肺癌脑转移的治疗进展

脑是肺癌常见的远处转移部位之一,脑转移是导致治疗失败的主要原因.随着肺癌发病率的上升,先进影像设备的使用、优化的系统治疗延长了总的生存期,肺癌脑转移的发生率呈现明显增高趋势[1].     

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。     

Surgical Treatment of Single Brain Metastases from Non-Small-Cell Lung Cancer

We analyzed the results of surgical treatment of 50 patients with brain metastases from non-small-cell lung cancer who underwent craniotomy between the years 1978 through 1983. The onset of brain metastases was synchronous in 14 patients, occurred within 1 year of treatment of the primary tumor in 21 patients, and after 1 year in 15 patients. A total of 28 patients had undergone curative resection of the lung tumor; 15 patients had undergone palliative resection with or without radioactive implants, and 7 patients did not undergo surgical treatment of their primary tumor. At time of craniotomy, 31 patients were considered to have disease limited to the central nervous system. Following surgery, 34 patients received radiation therapy (30 whole brain radiation, 4 focal radiation); 15 patients had previously undergone whole brain radiation (“radiation failures”), and there was 1 postoperative death. The overall median survival in this series was 18 months. Favorable prognostic variables included (a) curative resection of the primary tumor (median 28 months), (b) disease limited to the central nervous system (median 24 months), and (c) negative mediastinal nodes at time of thoracotomy (median 28 months). The incidence of local recurrence of intracranial tumor at the original site was higher in those patients who had failed previous radiation (53%) compared to those who received postoperative radiation (12%). Although the overall degree of neurological palliation was 75%, patients who had failed radiation were less successfully palliated, and the majority continued to require steroid therapy following tumor resection. These results suggest that patients with single brain metastases from non-small-cell lung cancer who have undergone curative resection of their primary tumor have considerable potential for long-term survival, and surgical resection prior to radiation should be considered. Even in symptomatic patients with controlled or limited extracranial disease, such treatment provides rapid effective neurological palliation and can be accomplished currently with minimal mortality and morbidity.     

肺癌脑转移的预防和治疗

本文对肺癌脑转移的预防和治疗进行了较系统的文献复习，并结合笔者近年来的临床实践，作一归纳性叙述。     

非小细胞肺癌脑转移治疗的研究进展

约30%~50%的非小细胞肺癌患者在疾病过程中发生脑转移。随着治疗手段的不断发展,患者的生存期得到明显改善。目前的治疗方法主要有手术、放疗、化疗和靶向药物治疗。虽然治疗方法众多,但如何针对不同患者制定最佳治疗方案,仍需要不断深入研究和总结。全文就近几年非小细胞肺癌脑转移治疗的研究进展作一综述。     

非小细胞肺癌脑转移治疗进展

脑是非小细胞肺癌常见的转移部位,手术和放疗是以往脑转移治疗的基石,但近年来随着对肿瘤发生发展机制的认识深化,靶向治疗在脑转移治疗中开始崭露头角。本文主要针对一些相关热点问题如脑转移治疗手段等（手术、放疗、化疗、靶向治疗）进行简要述评。     

Teniposide Sometimes Effective in Brain Metastases from Non-small Cell Lung Cancer

In a prospective study we have treated 13 patients with brain metastases from non-small cell lung cancer with intravenous teniposide, at a dose of 150mg/m2 on days 1, 3 and 5 given every 3 weeks on an out-patient basis. Six of the 13 patients had previously been treated for brain metastases by surgery and/or radiotherapy. Seven patients experienced neurological improvement. Objective response was obtained in 3 patients (23%) (2 PR, 1 CR), and stabilization in 5 patients. Duration of response in the 3 patients with objective response was 16 weeks, 40 weeks and 80 weeks, respectively. In 2 of these patients extracranial disease responded also to teniposide therapy. Although toxicity of teniposide therapy was relatively mild, there was one patient who died as a consequence of leukopenic sepsis. The results demonstrate that teniposide has some activity in de novo as well as recurrent brain metastases from non-small cell lung cancer.     

ALK阳性非小细胞肺癌脑转移患者的治疗

背景与目的间变性淋巴瘤激酶（anaplastic lymphoma kinase, ALK）阳性非小细胞肺癌（non-small cell lung cancer, NSCLC）是肺癌的一个重要亚型。ALK阳性NSCLC脑转移患者的治疗尚无标准模式。方法本研究对我院2013年3月-2016年3月期间确诊的ALK阳性NSCLC脑转移患者的临床资料和治疗情况进行回顾性分析,探讨不同治疗模式患者的转归。结果84例晚期ALK阳性NSCLC患者中,22例初诊时有脑转移,剔除3例合并表皮生长因子受体（epidermal growth factor receptor, EGFR）双突变患者,共19例纳入分析。中位颅内疾病进展时间（progression-free survival, PFS）为12.0个月,一线脑部局部治疗（P=0.021）及一线克唑替尼治疗（P=0.030）可延长PFS;一线克唑替尼联合脑部局部治疗的中位颅内PFS为27.0个月,而单纯克唑替尼治疗的PFS仅为4.2个月。结论一线克唑替尼联合脑部局部治疗有助于延长ALK阳性晚期NSCLC患者的颅内PFS,因例数少,尚有待大样本多中心前瞻性临床研究证实。     

Treatment of Breast Cancer Brain Metastases

Approximately 10% to 15% of women with metastatic breast cancer will develop brain metastases. Treatment options for these women remain limited, particularly at the time of central nervous system (CNS) relapse following completion of initial CNS-directed therapy. Historically, prior studies have broadly examined systemic treatments for breast cancer brain metastases with mixed, but overall disappointing, results. More recently, studies have increasingly selected patients based on breast cancer subtype and have examined novel, targeted agents that have preclinical suggestion of blood–brain barrier penetration. Correlative science objectives, with both tissue-based and novel imaging endpoints, are more frequently incorporated into trials of this nature, with the goal of enhancing our understanding of possible predictors of response. This review summarizes the current and emerging data on systemic therapy for breast cancer brain metastases and provides a framework for future directions in treating this clinically-challenging entity.     

