放疗联合替莫唑胺治疗肺癌脑转移瘤的疗效观察

目的探讨放疗联合替莫唑胺治疗肺癌脑转移瘤的临床疗效和不良反应。方法选取2012年5月至2016年6月间山东省济南市中西医结合医院收治的63例肺癌脑转移患者,采用随机数表法分为治疗组(32例)和对照组(31例)。治疗组患者采用放疗加口服替莫唑胺治疗,对照组患者采用单纯放疗治疗,比较两组患者的临床疗效和不良反应。结果两组患者脑部主要症状改善率比较,放疗剂量30Gy时,治疗组患者有效率为84. 4%(27例),对照组为61. 3%(19例),差异有统计学意义(P <0. 05)。治疗结束时,治疗组患者主要脑部症状总改善率为96. 9%(31例),对照组为77. 4%(24例),差异有统计学意义(P <0. 05)。两组患者治疗后脑转移灶直径变化情况中各项治疗效果比较,差异均无统计学意义(均P> 0. 05)。治疗后,治疗组患者生活质量评分提高率为90. 6%(29例),对照组为64. 5%(20例),差异有统计学意义(P <0. 05)。治疗组患者主要不良反应为血液毒性反应,Ⅱ～Ⅲ级骨髓抑制率为43. 8%(14例);消化道反应率为40. 6%(13例),主要为恶心、呕吐等,但均为Ⅰ～Ⅱ级。治疗后1年,治疗组患者生存率为62. 5%(20例),对照组为35. 5%(11例),差异有统计学意义(P <0. 05)。治疗组患者1年生存率与脑转移灶多少和有无颅外转移等有一定关系,单发脑转移患者的1、2年生存率明显高于多发患者,差异有统计学意义(P <0. 05)。结论放疗联合替莫唑胺治疗肺癌脑转移瘤患者症状改善快且明显,有较好的近期疗效,不良反应可耐受。     

脑转移瘤的放射治疗

目的　探讨脑转移瘤的治疗。方法　 1990年 10月～ 1999年 1月我科共收治脑转移瘤 36例 ,2 6例采用60 Co外照射 ,先予常规分割全颅放疗中平面剂量 35～ 40Gy ,后缩野针对病灶 ,常规分割放疗 15～ 2 0Gy ,多发病灶不缩野。放疗时给予脱水治疗。结果　 2 6例完成放疗者 2 4例 ,其中半年生存率 5 4% ,1年生存率为 13 %。结论　对恶性肿瘤出现脑转移病人 ,积极治疗仍可取得较满意疗效。     

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.     

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，     

脑转移瘤调强放射治疗疗效观察

目的 探讨调强放射治疗脑转移瘤的疗效及毒副反应.方法 实施5野调强放射治疗脑转移肿瘤18例.根据预后分级评分(GPA)分级,Ⅲ级11例,Ⅳ级7例.全脑剂量(PTV-CTV)1.9～2.4 Gy/次,DT 36～42 Gy;脑转移灶(PTV-GTV)2.2～3.0 Gy/次,DT 40～56 Gy;均为5次/周;同步加量结束.95%的等剂量曲线包括靶区.放疗结束后行脑部MRI评价疗效.结果 CR 4例(22.2%),PR 12例(66.7%),SD 1例(5.6%),PD 1例(5.6%),有效率88.9%.1年生存率71.2%.主要毒副反应为骨髓抑制、恶心呕吐、脑水肿等.结论 调强放射治疗脑转移瘤有较好的疗效,毒副反应轻.     

