Chemotherapy for brain metastases in small-cell lung cancer

PURPOSE: Brain metastasis occurs commonly in patients with small-cell lung cancer (SCLC). Herein, we report the efficacy of irinotecan and carboplatin in the treatment of brain metastases from SCLC. In addition, we review the existing data on chemotherapy for brain metastases in SCLC. PATIENTS AND METHODS: Eighty patients with metastatic or relapsed SCLC were enrolled in a phase II trial of irinotecan and carboplatin. Patients naive to chemotherapy were treated with irinotecan 200 mg/m2 and carboplatin AUC of 5, and patients previously treated with chemotherapy received irinotecan 150 mg/m2 and carboplatin AUC of 5, every 21 days for 6 cycles. RESULTS: Among the 80 patients, 15 (19%) presented with brain metastases. An analysis of 14 assessable patients with brain metastases revealed an overall response rate of 65% after 2 cycles of chemotherapy and a median survival of 6 months (range, 1-24 months). Upon review of the literature, 8 studies were identified as having > 10 patients who received chemotherapy for brain metastases from SCLC. Based on these studies, the response rate of brain metastases from SCLC to a variety of chemotherapy and median survival of patients ranged from 22% to 85% and 3 months to 9 months, respectively. CONCLUSION: Chemotherapy, including the regimen of irinotecan and carboplatin, is an effective treatment for SCLC brain metastases.     

Pronostic factors of synchronous brain metastases from lung cancer

BACKGROUND: The prognosis of brain metastases (BM) from lung cancer is poor. The management of lung cancer with BM is not clear. This retrospective study attempts to determine their prognostic factors, and to better define the role of different treatments. METHODS: We reviewed the clinical characteristics of 271 consecutive patients with synchronous brain metastases (SBM) from lung cancer (small-cell lung cancers and non-small-cell lung cancers), collected between January 1985 and May 1993. Data were available for all patients as well as follow-up information on all patients through to death. Patients had all undergone heterogeneous treatments. Each physician had chosen the appropriate treatment after collegiate discussion. Survival curves were compared using the log-rank test in univariate analysis, and Cox's Regression model in multivariate analysis. Statistical significance was defined as P<0.05. RESULTS: 249 patients were assessable. Treatments included: neurosurgical resection in 56 cases, brain irradiation in 87 cases, and chemotherapy in 126 cases. Median overall survival time from the date of histological diagnosis of SBM was 103 days (range, 1-1699). In multivariate analysis, prognostic factors for longer overall survival times were: absence of adrenal metastases (P=0.007), neurosurgical resection (P=0.028), chemotherapy (P=0.032) and brain irradiation (P=0.008). Moreover, risk factors of intracranial hypertension as cause of death were number of SBM and absence of neurosurgical resection. CONCLUSIONS: These results and others suggest that patients with SBM from lung cancer be considered for carcinologic treatment, and not only for best supportive care. However, further studies are necessary to evaluate quality of life with or without carcinologic treatment.     

化疗与放射外科结合治疗非小细胞肺癌脑转移

目的 探讨化疗与放射外科结合治疗非小细胞肺癌脑转移的效果。方法 对24例非小细胞肺癌脑转移患者进行了放射外科治疗加全身化疗的前瞻性临床观察。结果 （1）神经系统症状改善率为87．0％；（2）脑部病灶治疗客观有效率为58．3％；（3）X刀治疗后3－6个月随访期内脑部出现新病灶占70．8％；（4）中位存活时间10个月（3－34个月）；（5）1年生存率为37．5％。结论 （1）化疗与放射外科结合治疗肺癌脑转移可能是一种较为有效的疗法，且毒副作用可以接受；（2）此疗法未能有效地控制脑转移新病灶与复发。     

Chemotherapy for brain metastases of lung cancer: A review

In lung cancer patients brain metastases develop with a high frequency. For years radiotherapy has been the standard treatment for these patients. Here we review the experience with chemotherapy for brain metastases in lung cancer patients. The concept of the brain as pharmacological sanctuary site when brain metastases are present is challenged and it is argued that chemotherapy does play a role in this situation. Recent clinical trials indicate that the combination of chemotherapy and radiotherapy may become the standard treatment for lung cancer patients with brain metastases. It is unclear whether for micrometastatic disease to the brain, blood brain barrier function is of importance for the outcome of chemotherapy in lung cancer patients with respect to the development of overt brain metastases. Areas of improvement of delivery of cytotoxic agents to the brain when brain metastases have not yet developed are discussed.     

