非小细胞肺癌的放射治疗NCCN指南2017第3版

NCCN Guidelines Version 3.2017
NCCN指南2017第3版

Non-Small Cell Lung Cancer
非小细胞肺癌山东省肿瘤医院呼吸肿瘤内科张品良

Discussion
讨论

Treatment Approaches
治疗手段

Radiation Therapy

放疗

General Principles

一般原则

Target Volumes, Prescription Doses, and Normal Tissue Dose Constraints

靶区、处方剂量和正常组织的剂量限制

Radiation Simulation, Planning, and Delivery

放疗模拟、计划和交付

Stereotactic Ablative Radiotherapy

立体定向放疗

Whole Brain RT and Stereotactic Radiosurgery

全脑放疗和立体定向放射外科

Radiation Therapy
放疗

The Principles of Radiation Therapy in the NSCLC algorithm include the following: 1) general principles for early-stage, locally advanced, and advanced NSCLC; 2) target volumes, prescription doses, and normal tissue dose constraints for early-stage, locally advanced, and advanced NSCLC; and 3) RT simulation, planning, and delivery. These RT principles are summarized in this section. Whole brain RT and stereotactic radiosurgery (SRS) for brain metastases are also discussed in this section. The abbreviations for RT are defined in the NSCLC algorithm (see Table 1 in Principles of Radiation Therapy in the NCCN Guidelines for NSCLC).
在非小细胞肺癌工作步骤中放疗原则包括：1）早期、局部晚期、晚期非小细胞肺癌的一般原则；2）早期、局部晚期、晚期非小细胞肺癌的靶体积、处方剂量和正常组织剂量限制；和3）放疗的模拟、计划和交付。本节总结了放疗的这些原则。本节中还讨论了脑转移瘤的全脑放疗和立体定向放射外科（SRS）。放疗缩写在非小细胞肺癌工作步骤中明确说明（见非小细胞肺癌NCCN指南放射治疗原则中的表1）。

General Principles
一般原则

Treatment recommendations should be made by a multidisciplinary team. Because RT has a potential role in all stages of NSCLC, as either definitive or palliative therapy, input from board-certified radiation oncologists who perform lung cancer RT as a prominent part of their practice should be part of the multidisciplinary evaluation or discussion for all patients with NSCLC. Uses of RT for NSCLC include: 1) definitive therapy for locally advanced NSCLC, generally combined with chemotherapy; 2) definitive therapy for early-stage NSCLC in patients with contraindications for surgery; 3) preoperative or postoperative therapy for selected patients treated with surgery; 4) therapy for limited recurrences and metastases; and/or 5) palliative therapy for patients with incurable NSCLC. The goals of RT are to maximize tumor control and to minimize treatment toxicity. Advanced technologies such as 4D-conformal RT simulation, intensity-modulated RT/volumetric modulated arc therapy (IMRT/VMAT), image-guided RT, motion management strategies, and proton therapy have been shown to reduce toxicity and increase survival in nonrandomized trials. CT-planned 3D-conformal RT is now considered to be the minimum standard.
治疗建议应该由一个多学科协作组制定。由于放疗在各期非小细胞肺癌中都有潜在作用，无论是根治性还是姑息治疗，对于所有的非小细胞肺癌患者，由肺癌放疗作为其临床实践主要工作的认证放射肿瘤学家应该是多学科评估或讨论的成员。非小细胞肺癌放疗的应用包括：1）局部晚期非小细胞肺癌的根治性治疗，一般与化疗联合；2）有手术禁忌症的早期非小细胞肺癌患者的根治性治疗；3）选择性的手术治疗患者的术前或术后治疗；4）局部复发和转移的治疗；与/或5）不能治愈的非小细胞肺癌患者的姑息性治疗。放疗的目的是肿瘤控制最大化，同时使治疗毒性最小化。先进技术如4D-仿真适形放疗、调强放疗/旋转容积调强放疗（IMRT/VMAT）、图像引导放疗、运动管理策略以及质子治疗在非随机试验中均已证明能降低毒性且改善生存。目前认为CT计划的三维适形放疗是最低标准。

