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Background: Hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin and 5-fluorouracil was effective in unresectable hepatocellular carcinoma (HCC). The program of FOLFOX-HAIC in HCC was performed for 1 day (HAIC 1d) or 2 days (HAIC 2d). We hereby retrospectively compared the efficacy and safety between these two treatment regimens and explored the predictive power of thymidylate synthase (TYMS), an enzyme involved in the DNA synthesis process and metabolism of fluorouracil.Methods: This study included patients with a primary diagnosis of unresectable HCC. These patients received HAIC for 1 day or 2 days. The overall survival (OS), progression-free survival (PFS), tumor response, and adverse events were compared. The propensity score matching (PSM) was used to reduce bias. Peripheral blood samples before the treatments were collected and used to measure the concentration of TYMS through enzyme-linked immunosorbent assay (ELISA). ELISA was performed according to the manufacturers' guidelines.Results: We included 368 patients for this study: 248 in the HAIC 1d group and 120 in the HAIC 2d group. There was no significant difference of OS between the two groups (14.5 for HAIC 1d vs 15.3 months for HAIC 2d, p=0.46). Compared with the HAIC 1d group, the HAIC 2d group did not prolong the PFS (7.3 vs 7.5 months, p=0.91) or elevate the tumor response (42.5% vs 39.1%, p=0.53) per RECIST 1.1. In the PSM cohort, the efficacy between the two groups was similar. The total frequencies of grade 3-4 events were higher with the HAIC 2d group than with the HAIC 1d group, especially in the PSM cohort (p=0.043). Additionally, patients with TYMS low level might benefit longer OS from the HAIC 2d group (18.7 vs 13.6 months, p=0.014).Conclusions: There was not much of a difference in efficacy between the two groups, but the HAIC for 1 day might be safer, which needed further research. The level of TYMS might be the predictive biomarkers. [ABSTRACT FROM AUTHOR]

The combination of lenvatinib, toripalimab and hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) suggested encouraging antitumour activity in our retrospective study. We hereby prospectively establish the efficacy, safety and predictive biomarkers of the combination therapy as a first-line treatment in patients with high-risk advanced hepatocellular carcinoma (HCC). This phase II, single-centre, single-arm trial enrolled advanced HCC participants with high-risk. Of 51 screened participants, 36 received lenvatinib, toripalimab plus FOLFOX-HAIC. Participants received 21-day treatment cycles of lenvatinib, toripalimab, and FOLFOX-HAIC. The primary end-point was the progression-free survival (PFS) rate per RECIST at six months. Thirty-six participants (86.1% with high-risk features) were enrolled in our study. The primary end-point was met with a PFS rate of 80.6% (95% CI, 64.0%–91.8%) at six months. The median PFS was 10.4 months (95% CI, 5.8–15.0), and the median OS was not reached at the prespecified final analysis and was 17.9 months (95% CI, 14.5–21.3) after follow-up was extended. The ORR per RECIST was 63.9%, and per mRECIST was 66.7%. The median duration of response was 14.4 months (95% CI, 8.9–19.9). The most common adverse events were thrombocytopenia, elevated aspartate aminotransferase, and hypertension, and no treatment-related death was reported. Participants with low levels of both CCL28 and BTC had unsatisfactory prognosis. Lenvatinib, toripalimab and FOLFOX-HAIC showed safe and encouraging antitumour activity for advanced HCC with high-risk features. The levels of CCL28 and BTC might be the predictive biomarkers for the triple combination therapy. • High-risk advanced HCC is associated with poor outcomes of systemic therapy. • Combination FOLFOX-HAIC with lenvatinib and toripalimab was tolerable and effective. • CCL28 and BTC levels before therapy might be the predictive biomarkers of efficacy. [ABSTRACT FROM AUTHOR]

Babaodan (BBD) is a unique Chinese medication utilized in traditional Chinese medicine. It can eliminate toxins, induce diuresis, and eliminate yellowish hue. In addition to treating acute and chronic viral hepatitis, cholecystitis, cholangitis, and urinary tract infections, BBD has garnered popularity as a substitution treatment for several malignant cancers, particularly hepatocellular carcinoma (HCC). To elucidate the efficacy and mechanism of BBD alone and combined with camrelizumab (CLM) for treating HCC. We investigated the effects of BBD on the HCC tumor microenvironment in vivo. Furthermore, we evaluated its effects on tumor growth and metastasis induced by M2 macrophages in vitro. In a mouse model of orthotopic HCC, BBD decreased tumor growth. Furthermore, it increased the M1/M2 macrophage ratio and CD8+ T-cell abundance in mice. In addition, BBD reversed HCC cell proliferation and metastasis induced by M2 macrophages, increased the anti-HCC effect of low-dose CLM, and attenuated organ damage induced by high-dose CLM. Lastly, BBD enhanced the efficacy of CLM via the PI3K/AKT/mTOR signaling pathway. BBD increases the antitumor effect of CLM by modulating the tumor immune microenvironment and attenuating its the toxic side effects of CLM. BBD alone or in combination with low-dose CLM inhibits the proliferation and metastasis of HCC cells by inhibiting the PI3K/AKT/mTOR signalling pathway, and BBD in combination with high-dose CLM slows down the side effects of CLM via the TGF-β/pSmad3 signaling pathway. [Display omitted] • BBD modulates macrophage polarization and increases CD8+ T cell abundance in the tumor immune microenvironment to achieve anti-HCC effects. • BBD inhibits the proliferation and metastasis of HCC cells by remodeling tumor-associated macrophages in the tumor microenvironment. • BBD increases the anti-HCC effect of Camrelizumab by regulating the immune microenvironment and reduces the organ toxicity of Camrelizumab. [ABSTRACT FROM AUTHOR]