非小细胞肺癌脑转移综合治疗的疗效分析

目的:探讨非小细胞肺癌(NSCLC)脑转移不同治疗方法的疗效分析及预后因素.方法:回顾性分析2001-01-2006-06我科治疗的71例NSCLC脑转移患者,14例行手术+放疗±化疗,26例行单纯放疗,31例行放疗+化疗.42例行全脑放疗土局部加量,29例行全脑放疗+三维适形调强放疗.全部病例定期随访直至死亡,分别行单因素和多因素分析.结果:全组中位生存期为10个月,1、2和3年生存率分别为29.58%(21/71)、16.90%(12/71)和8.45%(6/71).单因素分析显示,KPS评分、病理类型、脑转移数目、脑转移大小、原发灶控制、中枢外转移、治疗方法、放疗剂量、放疗方式和近期疗效对生存期有影响.多因素分析显示,KPS评分、脑转移数目、原发灶控制、中枢外转移和近期疗效是独立的生存预后因素.结论:NSCLC脑转移的主要预后因素是KPS评分、脑转移数目、原发灶控制、中枢外转移、近期疗效.积极治疗可适当延长生存期.     

非小细胞肺癌伴单发脑转移瘤的外科治疗

目的 探讨非小细胞肺癌伴单发脑转移瘤的外科治疗及预后.方法 回顾我院1991年1月至2002年1月收治的56例非小细胞肺癌伴单发脑转移瘤患者临床资料,脑转移瘤伽马刀治疗后均行肺癌根治术,术后常规化疗和全脑放疗,并评估疗效.结果 本组患者均无严重手术并发症,1年生存率为73.5%(36/49),3年34.7%(17/49),5年16.3%(8/49),中位生存期20.5个月.结论 非小细胞肺癌伴单发脑转移瘤外科治疗可以延长患者的生存期和提高治疗效果.     

Chemotherapy and the treatment of brain metastases

Brain metastases have traditionally been treated with a surgical or radiotherapeutic approach. Chemotherapy is used occasionally as salvage therapy. The blood-brain barrier excludes most chemotherapeutic agents, rendering many systemic options ineffective within the CNS. Intrathecal chemotherapies do not penetrate into brain tissue or bulky parenchymal tumors, so are ineffective in treatment of brain metastases. However, some patients with brain metastases benefit from chemotherapy, and temozolomide or targeted therapies like gefitinib have demonstrated activity. A better understanding of the biological behavior of brain metastases may lead to development of effective treatments for this common complication of systemic cancer. The review discusses the biology of brain metastases and provides an update on current chemotherapeutic strategies.     

Recombinant human endostatin combined with radiotherapy in the treatment of brain metastases of non-small cell lung cancer

Objective

Since brain metastases (BM) is often accompanied by edema, and endostatin (ES) can prevent tumor tissue edema, we investigated the therapeutic effects of ES combined with radiotherapy in the treatment of BM of NSCLC. We also determined the patients who are suitable for this therapy.

Methods

Eighty patients with BM of NSCLC were randomly divided into combination group and radiotherapy alone group. The primary endpoint was overall response rate, and secondary endpoints were overall survival time, cerebral edema index and adverse reactions. These were observed and the expressions of vascular endothelial growth factor receptor 2 (VEGFR₂) protein and KDR gene in primary lesions were detected with immunohistochemical method and fluorescence in situ hybridization.

