Changes in Posttreatment Spleen Volume Associated with Immunotherapy Outcomes for Advanced Hepatocellular Carcinoma

Abstract

Purpose

We investigated whether spleen volume (SV) changes were associated with treatment outcomes in advanced hepatocellular carcinoma (HCC) patients who received immunotherapy or first-line sorafenib.

Patients and Methods

Patients with advanced HCC who underwent immunotherapy or first-line sorafenib at our institute were retrospectively analyzed. CT was used to measure SV before and within 3 months of treatment initiation. Tumor assessment followed Response Evaluation Criteria in Solid Tumors version 1.1. The association between SV change and tumor response or progression-free survival (PFS) was analyzed. The inverse probability of treatment weighting (IPTW) was used to adjust for differences in baseline characteristics.

Results

The immunotherapy group comprised 143 patients (124 men, mean age, 59.8 years ± 11.2 [standard deviation]), while the sorafenib group had 57 (47 men, mean age, 59.6 years ± 9.9). SV increased in 108 (75.5%) immunotherapy and 21 (36.8%) sorafenib patients. In the immunotherapy group, patients with increased SV were more likely than those with decreased SV to have a higher disease control rate (76.9% vs 57.1%, p = 0.024) and durable clinical benefit (52.8% vs 25.7%, p = 0.005). It was also associated with extended PFS in the immunotherapy group in both the univariate (p = 0.028) and multivariate (p = 0.014) analysis. By contrast, in the sorafenib group, an increased in SV was not associated with treatment response but was presumably associated with reduced PFS (p = 0.072) in the multivariate analysis. After IPTW adjustment, the increase in SV remained a significant predictor for DCB and PFS in the immunotherapy group.

Conclusion

Most patients exhibited an increase in SV after the initiation of immunotherapy, which may be used to predict response and prognosis. However, this association was not observed in patients who received sorafenib.

Plain Language Summary

The study provides significant evidence that an increase in spleen volume is associated with better treatment outcomes in advanced hepatocellular carcinoma patients undergoing immunotherapy. These findings offer oncologists a new potential biomarker for optimizing treatment strategies. Specifically, increased spleen volume could be used to predict higher rates of disease control and durable clinical benefits, allowing for more personalized care.

Graphical Abstract

Keywords:

• hepatocellular carcinoma
• immunotherapy
• sorafenib
• response
• survival

Abbreviations

HCC, Hepatocellular carcinoma; ICI, Immune checkpoint inhibitor; PD-L1, Programmed death ligand 1; AFP, α-Fetoprotein; SV, Spleen volume; PD-1, Programmed cell death protein 1; CTLA-4, Cytotoxic T-lymphocyte-associated protein 4; ALBI, Albumin-bilirubin; BCLC, Barcelona Clinic Liver Cancer; CT, Computed tomography; RECIST, Response Evaluation Criteria in Solid Tumors; DCR, Disease control rate; ORR, Objective response rate; DCB, Durable clinical benefit; PFS, Progression-free survival; CI, Confidence interval; HR, Hazard ratio.

Data Sharing Statement

For ethical reasons, the data are not publicly available. The data sets generated and analyzed in this study are available from the corresponding author upon reasonable request.

Ethics Approval and Informed Consent

Institutional Review Board approval of National Taiwan University Hospital was obtained.

This study was conducted in full compliance with the ethical principles outlined in the Declaration of Helsinki.

For patients receiving immunotherapy, written informed consent was waived by the Institutional Review Board because of retrospective analysis. Besides, stringent measures have been implemented to ensure the confidentiality and privacy of patient data. All medical records were anonymized and securely stored, accessible only to authorized research personnel. The data was handled in accordance with applicable privacy laws and guidelines to protect patient identities and maintain the integrity of the research.

For patients receiving sorafenib, written informed consent was obtained from all patients receiving sorafenib.

Acknowledgments

We would like to acknowledge the service provided by the RCF5 Lab. of Department of Medical Research at National Taiwan University Hospital.

Author Contributions

Study design and concept: Bang-Bin Chen, Yu-Yun Shao.

Data collection: All authors.

Study analysis: Bang-Bin Chen, Yu-Yun Shao.

Data interpretation and review and approval the manuscript submission: All authors.

Manuscript writing: Bang-Bin Chen, Yu-Yun Shao.

Disclosure

Dr Chih-Hung Hsu reports grants from Roche, grants from AstraZeneca, grants from Eli Lilly, grants from Surface Oncology, personal fees from MSD, personal fees from Eisai, outside the submitted work. The authors report no other competing interests in this work.

Additional information

Funding

This study has received funding by This study was funded by the Ministry of Science and Technology, Taiwan (MOST-103-2314-B-002-181-MY2, MOST-105-2314-B-002-194, MOST-106-2314-B-002-213, MOST-108-2314-B-002-072-MY3, MOST-110-2314-B-002-144, MOST-111-2314-B-002-120, and MOST-111-2314-B-002-130-MY2), National Science and Technology Council, Taiwan (NSC 112-2314-B-002-267), Ministry of Health and Welfare, Taiwan (MOHW109-TDU-B-211-114002 and MOHW112-TDU-B-211-144002), National Taiwan University Hospital (NTUH 105S2954 and NTUH 108-S4150), and Good Liver Foundation, Taiwan.