替莫唑胺联合放射治疗治疗恶性脑胶质瘤的疗效观察

目的探讨替莫唑胺(TMZ)联合放射治疗治疗恶性脑胶质瘤的临床疗效和安全性评价。方法收集56例病理学诊断为恶性脑胶质瘤的患者,其中III级患者为32例,IV级患者为24例。根据不同的治疗方法将患者分为TMZ联合放疗(TMZ-RT)组(30例)和单纯放疗(RT)组(26例)。TMZ-RT组患者采用放疗联合TMZ化疗(75 mg·m-2·d-1)治疗6周,放疗后继续给予TMZ序贯/辅助(150²00 mg·m-2·d-1)化疗2200 mg·m-2·d-1)化疗2⁴周。RT组患者接受立体定向适形放射治疗1.84周。RT组患者接受立体定向适形放射治疗1.8³Gy/d,部分患者接受超分割放射治疗,总剂量为603Gy/d,部分患者接受超分割放射治疗,总剂量为60⁷5 Gy。治疗结束后评估两组患者的生存率和近期疗效。结果影像学结果显示,TMZ-RT组完全缓解8例,部分缓解9例,稳定10例,进展3例;RT组完全缓解6例,部分缓解8例,稳定8例,进展4例,两组差异无统计学意义(P>0.05)。TMZ-RT组患者的1、2、3年生存率分别为86.7%、80.0%和56.7%。RT组患者的1、2、3年生存率分别为73.1%、30.8%和11.5%,两组患者的2年和3年生存率比较,差异有统计学意义(P<0.05)。TMZRT组和RT组患者的中位复发时间分别为(23.1±8.7)个月和(15.8±8.9)个月,两组差异有统计学意义(P<0.05)。TMZ-RT组和RT组患者化疗后KPS评分别为(89.8±9.7)分和(65.4±10.3)分,两组间差异有统计学意义(P<0.05)。TMZ-RT组患者的不良反应发生率较低且,患者的生活质量水平显著高于RT组患者(P<0.05)。结论 TMZ联合放疗与单纯放疗治疗恶性脑胶质瘤的近期疗效相当,但TMZ联合放疗能够显著提高2年和3年的生存率并延缓复发时间。TMZ联合放疗治疗不良反应轻,安全性高,能够改善患者的生活质量,值得临床进一步推广。     

28例脑转移瘤放射治疗疗效分析

目的:探讨脑转移瘤放疗疗效及预后因素。方法:从2000年5月～2002年5月对28例脑转移瘤进行放射治疗。采用6MV-X线,两侧平行相对野作全脑照射,(1.8～2)Gy/次,(36～40)Gy后缩野针对转移灶加量(14～20)Gy。结果:影像学有效率64.3%。中位生存期5.6个月,6个月生存率46.4%,1年生存率21.4%。结论:影响预后的因素主要有:KPS评分、脑转移数目、颅外有无转移和原发灶是否控制。     

同期推量调强放疗联合替莫唑胺治疗脑转移瘤的疗效观察

摘 要：［目的］ 评价同期推量调强放疗（SIB-IMRT）联合替莫唑胺（TMZ）治疗脑转移瘤的临床有效性和安全性。［方法］ 采用同期推量调强放疗联合替莫唑胺治疗经原发灶病理诊断的脑转移瘤患者83例。全脑放疗30Gy/10F,同期脑转移灶推量调强放疗50Gy/10F,放疗第一天开始口服替莫唑胺75mg/(m2·d),连续14天,放疗结束后1个月继续予6个周期替莫唑胺辅助化疗,150mg/(m2·d),连用5天,28天为1个周期。［结果］ 近期有效缓解率（RR）为91.56%,中位生存期为14.38个月,1年总生存率为63.85%。对预后因素行单因素和多因素分析显示KPS评分及脑转移个数对总生存有影响（P<0.05）。Ⅰ度和Ⅱ度中性粒细胞下降的比例为56.63%,Ⅰ度血小板下降的比例为24.1%,Ⅰ度和Ⅱ度恶心呕吐的比例为72.29%,Ⅰ度和Ⅱ度头痛的比例为62.66%,无Ⅳ度不良反应。［结论］ 同期推量调强放疗联合替莫唑胺治疗脑转移瘤可延长生存时间,不良反应轻。但是,同期推量调强放疗联合替莫唑胺治疗脑转移瘤的治疗是否可以成为脑转移治疗的一种有效方法,还需进一步的临床随机对照试验证实。     