Definitive RT, particularly SABR, is recommended for patients with early-stage NSCLC (ie, stage I-II, N0) who are medically inoperable or those who refuse surgery (see Stereotactic Ablative Radiotherapy in this Discussion). Interventional radiology ablation is an option for selected patients who are medically inoperable. By extrapolation from surgical data, adjuvant chemotherapy (category 2B) may be considered after definitive RT/SABR in patients with high-risk factors for recurrence (eg, large tumors >4 cm in size). SABR is also an option for patients at high surgical risk who cannot tolerate a lobectomy (eg, major medical comorbidity or severely limited lung function). However, resection is recommended for patients with early-stage NSCLC who are medically fit (see Principles of Surgical Therapy in the NCCN Guidelines for NSCLC). Definitive chemoradiation is recommended for patients with stage II to III disease who are not appropriate surgical candidates. Involved-field RT (also known as involved-field irradiation or IFI) is an option for treating nodal disease in patients with locally advanced NSCLC; IFI may offer advantages over elective nodal irradiation (ENI). For patients with advanced lung cancer (ie, stage IV) with extensive metastases, systemic therapy is recommended; palliative RT can be used for symptom relief and potentially for prophylaxis at primary or distant sites. Shorter courses of palliative RT are preferred for patients with symptomatic chest disease who have poor PS and/or shorter life expectancy (eg, 17 Gy in 8.5 Gy fractions) (see Table 4 in the Principles of Radiation Therapy in the NCCN Guidelines for NSCLC). Higher dose and longer course thoracic RT (eg, ≥30 Gy in 10 fractions) are associated with modestly improved survival and symptoms, especially in patients with good PS. The RT recommendations for patients with stages I to IV are described in the NSCLC algorithm (see Principles of Radiation Therapy in the NCCN Guidelines for NSCLC).
根治性放疗，尤其是立体定向消融放疗，推荐用于因内科因素不能手术或拒绝手术的早期非小细胞肺癌患者（即，Ⅰ-ⅡN0期）（见本讨论中的立体定向消融放疗）。对于选择的因内科因素不能手术的患者介入放射消融治疗是一种选择。根据手术数据推断，在复发高危因素（如>4cm的大肿瘤）的患者中，在根治性放疗/立体定向消融放疗后可以考虑辅助化疗（2B类）。对于手术风险高不能耐受肺叶切除（如重大并存疾病或肺功能严重受限）的患者，立体定向消融放疗也是一个选择。然而，对于无禁忌症的早期非小细胞肺癌患者推荐切除（见非小细胞肺癌NCCN指南中的外科治疗原则）。对于不适合手术的Ⅱ-Ⅲ期患者推荐根治性化放疗。累及野放疗（即累及野照射或IFI）是局部晚期非小细胞肺癌患者淋巴结病变治疗的一种选择；累及野照射可能优于选择性淋巴结照射（ENI）。对于广泛转移的晚期肺癌（即Ⅳ期）患者，建议全身治疗；姑息性放疗可用于缓解原发灶或远隔部位症状。对于有胸部疾病症状、一般情况差和/或预期寿命较短的患者，首选短疗程姑息性放疗（如17Gy每次分割8.5Gy）（见非小细胞肺癌NCCN指南放射治疗原则中的表4）。更高剂量和较长疗程的胸部放疗（如≥30Gy/10f）可适度改善症状与生存，尤其是在一般情况良好的患者中。对于Ⅰ-Ⅳ期患者的放疗建议，在非小细胞肺癌工作步骤中描述（见非小细胞肺癌NCCN指南中的放射治疗原则）。

