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关于 NSCLC 孤立性脑或孤立性肾上腺转移的治疗目前尚缺乏大样本的前瞻性随机对照研究,多为小样本回顾性研究,证据级别不高。
关于脑部病灶的处理参照脑单发或寡转移(包括其他实体瘤,其中绝大部分为 NSCLC) 的前瞻性随机对照临床研究的结果。对于 PS 评分为 0~1 分的患者,两项前瞻性随机对照临床研究比较了脑部手术 + WBRT 与单 WBRT 的疗效[1-2],结果显示手术可显著提高患者生存率及局部控制率。
关于肺部病灶的处理,多篇回顾性研究分析显示,PS 评分为 0~1 分,肺部病变为非 N2 且可完全切除患者,手术治疗较非手术治疗效果好[3-4]。部分研究显示 T1 患者手术的疗效优于 T2、T3[3-4];N0者手术疗效优于 N1、N2[4],对于 N2 患者,鉴于疗效差,不主张手术治疗[4]。
关于孤立肾上腺转移Ⅳ期 NSCLC 的治疗,多个回顾性研究提示,PS 评分为 0~1 分、肺部病变为非 N2 且可完全切除患者,给予肺部原发病灶完全性手术切除及根治性肾上腺切除术联合系统全身化疗,患者可获益,中位生存可达 11~31 个月[5-8]。研究同时提示,对于原发病灶分期较晚,特别是有 N2 淋巴结转移患者行手术治疗效果差,不建议手术治疗[5-7]。
对于脑部病灶不能或不愿手术的患者,基于 4 项前瞻性随机对照临床研究的结果(包括 2015 年 ASCO 摘要 LBA4):PS 评分为 0~1 分,脑部 SRS 联合 WBRT 较单纯 SRS 仅提高局部控制率,并无生存获益,且增加神经系统并发症,降低学习和记忆能力[11-13]。
关于脑部手术或 SRS/SRT 后是否加 WBRT 存在争议:目前缺乏前瞻性随机对照比较脑部手术 + WBRT 与单独手术的临床研究数据,既往研究样本量小、年代久远且对照组为单独 WBRT 而非单独手术。EORTC 22952-26001 研究比较了手术或 SRS 后根据是否行 WBRT 将患者随机分为两组,结果显示加用 WBRT 对总生存期无影响[11]。对于脑部 SRS/SRT 后是否加用 WBRT,多数研究显示加用 WBRT 仅可以提高颅内局部控制率,但不延长总生存期[11-13];RTOG 9508 和 JROSG 99-1,两项研究的二次分析显示:对于分级预后评估(graded prognostic assessment,GPA) 高者 SRS 联合 WBRT 有生存获益[14-15]。
WBRT 标准剂量包括 30Gy/10 次,也可以 37.5Gy/15 次,然而在 PS 状态差的患者也可以 20Gy/5次[10];SRS 单次最大边缘剂量根据肿瘤体积(最大径 ≤ 2.0cm、2.1~3.0cm、3.1~4.0cm) 可以为 24、 18、15Gy(RTOG 90-05)[15]。
对于不能或不愿意手术切除的肺部病灶,可考虑 SBRT 或放化疗[4,16-18]。其放疗参照非转移NSCLC 的放疗。
孤立性肾上腺转移Ⅳ期 NSCLC 的治疗中,对于不愿意或肺部病灶不能手术切除的患者,针对肺原发病灶SBRT 或放化疗联合肾上腺转移灶行放疗,患者有生存获益,中位生存达 10.2~23 个月[16-19]。
孤立性脑或肾上腺转移 NSCLC 患者的系统性全身治疗方案见指南其他章节中的Ⅳ期患者系统性全身治疗。
⏫ Ⅳ期孤立性转移非小细胞肺癌的治疗
参考指南:
中国临床肿瘤学会指南工作委员会.中国临床肿瘤学会 (CSCO) 非小细胞肺癌诊疗指南2024.人民卫生出版社.北京 2024
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