脑转移瘤的放射治疗

目的：探讨脑转移瘤的治疗。方法：1990年10月－1999年1月我科共收治脑转移瘤36例，26例采用^60Co外照射，先予常规分割全颅放疗中平面剂量35－40Gy，后缩野针对病灶，常规分割放疗15－20Gy，多发病灶不缩野。放疗时给予脱水治疗。结果：26例完成放疗者24例，其中半年生存率54％，1年生存率为13％。结论：对恶性肿瘤出现脑转移病人，积极治疗仍可取得较满意疗效。     

脑转移瘤放射治疗疗效及预后因素分析

目的：探讨脑转移瘤放疗疗效及预后因素。方法：从1997年6月－2000年10月对36例脑转移瘤进行放射治疗，采用6MV－X线，两侧平行相对野作全脑照射，1．8－3Gy／次，30－40Gy后缩野针对转移灶加量16－20Gy。结果：总的中位生存期为5．3个月，6个月生存率为44．4％（16／36），1年生存率为13．9％（5／36）。按RTOG脑转移瘤RPA预后分级，Ⅰ、Ⅱ和Ⅲ级中位生存期分别为10个月、5个月和2．8个月。I级中位生存期明显长于Ⅱ级（P＜0．05）和Ⅲ（P＜0．01）。结论：KPS、年龄、原发灶挖掘情况及颅外有无转移灶是脑转移患者的预后因素，RPA预后分级对脑转移瘤临床治疗有指导价值。     

全脑放疗联合替莫唑胺治疗肺癌脑转移疗效观察

目的:探讨全脑放疗（WBRT）联合替莫唑胺（TMZ）治疗非小细胞肺癌（NSCLC）脑转移的疗效。方法:回顾分析本院2010年-2014年收治的37例接受WBRT联合TMZ同步治疗及TMZ辅助治疗的NSCLC脑转移患者疗效。WBRT剂量30Gy,TMZ放疗同步口服75mg/(m2·d),序贯给予TMZ 150~200mg/(m2·d),连续5天,28天为1周期,3~6周期。结果:完全缓解10.8%(4/37),部分缓解40.5%(15/37)。中位无进展生存时间和中位生存时间分别为8和10个月。最常见不良反应恶心、呕吐,中性粒细胞减少和血小板减少的发生率分别为59.5%（22/37）,32.4%（12/37）,35.1%（13/37）。结论:WBRT联合TMZ同步治疗及TMZ辅助化疗治疗NSCLC脑转移癌安全有效,耐受性良好,不良反应轻,可作为脑转移癌放化疗综合治疗模式之一进行深入研究。     

Radio-chemo-immunotherapy (CCNU plus Levamisole) for treatment of metastatic brain tumors

Summary Thirty-one patients with metastatic brain tumors were treated with Radiotherapy (RT) and CCNU or with RT, CCNU and Levamisole (LMS) in a randomized clinical trial. Twenty-seven were evaluable. All patients were submitted to whole brain radiation (50 ± 5 Gy) and CCNU (130 mg/ m² p. o. every 8 weeks). 15 also received Levamisole (2.5 mg/ kg p.o. daily for 3 weeks in the first month, for 2 weeks in the second, and then once a week monthly until progression). Primary tumor was predominantly lung cancer (22/27) and brain lesions were generally multiple (24/27). The overall response rate was 35% in the RT plus CCNU treated group and 38% in the RT plus CCNU plus LMS treated group. The median survival time was similar and not statistically different in both groups (7 versus 6 months). No important side effects were observed either in the RT + CCNU or in the RT + CCNU + LMS treated groups. The absence of combined depression of T-cell levels and responsiveness of lymphocytes to mitogens suggests that thymus dependent immunity could be improved by LMS administration. However, such improvement had no impact on duration of survival in patients with metastatic brain tumors.     

