Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Ann Surg. 2020 Dec;272(6):1080-1085. doi: 10.1097/SLA.0000000000002245.
The aim of the study was to determine the prognostic impact of co-existence of APC and PIK3CA mutations in patients undergoing preoperative chemotherapy and resection for colorectal liver metastases (CLM).
Co-occurring genetic events have been shown to drive carcinogenesis in multiple malignancies.
We identified 396 patients with primary colorectal cancer and known somatic mutation status by next-generation sequencing who underwent hepatectomy for CLM (2005-2015). Survival after hepatectomy in patients with double mutation of APC and PIK3CA and others was analyzed. Predictors of pathologic response and survival were determined. The prognostic value of double mutation was evaluated with a separate cohort of 157 patients with CLM undergoing chemotherapy alone.
Forty-five patients had double mutation of APC and PIK3CA; 351 did not. Recurrence-free survival (RFS) and overall survival (OS) after hepatectomy were worse in patients with double mutation (3-year RFS, 3.1% vs 20% [P < 0.001]; 3-year OS, 44% vs 84% [P < 0.001]). Independent predictors of major pathologic response were bevacizumab use (odds ratio [OR] 2.22; P = 0.001), tumor size <3 cm (OR 1.97; P = 0.004), wild-type RAS (OR 2.00; P = 0.003), and absence of double mutation (OR 2.91; P = 0.002). Independent predictors of worse OS were primary advanced T category (hazard ratio [HR] 2.12; P = 0.021), RAS mutation (HR 1.74; P = 0.015), and double mutation (HR 3.09; P < 0.001). In the different medical cohort, patients with double mutation had worse 3-year OS of 18%, compared with 35% without double mutation (P = 0.023).
Double mutation of APC and PIK3CA predicts inferior response to preoperative chemotherapy and poor survival in patients with CLM.
本研究旨在确定接受术前化疗和结直肠肝转移（CLM）切除术的患者中 APC 和 PIK3CA 突变共存的预后影响。
已经表明，共存的遗传事件会驱动多种恶性肿瘤的癌变。
我们通过下一代测序确定了 396 名接受 CLM 肝切除术的原发性结直肠癌且具有已知体细胞突变状态的患者（2005-2015 年）。分析 APC 和 PIK3CA 双重突变患者与其他患者在肝切除术后的生存情况。确定病理反应和生存的预测因素。使用单独的接受化疗的 157 例 CLM 患者队列评估双重突变的预后价值。
45 例患者存在 APC 和 PIK3CA 双重突变，351 例患者没有双重突变。双重突变患者的肝切除术后无复发生存（RFS）和总生存（OS）更差（3 年 RFS，3.1% vs 20% [P < 0.001]；3 年 OS，44% vs 84% [P < 0.001]）。主要病理反应的独立预测因素是贝伐单抗的使用（比值比 [OR] 2.22；P = 0.001）、肿瘤大小 <3 cm（OR 1.97；P = 0.004）、野生型 RAS（OR 2.00；P = 0.003）和不存在双重突变（OR 2.91；P = 0.002）。OS 更差的独立预测因素是原发进展期 T 分期（风险比 [HR] 2.12；P = 0.021）、RAS 突变（HR 1.74；P = 0.015）和双重突变（HR 3.09；P < 0.001）。在不同的医疗队列中，双重突变患者的 3 年 OS 为 18%，而无双重突变患者为 35%（P = 0.023）。
APC 和 PIK3CA 的双重突变预测 CLM 患者对术前化疗的反应较差和生存不良。