The indications for using preoperative or postoperative chemoradiation or RT alone are described in the NSCLC algorithm (see Principles of Radiation Therapy in the NCCN Guidelines for NSCLC). In patients with clinical stage I or II NSCLC who are upstaged to N2+ after surgery, postoperative chemotherapy can be administered followed by postoperative RT (also known as PORT) depending on the margin status (see Adjuvant Treatment in the NCCN Guidelines for NSCLC). For clinical stage III NSCLC, definitive concurrent chemoradiation is recommended (category 1). However, the optimal management of patients with potentially operable stage IIIA NSCLC is controversial and is discussed in detail in the algorithm (see Principles of Surgical Therapy in the NCCN Guidelines for NSCLC). For patients undergoing preoperative therapy before surgical resection of stage IIIA NSCLC, some oncologists prefer chemotherapy alone rather than chemoradiotherapy for the preoperative treatment; RT should generally be given postoperatively if not given preoperatively. The NCCN Panel recommends a preoperative RT dose of 45 to 54 Gy based on a recent study. NCCN Member Institutions are evenly split in their use of neoadjuvant chemotherapy versus neoadjuvant chemoradiation in patients with stage IIIA N2 NSCLC. Similarly, some consider the need for pneumonectomy to be a contraindication to a combined modality surgical approach given the excess mortality observed in clinical trials, but NCCN Member Institutions are split on this practice as well.
术前或术后放化疗或单纯放疗的适应症在非小细胞肺癌工作步骤中描述（见非小细胞肺癌NCCN指南中的放射治疗原则）。临床Ⅰ或Ⅱ期术后分期升至N2 +的非小细胞肺癌患者，可给予术后化疗然后术后放疗（也称为PORT）取决于切缘情况（见非小细胞肺癌NCCN指南中的辅助治疗）。对于临床Ⅲ期非小细胞肺癌，推荐根治性同步放化疗（1类）。不过，潜在可手术的ⅢA期非小细胞肺癌患者的最佳治疗是有争议的，在工作步骤中详细讨论（见非小细胞肺癌NCCN指南中的外科治疗原则）。对于手术切除前接受术前治疗的ⅢA期非小细胞肺癌患者，对于术前治疗，一些肿瘤学家倾向于单纯化疗而不是放化疗；如果术前未给予放疗，术后一般应给予放疗。基于最近一项研究，NCCN小组推荐术前放疗剂量45-54 Gy。在ⅢA N2 非小细胞肺癌患者中，均有NCCN成员机构使用新辅助化疗与新辅助放化疗。同样，全肺切除需要考虑联合手术径路的某些禁忌症，在临床试验中观察到死亡率过高，但NCCN成员机构中对该做法也有分歧。

Surgery is associated with potentially greater risk of complications, particularly stump breakdown and bronchopleural fistula, in a field that has had high-dose RT (eg, 60 Gy). Thus, surgeons are often wary of resection in areas that have previously received RT doses of more than 45 to 50 Gy, especially patients who have received definitive doses of concurrent chemoradiation (ie, ≥60 Gy) preoperatively. Soft tissue flap coverage and reduced intraoperative fluid administration and ventilator pressures can reduce the risk of these complications. When giving preoperative RT to less than definitive doses (eg, 45 Gy), one should be prepared up front to continue to a full definitive dose of RT without interruption if the patient does not proceed to surgery for some reason. For these reasons, when considering trimodality therapy, the treatment plan—including assessment for resectability and the type of resection—should be decided before initiation of any therapy.
手术与潜在的并发症风险更大有关，尤其是在已接受高剂量放疗（如60Gy）的野内残端破裂和支气管胸膜瘘。因此，外科医生往往对既往接受放疗剂量超过45-50Gy区域的切除术小心谨慎，尤其是术前接受根治剂量（即≥60 Gy）同步放化疗的患者。软组织皮片覆盖以及减少术中液体和呼吸机压力，可以降低这些并发症的风险。当术前放疗给予小于根治剂量（如45Gy）时，如果患者因某些原因未进行手术，应准事先备好继续完整无中断的根治性放疗。由于这些原因，当考虑三联疗法时，治疗方案——包括评估可切除性和切除类型——应该在任何治疗开始前决定。

Target Volumes, Prescription Doses, and Normal Tissue Dose Constraints
靶区、处方剂量和正常组织的剂量限制