Whole brain irradiation and temozolomide based chemotherapy in melanoma brain metastases

Introduction Whole brain irradiation (WBRT) remains a recommended treatment for patients with brain metastases from malignant melanoma in terms of symptom palliation, especially when extracranial systemic disease is present. Temozolomide (TMZ) has shown efficacy in the treatment of metastatic melanoma. The objective was to evaluate the potential benefit in survival of two different schedules of total dose and fractionation (20 Gy/5 fractions vs 30 Gy/10 fractions) and further TMZ based chemotherapy. Materials and method We have conducted a retrospective study in a group of twenty-one patients (RTOG Recursive Partitioning Analysis class II) of the use of WBRT with 20 Gy/5 fractions (n=11) and 30 Gy/10 fractions (n=10). All patients received further TMZ based chemotherapy administered as a single chemotherapeutic agent or in combination with chemo-immunotherapy. Results Prognostic variables such as: age, Karnofsky performance status, extracranial metastases and number of brain metastases, were analyzed in both groups of treatment without statistically significant differences. The median survival time (MST) for WBRT 20 Gy group was 4 months (CI 95%: range 2–6 months) and for WBRT 30 Gy group was 4 months (CI 95%: range 0–7 months) without statistically significant differences (Log rank p=0.74). There was one complete response and two partial responses. Conclusions The results suggest that MST was not significantly affected by the total dose/fractionation schedule.     

3-D conformal radiotherapy with concomitant and adjuvant temozolomide for patients with glioblastoma multiforme and evaluation of prognostic factors

Background

The aim of the retrospective study was to evaluate the outcome and prognostic factors of newly diagnosed glioblastoma patients who received 3-D conformal radiotherapy (RT) combined with concomitant and/or adjuvant temozalamide (TMZ) postoperatively.

Patients and methods

Fifty patients with glioblastoma multiforme were treated with 3-D conformal RT combined with concomitant and/or adjuvant TMZ postoperatively. Median age was 57 years (range, 12–79) and median Karnofsky performance status (KPS) was 70 (range, 40–100). A multivariate Cox regression model was used to test the effect of age, sex, KPS, extent of surgery, tumour dimension (<5cm vs. ≥5cm), full dose RT (≥60 Gy vs. <60 Gy), concurrent TMZ and adjuvant TMZ treatment (adjuvant therapy plus 6 cycles of TMZ group versus <6 cycles of TMZ group) on the overall survival.

Results

The median follow up time was 10 months (range 3–42). One- and 2-year overall survival rates were 46% and 20%, respectively. The prognostic factors important for the overall survival were a full dose RT (≥60 Gy) (p=0.005) and the application of adjuvant TMZ for 6 cycles (p=0.009).

Conclusions

The results of our study confirm the efficiency of RT plus concomitant and adjuvant TMZ, with an acceptable toxicity in patients. We suggest that at least 6 cycles of adjuvant TMZ should be administered to obtain a benefit from the adjuvant treatment.     

放疗联合替莫唑胺与单纯放疗治疗脑转移瘤的临床对比观察

目的:观察放疗联合替莫唑胺与单纯放疗治疗脑转移瘤的临床疗效。方法:选取2010年5月-2013年5月94例脑转移瘤患者为研究对象,以住院号单双分成2组,对照组予单纯放疗治疗,观察组在对照组基础上联合替莫唑胺治疗,观察两组疗效。结果:对照组缓解率34.04%,总有效率72.34%;观察组缓解率55.31%,总有效率85.10%,两组比较差异有统计学意义（P<0.05）。生活质量对照组改善率27.66%、总有效率74.47%,观察组改善率44.68%、总有效率87.23%,两组比较差异有统计学意义（P<0.05）。两组在白细胞减少、血小板减少、肝肾功能损害、恶心呕吐、腹泻、口腔黏膜炎发生率和程度上比较差异有统计学意义（P<0.05）。结论:放疗联合替莫唑胺治疗脑转移瘤临床疗效显著,不良反应可耐受。     