Emerging Trends in the Management of Brain Metastases from Non-small Cell Lung Cancer

Purpose of Review

To summarize current approaches in the management of brain metastases from non-small cell lung cancer (NSCLC).

Recent Findings

Local treatment has evolved from whole-brain radiotherapy (WBRT) to increasing use of stereotactic radiosurgery (SRS) alone for patients with limited (1–4) brain metastases. Trials have established post-operative SRS as an alternative to adjuvant WBRT following resection of brain metastases. Second-generation TKIs for ALK rearranged NSCLC have demonstrated improved CNS penetration and activity. Current brain metastasis trials are focused on reducing cognitive toxicity: hippocampal sparing WBRT, SRS for 5–15 metastases, pre-operative SRS, and use of systemic targeted agents or immunotherapy.

Summary

The role for radiotherapy in the management of brain metastases is becoming better defined with local treatment shifting from WBRT to SRS alone for limited brain metastases and post-operative SRS for resected metastases. Further trials are warranted to define the optimal integration of newer systemic agents with local therapies.

     

甲状腺癌脑转移诊断及治疗的研究进展

摘 要：甲状腺癌是常见的内分泌肿瘤,针对甲状腺癌的发病机制及治疗方案越来越成熟,但由于甲状腺癌脑转移发病率很低,临床上对于甲状腺癌脑转移患者的诊断和治疗仍很局限。全文就甲状腺癌脑转移患者的临床表现、影像学特点、分子遗传学特点及治疗手段等研究进展进行综述。     

肺癌心脏转移瘤的临床诊治现状

提高肺癌心脏转移的诊治水平,对肺癌心脏转移的临床资料进行了分析,发现心脏恶性转移瘤主要来自肺癌,肺癌直接侵犯心脏或心脏转移,已成为部分肺癌患者突发死亡的主要原因。     

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.     

肺癌脑转移治疗研究进展

肺癌是中国发病率和死亡率最高的恶性肿瘤,而且在疾病发展过程中易发生脑转移,严重影响患者的生存质量以及生存期。肺癌脑转移的治疗方法包括外科手术、化疗、全脑放射治疗、立体定向放射外科治疗、分子靶向治疗、免疫治疗以及抗血管生成治疗等。对于不同患者如何选择合理且有效的治疗方案是目前研究的热点之一。本文将对肺癌脑转移治疗相关研究进展进行综述,以期为肺癌脑转移患者选择更合理的临床治疗方案提供参考。     

尼莫司汀配合全脑放疗治疗35例肺癌多发性脑转移的临床观察

背景与目的：肺癌脑转移的临床预后较差,本研究观察尼莫司汀配合放疗治疗肺癌多发性脑转移的疗效及不良反应。方法：35例肺癌多发脑转移患者。放疗后使用尼莫司汀单药化疗。全脑放疗为DT1．8～2Cy／次。5次,周,总剂量36～40Gy。尼莫司汀化疗平均剂量125mg/次,每4～6周重复,所有患者使用2～3次。治疗期间注意血常规及肝肾功能变化情况,并给予脱水、支持对症治疗。在放疗结束后3个月复查脑MR／,观察肿瘤大小,并统计1年生存情况。结果：所有病例在治疗期间无颅内、外病灶进展病例,28例伴有神经症状者均得到缓解。放疗结束后3个月单纯颅内病灶评价：其中CR5例,PR26例,SD4例,PD0例。颅内病灶有效率（CR＋PR）为88．6％（31／35）。一年生存率为45．7％（16／35）,中位生存期9．3个月。不良反应主要是脑充血水肿以及尼莫司汀化疗反应,多为Ⅰ、Ⅱ度,无Ⅳ度不良反应。结论：尼莫司汀配合放疗治疗肺癌多发性脑转移的疗效好,不良反应轻,远期效果尚需进一步观察。     

Treatment of Bone Metastases in Breast Cancer: an Update

Bone is the most common site of breast cancer metastases. When breast cancer has metastasized to bone, it is considered an incurable disease. Osseous metastases are associated with significant morbidities including pain, pathological fractures, hypercalcemia of malignancy, and spinal cord compression. In this setting, the palliative goals of care include preventing skeletal related events, managing complications, reducing bone pain, and improving quality of life. Antiresorptive agents such as bisphosphonates have been the mainstay of bone-directed treatment, along with radiation therapy, and surgery. Most recently, RANKL-inhibitors have become another tool in the treatment of bone metastases. This review discusses bone-modifying agents and other targeted interventions in breast cancer patients with skeletal metastases.     

X刀治疗肺癌脑转移39例疗效分析

目的评价X刀治疗肺癌脑转移瘤的效果并分析其预后因素。方法回顾性分析1994年2月-2002年11月在巴黎Tenon医院放疗科行X刀治疗的肺癌脑转移患者39例，共有转移灶49个，其中13例患者在行X刀前或后接受了全脑放疗（WBRT）。计算患者的生存期及局控率，并对潜在预后因素分别进行单因素和多因素分析。结果39例患者总体局控率和1年局控率分别为95．5％和95．0％，中位生存期为14个月。KPS〉70分、年龄≤60岁是独立的预后因素。结论X刀是肺癌脑转移的有效治疗方式，多种因素影响其预后。