The dose recommendations for preoperative, postoperative, definitive, and palliative RT are described in the Principles of Radiation Therapy in the NSCLC algorithm (see Table 4 in the NCCN Guidelines for NSCLC). After surgery, lung tolerance to RT is much less than for patients with intact lungs. Although the dose volume constraints for conventionally fractionated RT for normal lungs are a useful guide (see Table 5 in Principles of Radiation Therapy in the NCCN Guidelines for NSCLC), more conservative constraints should be used for postoperative RT. For the 2017 update (Version 1), the NCCN Panel noted that the doses and constraints provided in the tables are useful reference doses that have been commonly used or are from previous clinical trials rather than specific prescriptive recommendations.
术前、术后、根治性和姑息性放疗的推荐剂量，在非小细胞肺癌工作步骤的放射治疗原则中描述（见非小细胞肺癌NCCN指南中的表4）。术后，肺对放疗的耐受性远不如有完整肺的患者。尽管常规分割放疗正常肺剂量体积限制是一个有用的指导（见非小细胞肺癌NCCN指南放射治疗原则中的表5），但是，对于术后放疗使用应更加谨慎。2017第1版更新，NCCN 小组指出，表中提供的剂量与限制是已常规或既往临床试验使用的有用的参考剂量，而不是具体的规范性推荐。

For definitive RT, the commonly prescribed dose is 60 to 70 Gy in 2 Gy fractions over 6 to 7 weeks. The use of higher RT doses is discussed in the NSCLC algorithm (see Principles of Radiation Therapy in the NCCN Guidelines for NSCLC). Doses more than 74 Gy are not currently recommended for routine use. Results from a phase 3 randomized trial (RTOG 0617) suggest that high-dose radiation using 74 Gy with concurrent chemotherapy does not improve survival, and might be harmful, when compared with a standard dose of 60 Gy. Although optimal RT dose intensification remains a valid question, at higher RT doses, normal tissue constraints become even more important. Although the RT dose to the heart was decreased in the RTOG 0617 trial, survival was decreased; thus, more stringent constraints may be appropriate.
根治性放疗常用处方剂量是60-70Gy，2Gy/f，6-7周。在非小细胞肺癌工作步骤中讨论了使用更高放疗剂量（见非小细胞肺癌NCCN指南中的放射治疗原则）。超过74 Gy的剂量目前不推荐常规使用。一项3期随机试验（RTOG 0617）的结果表明，与60Gy的标准剂量相比，使用74Gy高剂量放疗同步化疗并不能改善生存，甚至可能有害。尽管最佳的强化放疗剂量仍然是一个悬而未决的问题，但是，在更高的放疗剂量时，正常组织的限制变得更加重要。在RTOG 0617试验中，尽管降低了心脏的放疗剂量，但生存仍缩短；因此，更严格的限制可能是合适的。

Reports 50, 62, and 83 from the International Commission on Radiation Units and Measurements provide a formalism for defining RT target volumes based on grossly visible disease, potential microscopic extension, and margins for target motion and daily positioning uncertainty (see Figure 1 in Principles of Radiation Therapy in the NCCN Guidelines for NSCLC); the ACR Practice Parameters and Technical Standards are also a helpful reference. It is essential to evaluate the dose volume histogram (DVH) of critical structures and to limit the doses to the organs at risk (such as spinal cord, lungs, heart, esophagus, and brachial plexus) to minimize normal tissue toxicity (see Table 5 in Principles of Radiation Therapy). These constraints are mainly empirical and have for the most part not been validated rigorously. However, the QUANTEC review provides the most comprehensive estimates from clinical data of dose-response relationships for normal tissue complications.As previously mentioned, for patients receiving postoperative RT, stricter DVH parameters should be considered for the lungs.
基于肉眼可见病变、潜在微扩散和靶体运动边界以及每日摆位误差，国际辐射单位与测量委员会的50、62和83报告提供了根治性放疗靶区体系（见非小细胞肺癌NCCN指南中的放射治疗原则图1）；美国放射学会实践参数和技术标准也是一个有用的参考。必须对关键结构和剂量限制危险器官（如脊髓、肺、心脏、食管以及臂丛）的剂量体积直方图（DVH）进行评估，以最大程度降低正常组织的毒性（见放射治疗原则中的表5）。这些限制主要是经验性的，并且大都未经过严格验证。不过，QUANTEC对正常组织并发症的量-效关系的临床数据的回顾提供了最全面的评价。如前所述，接受术后放疗的患者，应该更严格考虑肺的剂量体积直方图（DVH）参数。

