非小细胞肺癌NCCN2017V5讨论：初始治疗 IV期

Discussion讨论

Initial Therapy 初始治疗

Stage IV Disease Ⅳ期疾病山东省肿瘤医院呼吸肿瘤内科张品良

In general, systemic therapy is recommended for patients with metastatic disease (see Systemic Therapy for Advanced or Metastatic Disease in the NCCN Guidelines for NSCLC). In addition, palliative treatment, including RT, may be needed during the disease course to treat localized symptoms, diffuse brain metastases, or bone metastases (see Therapy for Recurrence and Metastases in the NCCN Guidelines for NSCLC). This section focuses on patients with limited metastatic disease; management of widespread distant metastases is described in another section (see Treatment of Recurrences and Distant Metastases in this Discussion and Systemic Therapy for Metastatic Disease in the NCCN Guidelines for NSCLC). Pleural or pericardial effusion is a criterion for stage IV, M1a disease. T4 with pleural effusion is classified as stage IV, M1a (see Table 3 in Staging in the NCCN Guidelines for NSCLC). Although pleural effusions are malignant in 90% to 95% of patients, they may be related to obstructive pneumonitis, atelectasis, lymphatic or venous obstruction, or a pulmonary embolus. Therefore, pathologic confirmation of a malignant effusion by using thoracentesis or pericardiocentesis is recommended. In certain cases where thoracentesis is inconclusive, thoracoscopy may be performed. In the absence of nonmalignant causes (eg, obstructive pneumonia), an exudate or sanguinous effusion is considered malignant regardless of the results of cytologic examination. If the pleural effusion is considered negative for malignancy (M0), recommended treatment is based on the confirmed T and N stage (see the NCCN Guidelines for NSCLC). However, all pleural effusions, whether malignant or not, are associated with unresectable disease in 95% of cases. In patients with effusions that are positive for malignancy, the tumor is treated as M1a with local therapy (ie, ambulatory small catheter drainage, pleurodesis, and pericardial window) in addition to treatment as for stage IV disease (see the NCCN Guidelines for NSCLC). 通常情况下，对于转移性患者推荐全身治疗（见NSCLC NCCN指南中晚期或转移性疾病的全身治疗）。此外，在病程期间，为了处理局部症状、弥漫性脑转移或骨转移可能需要姑息治疗，包括放疗（见NSCLC NCCN指南中的复发和转移的治疗）。本节着重于局限性转移患者；广泛远处转移的处理在另外一节中描述（见本讨论中复发和远处转移的治疗以及NSCLC NCCN指南中转移性疾病的全身治疗）。胸腔或心包积液是一个Ⅳ期、M1a疾病标准。有胸腔积液的T4分类为Ⅳ期、M1a（见NSCLC NCCN指南中分期表3）。尽管90%-95%的患者胸腔积液是恶性的，但是，其可能与阻塞性肺炎、肺不张、淋巴或静脉阻塞或肺栓塞有关。因此，推荐采用胸腔或心包穿刺病理证实恶性积液。在某些情况下，胸腔穿刺不能确定，则可以进行胸腔镜检查。在没有非恶性病因（如阻塞性肺炎）的情况下，渗出液或血性积液被认为是恶性的而不管细胞学检查结果。如果认为胸腔积液不是恶性的（M0），推荐的治疗是基于确认的T和N分期（见NSCLC NCCN指南）。不过，所有的胸腔积液，无论恶性与否，95%的病例不能手术切除。在恶性积液患者中，肿瘤治疗除了按照Ⅳ期疾病治疗外还要按照M1a局部治疗（即不卧床细导管引流术、胸膜固定术和心包开窗术）（见NSCLC NCCN指南）。

Management of patients with distant metastasis in limited sites (ie, stage IV, M1b) and good PS depends on the location and number of the metastases; the diagnosis is aided by mediastinoscopy, bronchoscopy, FDG PET/CT scan, and brain MRI (with contrast). The increased sensitivity of FDG PET/CT scans, compared with other imaging methods, may identify additional metastases and, thus, spare some patients from unnecessary futile surgery. However, positive FDG PET/CT scan findings for distant disease need pathologic or other radiologic confirmation. If the FDG PET/CT scan is positive in the mediastinum, the lymph node status needs pathologic confirmation. Patients with limited oligometastatic disease (eg, brain metastases) and otherwise limited disease in the chest may benefit from aggressive local therapy to both the primary chest and metastatic sites. 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 (see Whole Brain RT and Stereotactic Radiosurgery in this Discussion text). Clinicians are not using whole brain RT as often in patients with limited brain metastases because of concerns about neurocognitive problems. Aggressive local therapy may comprise surgery and/or definitive RT including SRS and SABR, and may be preceded or followed by chemotherapy. After progression on TKIs, patients with EGFR mutations may be able to continue with their current TKIs; local therapy can be considered to treat their limited metastases (eg, SRS to brain metastases or other sites, SABR for thoracic disease). Metastases to the adrenal gland from lung cancer are a common occurrence, with approximately 33% of patients having such disease at autopsy. In patients with otherwise resectable primary tumors, however, many solitary adrenal masses are not malignant. Any adrenal mass found on a preoperative CT scan in a patient with lung cancer should be biopsied to rule out benign adenoma. Local therapy (category 2B) of the adrenal lesion has produced some long-term survivors when an adrenal metastasis has been found and the lung lesion has been curable (see the NCCN Guidelines for NSCLC). Some NCCN Panel Members feel that local therapy for adrenal metastases is only advisable if the synchronous lung disease is stage I or possibly stage II (ie, resectable). Systemic therapy is another treatment option for adrenal metastasis.一般情况好、部位局限的远处转移（即Ⅳ期M1b）患者的管理，取决于转移的部位和数量；通过纵隔镜、支气管镜、FDG PET/CT扫描和脑MRI（强化）辅助诊断。与其它影像手段相比，FDG PET/CT扫描的敏感性增加，可能发现其他的转移灶，从而使某些患者避免不必要的无用的手术。不过，FDG PET/CT扫描发现的阳性远隔病变需要病理或其他影像学确认。如果FDG PET/CT扫描纵隔淋巴结阳性，该淋巴结情况需要病理学证实。局限寡转移病变（如脑或肾上腺转移）患者及其他胸部局限性病变可能获益于对原发胸部和转移部位积极的局部治疗。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（见本讨论中的全脑放疗和立体定向放射治疗）。在局限性脑转移患者中，临床医生往往不使用用全脑放疗，因为担心神经认知问题。积极的局部治疗可包括手术和/或根治性放疗包括立体定向消融放疗，可在化疗前或化疗后实施。在TKIs进展后，EGFR突变的患者可以继续使用其当前的TKIs；可以考虑局部治疗来处理其局限的转移灶（如对于脑或其他部位的转移灶使用立体定向放疗，对胸腔病变使用立体定向消融放疗）。肺癌肾上腺转移是一个常见的现象，在尸检时约33%的患者存在这种情况。不过，在原发肿瘤原本可切除的患者中，许多孤立性肾上腺肿块不是恶性的。肺癌患者术前CT扫描发现的任何肾上腺肿块均应该活检以排除良性腺瘤。当发现肾上腺转移而肺部病变已治愈时，肾上腺病变的局部治疗（2B类）已经有一些长期生存者（见NSCLC NCCN指南）。一些NCCN小组成员认为如果同期肺部疾病是I期或Ⅱ期（即，可切除），肾上腺转移灶的局部治疗才是明智的。全身性治疗是肾上腺转移的另一种治疗选择。