Hepatic artery infusion chemotherapy (HAIC) is a well-established and common treatment for advanced hepatocellular carcinoma (HCC), particularly in East Asia. However, HAIC is not recognized internationally. Although several trials have demonstrated the safety and efficacy of HAIC, evidence corroborating its overall survival (OS) benefits compared with standard treatments is insufficient. Nevertheless, HAIC may provide prominent benefits in selected patients such as patients with portal vein thrombosis or high intrahepatic tumor burden. Moreover, HAIC has been combined with several therapeutic agents and modalities, including interferon-alpha, multikinase inhibitors, radiation therapy, and immunotherapy, to augment its treatment efficacy. Most of these combinations appeared to increase overall response rates compared with HAIC alone, but results regarding OS are inconclusive. Two prospective randomized controlled trials comparing HAIC plus sorafenib with sorafenib alone have reported conflicting results, necessitating further research. As immunotherapy-based combinations became the mainstream treatments for advanced HCC, HAIC plus immunotherapy-based treatments also showed encouraging preliminary results. The trials of HAIC were heterogeneous in terms of patient selection, chemotherapy regimens and doses, HAIC combination agent selections, and HAIC technical protocols. These heterogeneities may contribute to differences in treatment efficacy, thus increasing the difficulty of interpreting trial results. We propose that future trials of HAIC standardize these key factors to reveal the clinical value of HAIC-based treatments for HCC.

In patients with advanced soft tissue sarcoma (STS), surgery had been reported to be associated with superior overall survival (OS). Chemotherapy details for such patients were less reported, and whether multimodal treatment with surgery and chemotherapy provides extra survival benefit remains unclear. We retrospectively reviewed patients with newly diagnosed advanced STS treated at National Taiwan University Hospital from January 1, 2011, to December 31, 2017. OS was calculated from the day of diagnosis of advanced STS to the day of death or last follow-up. Baseline patient characteristics and details regarding surgery and chemotherapy were recorded. A total of 545 patients were diagnosed with STS from 2011 to 2017, of which 226 patients had advanced STS. The median age was 54.7 years, and 54% of patients were women. Approximately 38% of patients with advanced STS underwent surgery and exhibited a trend of longer OS compared with who did not (median = 18.6 vs. 11.9 months, p = 0.083). In the chemotherapy subgroup, the benefit of surgery was more prominent (median = 21.9 vs. 16.5 months, p = 0.037). Patients who received chemotherapy prior to surgery exhibited numerically longer OS than those who underwent surgery first (median = 33.9 vs. 18.3 months, p = 0.155). After adjusting other clinical factors, chemotherapy remained an independent factor associated with favourable OS. Surgery may be more beneficial for the patients who receive chemotherapy. Our results support evaluation of sequential multimodal treatments strategy including surgery and chemotherapy in patients with advanced STS.

Immunotherapy combinations, such as atezolizumab plus bevacizumab (Atezo-Bev) or durvalumab plus tremelimumab, have been established as standard treatments for patients with advanced hepatocellular carcinoma (HCC). Durable responses and long-term survival have been reported following dual immunotherapy. However, the long-term outcomes associated with Atezo-Bev treatment remain unclear. To evaluate survival outcomes, we retrospectively analyzed medical records for patients with Child-Pugh class A liver function who received first-line Atezo-Bev for advanced HCC from January 2018 to May 2021 from four medical centers in Taiwan. A total of 54 patients were included in the analysis. This cohort was predominantly male (90.7%) and had a median age of 65 years. After a median follow-up period of 61.9 months, the median overall survival (OS) was 19.6 months (95% confidence interval, 10.1-20.1 months). The OS rates at 36, 48, and 60 months were 31.6%, 19.6%, and 19.6%, respectively. Younger age (≤70 years), absence of intrahepatic tumors, absence of macrovascular invasion (MVI), and Albumin-Bilirubin (ALBI) grade 1 liver function were associated with long-term survival (>36 months). A multivariate analysis revealed the absence of intrahepatic tumors (odds ratio [OR] = 5.36, p = 0.047) and ALBI grade 1 (OR = 10.02, p = 0.037) as independent predictors of long-term survival. Among patients achieving complete or partial response, the 60-month OS rate was 47.4%. Among patients with advanced HCC treated with first-line Atezo-Bev, approximately 30% survived beyond 3 years. The absence of intrahepatic tumors and preserved liver function were predictive of such prolonged survival.

Background and Aims: Early alpha-fetoprotein (AFP) response has been reported to predict the treatment efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced hepatocellular carcinoma (HCC). We evaluated the predictive value of another HCC tumor marker, protein induced by vitamin K absence/antagonists-II (PIVKA-II). Methods: We prospectively established a cohort of advanced HCC patients who received ICI treatment at two medical centers. Serum PIVKA-II levels were obtained before and within 4 weeks after treatment initiation. Any decline in serum PIVKA-II levels was defined as an early PIVKA-II response. Treatment response, overall survival (OS), and progression-free survival (PFS) were compared between patients with and without an early PIVKA-II response. Results: In total, 67 patients were included; liver reserve was Child–Pugh class A in all patients and albumin–bilirubin grade 1 in 67.2% of the patients. An early PIVKA-II response, which was observed in 19 (28.4%) patients, was associated with a higher objective response rate (50.0% vs 16.4%, p = 0.002). Patients with an early PIVKA-II response had superior OS (median 34.3 vs 13.7 months, p = 0.015) and PFS (median 8.4 vs 4.0 months, p = 0.049) compared with those without a response. In multivariate analysis, an early PIVKA-II response remained an independent predictor for longer OS (p = 0.012) and PFS (p = 0.044). An early PIVKA-II response can complement an early AFP response in predicting prognosis. Conclusion: An early PIVKA-II response is predictive of tumor response and superior survival outcomes in patients who received ICIs for advanced HCC. Plain Language Summary: PIVKA-II is an emerging tumor marker for HCC, widely used in diagnosis and prognostic stratification. Early PIVKA-II response, defined as any decline of serum PIVKA-II level within 4 weeks after initiation of ICIs treatment, may predict treatment efficacy for patients with advanced HCC.