Results

Compared with radiotherapy alone, brain edema was significantly reduced in the ES group (P = 0.003) without marked adverse reactions. For the overall response rate, there was no statistical significant difference between the two groups (control, 90 % vs. ES, 75 %, P = 0.07), but there was statistical significance in the patients with positive VEGFR₂ (93 vs. 67.7 %, P = 0.012) or positive KDR gene (94.4 vs. 47.3 %, P = 0.002). In overall survival time, there was no statistical significance in the two groups (P = 0.35), in the tumors with positive VEGFR₂ (P = 0.109) or with positive KDR gene (P = 0.147).

Conclusion

Compared with radiotherapy alone, ES combined with radiotherapy can reduce brain edema in NSCLC patients with BM and obtain better short-term response rate in tumors with positive VEGFR₂ or positive KDR gene, but does not improve the overall survival.     

Chemotherapy for breast cancer brain metastases

Breast cancer is the second most common cause of brain metastases, and 10-15% of patients develop clinically overt central nervous system disease. Radiotherapy is the standard treatment for patients with brain metastases. Surgical resection should be considered in patients with isolated brain metastasis and no extracranial disease. The role of chemotherapy in breast cancer brain metastases is not clearly defined; the results of the 8 trials found in the literature are reported. Most experience has been gained with the CMF (cyclophosphamide, methotrexate and fluorouracil) and PE (cisplatin and etoposide) regimens; here the median survival of 6 months is similar to radiotherapy. The blood-brain barrier, maintained by tight endothelial junctions and active transport mechanisms, is a major reason for the lower activity of most chemotherapeutic agents compared to other sites of metastatic disease. Most substances with good penetration of the blood-brain barrier have limited activity against breast cancer and some of the most active substances in breast cancer - including doxorubicine, the taxanes and trastuzumab - appear not to reach the central nervous system in sufficient concentrations. Approaches to overcome the blood-brain barrier are still experimental, and more research is clearly needed to identify chemotherapeutic agents both active in breast cancer and with good penetration of the blood-brain barrier. With the exception of patients with resectable brain metastases, danger of cranial herniation or poor general condition, chemotherapy should be offered to breast cancer patients with brain metastases that have progressive extracranial metastatic disease or relapse after radiotherapy.     

SIMULTANEOUS THORACO－CRANIAL OPERATION FOR THE TREATMENT OF LUNG CANCER WITH BRAIN METASTASES

ＳＩＭＵＬＴＡＮＥＯＵＳＴＨＯＲＡＣＯ－ＣＲＡＮＩＡＬＯＰＥＲＡＴＩＯＮＦＯＲＴＨＥＴＲＥＡＴＭＥＮＴＯＦＬＵＮＧＣＡＮＣＥＲＷＩＴＨＢＲＡＩＮＭＥＴＡＳＴＡＳＥＳＣｈｅｎＪｉａｎ陈建；ＬｉｕＤａｏｋｕｎ刘道坤；ＬｉｕＪｕｎｈｕａ刘俊华；ＳｈｉＺｈｏ...     

非小细胞肺癌脑转移治疗的研究进展

肺癌是全球范围内发病率和死亡率最高的恶性肿瘤,非小细胞肺癌（non-small cell lung cancer,NSCLC）约占肺癌的80%,其中超过40%的晚期NSCLC患者在疾病病程中会发生脑转移,导致预后不良。传统的治疗方法如单纯放疗,化疗,外科手术对于改善肺癌脑转移的预后非常有限。近些年来随着立体定向放射治疗、靶向治疗的发展,尤其是化疗联合靶向,放疗联合靶向等交叉领域的联合治疗,NSCLC脑转移患者的生存质量得到提高,中位总生存期（median overall survival,mOS）得以延长。然而对于NSCLC脑转移的最佳治疗方案,仍然存在争议,本文将针对NSCLC脑转移领域的最新研究进展进行阐述,以期对肺癌脑转移患者选择合理治疗方案提供理论依据。      

Update in the treatment of brain metastases from lung cancer

Brain metastases from lung cancer represent a prevalent and challenging clinical dilemma. The brain is an extremely common site of failure for non-small-cell lung cancer and small-cell lung cancer, often as a solitary site of disease. Despite steady research developments during recent years, survival rates remain poor. Some research suggests that the outcomes and characteristics of brain metastases that result from lung cancer primary sites are perhaps different than those from other primary sites. Clinical treatment strategies should therefore be adjusted accordingly. This article reviews the clinical characteristics, prognostic factors, and treatment strategies of brain metastases from lung cancer with a particular emphasis on recent research developments in the field.     

