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

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.

Graphical Abstract

Keywords:

• unresectable hepatocellular carcinoma
• PD-1 inhibitor
• PD-L1 inhibitor
• PET/CT
• metabolic tumor volume
• prognostic model

Abbreviations

¹⁸F-FDG PET/CT, ¹⁸F-fluorodeoxyglucose positron emission tomography–computed tomography; AASLD, American Association for the Study of Liver Diseases; AFP, alpha-fetoprotein; BCLC, Barcelona Clinic Liver Cancer; CI, confidence interval; ECOG-PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; MTV, metabolic tumor volume; OS, overall survival; PUMCH, Peking Union Medical College Hospital; ROI, region of interest; SUV_max, maximum standardized uptake values; TLG, total lesion glycolysis; uHCC, unresectable hepatocellular carcinoma.

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Ethical Approval

The study was conducted according to the guidelines of the Declaration of Helsinki of 1975 and approved by the Ethical Committee of PUMCH (IRB protocol number # ZS-1238, date of approval 20 December 2016).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Consent for Publication

All authors gave their consent for publication.

Author Contributions

All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no competing interests.

Additional information

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).