编者按：一些研究者开始对在传统治疗中被作为脑转移治疗基础的全脑放疗（WBRT）提出了质疑。《肿瘤瞭望》采访了英国伦敦皇家马斯登医院、利物浦大学放射肿瘤学教授Michael Brada教授，Brada教授在5月30日做主题报道“放疗和局部管理对于肺癌脑转移和软脑膜疾病的作用（Radiation and Localized Management of Brain Metastases and Leptomeningeal Disease）”。
在“放疗和局部管理对于肺癌脑转移和软脑膜疾病的作用”的报告中，Brada教授介绍了非小细胞肺癌（NSCLC）脑转移管理策略、基于证据的放疗治疗策略、全身治疗联合放疗的策略。
NSCLC脑转移应该如何管理？
调查显示①单纯化疗：15%；②化疗&脑部放疗（SRS或任何形式的放疗）：58%；③化疗&脑部和肺部放疗：15%；④单纯放疗（脑部和肺部）：8%；⑤监测&症状管理：3%。
Brada教授引用了QUARTZ UK NCRI随机临床试验的初步研究结果，即OSC+WBRT 与单纯OSC组的生存和Qol无显著差异。Lim SH等人对98例患者进行分析，结果显示相比初始化疗（upfront chemotherapy），立体定位放射手术（SRS）后续化疗的方案并不能提高寡脑转移瘤（oligo-brain metastases）NSCLC患者的OS（Lim et al. 2015 Annals of Oncology. 2015;26(4):762-768.）。
如何选择脑转移放疗策略？
调查显示①无：0%；②WBRT：14% ；③SRS：69%；④SRS & WBRT：17%。研究显示相比单纯WBRT治疗，WBRT+ SRS治疗单个无法手术脑转移在局部PFS和OS上有优势(Andrew et al. 2004 Lancet 363 1665-72）。RTOG 9508研究发现WBRT联合 SRS获益患者主要是单发脑转移患者（6.5个月 vs. 4.9个月，P=0.039）; EORTC 22952-26001研究显示1~3个脑转移瘤手术或放射外科治疗后的辅助WBRT能降低颅内复发率和颅内肿瘤病灶进展致死率，但未能提高生存时间。Chang EL的研究显示，1~3个脑转移灶的患者，SRS治疗增加WBRT治疗可显著降低患者认知和记忆能力（Chang et al. 2009 Lancet Oncol， 10:1037-44）。
NSCLC脑转移治疗总结——基于证据
单发脑转移：SRS 或仅手术治疗（增加WBRT无临床获益）；
寡转移（2-3）：WBRT/WFRT 或SRS（SRS后WBRT治疗，或WBRT后SRS无临床获益）；
多发性脑转移：WBRT（SRS治疗，或WBRT后增加SRS治疗无临床获益）。
联合哪种全身治疗药物可增加放疗有效？
调查显示①替莫唑胺（TMZ）：17%；②厄洛替尼：15%；③贝伐珠单抗：21%；④其他：3%；⑤无：44%。研究显示WBRT & TMZ 相比WBRT，可能提高了即期疗效，提高了局部控制率，但没有显著提高患者生存期[Verger et al. 2005 Int J Radiat Oncol Biol Phys. 61（1）:185-191.]。 RTOG0320——WBRT+SRS对比WBRT+SRS联合替莫唑胺或厄洛替尼治疗1～3个脑转移的NSCLⅢ期临床试验，结果显示加用这两种药物没有增加患者的生存期，反而增加了放疗毒副反应的发生机率。全脑放疗联合莫特沙芬钆（motexafin gadolinium，MGd）的Ⅲ期临床试验，证实加用MGd未显著改善生存（Mehta MP， et al 2003 J Clin Oncol， 21(13):2529-2536）。
报告结束后《肿瘤瞭望》记者对Brada教授进行了采访。
Oncology Frontier: Would you please introduce the effective options to controlbrain metastases in lung cancer?