Sensitivity to temozolomide in brain tumor initiating cells

Molecular alterations in glioblastoma have the potential to guide treatment. Here, we explore the relationship between temozolomide (TMZ) response and O⁶-methylguanine DNA methyltransferase (MGMT) status in brain tumor initiating cells (BTICs). Methylation, expression, and sensitivity were assessed in 20 lines; associations were evaluated by Fisher''s exact test. Some BTICs were sensitive. Sensitivity to TMZ was only associated with protein expression (P = .001). There were atypical BTICs including TMZ-resistant lines in which the methylation-specific PCR reaction revealed both methylated and unmethylated bands. BTICs are not uniformly resistant to TMZ; some are sensitive. MGMT status does not predict TMZ response with high precision.     

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.     

贝伐珠单抗注射液联合替莫唑胺同步放疗治疗脑转移的疗效及安全性

目的:探讨贝伐珠单抗注射液联合替莫唑胺同步放疗治疗脑转移的疗效及安全性。方法:于2016年01月至2018年06月,将我院救治的60例脑转移患者纳入研究,按照随机数字表法将患者随机分为两组,30例每组。对照组实施替莫唑胺同步放疗,观察组实施贝伐珠单抗注射液联合替莫唑胺同步放疗,比较两组患者的临床总有效率、癌因性疼痛评分、癌因性疲乏评分、生存质量评分、不良反应发生率、远期存活率。结果:观察组患者临床总有效率为70.00%,高于对照组的43.33%（P<0.05）。治疗后3个月、6个月,观察组患者癌因性疼痛评分、癌因性疲乏评分均低于对照组（P<0.05）,观察组患者生存质量评分高于对照组（P<0.05）。观察组患者恶心呕吐、骨髓抑制、贫血、脱发、白细胞减少、血小板减少等不良反应发生率与对照组比较,差异均无统计学意义（P>0.05）。随访2年,观察组患者1年存活率、2年存活率均高于对照组（P<0.05）。结论:在替莫唑胺同步放疗基础上应用贝伐珠单抗注射液,可提高脑转移患者的近期疗效,有效控制病情,减轻癌因性疼痛和疲乏症状,有利于提高患者生存质量和远期存活率,且不良反应未增加,安全性良好。     

Phase 2 trial of temozolomide using protracted low-dose and whole-brain radiotherapy for nonsmall cell lung cancer and breast cancer patients with brain metastases

BACKGROUND.

Temozolomide (TMZ), an oral methylating imidazotetrazinone, has antitumor activity against gliomas, malignant melanomas, and brain metastasis and is presently administered as a 5‐day oral schedule every 4 weeks.

METHODS.

A single‐institution phase 2 clinical trial was conducted to determine the efficacy and the safety profile of a new regimen based on a dose‐intensified, protracted course of TMZ after whole‐brain radiotherapy (WBRT). Patients were eligible if they had at least 1 bidimensionally measurable brain metastasis from breast cancer and nonsmall cell lung cancer (NSCLC). Twenty‐seven patients were treated with 30 grays (Gy) of WBRT with concomitant TMZ (75 mg/m²/day) for 10 days, and subsequent TMZ at a dose of 75 mg/m² per day for 21 days every 4 weeks, for up to 12 cycles.

RESULTS.

Two complete responses (7.4%) and 11 partial responses (40.7%) were achieved. The schedule appeared to be well tolerated, with grade 3 toxicity (graded according to National Cancer Institute Common Toxicity Criteria) observed in only 2 patients. The overall median survival was 8.8 months and the median progression‐free survival was 6 months.

CONCLUSIONS.

The concomitant use of WBRT and protracted low‐dose TMZ appears to be an active, well‐tolerated regimen. The observed antitumor activity suggests the need for further investigation of this schedule in combination with other anticancer agents for the concomitant treatment of brain metastases and primary cancers. Cancer 2008. © 2008 American Cancer Society.