Radiation Simulation, Planning, and Delivery
放疗模拟、计划和交付

Treatment planning should be based on CT scans obtained in the treatment position. Intravenous contrast CT scans are recommended for better target delineation whenever possible, especially in patients with central tumors or nodal involvement. FDG PET/CT can significantly improve target delineation accuracy, especially when there is atelectasis or contraindications to intravenous CT contrast. In the NSCLC algorithm, recommendations are provided for patients receiving chemoradiation (including those with compromised lung or cardiac function), photon beams, or IMRT (see Radiation Therapy Simulation, Planning, and Delivery in the Principles of Radiation Therapy in the NCCN Guidelines for NSCLC). Respiratory motion should be managed. The report from the AAPM Task Group 76 is a useful reference for implementing a broad range of motion management strategies as described in the NSCLC algorithm (see Radiation Therapy Simulation, Planning, and Delivery in the NCCN Guidelines for NSCLC).
治疗计划应根据CT扫描获得的治疗位置。为更好地勾画靶区，只要有可能，推荐静脉强化CT扫描，尤其是中心型肿瘤或淋巴结受累的患者。FDG PET / CT可以显著提高靶区勾画的准确性，尤其是有肺不张或有静脉CT造影禁忌症时。对于接受放化疗（包括肺或心脏功能受损者）、光子束或调强放疗的患者，在非小细胞肺癌工作步骤中提供了建议（见非小细胞肺癌NCCN指南放射治疗原则中的放疗模拟、计划和交付）。应控制呼吸运动。非小细胞肺癌工作步骤中描述运动范围大的实施管理策略，AAPM工作组76号报告是一个有用的参考（见非小细胞肺癌NCCN指南中的放射治疗模拟、计划和交付）。

Stereotactic Ablative Radiotherapy
立体定向放疗

SABR (also known as SBRT) uses short courses of very conformal and dose-intensive RT precisely delivered to limited-size targets. Studies, including prospective multi-institutional trials, have demonstrated the efficacy of SABR for patients with inoperable stage I NSCLC or for those who refuse surgery. With conventionally fractionated RT, 3-year survival is only about 20% to 35% in these patients, with local failure rates of about 40% to 60%. In prospective clinical trials, local control and overall survival appear to be considerably increased with SABR, generally more than 85% and about 60% at 3 years (median survival, 4 years), respectively, in patients who are medically inoperable. Substantially higher survival has been observed in patients with potentially operable disease who are treated with SABR; survival is comparable in population-based comparisons to surgical outcomes, but locoregional recurrences are more frequent. It has not been shown that use of SABR for medically operable patients provides long-term outcomes equivalent to surgery. Late recurrences have been reported more than 5 years after SABR, highlighting the need for careful surveillance. If possible, biopsy should confirm NSCLC before use of SABR.
立体定向消融（SABR）（也称为立体定向放疗[SBRT]）对尺寸有限的靶点使用非常适形且剂量密集的短程精确放疗。一些研究，包括前瞻性多中心试验，已证实了立体定向消融（SABR）治疗不能手术或拒绝手术的Ⅰ期非小细胞肺癌患者的疗效。与常规分割放疗相比，在这些患者中，3年生存率大约只有20%-35%，局部失败率约40%-60%。在前瞻性临床试验中，在因内科因素不能手术的患者中，立体定向消融（SABR）似乎大大提高局部控制率和总生存率，通常在85%以上，3年生存率大约60%（中位生存期4年）。已观察到在用立体定向消融（SABR）治疗的潜在可手术的患者中生存率显著更高；以人群为基础，与手术相比，生存相似，但局部区域复发更常见。对于医学上可手术的患者，尚未证明立体定向消融（SABR）的远期结局与手术相当。已报告在立体定向消融（SABR）5年以后晚期复发，因此需要严密监测。如有可能，在使用立体定向消融（SABR）前应活检证实非小细胞肺癌。

