Differential Radiographic Appearance of BRAF V600E-Mutant Metastatic Colorectal Cancer in Patients Matched by Primary Tumor Location
Differential Radiographic Appearance of BRAF V600E-Mutant Metastatic Colorectal Cancer in Patients Matched by Primary Tumor Location
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DOI：
10.6004/jnccn.2016.0165
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发表时间：
2016-12-01
影响因子：
13.4
通讯作者：
Behr, Spencer C.
中科院分区：
文献类型：
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作者：
Atreya, Chloe E.;Greene, Claire;Behr, Spencer C.
背景资料：BRAF突变转移性结直肠癌（mCRC）与右侧结肠肿瘤有许多共同的临床病理特征，包括频繁的腹膜受累。由于与BRAF突变相关的不良结局，鼓励早期入组临床试验。然而，使用标准的资格和评估标准，如可测量的疾病，阻碍了患者的增加和限制了对治疗反应的评估。我们研究了BRAF V600E突变的存在是否与原发肿瘤位置匹配的患者的转移性疾病的部位和外观差异相关。研究方法：共有40例BRAF突变型mCRC患者与80例BRAF野生型mCRC患者根据原发肿瘤的位置（右或左结肠;直肠）、性别和年龄进行匹配。采用比例检验分析BRAF突变状态与临床病理特征和转移部位之间的关系。采用Kaplan-Meier和考克斯回归方法总结生存期。结果：原发部位右半结肠占60%，左半结肠占30%，直肠占10%。与BRAF野生型肿瘤相比，BRAF突变型肿瘤更常伴有腹膜转移（50% vs 31%; P = 0.045）和腹水（50% vs 24%; P = 0.0038）。在左结肠原发灶患者中，BRAF突变与更频繁的腹水（58% vs 12%; P = 0.0038）和更少的肝转移（42% vs 79%; P = 0.024）相关。在右半结肠原发灶患者中，BRAF突变状态的疾病部位无显著差异。根据RECIST 1.1，24%的右侧原发性肿瘤患者的疾病不可测量，无论BRAF突变状态如何。在BRAF突变的队列中，腹水与生存率不利相关（风险比，2.35; 95%CI，1.14，4.83; P = 0.02）。结论：腹水和腹膜转移的频率更高，这对RECIST 1.1解释治疗结果提出了挑战，即使患者的原发肿瘤位置匹配，BRAF突变型mCRC也会出现。
Background: BRAF-mutant metastatic colorectal cancers (mCRCs) share many clinicopathologic features with right-sided colon tumors, including frequent peritoneal involvement. Because of the poorer outcomes associated with BRAF mutations, early enrollment in clinical trials has been encouraged. However, the use of standard eligibility and assessment criteria, such as measurable disease, has anecdotally impeded patient accrual and restricted appraisal of treatment response. We investigated whether the presence of a BRAF V600E mutation is differentially associated with sites and appearance of metastatic disease in patients matched by primary tumor location. Methods: A total of 40 patients with BRAF-mutant mCRC were matched to 80 patients with BRAF wild-type mCRC by location of primary tumor (right or left colon; rectum), sex, and age. Associations between BRAF mutation status and clinicopathologic characteristics and metastatic sites were analyzed using proportion tests. Survival was summarized with Kaplan-Meier and Cox regression methods. Results: The distribution of primary tumor locations was: 60% right colon, 30% left colon, and 10% rectum. Compared with BRAF wild-type tumors, BRAF-mutant tumors more commonly associated with peritoneal metastases (50% vs 31%; P=.045) and ascites (50% vs 24%; P=.0038). In patients with left colon primaries, BRAF mutations were associated with more frequent ascites (58% vs 12%; P=.0038) and less frequent liver metastases (42% vs 79%; P=.024). Among patients with right colon primaries, no significant difference in sites of disease by BRAF mutation status was observed. Disease was not measurable by RECIST 1.1 in 24% of patients with right-sided primary tumors, irrespective of BRAF mutation status. In the BRAF-mutated cohort, ascites correlated unfavorably with survival (hazard ratio, 2.35; 95% CI, 1.14, 4.83; P=.02). Conclusions: Greater frequency of ascites and peritoneal metastases, which pose challenges for RECIST 1.1 interpretation of therapeutic outcomes, are seen with BRAF-mutant mCRC, even when patients are matched for primary tumor location.