Stereotactic Ablative Radiotherapy
立体定向消融放疗

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.
SABR（也称为SBRT）使用非常适形且剂量密集的短程放疗，精确传递到大小有限的目标。包括前瞻性多中心试验在内的若干研究已经证明了SABR对不能手术或拒绝手术的Ⅰ期NSCLC患者的疗效。使用常规分割放疗，这些患者的3年生存率仅为约20%-35%，局部失败率约为40%-60%。在前瞻性临床试验中，SABR治疗因内科因素不能手术患者的局部控制率和总生存率似乎大大增加，一般都在85%以上，3年时大约60%（中位生存期4年）。在用SABR治疗的潜在可手术的患者中已观察到显著更高的生存率；在以人群为基础的比较中，生存可媲美手术治疗，但局部区域复发更常见。目前尚未证明，对于医学上可手术的患者，使用SABR的远期疗效与手术相当。已报道在SABR超过5年后晚期复发，强调需要仔细监测。如有可能，在使用SABR前应活检证实NSCLC。

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NSCLC工作步骤中，推荐SABR用于因内科因素不能手术的I期和Ⅱ期（T1-3N0M0）NSCLC患者；对于高危、老年或在适当协商后拒绝手术的潜在可手术的患者，SABR是一个合理的手术替代方案（参见NSCLC NCCN指南）。两项随机临床试验的一项合并分析（未全部入组）评估比较了SABR与肺叶切除术治疗可手术的患者。该分析并未改变对于可手术的患者推荐手术切除且通常使用的事实，但对于有手术禁忌症或拒绝手术的患者，有助于确认SABR的指征。SABR还可用于肺或其他部位局限性转移的患者。在SABR之后，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，可以在治疗后2年或更长时间内FDG-PET仍高摄取，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SABR后局部复发的选择性患者，可能从手术或再次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 has been validated as a maximally tolerated dose, 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.
在NSCLC工作步骤中提供了SABR分割方案和有限的历史上使用最大剂量限制的亚组（参见NSCLC NCCN指南放射治疗原则中的表2和表3）。这些剂量限制是参考点剂量，并不是规定性的；已普遍使用或已在临床试验中使用。尽管这些剂量限制均未被证实为最大耐受剂量，但迄今为止的临床试验结果表明它们是安全的限制。支气管树、食管、臂丛是SABR的关键结构。对于位于中央的肿瘤——在各个方向2cm内的任何纵隔关键结构包括支气管树、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SABR方案似乎是安全有效的（参见NSCLC 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。

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. Nonrandomized clinical data indicate that local tumor control with SABR is higher than with interventional radiology ablation techniques. Interventional radiology ablation may be appropriate for selected patients for whom local control is not necessarily the highest priority.
对于脑或身体其他部位的局限性寡转移，SRS或SABR对于PS好且胸部病变可进行根治性治疗的患者可能是有用的（参见NSCLC NCCN指南中的Ⅳ期M1b：局限部位）。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2A类推荐。决定是否推荐SABR应基于多学科讨论。如果确定SABR计划不可用，则可以选择大分割或剂量强化的常规三维适形放疗。非随机临床资料表明，SABR的肿瘤局部控制高于介入消融技术。介入放射消融可能适用于选择的、局部控制不一定是最优先考虑的患者。

Combined Modality Therapy
综合治疗

As previously mentioned, surgery provides the best chance for cure for patients with stage I or II disease who are medically fit and can tolerate surgery. SABR can be considered for patients with unresectable stage I or II (T1–3, N0) disease or those who refuse surgery if their disease is node negative (see Stereotactic Ablative Radiotherapy in this Discussion and see the NCCN Guidelines for NSCLC). In patients with completely resected NSCLC, adjuvant (postoperative) chemotherapy has been shown to improve survival in patients with early-stage disease. Some studies suggest that preoperative chemotherapy (also referred to as neoadjuvant chemotherapy or induction chemotherapy) is as effective as and better tolerated than postoperative chemotherapy (see Preoperative Chemotherapy Followed by Surgery: Trial Data in this Discussion). A randomized trial found no difference in survival with preoperative versus postoperative chemotherapy. The NCCN Guidelines state that patients with stage II or IIIA (T3, N1) disease may be treated with induction chemotherapy before surgery if they are candidates for therapy after surgery. Concurrent chemoradiation is more efficacious than sequential chemoradiation for patients with unresectable stage III disease.
如前所述，对于无禁忌症且能耐受手术的Ⅰ/Ⅱ期患者，手术提供了最佳的治愈机会。SABR可以考虑用于无法切除的I或Ⅱ期（T1-3N0）疾病或那些拒绝手术的患者，如果其淋巴结阴性（参见本讨论及NSCLC NCCN指南中的立体定向消融放疗）。在完全切除的NSCLC患者中，辅助（术后）化疗已证明可改善早期疾病患者的生存。一些研究表明，术前化疗（也称新辅助化疗或诱导化疗）与术后化疗同样有效且耐受性更好（参见术前化疗然后手术：本讨论中的试验数据）。一项随机试验发现，术前与术后化疗的生存无差异。NCCN指南指出，Ⅱ或ⅢA期（T3N1）患者如果适于术后治疗，可在手术前接受诱导化疗。对于无法切除的Ⅲ期患者，同步放化疗比序贯放化疗更有效。

For patients with stage IV disease who have a good PS, platinum-based chemotherapy is beneficial. Data show that early palliative care combined with systemic therapy improved quality of life, mood, and survival in patients with metastatic NSCLC, even if these patients had less aggressive end-of-life care, when compared with those not receiving palliative care alone. Patients should receive treatment for debilitating symptoms. A study also suggests that social support, such as being married, is as effective as systemic therapy. Preliminary results from a recent study indicate that systematic symptom monitoring during outpatient chemotherapy treatment increases overall survival when compared with usual care. Surgery is rarely recommended for patients with stage IV disease. However, surgical resection of limited brain metastases may improve survival in selected patients with stage IV disease and is recommended for selected patients in the NCCN Guidelines (see the NCCN Guidelines for NSCLC, available at www.NCCN.org). Definitive local therapy with surgical resection or RT is recommended for limited metastases located in sites other than the brain if definitive thoracic therapy is feasible (see Stage IVA, M1b: Limited Sites in the NCCN Guidelines for NSCLC). The trials supporting the recommendations for combined modality therapy are discussed in the following sections.
对于PS良好的Ⅳ期患者，以铂类为基础的化疗是有益的。数据显示，与那些未接受姑息治疗单纯接受全身治疗的患者相比，早期姑息治疗结合全身治疗可改善转移性NSCLC患者的生活质量、情绪和生存，即使这些患者的临终关怀较不积极。应该处理患者的虚弱症状。一项研究还表明，社会支持，如结婚，与全身治疗一样有效。最近一项研究的初步结果表明，与常规治疗相比，门诊化疗期间系统的症状监测改善总生存。对于Ⅳ期患者很少推荐手术治疗。不过，在选择性Ⅳ期患者中，手术切除局限的脑转移灶可改善生存，因此NCCN指南推荐用于选择性患者（参见NSCLC NCCN指南，可在www.NCCN.org获得）。对于位于脑部以外部位局限的转移，如果可以进行根治性胸部治疗，推荐进行手术切除或放疗的根治性局部治疗（参见NSCLC NCCN指南中的IVA期，M1b：部位局限）。以下章节将讨论推荐综合治疗的支持试验。