肿瘤直径对结直肠癌肺转移患者射频消融术后生存及局部进展风险的影响研究

应磊磊, 李珂宁, 陈超, 王英, 黄浩哲, 王标, 李文涛, 何新红

  1. 复旦大学附属肿瘤医院介入治疗科,复旦大学上海医学院肿瘤学系,上海 200032
  • 收稿日期:2025-03-25 修回日期:2025-05-09 出版日期:2025-05-30 发布日期:2025-06-10
  • 通信作者: 何新红
  • 作者简介:应磊磊(ORCID: 0009-0008-6713-6822),硕士。
  • 基金资助:
    国家自然科学基金面上项目(82072034)

摘要/Abstract

摘要:

背景与目的: 约30%的转移性结直肠癌(colorectal cancer,CRC)患者会发生肺转移,但仅不足10%符合外科手术指征。射频消融(radio frequency ablation,RFA)作为不可手术患者的替代疗法,其疗效与转移灶直径的关系尚存在争议。本研究旨在探讨肿瘤直径对CRC肺转移患者RFA术后生存及局部进展风险的影响,验证3 cm作为疗效分界阈值的临床适用性。方法: 回顾性纳入2016年1月—2024年12月复旦大学附属肿瘤医院收治的接受RFA治疗的CRC肺转移患者,按病灶最大直径分为≤3 cm组(Small组)和3~5 cm组(Large组)。患者纳入标准:⑴ 病理学检查证实为CRC来源的肺转移,且仅限于肺转移,或肺外转移病灶已得到根治;⑵ 病灶最大直径<5 cm;⑶ 有完整的临床资料;⑷ 有完整的影像学资料,包括消融术中计算机体层成像(computed tomography,CT)图像和术后随访增强CT图像;⑸ RFA术后随访时间至少超过6个月;⑹ 技术性完全消融;⑺ 肺内转移灶数量少于3个。排除标准:⑴ 靶病灶既往接受过RFA治疗或放疗等局部治疗;⑵ 患者无法耐受RFA治疗;⑶ 患者在RFA术后随访时间小于6个月。3名资深介入治疗科医师在64排螺旋CT扫描仪的引导下,经皮穿刺进行RFA治疗。以RFA术后1个月的胸部增强CT作为基线,之后每3个月扫描1次增强CT,持续1年后,改为每6个月扫描1次增强CT进行随访。本研究已通过复旦大学附属肿瘤医院医学伦理委员会的审查(伦理编号:2108241-11)。主要观察指标为总生存期(overall survival,OS)、无进展生存期(progression-free survival,PFS)及局部肿瘤进展(local tumor progression,LTP),采用Kaplan-Meier生存分析及多因素COX回归模型评估肿瘤直径的独立预测价值。结果: 最终筛选出134例符合入组条件的患者,其中Small组77例,Large组57例。中位随访35个月,≤3 cm组1、3和5年OS率分别为100.0%、95.1%和74.2%,显著优于3~5 cm组(94.7%、36.8%和27.0%,P<0.000 1),1、3和5年PFS率分别为90.9%、34.4%和23.3%,而3~5 cm组仅为13.8%、0.0%和0.0%(P<0.000 1)。此外,≤3 cm组1、3和5年LTP率(0.0%、19.7%和33.6%)显著低于3~5 cm组(46.0%、75.5%和75.5%,P <0.000 1)。多因素分析显示,肿瘤直径>3 cm是影响OS[风险比(hazard ratio,HR)=6.49,95% CI:3.18~13.24,P<0.001]的独立危险因素,术前癌胚抗原(carcinoembryonic antigen,CEA)≥5 ng/mL与OS负相关(HR=1.82,P=0.033)。结论: 肿瘤直径为3~5 cm组的CRC肺转移患者RFA术后生存结局显著劣于≤3 cm组,3 cm可作为筛选RFA适应证的关键阈值,联合术前CEA水平可优化患者分层。

关键词: 结直肠癌, 肺转移, 射频消融, 肿瘤直径, 生存分析

Abstract:

Background and purpose: Approximately 30% of patients with metastatic colorectal cancer (CRC) develops pulmonary metastasis, yet less than 10% are eligible for surgical resection. Radiofrequency ablation (RFA) serves as an alternative therapy for non-surgical candidates, but the relationship between its efficacy and tumor diameter remains controversial. This study aimed to investigate the impact of tumor size on survival outcomes and local progression risk in CRC patients with pulmonary metastasis after RFA, and to validate the clinical utility of a 3 cm threshold for prognosis. Methods: This retrospective study included CRC patients with pulmonary metastasis who underwent RFA at Fudan University Shanghai Cancer Center between January 2016 and December 2024. Patients were stratified into two groups based on maximum lesion diameter: ≤3 cm (Small group) and 3-5 cm (Large group). Patient inclusion criteria: ⑴ pathologically confirmed lung metastases originating from CRC, with metastases limited to the lungs or extra-pulmonary metastatic lesions having been radically treated; ⑵ maximum lesion diameter <5 cm; ⑶ complete clinical data available; ⑷ complete imaging data available, including computed tomography (CT) images during ablation and contrast-enhanced CT images during postoperative follow-up; ⑸ follow-up time of at least >6 months after RFA; ⑹ technical complete ablation; ⑺ fewer than 3 pulmonary metastatic lesions. Exclusion criteria: ⑴ target lesions previously treated with local therapies such as RFA or radiotherapy; ⑵ patients unable to tolerate RFA; ⑶ patients with follow-up time <6 months after RFA. Three senior interventional physicians performed percutaneous RFA under guidance of a 64-slice spiral CT scanner. Chest contrast-enhanced CT scans obtained 1 month after RFA were used as the baseline, followed by contrast-enhanced CT scans every 3 months for 1 year, then every 6 months for subsequent follow-up. This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center (ethical approval number: 2108241-11). Primary endpoints included overall survival (OS), progression-free survival (PFS), and local tumor progression (LTP). Kaplan-Meier analysis and multivariate COX regression were employed to evaluate the independent prognostic value of tumor size. Results: A total of 134 patients who met the inclusion criteria were ultimately enrolled, including 77 in the Small group and 57 in the Large group. With a median follow-up of 35 months, the ≤3 cm group demonstrated superior 1-, 3-, and 5-year OS rates (100.0%, 95.1%, 74.2%) compared to the 3-5 cm group (94.7%, 36.8%, 27.0%, P<0.0001), and the ≤3 cm group demonstrated superior 1-, 3-, and 5-year PFS rates (90.9%, 34.4%, 23.3%) compared to the 3-5 cm group (13.8%, 0.0%, 0.0%, P<0.000 1). The ≤3 cm group also exhibited significantly lower 1-, 3-, and 5-year LTP rates (0.0%, 19.7%, 33.6%) compared to the 3-5 cm group (46.0%, 75.5%, 75.5%, P<0.000 1). Multivariable analysis identified tumor diameter >3 cm as an independent predictor of worse OS [hazard ratio (HR)=6.49, 95% CI: 3.18-13.24, P<0.001], while elevated preoperative carcinoembryonic antigen (CEA) (≥5 ng/mL) correlated with shorter OS (HR=1.82, P=0.033). Conclusion: CRC patients with pulmonary metastasis and tumor diameters of 3-5 cm exhibited significantly inferior survival outcomes after RFA compared to the ≤3 cm group. A tumor diameter of 3 cm can serve as a critical threshold for selecting RFA indications, and combining preoperative CEA levels can optimize patient stratification.

Key words: Colorectal cancer, Pulmonary metastases, Radiofrequency ablation, Tumor diameter, Survival analysis

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