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Survival benefit and impact of adjuvant therapies following FOLFOX-HAIC-based conversion therapy with unresectable hepatocellular carcinoma: a retrospective cohort study

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Abstract

Background

Recently, the conversion therapies of FOLFOX-HAIC for patients with unresectable hepatocellular carcinoma (uHCC) have dramatically increased the tumor responses and conversion rate; thus, the prognosis of uHCC patients was expected to be prolonged. However, the postoperative recurrence of uHCC patients who successfully underwent conversion therapies stayed high. The present study evaluated the efficacy and safety of postoperatively adjuvant therapy in treating uHCC patients who received FOLFOX-HAIC-based conversion therapy.

Methods

In this real-world retrospective study, uHCC patients who received FOLFOX-HAIC-based conversion therapy were included. The recurrence-free survival (RFS), as primary outcomes, was compared between patients who received adjuvant therapy (AT group) or non-adjuvant therapy (nAT group) using survival analysis and Cox regression. Imbalances in baseline clinical features between the two groups were adjusted through propensity score matching (PSM) and inverse probability of treatment weighting (IPTW).

Results

Between January 2016 and December 2022, 204 uHCC patients who received FOLFOX-HAIC-based conversion therapy were included and assigned into AT group (n = 47) and nAT group (n = 157), respectively. The median RFS was significantly longer in the AT group than the nAT group before adjustment [19.2 vs. 10.8 months; hazard ratio (HR), 0.584; 95% CI, 0.383–0.892; P = 0.028], after PSM and after IPTW. Subsequent subgroup analyses revealed the RFS of adjuvant therapy was best in uHCC patients with younger than 60 years, macrovascular invasion, and positive hepatitis B surface antigen.

Conclusion

Postoperatively, adjuvant therapy was associated with improved survival outcomes compared with non-adjuvant therapy after FOLFOX-HAIC-based conversion therapy among uHCC patients, especially for patients with macrovascular invasion and positive hepatitis B surface antigen.

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Data availability

The data were availability on https://www.researchdata.org.cn/ after publishment.

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Funding

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Author notes

  1. Yangxun Pan, Ze Yuan, Jiongliang Wang and Siegmund Ngai contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651# East Dongfeng Road, Guangzhou, 510060, People’s Republic of China

    Yangxun Pan, Ze Yuan, Jiongliang Wang, Siegmund Ngai, Zhiwen Hu, Liyang Sun, Zhenyun Yang, Dandan Hu, Minshan Chen, Zhongguo Zhou & Yaojun Zhang

  2. Department of Liver Surgery, Sun Yat-Sen University Cancer Center, 651# East Dongfeng Road, Guangzhou, 510060, People’s Republic of China

    Yangxun Pan, Ze Yuan, Jiongliang Wang, Siegmund Ngai, Zhiwen Hu, Liyang Sun, Zhenyun Yang, Dandan Hu, Minshan Chen, Zhongguo Zhou & Yaojun Zhang

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Contributions

YP, ZY, JW, and SN designed experiments and drafted the manuscript. ZH, LS, and ZY were responsible for data collection. DH and ZY were responsible for statistical analysis. YZ and MC helped revise the manuscript. ZZ and YZ approved the final version.

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Correspondence to Zhongguo Zhou or Yaojun Zhang.

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Figure S1

. The distributions of tumor stages based on CNLC before and after PSM. CNLC China liver cancer staging, PSM propensity score matching. Figure S2. The distributions of the propensity score for unweighted and weighted cohorts by IPTW (A), and the distributions of covariate balance for unbalanced variables before and after introduced to IPTW (B). IPTW inverse probability treatment weighting, PS propensity score, CNLC China liver cancer staging. Figure S3. Forest plots of overall survival in different patient subgroups. HR hazard ratio, CI confidence interval, CNLC China liver cancer staging, BCLC Barcelona-clinic liver cancer, PVTT portal vein tumor thrombus, HVTT hepatic vein tumor thrombus, HAIC hepatic arterial infusion chemotherapy, HBV hepatitis B virus, ALBI Grade albumin-bilirubin grade, AFP alpha-fetoprotein, PIVKA-II protein induced vitamin K absence or antagonist II. (PDF 92 KB)

Supplementary file2 (PDF 129 KB)

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Pan, Y., Yuan, Z., Wang, J. et al. Survival benefit and impact of adjuvant therapies following FOLFOX-HAIC-based conversion therapy with unresectable hepatocellular carcinoma: a retrospective cohort study. J Cancer Res Clin Oncol 149, 14761–14774 (2023). https://doi.org/10.1007/s00432-023-05243-7

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