Christensen Troels Dreier, Palshof Jesper Andreas, Larsen Finn Ole, Høgdall Estrid, Poulsen Tim Svenstrup, Pfeiffer Per, Jensen Benny Vittrup, Yilmaz Mette Karen, Christensen Ib Jarle, Nielsen Dorte
a Department of Oncology , Herlev and Gentofte Hospital, University of Copenhagen , Herlev , Denmark.
b Department of Pathology , Herlev and Gentofte Hospital, University of Copenhagen , Herlev , Denmark.
Acta Oncol. 2017 May;56(5):639-645. doi: 10.1080/0284186X.2017.1290272. Epub 2017 Feb 22.
Brain metastases (BM) from colorectal cancer (CRC) are rare, but the incidence is suspected to rise as treatment of metastatic (m) CRC improves. The aim of this study was to identify possible biological and clinical characteristics at initial presentation of mCRC that could predict later risk of developing BM. Furthermore, we wished to estimate the incidence of BM in long-term surviving patients.
We conducted a retrospective study on a Danish multicenter cohort of patients with mCRC who received cetuximab and irinotecan (CetIri) as third-line treatment. All patients had previously progression on 5-FU, irinotecan and oxaliplatin containing regimens and received CetIri treatment independent of RAS mutations status. We subsequently performed KRAS, NRAS, BRAF, PIK3CA, PTEN, ERBB2 and EGFR sequencing of DNA extracted from primary tumor tissue.
Totally, 480 patients were included in our study. BM were diagnosed in 42 [8.8%; 95% confidence interval (CI) 6.4-11.6%] patients. Patients with BM had a significantly longer survival from mCRC diagnosis than non-BM patients (median = 32 versus 28 months, p = 0.001). On univariate cox regression analysis, the risk of developing BM was significantly increased in patients with rectal cancer (HR = 3.9; 95% CI = 1.2-13.3), metachronous metastatic disease (HR = 2.3; 95% CI = 1.2-4.4) and lung metastases (HR = 4.2; 95% CI = 2.2-7.9). On multivariate cox regression analysis only lung metastases were significantly associated BM (HR = 3.5; 95% CI = 1.8-6.8). None of the investigated mutations were associated with BM.
The incidence of BM was 8.8% in patients with mCRC who received third-line therapy. The most important risk factor for developing BM was lung metastases. Furthermore, rectal cancer, metachronous metastatic disease and long survival were linked to BM development.
结直肠癌（CRC）脑转移（BM）罕见，但随着转移性（m）CRC治疗的改善，其发病率可能上升。本研究旨在确定mCRC初诊时可能预测后续发生BM风险的生物学和临床特征。此外，我们希望估计长期存活患者中BM的发病率。
我们对丹麦多中心队列中接受西妥昔单抗和伊立替康（CetIri）作为三线治疗的mCRC患者进行了一项回顾性研究。所有患者先前在含5-氟尿嘧啶、伊立替康和奥沙利铂的方案中出现进展，且接受CetIri治疗与RAS突变状态无关。随后，我们对从原发性肿瘤组织中提取的DNA进行了KRAS、NRAS、BRAF、PIK3CA、PTEN、ERBB2和EGFR测序。
我们的研究共纳入480例患者。42例[8.8%；95%置信区间（CI）6.4-11.6%]患者被诊断为BM。与无BM患者相比，发生BM的患者从mCRC诊断开始的生存期显著更长（中位数分别为32个月和28个月；p = 0.001）。单因素cox回归分析显示直肠癌患者（HR = 3.9；95% CI = 1.2-13.3）、异时性转移性疾病患者（HR = 2.3；95% CI = 1.2-4.4）和肺转移患者（HR = 4.2；95% CI = 2.2-7.9）发生BM的风险显著增加。多因素cox回归分析显示仅肺转移与BM显著相关（HR = 3.5；95% CI = 1.8-6.8）。所研究的突变均与BM无关。
接受三线治疗的mCRC患者中BM的发病率为8.8%。发生BM的最重要风险因素是肺转移。此外，直肠癌、异时性转移性疾病和长期生存与BM的发生有关。