厄洛替尼辅助全脑放疗治疗肺癌脑转移的临床疗效

目的探讨厄洛替尼辅助全脑放疗治疗肺癌脑转移的临床效果。方法选取2011年1月至2014年10月间接受治疗的72例肺癌脑转移患者,其中小细胞肺癌32例,腺癌24例,鳞癌16例。所有患者均给予常规支持治疗,如减轻颅内水肿等。在此基础上进行全脑放疗治疗以及厄洛替尼辅助治疗,分析2个月后患者的临床治疗效果。结果 72例患者部分缓解52例,疾病稳定20例,临床获益率为100.0%,临床有效率为72.2%。其中,小细胞肺癌的临床有效率为68.8%,腺癌临床有效率为75.0%,鳞癌临床有效率为75.0%。36例患者治疗后出现皮疹30例(41.7%),腹泻30例(41.7%),乏力64例(88.9%),脱发16例(22.2%),粒细胞降低6例(8.3%)。结论厄洛替尼辅助全脑放疗治疗肺癌脑转移疗效较为显著,可有效改善患者临床症状、延长患者生存期,且安全性较好,在临床上值得推广。     

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。     

非小细胞肺癌脑转移的放射治疗--附32例报告

收集 1995年 6月～ 2 0 0 2年 6月非小细胞肺癌 (non smallcelllungcancer ,NSCLC)脑转移住院患者 3 2例 ,采用放疗或放疗加化疗等综合性治疗 (颅内转移病灶采用全颅二侧野对穿照射 ,中线剂量 :3 0～ 40Gy/15～ 2 0次 ,后缩野追加肿瘤量 16～ 2 0Gy/8～ 10次 ,同时给EP、NP等方案化疗的综合方法治疗 )观察其疗效。初步研究结果提示 ,所有患者在顺利完成治疗后 ,平均存活期达 7个月。肺癌脑转移采用放疗、化疗的综合治疗 ,可延长生存时间 ,提高生存质量     

Pulmonary resection in patients with nonsmall-cell lung cancer treated with gamma-knife radiosurgery for synchronous brain metastases

BACKGROUND: The aim of the current study was to determine whether a pulmonary resection and gamma-knife radiosurgery (GKRS) protocol is superior to GKRS alone in selected patients with stage IV nonsmall-cell lung cancer (NSCLC). METHODS: The authors performed a retrospective case-control study of 232 consecutive patients with newly diagnosed NSCLC from January 1998 to December 2005 and screened them to identify a study cohort in which all patients had thoracic stage I or II, Karnofsky performance status >or= 70, no extracranial metastases, and 1-3 synchronous brain metastases of less than 3 cm, and were treated with GKRS (n=31). The study cohort was divided into 2 groups, those with and without concomitant pulmonary resection. RESULTS: Sixteen patients with pulmonary resection were assigned to the treatment group and 15 without pulmonary resection were assigned to the control group. Median follow-up was 27.3 months (range, 4.4 months to 90.9 months). Mean survivals for the treatment group and the control group were 64.9 and 18.1 months, respectively (P< .001). There was a statistically significant association between pulmonary resection and better survival (OR=78.408). One-year and 5-year local brain tumor control rates were 97.1% and 93.5%, respectively. CONCLUSIONS: The pulmonary resection and GKRS protocol could prolong survival in patients with thoracic stage I or II NSCLC, no extracranial metastases, and a limited number of small synchronous brain metastases.     

