不可切除肝细胞癌患者接受三联联合治疗时早期甲胎蛋白和去γ羧基凝血酶原反应的预后意义
Prognostic significance of early alpha fetoprotein and des-gamma carboxy prothrombin responses in unresectable hepatocellular carcinoma patients undergoing triple combination therapy.
作者信息
Zhang Teng, Li Wengang, Chen Qian, He Weiping, Sun Jing, Li Dong, Wang Quan, Duan Xuezhang
机构信息
Department of Radiation Oncology, Senior Department of Oncology, The Fifth Medical Center of PLA General Hospital, Beijing, China.
Department of Oncology, The 983rd Hospital of Joint Logistic Support Force of PLA, Tianjin, China.
出版信息
Front Immunol. 2024 Dec 12;15:1508028. doi: 10.3389/fimmu.2024.1508028. eCollection 2024.
BACKGROUND
Recent advancements in combination therapy for unresectable hepatocellular carcinoma (uHCC) have shown promise, but reliable serological prognostic indicators are currently lacking for patients undergoing triple combination therapy of stereotactic body radiation therapy (SBRT), immunotherapy, and targeted therapy. We aimed to investigate the prognostic significance of early alpha fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) responses in these patients.
METHODS
This retrospective research included 115 uHCC patients treated with SBRT in combination with immunotherapy and targeted therapy (triple therapy) at our institution from April 2021 to December 2022. Participants were categorized into high AFP and high DCP cohorts based on baseline levels. AFP and DCP responses were defined as decreases from baseline of over 50% and 70%, respectively, according to ROC curve analysis. Differences in overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were assessed between the tumor biomarker response and non-response groups.
RESULTS
Multivariate analysis indicated that AFP or DCP response at 6-8 weeks post-therapy significantly influenced ORR (high AFP cohort: odds ratio [OR] 5.50, 95% CI 2.04-14.83, p=0.001; high DCP cohort: OR 7.99, 95%CI 2.82-22.60, p<0.001). The median PFS was notably longer in tumor biomarker response groups (high AFP cohort: 13.7 vs 6.2 months, hazard ratio [HR] 0.36, 95% CI 0.20-0.62, p<0.001; high DCP cohort: 15.6 vs 9.3 months, HR 0.44, 95% CI 0.26-0.74, p=0.002). AFP or DCP response was associated with prolonged OS (high AFP cohort: not reached vs. 21.9 months, HR 0.47, 95% CI 0.22-0.99, p=0.047; high DCP cohort: not reached vs. 20.6 months, HR 0.35, 95% CI 0.14-0.86, p=0.022).
CONCLUSION
AFP or DCP response at 6-8 weeks post-therapy predicts better oncological outcomes in patients with uHCC treated with triple therapy.
背景
不可切除肝细胞癌（uHCC）联合治疗的最新进展显示出前景，但目前对于接受立体定向体部放射治疗（SBRT）、免疫治疗和靶向治疗三联联合治疗的患者，缺乏可靠的血清学预后指标。我们旨在研究这些患者早期甲胎蛋白（AFP）和异常凝血酶原（DCP）反应的预后意义。
方法
这项回顾性研究纳入了2021年4月至2022年12月在我们机构接受SBRT联合免疫治疗和靶向治疗（三联治疗）的115例uHCC患者。根据基线水平将参与者分为高AFP和高DCP队列。根据ROC曲线分析，AFP和DCP反应分别定义为较基线水平下降超过50%和70%。评估肿瘤生物标志物反应组和无反应组之间的总生存期（OS）、无进展生存期（PFS）和客观缓解率（ORR）的差异。
结果
多因素分析表明，治疗后6 - 8周的AFP或DCP反应显著影响ORR（高AFP队列：比值比[OR] 5.50，95%可信区间[CI] 2.04 - 14.83，p = 0.001；高DCP队列：OR 7.99，95%CI 2.82 - 22.60，p < 0.001）。肿瘤生物标志物反应组的中位PFS明显更长（高AFP队列：13.7个月对6.2个月，风险比[HR] 0.36，95%CI 0.20 - 0.62，p < 0.001；高DCP队列：15.6个月对9.3个月，HR 0.44，95%CI 0.26 - 0.74，p = 0.002）。AFP或DCP反应与OS延长相关（高AFP队列：未达到对21.9个月，HR 0.47，95%CI 0.22 - 0.99，p = 0.047；高DCP队列：未达到对20.6个月，HR 0.35，95%CI 0.14 - 0.86，p = 0.022）。
结论
治疗后6 - 8周的AFP或DCP反应预示着接受三联治疗的uHCC患者有更好的肿瘤学结局。
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