Antinuclear antibody (ANA) status predicts immune-related adverse events in liver cancer patients undergoing anti-PD-1 therapy.

Immune-related adverse events (irAEs) clinically resemble autoimmune diseases, indicating autoantibodies could be potential biomarkers for the prediction of irAEs. This study aimed to assess the predictive value of peripheral blood antinuclear antibody (ANA) status for irAEs, considering the time and severity of irAEs, as well as treatment outcome in liver cancer patients administered anti-PD-1 therapy. Ninety-three patients with advanced primary liver cancer administered anti-PD-1 treatment were analyzed retrospectively. They were divided into the ANA positive (ANA+, titer ≥ 1:100) and negative (ANA-, titer < 1:100) groups. Development of irAEs, progression-free survival (PFS), and overall survival (OS) were assessed. Compared with ANA- patients, ANA+ cases were more prone to develop irAEs (43.3% vs. 19.2%, P = 0.031). With the increase of ANA titers, the frequency of irAEs increased. The time interval between anti-PD-1 therapy and the onset of irAEs was significantly shorter in ANA+ patients compared with the ANA- group (median, 1.7 months vs. 5.0 months, P = 0.022). Moreover, the time between anti-PD-1 therapy and irAE occurrence decreased with increasing ANA titer. In addition, PFS and OS were decreased in ANA+ patients compared with the ANA- group (median PFS, 2.8 months vs. 4.2 months, P = 0.043; median OS, 21.1 months vs. not reached, P = 0.041). IrAEs occur at higher frequency in ANA+ liver cancer patients undergoing anti-PD-1 therapy. ANA titer could help predict irAE development and treatment outcome in these patients.

Hepatic Arterial Infusion Chemotherapy with Modified FOLFOX as an Alternative Treatment Option in Advanced Hepatocellular Carcinoma Patients with Failed or Unsuitability for Transarterial Chemoembolization.

OBJECTIVE: This study aimed to assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with modified FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) as an alternative treatment option in advanced hepatocellular carcinoma (HCC) patients with failed or unsuitability for transarterial chemoembolization (TACE). MATERIALS AND METHODS: From September 2018 to January 2020, 87 advanced HCC patients who progressed on TACE or were not eligible for TACE received HAIC treatment with modified FOLFOX. The primary endpoint was overall survival (OS) and secondary endpoints included progression-free survival (PFS), tumor response assessed by Response Evaluation Criteria in Solid Tumors 1.1, and adverse events graded according to CTCAE 5.0. Based on prognostic factors determined by multivariate analysis, a nomogram was developed to predict patient survival. RESULTS: The median OS and PFS were 9.0 months (95%CI 7.6-10.4) and 3.7 months (95%CI 3.1-4.3), respectively. The objective response rate was 13.8%, with a disease control rate of 48.3%. Grade 3 adverse events were observed, such as infection (9.2%), thrombocytopenia (5.7%), hyperbilirubinemia (3.4%), abdominal pain (2.3%) and alanine aminotransferase increase (2.3%). Albumin, AST, and extrahepatic metastasis were incorporated to construct a new nomogram that could stratify patients into three prognostic subgroups, including low-, intermediate-, and high-risk groups, with significant differences in 9-month OS rates (71%, 42% and 6%, respectively; p< 0.001). The nomogram was better than the Okuda, AJCC, and CLIP staging systems for OS prediction. CONCLUSION: These findings support the feasibility of HAIC with modified FOLFOX as an alternative treatment strategy for advanced HCC when TACE is ineffective or unsuitable.