PO.CL12.04 · 临床研究

68Ga-PSMA PET成像在接受一线免疫治疗的晚期肝细胞癌患者中的前瞻性评估

Prospective evaluation of 68Ga-PSMA PET imaging in advanced hepatocellular carcinoma patients undergoing first line immunotherapy

编号 2611 展板 2 时间 4/20 09:00–12:00 区域 Section 47 主讲 Nguyen Tran, MD;MPH

分会场 Molecular Imaging, Radiomics, and Theranostics

查看 PDF 下载 PDF 🔒 查看 / 下载完整 PDF 需登录并开通下载套餐 · 查看套餐 / 开通 AACR 官方页面

作者与单位 Authors & Affiliations

Nguyen H. Tran¹, Jacob Hirdler¹, Ajith Antony², Jacob Teske¹, Sudhakar K. Venkatesh¹, Amit Mahipal³, Michael S. Torbenson¹, Scott M. Thompson¹, Thor R. Halfdanarson¹, Zhaohui Jin¹, Lionel Aurelien Kankeu Fonkoua¹, Leslie A. Washburn¹, Alexander Revzin¹, Haidong Dong¹, Robert R. Mcwilliams¹, Aminah Jatoi¹, Hani M. Babiker⁴, Mitesh J. Borad⁵, Tanios Bekaii-Saab⁵, Gregory J. Gores¹, Lewis R. Roberts¹, Geoffrey B. Johnson¹, Ajit H. Goenka¹

¹Mayo Clinic, Rochester, MN,²MD Anderson, Houston, TX,³University Hospital, Cleveland, OH,⁴Mayo Clinic Florida, Jacksonville, FL,⁵Mayo Clinic Arizona, Scottsdale, AZ

摘要 Abstract

中文摘要

前列腺特异性膜抗原（PSMA）在肝细胞癌（HCC）的肿瘤相关新生血管中高表达，凸显了其作为诊疗一体化靶点的潜力。这项前瞻性研究旨在评估源自PSMA正电子发射断层扫描/计算机断层扫描（PET/CT）的新型生物标志物在评估接受一线免疫检查点抑制剂（ICI）治疗的晚期HCC患者（pts）治疗反应中的效用。方法：本研究（NCT05176223）纳入了适合接受一线ICI（atezolizumab/bevacizumab [A/B] 或 durvalumab/tremelimumab [D/T]）、且依据RECIST标准具有可测量病灶的不可切除晚期HCC患者。主要终点：按RECIST 1.1和mRECIST评定的无进展生存期（PFS）；总生存期（OS）；以及最佳总体反应。采用Kaplan-Meier法估计生存分布。观察一致性定义为PET/CT或CT分类的反应相符的患者比例。使用加权kappa和Cohen's kappa量化PET/CT与CT之间一致性的强度。患者最多完成五次68Ga-PSMA PET/CT扫描和血液采集。结果：2022年10月至2024年11月间共纳入26名患者（25名可评估）。中位随访时间为22.1个月（m）（Q1，Q3：14.5-23.7）。中位年龄68岁，72%为男性，88%为白人，68%为Child-Pugh [CP] A级，32%为CP B级，32%为巴塞罗那临床肝癌[BCLC]分期B期，68%为BCLC C期，36%伴有微血管侵犯；56%接受A/B治疗，40%接受D/T治疗。96%的患者在基线时PSMA阳性，中位SUVmax为14.3（范围5.1-40.5），中位背景肝脏SUVmax为3.9（范围2.1-6.8）。按RECIST和mRECIST评定的中位（95%CI）PFS均为5.6 m（4.6-12.5）。中位（95%CI）OS为18.6 m（7.2-无法估计），56%的患者死亡。在判定最佳反应时，经PET/CT改良的PERCIST标准与RECIST和mRECIST相比的观察一致性分别为46%和50%，加权kappa分别为0.63（95% CI：0.37-0.90）和0.66（0.41-0.92）。在应答者评估方面，PERCIST与RECIST和mRECIST相比的观察一致性分别为67%和71%，Cohen's kappa分别为0.36（0.03-0.68）和0.43（0.11-0.76）。结论：在该队列中，除一名患者外，所有晚期HCC患者均观察到PSMA PET/CT亲和性，每例均表现出中至高的SUVmax值。中位OS和PFS与临床试验报道的结果一致。使用68Ga-PSMA PET/CT依据PERCIST标准进行的反应评估与RECIST和mRECIST标准均显示良好的一致性。免疫生物标志物的分析正在进行中。

