Metabolic Tumor Volume Measured by 18F-FDG PET/CT is Associated with the Survival of Unresectable Hepatocellular Carcinoma Treated with PD-1/PD-L1 Inhibitors Plus Molecular Targeted Agents

Xuezhu Wang; Xu Yang; Jingnan Wang; Chengyan Dong; Jie Ding; Meiqi Wu; Yanyu Wang; Haiyan Ding; Hui Zhang; Xinting Sang; Haitao Zhao; Li Huo

doi:10.2147/JHC.S401647

Metabolic Tumor Volume Measured by ¹⁸F-FDG PET/CT is Associated with the Survival of Unresectable Hepatocellular Carcinoma Treated with PD-1/PD-L1 Inhibitors Plus Molecular Targeted Agents

J Hepatocell Carcinoma. 2023 Apr 8:10:587-598. doi: 10.2147/JHC.S401647. eCollection 2023.

Authors

Xuezhu Wang^#¹, Xu Yang^#², Jingnan Wang¹, Chengyan Dong³, Jie Ding¹, Meiqi Wu¹, Yanyu Wang², Haiyan Ding⁴, Hui Zhang⁴, Xinting Sang², Haitao Zhao², Li Huo¹

Affiliations

¹ Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Center for Rare Diseases Research, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
² Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
³ GE Healthcare China, Beijing, People's Republic of China.
⁴ Department of Biomedical Engineering, Tsinghua University, Beijing, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: The combination of PD-1/PD-L1 inhibitors and molecular targeted agents showed promising efficacy for unresectable hepatocellular carcinoma (uHCC). This study aimed to investigate the prognostic value of metabolic parameters from ¹⁸F-fluorodeoxyglucose positron emission tomography-computed tomography (¹⁸F-FDG PET/CT) in patients with uHCC underwent the combined therapies.

Patients and methods: Patients with uHCC treated with a combination of immunotherapy and targeted therapy who underwent baseline ¹⁸F-FDG PET/CT between July 2018 and December 2021 were recruited retrospectively. The metabolic tumor volume (MTV), total lesion glycolysis (TLG), maximum standardized uptake values (SUV_max), and clinical and biological parameters were recorded. A multivariate prediction model was developed for overall survival (OS) using these parameters together with clinical prognostic factors.

Results: Seventy-seven patients were finally included. The median OS was 16.8 months. We found that a high MTV (≥39.65 cm³ as the median value) was significantly associated with OS (P<0.05). In multivariate analyses for OS, a high MTV, high Eastern Cooperative Oncology Group performance status (ECOG-PS, ≥1), Child-Pugh (B-C) grade, and the presence of bone metastasis were significantly associated with poor OS (HR 1.371, HR 3.73, HR 15.384, and HR 2.994, all P<0.05, respectively). A multivariate prognostic model including MTV and prognostic factors, such as ECOG-PS, Child-Pugh grade, and bone metastasis, further improved the identification of different OS subgroups.

Conclusion: High MTV is an adverse prognostic factor in patients with uHCC treated with a combination of immunotherapy and molecular targeted agents. Integrating PET/CT parameters with clinical prognostic factors could help to personalize immunotherapy.

Keywords: PD-1 inhibitor; PD-L1 inhibitor; PET/CT; metabolic tumor volume; prognostic model; unresectable hepatocellular carcinoma.

Grants and funding

This work was supported in part by the National Key Research and Development Program of China (No. 2016YFC0901500, 2020YFC2002702), the National Natural Science Foundation of China (No. 82071967), and the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-061, 2022-I2M-C&T-A-003).