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. 2023 May 1;277(5):813-820. doi: 10.1097/SLA.0000000000005461. Epub 2022 Jul 6.
To evaluate the association of perioperative ctDNA dynamics on outcomes after hepatectomy for CLM.
Prognostication is imprecise for patients undergoing hepatectomy for CLM, and ctDNA is a promising biomarker. However, clinical implications of perioperative ctDNA dynamics are not well established.
Patients underwent curative-intent hepatectomy after preoperative chemotherapy for CLM (2013-2017) with paired prehepatectomy/postoperative ctDNA analyses via plasma-only assay. Positivity was determined using a proprietary variant classifier. Primary endpoint was recurrence-free survival (RFS). Median follow-up was 55 months.
Forty-eight patients were included. ctDNA was detected before and after surgery (ctDNA+/+) in 14 (29%), before but not after surgery (ctDNA+/-) in 19 (40%), and not at all (ctDNA-/-) in 11 (23%). Adverse tissue somatic mutations were detected in TP53 (n = 26; 54%), RAS (n = 23; 48%), SMAD4 (n = 5; 10%), FBXW7 (n = 3; 6%), and BRAF (n = 2; 4%). ctDNA+/+ was associated with worse RFS (median: ctDNA+/+, 6.0 months; ctDNA+/-, not reached; ctDNA-/-, 33.0 months; P = 0.001). Compared to ctDNA+/+, ctDNA+/- was associated with improved RFS [hazard ratio (HR) 0.24 (95% confidence interval (CI) 0.1-0.58)] and overall survival [HR 0.24 (95% CI 0.08-0.74)]. Adverse somatic mutations were not associated with survival. After adjustment for prehepatectomy chemotherapy, synchronous disease, and ≥2 CLM, ctDNA+/- and ctDNA-/- were independently associated with improved RFS compared to ctDNA+/+ (ctDNA+/-: HR 0.21, 95% CI 0.08-0.53; ctDNA-/-: HR 0.21, 95% CI 0.08-0.56).
Perioperative ctDNA dynamics are associated with survival, identify patients with high recurrence risk, and may be used to guide treatment decisions and surveillance after hepatectomy for patients with CLM.
评估围手术期 ctDNA 动态变化与 CLM 肝切除术后结局的关系。
对于接受 CLM 肝切除术的患者，预后预测并不准确，ctDNA 是一种很有前途的生物标志物。然而，围手术期 ctDNA 动态变化的临床意义尚未得到充分确立。
2013 年至 2017 年间，对接受术前化疗的 CLM 患者进行根治性肝切除术，并通过仅血浆检测法进行术前和术后配对 ctDNA 分析。采用专有的变异分类器确定阳性。主要终点是无复发生存率（RFS）。中位随访时间为 55 个月。
共纳入 48 例患者。14 例（29%）患者术前和术后均检测到 ctDNA（ctDNA+/+），19 例（40%）患者仅术前检测到 ctDNA（ctDNA+/-），11 例（23%）患者未检测到 ctDNA（ctDNA-/-）。在 TP53（n=26；54%）、RAS（n=23；48%）、SMAD4（n=5；10%）、FBXW7（n=3；6%）和 BRAF（n=2；4%）中检测到不良组织体细胞突变。ctDNA+/+与较差的 RFS 相关（中位：ctDNA+/+，6.0 个月；ctDNA+/-，未达到；ctDNA-/-，33.0 个月；P=0.001）。与 ctDNA+/+相比，ctDNA+/-与改善的 RFS[风险比（HR）0.24（95%置信区间（CI）0.1-0.58）]和总生存[HR 0.24（95% CI 0.08-0.74）]相关。不良体细胞突变与生存无关。在调整术前化疗、同步疾病和≥2 个 CLM 后，ctDNA+/-和 ctDNA-/-与 ctDNA+/+相比，RFS 改善相关（ctDNA+/-：HR 0.21，95% CI 0.08-0.53；ctDNA-/-：HR 0.21，95% CI 0.08-0.56）。
围手术期 ctDNA 动态变化与生存相关，可识别高复发风险患者，并可能用于指导 CLM 肝切除术后的治疗决策和监测。