SABR is recommended in the NSCLC algorithm for patients with stage I and II (T1-3,N0,M0) NSCLC who are medically inoperable; SABR is a reasonable alternative to surgery for patients with potentially operable disease who are high risk, elderly, or refuse surgery after appropriate consultation (see the NCCN Guidelines for NSCLC). A combined analysis of 2 randomized trials (that did not complete accrual) assessed SABR compared with lobectomy in operable patients. The analysis does not alter the fact that surgical resection is recommended and typically used for operable patients, but it helps to confirm the indication of SABR for patients with contraindications for surgery or those who refuse surgery. SABR can also be used for patients with limited lung metastases or limited metastases to other body sites. After SABR, assessment of recurrences by imaging can be challenging because of benign inflammatory/fibrotic changes that can remain FDG-PET avid for 2 or more years after treatment, emphasizing the importance of follow-up by a team with experience interpreting such post-treatment effects. This careful follow-up is particularly relevant, because selected patients with localized recurrences after SABR may benefit from surgery or re-treatment with SABR.
在非小细胞肺癌工作步骤中，立体定向消融（SABR）推荐用于因内科因素不能手术的I期和Ⅱ期（T1-3N0M0）非小细胞肺癌患者；对于高危、老年或在恰当协商后拒绝手术的潜在可手术患者，立体定向消融（SABR）是一个合理的手术替代治疗（见非小细胞肺癌NCCN指南）。一项2个随机试验的联合分析（非完全累加）评估了在可手术患者中立体定向消融（SABR）与叶切除术。该分析并未改变推荐手术切除和通常用于可手术的患者这一事实，但对于有手术禁忌症或拒绝手术的患者有助于证实立体定向消融（SABR）的适应症。立体定向消融（SABR）也可用于局限肺转移或身体其他部位局限转移的患者。立体定向消融（SABR）后，通过影像学评估复发可能具有挑战性，因为良性炎症/纤维化改变，治疗后2年或以上FDG-PET仍高代谢，因此强调能够解释这种治疗后影响的有经验的团队随访的重要性。这种情况下细致的随访尤其有意义，因为选择性的在立体定向消融（SABR）后局部复发患者，可能从手术或再次立体定向消融（SABR）治疗中获益。

