Microwave versus radiofrequency ablation for the treatment of liver malignancies: a randomized controlled phase 2 trial

Microwave (MWA) and radiofrequency ablation (RFA) are main ablative techniques for hepatocellular carcinoma (HCC) and colorectal liver metastasis (MT). This randomized phase 2 clinical trial compares the effectiveness of MWA and RFA as well as morphology of corresponding ablation zones. HCC and MT patients with 1.5–4 cm tumors, suitable for ablation, were randomized into MWA or RFA Groups. The primary endpoint was short-to-long diameter ratio of ablation zone (SLR). Primary technical success (TS) and a cumulative local tumor progression (LTP) after a median 2-year follow-up were compared. Between June 2015 and April 2020, 82 patients were randomly assigned (41 patients per group). For the per-protocol analysis, five patients were excluded. MWA created larger ablation zones than RFA (p = 0.036) although without differences in SLR (0.5 for both groups, p = 0.229). The TS was achieved in 98% (46/47) and 90% (45/50) (p = 0.108), and LTP was observed in 21% (10/47) vs. 12% (6/50) (OR 1.9 [95% CI 0.66–5.3], p = 0.238) of tumors in MWA vs. RFA Group, respectively. Major complications were found in 5 cases (11%) vs. 2 cases (4%), without statistical significance. MWA and RFA show similar SLR, effectiveness and safety in liver tumors between 1.5 and 4 cm.

Combining Transarterial Radioembolization (TARE) and CT-Guided High-Dose-Rate Interstitial Brachytherapy (CT-HDRBT): A Retrospective Analysis of Advanced Primary and Secondary Liver Tumor Treatment

Purpose: Treatment of patients with primary and secondary liver tumors remains challenging. This study analyzes the efficacy and safety of transarterial radioembolization (TARE) combined with CT-guided high-dose-rate interstitial brachytherapy (CT-HDRBT) for the treatment of primary and secondary liver tumors. Patients and Methods: A total of 77 patients (30 female) with various liver malignancies were treated. Primary endpoints were median overall survival (OS) and time to untreatable progression (TTUP). Additionally, subgroup analyses were performed in consideration of diagnosis and procedure sequence. Median OS and TTUP prediction were estimated using Kaplan–Meier analysis and hazard ratios (HR) were calculated using a multivariate Cox proportional hazard model. Results: A total of 115 CT-HDRBT and 96 TARE procedures were performed with no significant complications recorded. Median OS and TTUP were 29.8 (95% CI 18.1–41.4) and 23.8 (95% CI 9.6–37.9) months. Median OS for hepatocellular carcinoma (HCC)-, cholangiocarcinoma carcinoma (CCA) and colorectal cancer (CRC) patients was 29.8, 29.6 and 34.4 months. Patients starting with TARE had a median OS of 26.0 (95% CI 14.5–37.5) compared to 33.7 (95% CI 21.6–45.8) months for patients starting with CT-HDRBT. Hazard ratio of 1.094 per month was shown for patients starting with CT-HDRBT. Conclusion: Combining TARE and CT-HDRBT is effective and safe for the treatment of advanced stage primary and secondary liver tumors. Our data indicate that early TARE during the disease progression may have a positive effect on survival.

Recent Advances in Photodynamic Imaging and Therapy in Hepatobiliary Malignancies: Clinical and Experimental Aspects

The therapeutic and diagnostic modalities of light are well known, and derivative photodynamic reactions with photosensitizers (PSs), specific wavelengths of light exposure and the existence of tissue oxygen have been developed since the 20th century. Photodynamic therapy (PDT) is an effective local treatment for cancer-specific laser ablation in malignancies of some organs, including the bile duct. Although curability for extrahepatic cholangiocarcinoma is expected with surgery alone, patients with unresectable or remnant biliary cancer need other effective palliative therapies, including PDT. The effectiveness of PDT for cholangiocarcinoma has been reported experimentally or clinically, but it is not the standard option now due to problems with accompanied photosensitivity, limited access routes of irradiation, tumor hypoxia, etc. Novel derivative treatments such as photoimmunotherapy have not been applied in the field hepatobiliary system. Photodynamic diagnosis (PDD) has been more widely applied in the clinical diagnoses of liver malignancies or liver vascularization. At present, 5-aminolevulinic acid (ALA) and indocyanine green (ICG) dyes are mainly used as PSs in PDD, and ICG has been applied for detecting liver malignancies or vascularization. However, no ideal tools for combining both PDD and PDT for solid tumors, including hepatobiliary malignancies, have been clinically developed. To proceed with experimental and clinical trials, it is necessary to clarify the effective photosensitive drugs that are feasible for photochemical diagnosis and local treatment.