查看英文原文 English abstract

Prostate-specific membrane antigen (PSMA) is highly expressed in tumor-associated neovasculature in hepatocellular carcinoma (HCC), highlighting its promise as a theranostic target. This prospective study aimed to evaluate the utility of novel biomarkers derived from PSMA positron emission tomography computed tomography (PET/CT) to assess treatment response in advanced HCC patients (pts) receiving first line immune checkpoint inhibitors (ICI). Methods: This study (NCT05176223) enrolled unresectable, advanced HCC pts eligible for first-line ICI (atezolizumab/bevacizumab [A/B] or durvalumab/tremelimumab [D/T]) with measurable disease according to RECIST criteria. Primary endpoints: progression-free survival (PFS) per RECIST 1.1 and mRECIST; overall survival (OS); and best overall response. The survival distribution was estimated using the Kaplan-Meier method. Observed agreement is defined as the proportion of pts whose responses, as classified by PET/CT or CT, were concordant. Weighted kappa and Cohen's kappa were used to quantify the strength of agreement between PET/CT and CT. Pts completed up to five 68Ga-PSMA PET/CT scans and blood collections. Results: Twenty-six pts were enrolled (25 evaluable) between Oct 2022 and Nov 2024. Median follow up was 22.1 months (m) (Q1, Q3: 14.5-23.7). Median age 68 yrs, 72% male, 88% White, 68% Child-Pugh [CP] A, 32% CP B, 32% Barcelona Clinic Liver Cancer [BCLC] stage B, 68% BCLC stage C, 36% with microvascular invasion; 56% received A/B and 40% received D/T treatment. PSMA was positive in 96% of pts at baseline with median SUVmax 14.3 (range 5.1-40.5) and median background liver SUVmax 3.9 (range 2.1-6.8). Median (95%CI) PFS was 5.6 m (4.6-12.5) by both RECIST and mRECIST. Median (95%CI) OS was 18.6 m (7.2-not estimable), with 56% deceased. The observed agreement between PET/CT adapted PERCIST criteria compared to RECIST and mRECIST in determining the best response was 46% and 50% and weighted kappa of 0.63 (95% CI: 0.37-0.90) and 0.66 (0.41-0.92), respectively. Observed agreement between PERCIST compared to RECIST and mRECIST for responders' assessment was 67% and 71% with Cohen's kappa of 0.36 (0.03-0.68) and 0.43 (0.11-0.76), respectively. Conclusion: In this cohort, PSMA PET/CT avidity was observed in all but one pt with advanced HCC, each demonstrating moderate to high SUVmax values. Median OS and PFS were consistent with outcomes reported in clinical trials. Response assessment using 68Ga-PSMA PET/CT according to PERCIST criteria showed good concordance with both RECIST and mRECIST standards. Analysis of immune biomarkers is ongoing.

利益披露 Disclosure

N. H. Tran, AstraZeneca ). Exelixis Other, Ad board. DAVA Oncology Travel. Elevar Therapeutics Other, Ad board. Genentech ). Ipsen Other, ad board. MD outlook Other, Talks. J. Hirdler, None.. A. Antony, None.. J. Teske, None.. S. K. Venkatesh, None.. A. Mahipal, None.. M. S. Torbenson, None.. S. M. Thompson, None.. T. R. Halfdanarson, None.. Z. Jin, None.. L. A. Kankeu Fonkoua, None.. L. A. Washburn, None.. A. Revzin, None.. H. Dong, None.. R. R. Mcwilliams, None.. A. Jatoi, None.. M. J. Borad, None.. G. J. Gores, None.. L. R. Roberts, None.. G. B. Johnson, None.. A. H. Goenka, None.

← 返回 AACR 2026 检索