Comparison of Baseline 68Ga-FAPI and 18F-FDG PET/CT for Prediction of Response and Clinical Outcome in Patients with Unresectable Hepatocellular Carcinoma Treated with PD-1 Inhibitor and Lenvatinib.

IF 9.1 1区 医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING Journal of Nuclear Medicine Pub Date : 2023-10-01 Epub Date: 2023-07-27 DOI:10.2967/jnumed.123.265712
Meiqi Wu, Yanyu Wang, Qiao Yang, Xuezhu Wang, Xu Yang, Haiqun Xing, Xinting Sang, Xiang Li, Haitao Zhao, Li Huo
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引用次数: 1

Abstract

Fibroblast activation protein contributes to immunosuppression and resistance to immunotherapies. This study aimed to compare baseline 68Ga-labeled fibroblast activation protein inhibitor (68Ga-FAPI) PET/CT and 18F-FDG PET/CT in response and survival prediction in unresectable hepatocellular carcinoma (uHCC) patients treated with the combination of programmed cell death 1 (PD-1) inhibitor and lenvatinib. Methods: In this prospective cohort study, 22 patients with uHCC who underwent baseline 18F-FDG and 68Ga-FAPI PET/CT and soon began taking a combination of PD-1 inhibitor and lenvatinib were recruited. Semiquantitative indices of baseline PET/CT were measured as 18F-FDG SUVmax, metabolic tumor volume, total lesion glycolysis, 68Ga-FAPI SUVmax, 68Ga-FAPI-avid tumor volume (FTV), and total lesion fibroblast activation protein expression (TLF). The primary endpoint was durable or nondurable clinical benefit after treatment, and the secondary endpoints were progression-free survival (PFS) and overall survival (OS). Results: The overall response rate of the combination therapy was 41% (9/22). Fifty percent of patients had durable clinical benefit. Median PFS and OS were 4.8 and 14.4 mo, respectively. Patients with nondurable clinical benefit showed a significantly higher FTV and TLF than those with durable clinical benefit, whereas 18F-FDG parameters overlapped. A higher 68Ga-FAPI-avid tumor burden (FTV > 230.46 cm3 or TLF > 961.74 SUVbody weight⋅cm3) predicted both shorter PFS (4.0 vs. 13.5 mo, P = 0.016) and shorter OS (7.8 mo vs. not reached, P = 0.030). Patients with a higher metabolic tumor burden (metabolic tumor volume > 206.80 cm3 or total lesion glycolysis > 693.53 SUVbody weight⋅cm3) showed a shorter OS although the difference did not reach statistical significance (P = 0.085). In multivariate analysis, a higher 68Ga-FAPI-avid tumor burden (hazard ratio [HR], 3.88 [95% CI, 1.26-12.01]; P = 0.020) and macrovascular invasion (HR, 4.00 [95% CI, 1.06-15.14]; P = 0.039) independently predicted a shorter PFS, whereas a higher 68Ga-FAPI-avid tumor burden (HR, 5.92 [95% CI, 1.19-29.42]; P = 0.035) and bone metastases (HR, 5.88 [95% CI, 1.33-25.93]; P = 0.022) independently predicted a shorter OS. Conclusion: Volumetric indices on baseline 68Ga-FAPI PET/CT were potentially independent prognostic factors to predict durable clinical benefit, PFS, and OS in uHCC patients treated with a combination of PD-1 and lenvatinib. Baseline 68Ga-FAPI PET/CT may facilitate uHCC patient selection before combination therapy.

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基线68Ga FAPI和18F-FDG PET/CT预测PD-1抑制剂和乐伐替尼治疗的不可切除肝细胞癌患者的反应和临床结果的比较。
成纤维细胞活化蛋白有助于免疫抑制和对免疫疗法的抵抗。本研究旨在比较68Ga标记的成纤维细胞活化蛋白抑制剂(68Ga-FAPI)PET/CT和18F-FDG PET/CT在程序性细胞死亡1(PD-1)抑制剂和乐伐替尼联合治疗的不可切除肝细胞癌(uHCC)患者中的反应和生存预测。方法:在这项前瞻性队列研究中,招募了22名uHCC患者,他们接受了18F-FDG和68Ga FAPI PET/CT基线检查,并很快开始服用PD-1抑制剂和乐伐替尼的联合用药。基线PET/CT的半定量指标测量为18F-FDG SUVmax、代谢性肿瘤体积、总病变糖酵解、68Ga-FAPI SUVmax和68Ga-FAPI狂热肿瘤体积(FTV)以及总病变成纤维细胞活化蛋白表达(TLF)。主要终点是治疗后的持久或非持久临床获益,次要终点是无进展生存期(PFS)和总生存期(OS)。结果:综合治疗总有效率为41%(9/22)。50%的患者具有持久的临床益处。中位PFS和OS分别为4.8和14.4 mo。具有非持久性临床获益的患者显示出比具有持久性临床受益的患者显著更高的FTV和TLF,而18F-FDG参数重叠。较高的68Ga FAPI狂热肿瘤负荷(FTV>230.46 cm3或TLF>961.74 SUV体重·cm3)可预测两种疾病的PFS较短(4.0 vs.13.5 mo,P=0.016)和较短OS(7.8 mo与未达到,P=0.030)。代谢肿瘤负荷较高(代谢肿瘤体积>206.80 cm3或总病变糖酵解>693.53 SUV体重·cm3)的患者表现出较短的OS,尽管差异没有达到统计学意义(P=0.085)。在多变量分析中,较高的68Ga FAPI狂热肿瘤负荷(危险比[HR],3.88[95%CI,1.26-12.01];P=0.020)和大血管侵袭(HR,4.00[95%CI:1.06-15.14];P=0.039)独立预测PFS较短,而较高的68Ga FAPI狂热瘤负荷(HR,5.92[95%CI;1.19-29.42];P=0.035)和骨转移(HR,5.88[95%CI:1.33-25.93];P=0.022)独立预测OS较短。结论:68Ga FAPI PET/CT基线体积指数是预测PD-1和乐伐替尼联合治疗uHCC患者持久临床获益、PFS和OS的潜在独立预后因素。基线68Ga FAPI PET/CT可能有助于uHCC患者在联合治疗前的选择。
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来源期刊
Journal of Nuclear Medicine
Journal of Nuclear Medicine 医学-核医学
CiteScore
13.00
自引率
8.60%
发文量
340
审稿时长
1 months
期刊介绍: The Journal of Nuclear Medicine (JNM), self-published by the Society of Nuclear Medicine and Molecular Imaging (SNMMI), provides readers worldwide with clinical and basic science investigations, continuing education articles, reviews, employment opportunities, and updates on practice and research. In the 2022 Journal Citation Reports (released in June 2023), JNM ranked sixth in impact among 203 medical journals worldwide in the radiology, nuclear medicine, and medical imaging category.
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