘤患者分别采用全脑照射、立体定向放射治疗以及全脑照射结合立体定向放射治疗，分析不同放疗方法的生存期及脑转移致死率。结果 全脑照射、立体定向放射治疗以及全脑照射结合立体定向放射治疗组的中位生存期分别为3．8、7．8及8．0个月。脑转移致死率全脑照射组67．7％，立体定向放射治疗组15．7％，全脑照射结合立体定向放射治疗组11．6％。结论 立体定向放射治疗可使脑转移灶较少的患者局控率提高，生存期延长。     

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.