全脑适形调强放疗同步加量治疗脑转移瘤疗效分析

目的探讨全脑适形调强放疗（IMRT）同步加量治疗脑转移瘤的剂量学优势、患者依从性、疗效和预后因素。方法回顾性分析41例脑转移瘤患者临床资料,均经增强脑CT或磁共振成像（MRI）证实为脑转移,均接受全脑IMRT同步加量,大体肿瘤体积（GTV）（影像学可见的脑转移灶）：DT4994～6990cGy／22—30次,每4．4—6．0周;全脑：DT3990～5000cGy／22～30次,每4．4—6．0周。结果中位随访时间6．4个月。41例患者均完成整个放疗过程,其中完全及部分缓解27例,未控11例,其余3例无治疗后影像资料对照,缓解情况不详。总有效率、中位生存时间、1年生存率分别为65．8％、8个月、24．4％。脑干、脊髓、左晶体、右晶体、左视神经、右视神经、视交叉接受的最高剂量平均值分别为48．7、32．4、7．3、7．0、40．2、39．5、47．1Gy,均在安全剂量范围之内,仅21例发生放射性脑水肿,其余未出现早期及晚期放射性不良反应。结论脑转移瘤接受全脑IMRT同步加量可使靶区剂量分布均匀,有效保护脑干和其他重要器官,患者治疗依从性高,可作为脑转移瘤患者的一种有效治疗方法。     

康莱特注射液配合化疗治疗晚期非小细胞肺癌的临床观察

目的比较康莱特注射液加化疗与单独化疗治疗晚期非小细胞肺癌患者的疗效和毒副反应。方法将288例经病理组织学确诊的晚期非小细胞肺癌患者分成2组,每组144例。治疗组：NP方案（诺维本＋顺铂）＋康莱特注射液200 mL,每天1次,连用20天;对照组：单用NP方案。完成2周期后作疗效评价。结果治疗组有效率44.4%,对照组33.3%,两组差异无统计学意义（P〉0.05）。治疗组血液毒副反应和消化道反应低于对照组,两组差异有统计学意义（P〈0.05）。生活质量评分治疗组高于对照组,两组间差异有统计学意义（P〈0.01）。治疗组化疗后较化疗前比较,CD 3比例略有上升,CD 4和CD 4/CD 8明显上升,CD 8明显下降（均P〈0.05）。结论康莱特注射液与化疗联合治疗晚期非小细胞肺癌可降低化疗对患者的毒副反应,提高细胞免疫功能,改善患者的生活质量。     

Preoperative prognosis of the outcome of the surgical treatment of patients for lung cancer metastases to the brain

Quantitative analysis of patients' history, catamnesis, clinical and X-ray data formed the basis for a statistically reliable evaluation of the significance of each factor or symptom in making prognosis for surgical treatment of patients with lung cancer metastases into the brain. Such data provide a rationale for admission of such cases to neurosurgical wards.     

全脑放疗联合化疗在非小细胞肺癌脑转移中的应用

目的探讨全脑放疗联合化疗在非小细胞肺癌脑转移中的应用。方法选取2011年1月至2014年12月间临清市人民医院收治的120例非小细胞肺癌脑转移患者作为研究对象,按照入院顺序,将2011年1月至2012年12月间入院的60例患者分为对照组,将2013年1月至2014年12月间入院的60例患者分为观察组。观察组患者用全脑放疗联合替莫唑胺治疗,对照组患者用全脑放疗。治疗后3个月比较两组患者的近期疗效,统计两组患者的无进展生存期(PFS)和1年生存率,并比较两组患者的不良反应发生情况。结果观察组患者的客观缓解率为91.7%,对照组为51.7%,差异有统计学意义(P<0.05),两组患者PFS的差异无统计学意义(P>0.05),观察组患者的1年生存率明显高于对照组,差异有统计学意义(P<0.05),两组患者不良反应发生情况的差异无统计学意义(P>0.05)。结论全脑放疗联合替莫唑胺治疗非小细胞肺癌脑转移具有疗效好,生存率高且不良反应未增加等优势,适合临床推广应用。