《肿瘤瞭望》：请您介绍能有效控制肺癌脑转移的治疗方式？
Dr Brada: When we are talking about the treatment of brain metastases， we need to distinguish whether they are synchronous brain metastases from the beginning of the patient’s journey at diagnosis or at the time of recurrent or end-stage disease. In the past， there used to be a single treatment option， which was whole-brain irradiation. Now， there are many systemic treatments and different forms of radiation. I am very much aware that systemic treatment is playing an increasing role and certainly in patients who have chemo-responsive disease or disease responsive to targeted agents， the presence of brain metastases should not single them out for a different treatment. They should receive primary treatment with systemic therapy. The only question that remains is when they respond whether they should also receive adjuvant radiotherapy most commonly in the form of whole-brain irradiation， because， as shown in a number of studies， the control rate in the brain is limited.
Brada教授：治疗脑转移瘤时，要考虑其为肺癌确诊时伴有的同步脑转移瘤，还是复发疾病或疾病终末期的脑转移瘤。过去二者的治疗方式相同——全脑放疗。现在，治疗选项包括多种全身治疗方式和不同形式的放疗。全身治疗正发挥着越来越重要的作用，特别是化疗反应型或靶向药物反应型的患者，脑转移瘤的存在并不意味着患者应另选择一种不同的治疗，而是应以全身治疗为主要治疗。关键问题是，这类患者在全身治疗有反应时是否应加上辅助放疗（通常是全脑放疗），因为多项研究显示脑转移控制率较低。
Oncology Frontier: What’s the role of radiation and localized management of brain metastases and leptomeningeal disease in lung cancer patients?
《肿瘤瞭望》：放疗和局部管理对于肺癌脑转移和软脑膜疾病的作用？
Dr Brada: Radiotherapy remains very important and an essential treatment in patients with lung cancer and brain metastases. It has little or limited role in patients with leptomeningeal disease. It is an effective palliative treatment， both in improving function and survival in good prognosis patients. It is usually used in conjunction with other therapies. The changes that have happened over the last decade or so are the introduction of more localized forms of radiation. This includes more focal radiation using conventional radiotherapies， either wide-field or localized therapy where there are only one or two lesions， or the use of radiosurgery using single large doses of radiation for individual lesions. The evidence that exists at present is that radiosurgery is of value in terms of survival only in patients with single brain metastases. In patients with two or three lesions， radiosurgery is equivalent to the use of whole-brain radiotherapy in terms of survival and disease control. I think the issue as to whether there is a difference in toxicity remains unanswered. The only other new information regarding radiation is that in patients who develop brain metastases at the end of life with poor prognosis， there was a trial presented at this meeting showing that the use of radiation does not prolong survival or quality of life so systemic and supportive care is probably best.
Brada教授：对于肺癌患者和脑转移患者，放射治疗仍然非常重要，但对软脑膜病变效果有限。放疗是一种有效的姑息性治疗，可改善预后良好患者的功能和生存期，放疗通常与其他疗法联合使用。在过去十年中增加了许多局部放疗的方式。目前有证据表明，立体定向放射手术（SRS）治疗单个病灶的脑转移有改善生存的价值；当患者有2~3个脑转移病灶时，SRS与全脑放疗在生存和疾病控制方面效果相当，但还不知道二者的毒性差异。对于发生脑转移、预后不良的生命终末期患者，2015 ASCO会议上一项试验显示，全脑放疗不能显著改善患者生存和生活质量（如下所示）。因此患者最好的选择可能是全身治疗和支持治疗。
Oncology Frontier: Can whole-brain radiotherapy for metastases boost survival?
《肿瘤瞭望》：脑转移患者全脑放疗能否延长生存？
Dr Brada: That’s a very good question and the answer is that it is not known. There has not been a trial that compares whole-brain radiotherapy and without whole-brain radiotherapy in asymptomatic patients. So we don’t have an answer， but the belief is that it prolongs survival. But we don’t have any evidence from a randomized trial.
Brada教授：这是一个很好的问题，答案是不知道。目前还没有针对无症状患者的全脑放疗vs.无全脑放疗的试验。我们相信全脑放疗能延长生存期，只是没有随机试验的证据。