SABR fractionation regimens and a limited subset of historically used maximum dose constraints are provided in the NSCLC algorithm (see Tables 2 and 3 in the Principles of Radiation Therapy in the NCCN Guidelines for NSCLC). These dose constraints are point of reference doses and are not intended to be prescriptive; they are used commonly or have been used in clinical trials. Although none of these dose constraints have been validated as maximally tolerated doses, outcomes of clinical trials to date suggest that they are safe constraints. The bronchial tree, esophagus, and brachial plexus are critical structures for SABR. For centrally located tumors—those within 2 cm in all directions of any mediastinal critical structure including the bronchial tree, esophagus, heart, brachial plexus, major vessels, spinal cord, phrenic nerve, and recurrent laryngeal nerve—regimens of 54 to 60 Gy in 3 fractions are not safe and should be avoided; 4 to 10 fraction SABR regimens appear to be effective and safe (see Principles of Radiation Therapy in the NCCN Guidelines for NSCLC). Preliminary results (RTOG 0813) suggest that 5-fraction regimens are safe. SRS or SABR for limited oligometastases to the brain or other body sites, respectively, may be useful for patients with good PS and thoracic disease that can be treated with definitive therapy (see Stage IV, M1b: Limited Sites in the NCCN Guidelines for NSCLC). Local therapy combined with targeted therapy is a category 2A recommendation for patients with ALK or ROS1 rearrangements or sensitizing EGFR mutations. Decisions about whether to recommend SABR should be based on multidisciplinary discussion. Hypofractionated or dose-intensified conventional 3D-conformal RT is an option if an established SABR program is not available. Current nonrandomized clinical data indicate that local tumor control with SABR is higher than with interventional radiology ablation techniques. However, interventional radiology ablation may be appropriate for selected patients for whom local control is not necessarily the highest priority.
在非小细胞肺癌工作步骤中提供了立体定向消融（SABR）分割方案和有限的历史上使用最大剂量限制的亚组（见非小细胞肺癌NCCN指南放射治疗原则中的表2和表3）。这些剂量限制指的是参考剂量，并不打算指定；这些剂量已普遍使用或已在临床试验中使用。虽然这些剂量限制没有一个已被验证为最大耐受剂量，但临床试验结果表明，这是安全的限制。支气管树、食管、臂丛是立体定向消融（SABR）的关键结构。对于位于中央的肿瘤——在各个方向2cm内的任何纵隔危险结构包括支气管树、食管、心脏、臂丛神经、大血管、脊髓、膈神经和喉返神经——54-60Gy/3f方案是不安全的，应该避免；4-10分割的立体定向消融（SABR）方案似乎是安全有效的（见非小细胞肺癌NCCN指南中的放射治疗原则）。初步结果（RTOG 0813）提示5分割方案是安全的。对于脑或身体其他部位的局限性寡转移，立体放射外科（SRS）或立体定向消融（SABR）对于一般情况好且胸部病变可根治性治疗的患者可能是有用的（见非小细胞肺癌NCCN指南中的Ⅳ期M1b部位局限）。对于ALK或ROS1重排或敏感EGFR突变的患者，局部治疗联合靶向治疗是一个2A类推荐。决定是否推荐立体定向消融（SABR）应该根据多学科讨论。如果确定立体定向消融（SABR）计划不可用，大分割或加大剂量的传统三维适形放疗是一种选择。目前的非随机临床资料表明，立体定向消融（SABR）的肿瘤局部控制高于介入消融技术。不过，对于选择的局部控制不是必须首选的患者，介入放射学消融可能是适当的。

Whole Brain RT and Stereotactic Radiosurgery
全脑放疗和立体定向放射外科

Many patients with NSCLC have brain metastases (30%–50%), which substantially affect their quality of life. For the 2017 update (Version 1), the NCCN Panel revised the recommendations for treatment of limited brain metastases by decreasing recommendations for whole brain RT. Options for treatment of limited brain metastases now include 1) SRS alone; and 2) surgical resection for selected patients followed by SRS or whole brain RT; selected patients include those with symptomatic metastases or whose tumor tissue is needed for diagnosis (see the NCCN Guidelines for NSCLC). Treatment of limited brain metastases in patients with NSCLC differs from that recommended in the NCCN Guidelines for Central Nervous System Cancers, because patients with NSCLC and brain metastases often have long-term survival; therefore, the potential neurocognitive issues that may occur with whole brain RT are a concern. Clinicians are not using whole brain RT as often in patients with limited brain metastases, which is reflected in the revised recommendations in the 2017 update (Version 1).
许多非小细胞肺癌患者有脑转移（30% - 50%），这严重影响了他们的生活质量。2017第1版更新，NCCN小组修订了局限性脑转移瘤的治疗推荐，减少了全脑放疗的推荐。目前，局限性脑转移的治疗选择包括1)单纯立体放射外科（SRS）；和2）对于选择性的患者，手术切除然后立体放射外科（SRS）或全脑放疗；挑选的患者包括症状性转移或肿瘤组织需要诊断 （见非小细胞肺癌NCCN指南）。非小细胞肺癌患者局限性脑转移瘤的治疗有别于中枢神经系统癌症NCCN指南中的建议，因为非小细胞肺癌脑转移患者往往有长期生存；因此，全脑放疗担心可能发生神经认知问题。在局限性脑转移患者中，临床医生往往不使用用全脑放疗，这反映出2017第1版更新的改进建议。

