Zuo Daocheng, Wang Lu, Jin Kangpeng, Zhang Yue, Wang Yaping, Sun Yueming, Tang Junwei
The First Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, China.
Department of General Surgery, Colorectal Institute of Nanjing Medical University, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, Jiangsu, China.
Ann Surg Oncol. 2025 Jul 14. doi: 10.1245/s10434-025-17809-5.
Colorectal cancer liver metastases (CRLM) present significant treatment challenges, requiring multimodal conversion therapies. Identifying factors that influence treatment outcomes is crucial for improving clinical management.
This retrospective cohort study included 286 patients with synchronous CRLM who underwent conversion therapies on the basis of sequencing results. Patients were categorized into successful conversion therapy group (SCTG) and failed conversion therapy group (FCTG). Clinical factors and genomic mutations were analyzed for associations with therapy outcomes and survival.
Among the patients, 106 (37.1%) achieved successful conversion (SCTG), while 180 (62.9%) failed (FCTG). Compared with SCTG, patients in the FCTG had significantly larger metastatic lesions, higher preoperative mesenteric lymph node positivity, and elevated carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels. Six genes (FAT, BRAF, SERPINA3, GRIN2A, ERBB2, and ALK) showed the highest mutation frequency differences in FCTG, correlating with worse outcomes. Any of these mutations was associated with shorter overall survival compared with wild-type patients. A nomogram model using tumor mutation status, CEA, CA19-9, lesion diameter ≥ 5 cm, and positive lymph nodes at diagnosis predicted conversion efficacy (area under the curve = 89.6, 95% confidence interval 22.6-92.4). An extended conversion-related clinical risk score scoring system incorporating these factors effectively stratified poor prognosis populations, serving as a prognostic tool for patients with unresectable CRLM.
Genomic profiling improves precision management of CRLM, facilitating tailored conversion strategies and better prognostic prediction. Future studies should validate these findings in prospective cohorts to refine personalized treatment for patients with initially unresectable CRLM.
结直肠癌肝转移（CRLM）带来了重大的治疗挑战，需要多模式转化治疗。识别影响治疗结果的因素对于改善临床管理至关重要。
这项回顾性队列研究纳入了286例接受基于测序结果的转化治疗的同步CRLM患者。患者被分为成功转化治疗组（SCTG）和失败转化治疗组（FCTG）。分析临床因素和基因组突变与治疗结果及生存的相关性。
在这些患者中，106例（37.1%）实现了成功转化（SCTG），而180例（62.9%）失败（FCTG）。与SCTG相比，FCTG中的患者转移灶明显更大，术前肠系膜淋巴结阳性率更高，癌胚抗原（CEA）和糖类抗原19-9（CA19-9）水平升高。六个基因（FAT、BRAF、SERPINA3、GRIN2A、ERBB2和ALK）在FCTG中显示出最高的突变频率差异，与较差的结果相关。与野生型患者相比，这些突变中的任何一种都与较短的总生存期相关。使用肿瘤突变状态、CEA、CA19-9、病变直径≥5 cm和诊断时阳性淋巴结构建的列线图模型预测了转化疗效（曲线下面积 = 89.6，95%置信区间22.6 - 92.4）。纳入这些因素的扩展转化相关临床风险评分系统有效地对预后不良人群进行了分层，可作为不可切除CRLM患者的预后工具。
基因组分析改善了CRLM的精准管理，有助于制定个性化的转化策略和更好的预后预测。未来的研究应在前瞻性队列中验证这些发现，以优化对初始不可切除CRLM患者的个性化治疗。
