Kothari Nishi, Kim Richard, Jorissen Robert N, Desai Jayesh, Tie Jeanne, Wong Hui-Li, Faragher Ian, Jones Ian, Day Fiona L, Li Shan, Sakthinandeswaren Anuratha, Palmieri Michelle, Lipton Lara, Schell Michael, Teer Jamie K, Shibata David, Yeatman Timothy, Sieber Oliver M, Gibbs Peter, Tran Ben
Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute , Tampa , USA.
Acta Oncol. 2015 Apr;54(4):487-92. doi: 10.3109/0284186X.2014.990158. Epub 2014 Dec 31.
Recent data have suggested that regular aspirin use improves overall and cancer-specific survival in the subset of colorectal cancer (CRC) patients harboring PIK3CA mutations. However, the number of PIK3CA-mutated CRC patients examined in these studies was modest. Our collaborative study aims to validate the association between regular aspirin use and survival in patients with PIK3CA-mutated CRC.
Patients with PIK3CA-mutated CRC were identified at Moffitt Cancer Center (MCC) in the United States and Royal Melbourne Hospital (RMH) in Australia. Prospective clinicopathological data and survival data were available. At MCC, PIK3CA mutations were identified by targeted exome sequencing using the Illumina GAIIx Next Generation Sequencing platform. At RMH, Sanger sequencing was utilized. Multivariate survival analyses were conducted using Cox logistic regression.
From a cohort of 1487 CRC patients, 185 patients harbored a PIK3CA mutation. Median age of patients with PIK3CA-mutated tumors was 72 years (range: 34-92) and median follow up was 54 months. Forty-nine (26%) patients used aspirin regularly. Regular aspirin use was not associated with improved overall survival (multivariate HR 0.96, p = 0.86). There was a trend towards improved cancer-specific survival (multivariate HR 0.60, p = 0.14), but this was not significant.
Despite examining a large number of patients, we did not confirm that regular aspirin use was associated with statistically significant improvements in survival in PIK3CA-mutated CRC patients. Prospective evaluation of this relationship is warranted.
近期数据表明，对于携带PIK3CA突变的结直肠癌（CRC）患者亚组，规律使用阿司匹林可改善总体生存率和癌症特异性生存率。然而，这些研究中检测的PIK3CA突变CRC患者数量并不多。我们的合作研究旨在验证规律使用阿司匹林与PIK3CA突变CRC患者生存率之间的关联。
在美国的莫菲特癌症中心（MCC）和澳大利亚的皇家墨尔本医院（RMH）识别出PIK3CA突变的CRC患者。可获取前瞻性临床病理数据和生存数据。在MCC，使用Illumina GAIIx下一代测序平台通过靶向外显子测序识别PIK3CA突变。在RMH，采用桑格测序法。使用Cox逻辑回归进行多变量生存分析。
在1487例CRC患者队列中，有185例患者携带PIK3CA突变。PIK3CA突变肿瘤患者的中位年龄为72岁（范围：34 - 92岁），中位随访时间为54个月。49例（26%）患者规律使用阿司匹林。规律使用阿司匹林与总体生存率改善无关（多变量风险比0.96，p = 0.86）。癌症特异性生存率有改善趋势（多变量风险比0.60，p = 0.14），但未达显著水平。
尽管研究了大量患者，但我们并未证实规律使用阿司匹林与PIK3CA突变CRC患者生存率的统计学显著改善相关。有必要对这种关系进行前瞻性评估。