A recent randomized trial assessed cognitive function in 213 patients with 1 to 3 brain metastases who received SRS alone versus SRS with whole brain RT; most patients had lung cancer. At 3 months after SRS alone, patients had less cognitive deterioration (40/63 patients [63.5%]) than those receiving SRS plus whole brain RT (44/48 patients [91.7%]; difference, -28.2%; 90% CI, -41.9% to -14.4%; P < .001). Decisions about whether to recommend SRS alone or brain surgery followed by whole brain RT or SRS for limited brain metastases should be based on multidisciplinary discussion, weighing the potential benefit over the risk for each individual patient. Treatment should be individualized for patients with recurrent or progressive brain lesions.
最近的一项随机试验评估了213例1-3个脑转移、接受单纯立体定向放射手术（SRS）与立体定向放射手术（SRS）加全脑放疗患者的认知功能；大多数患者为肺癌。在单纯立体定向放射手术（SRS）后3个月时，患者认知降低(40/63[63.5%])少于接受立体定向放射手术（SRS）+全脑放疗(44/48(91.7%)者，差异，-28.2%；90%CI，-41.9%至-14.4%；P<0.001)。对于局限性脑转移，单纯立体定向放射手术（SRS）或脑外科手术然后全脑放疗或立体定向放射手术（SRS）的决定，应基于多学科的讨论，权衡每例患者可能获益超过风险。复发性或进行性脑损伤患者应采用个体化治疗。

For multiple metastases (eg, >3), whole brain RT is recommended; SRS may be preferred for patients who have good PS and low systemic tumor burden (see the NCCN Guidelines for Central Nervous System Cancers, available at NCCN.org). Whole brain RT is associated with measurable declines in neurocognitive function in clinical trials, particularly with increasing dose and advanced age of the patient. However, control of brain metastases confers improved neurocognitive function. For limited metastases, randomized trials have found that the addition of whole brain RT to SRS decreases intracranial recurrence but does not improve survival and may increase the risk of cognitive decline. Thus, SRS or whole brain RT alone is recommended for patients with limited volume metastases. Some have suggested that resection followed by SRS to the cavity (instead of resection followed by whole brain RT) will decrease the risk of neurocognitive problems. A study suggests that using IMRT to avoid the hippocampus may help decrease memory impairment after whole brain RT. A recent phase 3 randomized trial assessed optimal supportive care (including dexamethasone) with whole brain RT versus optimal supportive care alone in patients with NSCLC and brain metastases who were not eligible for brain surgery or SRS. Overall survival was similar between the groups (HR, 1.06; 95% CI, 0.90–1.26). Overall quality of life, use of dexamethasone, and reported adverse events were also similar between the arms.
对于多发转移（如> 3），推荐全脑放疗；对于一般情况好、全身肿瘤负荷低的患者，立体定向放射外科（SRS）可能是首选的（见中枢神经系统癌症NCCN指南，可在NCCN.org获得）。在临床试验中，全脑放疗与神经认知功能下降有关，尤其是随着剂量的增加和老年患者。然而，脑转移的控制可改善神经认知功能。对于局限性转移，随机试验发现，立体放射外科（SRS）加全脑放疗降低颅内复发但并不能提高生存率，并可能增加认知能力下降的风险。因此，对于转移性灶体积局限的患者，推荐立体放射外科（SRS）或单纯全脑放疗。有人建议，手术切除然后对残腔进行立体放射外科（而不是切除术后全脑放疗）会降低认知问题的风险。一项研究表明，在全脑放疗后使用避开海马的调强放疗（IMRT）可能有助于减少记忆障碍。最近一项3期随机试验在非小细胞肺癌脑转移、不适合脑部手术或立体放射外科（SRS）的患者中评估了最佳支持治疗（包括地塞米松）联合全脑放疗与单纯最佳支持治疗。组间总生存率相似（HR，1.06；95% CI，0.90 - 1.26）。总体生活质量，使用的地塞米松和报告的不良事件组间也是相似的。