为肝细胞癌武装 GPC3 CAR T 细胞:多少才足够,下一步是什么?
Armouring GPC3 CAR T cells for hepatocellular carcinoma: how much is enough and what comes next?
英文原题:Real-world status, efficacy and prognosis analysis of first-line treatment for unresectable hepatocellular carcinoma in patients treated at multiple centres.
TI 是 uHCC 患者最常用的一线全身治疗,在特定人群中与局部区域治疗联合时疗效和结局更好。
目的:描述不可切除肝细胞癌(uHCC)一线治疗的真实世界现状,并探索疗效和预后的预测因素。方法:回顾性收集2019年7月至2022年12月中国皖北4家医院接受一线治疗的uHCC患者真实世界数据,分析临床病理特征、超氧化物歧化酶(SOD)和血管内皮生长因子A(VEGF-A)等血液学指标、疗效及安全性。结果:共纳入153例患者,多数接受靶向治疗联合免疫治疗(TI)。与TI组相比,靶向加免疫并联合局部区域治疗(TIL)组无进展生存期中位数(mPFS)和总生存期中位数(mOS)均更长(均P<0.05),且安全性可控。基线血清SOD水平较高的患者较低水平者疗效更好,mPFS和mOS更长(均P<0.05)。亚组分析显示,低SOD患者接受TIL较TI的mPFS更长(P=0.005);而高SOD患者TIL与TI的预后无显著差异(P>0.05)。低VEGF-A组患者mOS较高VEGF-A组更长(P=0.004)。与TI相比,TIL可延长高VEGF-A患者生存,但低VEGF-A患者未见这一获益。结论:TI是uHCC最常用的一线全身治疗,在特定患者中联合局部区域治疗可改善疗效和结局。基线血清SOD和VEGF-A可能是基层临床决策、治疗反应及结局的预测生物标志物。补充要点:TI是皖北uHCC患者最常见的一线全身治疗方案;特定人群中TIL可能较TI具有更好的疗效和结局。基线SOD水平与疗效和预后正相关,低SOD且预后不良的患者可能从TIL中获益。基线VEGF-A较高与疗效较差和OS较短相关;此类患者建议一线采用TIL。
OBJECTIVE: To present the real-world status and explore the predictors of the efficacy and prognosis of first-line treatment for unresectable hepatocellular carcinoma (uHCC). METHODS: Real-world data of uHCC patients who underwent first-line treatment at 4 hospitals in Northern Anhui, China, from July 2019 to December 2022 were retrospectively collected. The clinicopathological features, haematological indicators, including superoxide dismutase (SOD) and vascular endothelial growth factor-A (VEGF-A), efficacy and safety data were analysed. RESULTS: A total of 153 patients were enrolled and most of them treated with targeted therapy combined with immunotherapy (TI). Compared to patients treated with TI, patients who were administrated with TI plus locoregional therapy (TIL) showed longer median progression-free survival (mPFS) and median overall survival (mOS) times (both p < 0.05), with manageable safety profiles. Moreover, compared to patients with low baseline serum levels of SOD, patients with high baseline serum SOD levels had a better treatment efficacy and had longer mPFS and mOS times (all p < 0.05). Subgroup analyses indicated that patients with low SOD levels had longer mPFS times when receiving TIL than when receiving TI ( p = 0.005), but, among patients with high SOD levels, their prognoses were not substantially different between TIL and TI ( p > 0.05). Additionally, patients in the low-VEGF-A group had a longer mOS time than patients in the high-VEGF-A group ( p = 0.004). In comparison with TI, TIL can improve the survival time among patients with high VEGF-A levels but not among patients with low VEGF-A levels. CONCLUSIONS: TI was the most commonly first-line systemic therapy for uHCC patients, with better efficacy and outcomes when combined with locoregional therapy in a certain population. Baseline serum SOD and VEGF-A were found to be potential predictive biomarkers for decision-making, treatment response, and outcome in patients with uHCC in the primary care setting. TI was the most commonly used first-line systemic therapy regimen for uHCC patients in Northern Anhui, China.TIL might conferred better therapeutic efficacy and outcome than TI in specific uHCC populations.The baseline serum SOD level was found to be positively correlated with first-line treatment efficacy and patients prognosis in uHCC, and low-SOD patients with a dismal prognosis was identified to have potential to benefit from TIL.High baseline serum VEGF-A levels were associated with poor efficacy and short OS times in uHCC patients. For patients with a high baseline VEGF-A, TIL is recommended as the first-line treatment.
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