作者：周斐 周彩存
来源：肿瘤瞭望
第六届欧洲肺癌大会（ELCC）最新报道的一项回顾性研究显示，约10%的III期非小细胞肺癌患者在接受放化疗后1年内发生脑转移，而同步放化疗中不同的化疗方案对脑转移的发生并无影响[摘要号115PD- Brain metastases (BM) development after chemoradiation (CRT) for stage III non-small cell lung cancer (NSCLC): Does the type of chemotherapy matter]。
研究共入组了838例患者，其中接受同步放化疗者为737例，接受序贯放化疗者为101例。研究者发现，11%的患者在1年内发生脑转移，其中5%的患者以脑转移为唯一的首次复发原因，年轻的、女性、肺腺癌患者更容易发生脑转移。接受同步放化疗患者1年内脑转移发生率为11%，而接受序贯放化疗的患者为10%，以脑转移为唯一的首次复发原因的患者分别为5%和4%，均无显著差别。研究者进一步对“同步放化疗中不同的化疗方案对脑转移的发生的影响”进行了探索分析（低剂量顺铂单药、VP-16联合顺铂方案、长春瑞滨联合顺铂方案、多西紫杉醇联合顺铂周疗方案）。结果发现，不同化疗方案之间，无论是第1年的脑转移发生率还是以脑转移为唯一的首次复发原因的比例，均无显著差别。
同步放化疗是不可切除的III期非小细胞肺癌的标准治疗。多项Meta分析及III期临床研究均证实，与序贯放化疗相比，同步放化疗可显著改善患者的长期生存，同时局部控制更佳。但是，研究同样也显示，同步放化疗相对于序贯放化疗，在远处转移控制方面并无优势。在Auperin等进行的meta分析中（J Clin Oncol. 2010 May 1;28(13):2181-90），接受同步放化疗的患者3年和5年远处转移发生率分别为40.6%和39.5%，而接受序贯放化疗的患者为39.5%和39.1% （HR 1.04, 95% CI, 0.86-1.25, P=0.69），均无显著差别。同样，在Curran等进行的研究中（J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60），在序贯放化疗组，脑转移发生率为12%，而在同步放化疗组，脑转移发生率为14%和13%，同样无显著差别。因此，该项回顾性研究再次证实，同步放化疗相对于序贯放化疗，在远处转移（脑转移）控制方面并无优势。
研究者同时对同步放化疗中不同的化疗方案对脑转移的发生的影响进行了探索分析，但发现不同的化疗方案对脑转移的发生并无影响，这可能与血脑屏障对化疗药物的天然屏蔽作用相关。在Ortuzar等联合JMDB和JMEI研究的回顾性分析中，培美曲塞在预防脑转移方面展现了一些优势，与非培美曲塞方案相比，培美曲塞方案可降低晚期非小细胞肺癌患者的脑转移发生率（3.2% vs. 6.6%, OR 0.49, 95% CI, 0.32-0.76; P=.001），但该研究仅为回顾性分析，且仅纳入了有症状脑转移患者，因而结果仍需进一步前瞻性研究验证。而在最新发表的PROCLAIM研究中（J Clin Oncol. 2016 Mar 20;34(9):953-62），与EP方案相比，培美曲塞联合顺铂方案在预防脑转移方面并无优势（以脑转移为首次复发的比例：18.7% vs. 19.5%, P=0.893），因此仍需进一步前瞻性研究探索同步放化疗中不同的化疗方案对脑转移的发生的影响，特别是培美曲塞在脑转移中的作用。
责任编辑：Dr.q
摘要原文
115PD- Brain metastases (BM) development after chemoradiation (CRT) for stage III non-small cell lung cancer (NSCLC): Does the type of chemotherapy matter?
Background：BM occur frequently within 1 year after CRT for stage III NSCLC. It is unknown whether the specific chemotherapy used influences subsequent BM development.
Methods：Retrospective multicenter study including all consecutive stage III NSCLC patients (pts) who completed CRT. Primary endpoints: BM development within the 1st year and whether this was the only site of first relapse. Differences between regimens were assessed with a logistic regression model including known BM risk factors (age, gender, histology, T- and N-status) and the specific chemotherapy used (concurrent (cCRT) vs sequential (sCRT), within cCRT: low dose cisplatin monotherapy (LDC) – high dose polychemotherapy; (non-)taxane high dose polychemotherapy – LDC; chemotherapy subgroups of ≥50 pts).
Results：Between January 2006 and June 2014, 838 pts were eligible (737 cCRT, 101 sCRT). 11% developed BM within a year, 5% had BM as only site of first relapse. BM pts were significantly younger (mean age 59 vs 63 years, p<0.001), female (49% vs 35%, p=0.009), and had adenocarcinoma histology (51% vs 37%, p<0.001). 11% of cCRT and 10% of sCRT pts developed BM (p=0.834). For 5% and 4% respectively, this was the only site of first relapse (p=0.724). In both high dose cCRT (N=346) and LDC (N=391) BM were found in 11% within one year of stage III NSCLC diagnosis (p=0.927). In 4% and 5%, respectively, BM were the only site of first relapse (p=0.399).
The chemotherapy used (cCRT versus sCRT) had no influence on BM development, not within one year nor as only site of first relapse (OR 0.87 (p=0.695) and OR 0.89 (p=0.838), respectively). LDC versus high dose cCRT was not significantly different: neither within one year nor as only site of first relapse (OR 0.96 (p=0.861) and OR 1.36 (p=0.404), respectively). Comparable results were found for LDC versus high dose non-taxane (N=277) and high dose taxane regimens (N=69) and for cCRT regimens with ≥50 patients (LDC versus cisplatin/etoposide (N=188), cisplatin/vinorelbin (N=65), weekly cisplatin/docetaxel (N=60)).
Conclusions：Approximately 1 out of 10 pts will develop BM within the 1st year after stage III NSCLC diagnosis, but this does not depend on the type of chemotherapy regimen used within a CRT regimen.
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