Horizons of development of immunotherapy for malignant liver tumors

Primary liver tumors are one of the most common types of malignant neoplasms. Surgical excision is still the most effective treatment in the early stages of the disease, however in most cases early diagnosis is difficult. Moreover, even if the treatment is carried out according to a radical program, the risk of relapse remains extremely high. In this regard, the search for new strategies for the treatment of liver malignancies that differ from traditional methods of treatment is not terminated. One of such promising approaches is immunotherapy. The present review is devoted to the current understanding of the mechanisms of action and the available clinical experience in the use of immunotherapy approaches in the treatment of liver malignancies. Combining different types of immunotherapy or combining immunotherapy with traditional therapeutic approaches can facilitate a synergistic effect and contribute to the development of personalized medicine.

Bi-Centric Independent Validation of Outcome Prediction after Radioembolization of Primary and Secondary Liver Cancer

Background: Yttrium-90 radioembolization (RE) plays an important role in the treatment of liver malignancies. Optimal patient selection is crucial for an effective and safe treatment. In this study, we aim to validate the prognostic performance of a previously established random survival forest (RSF) with an external validation cohort from a different national center. Furthermore, we compare outcome prediction models with different established metrics. Methods: A previously established RSF model, trained on a consecutive cohort of 366 patients who had received RE due to primary or secondary liver tumor at a national center (center 1), was used to predict the outcome of an independent consecutive cohort of 202 patients from a different national center (center 2) and vice versa. Prognostic performance was evaluated using the concordance index (C-index) and the integrated Brier score (IBS). The prognostic importance of designated baseline parameters was measured with the minimal depth concept, and the influence on the predicted outcome was analyzed with accumulated local effects plots. RSF values were compared to conventional cox proportional hazards models in terms of C-index and IBS. Results: The established RSF model achieved a C-index of 0.67 for center 2, comparable to the results obtained for center 1, which it was trained on (0.66). The RSF model trained on center 2 achieved a C-index of 0.68 on center 2 data and 0.66 on center 1 data. CPH models showed comparable results on both cohorts, with C-index ranging from 0.68 to 0.72. IBS validation showed more differentiated results depending on which cohort was trained on and which cohort was predicted (range: 0.08 to 0.20). Baseline cholinesterase was the most important variable for survival prediction. Conclusion: The previously developed predictive RSF model was successfully validated with an independent external cohort. C-index and IBS are suitable metrics to compare outcome prediction models, with IBS showing more differentiated results. The findings corroborate that survival after RE is critically determined by functional hepatic reserve and thus baseline liver function should play a key role in patient selection.

Hepatoblastomas with carcinoma features (HBCs) represent a biological spectrum of aggressive neoplasms in children and young adults

Malignant hepatocellular cancers are the most common primary liver malignancies in children, and hepatoblastomas (HBs) account for more than two-thirds of these cases. While most HBs respond to chemotherapy and have favorable outcomes, the 3-year overall survival rate for high-risk HBs is below 50% and guidelines for their classification and treatment are still evolving. HB risk-stratification efforts using clinical, histological, and molecular parameters have been reported to help identify patients that require more or less aggressive therapies in retrospective studies, and are being validated in clinical trials. However, risk assessment is particularly challenging for cancers with certain histologies, including tumors in the recently proposed provisional hepatocellular neoplasm not otherwise specified (HCN NOS) category. HCN NOSs exhibit either intermediate or combined HB and hepatocellular carcinoma (HCC) histological features, and while neoplasms with such features were observed over a decade ago, only a handful have been characterized and little is known about their biology and clinical features. Here, we molecularly characterized a series of clinically annotated HCN NOSs that demonstrated either intermediate HB/HCC histology or distinct coexisting areas with HB and HCC histological features. In addition, molecular profiling of HBs demonstrating focal pleomorphism or anaplasia (HB FPA) after chemotherapy revealed underlying biological features previously observed in HCCs. Our study suggested that HCN NOSs and HB FPAs are aggressive tumors, irrespective of patient age or resectability. Consequently, we designated them collectively as HBs with carcinoma features (HBCs) and outlined histological and molecular characteristics for their diagnosis and treatment. In our single-institution study, transplanted HBC patients were significantly and more than twice as likely to have good outcomes, highlighting the importance of molecular testing and aggressive early intervention.