Aims To describe treatment patterns and outcomes in patients with unresectable hepatocellular carcinoma (uHCC) treated with embolization.Materials & methods This retrospective observational study used Optum’s de-identified Market Clarity Data. US adults with HCC treated with embolization between July 2016–September 2022 were followed from first embolization following diagnosis until death and end of enrollment or study period.Results Of 1,458 patients, 41.9%, 33.5%, and 24.6% received transarterial radioembolization (TARE), transarterial chemoembolization (TACE), and transarterial embolization (TAE), respectively, as initial embolization therapy; TARE use increased over time. Most were male (74.6%), white (66.5%), with a median age at index of 65.0 years, and 63.1% required ≥1 subsequent treatment (median treatment pattern follow-up: 16.3 months). Median (95% CI) time to first follow-up treatment or death was 5.9 (5.5–6.4) months. Compared with TARE, risk of death was lower with TACE (HR [95% CI] 0.82 [0.69–0.97]; P = 0.0242], non-significant in missingness sensitivity analysis) and higher with TAE (HR [95% CI] 1.25 [1.05–1.49]; P = 0.0135]).Conclusion TARE was the most common initial embolization therapy and its use increased over time. Time to first follow-up treatment or death was relatively short. Future studies are needed to identify optimal treatment approaches.
Transplant Oncology is an evolving field. While liver transplantation was once contraindicated in patients with cancer, the safety and survival benefit of utilizing transplantation as a curative-intent treatment for primary and metastatic hepatic malignancies has been demonstrated. Currently, liver transplantation is offered to selected patients with hepatocellular carcinoma, perihilar and intrahepatic cholangiocarcinoma, colorectal cancer with isolated liver metastases, and neuroendocrine tumors with isolated liver metastases. We will cover the current inclusion and exclusion criteria and clinical and pathologic factors of each oncologic indication, and future directions in liver transplant oncology. Successful oncologic outcomes for liver transplantation hinge on careful selection of patients. The evolving role of immunotherapy and targeted tumor therapies have allowed for previously transplant-ineligible patients to be considered for curative-intent transplantation, rather than palliative-intent care. Increasing our knowledge through coordinated multi-institutional studies of each disease process with liver transplantation will be imperative to continue to safely broaden the indications and offer hope to these complex groups of patients. Reframing recipients with oncologic indications for transplant should occur carefully and with attention to rigorous analysis of clinical outcomes. The objective of this article is to situate the evolving treatments for hepatic malignancies within the expanding scope of transplant oncology.
Introduction Hepatocellular carcinoma (HCC) remains difficult to treat, highlighting the need for new therapeutic strategies. RTA-408 (omaveloxolone), a synthetic oleanane triterpenoid and NRF2 pathway modulator, has reported anticancer activity, but its mechanisms in HCC are not fully understood.Materials and methods HepG2 and PLC/PRF/5 (PP5) cells were treated with RTA-408 for 24 h. Cell viability, apoptosis, and signaling pathways were evaluated using MTT assay, Annexin V/7-AAD flow cytometry, and western blotting. The role of p38 signaling was examined using the p38 inhibitor SB203580.Results RTA-408 reduced cell viability in a concentration-dependent manner and increased apoptosis in both cell lines. At 600 nM, apoptosis increased to approximately 18.43% in HepG2 cells and 24.71% in PP5 cells. RTA-408 increased p38 phosphorylation and NRF2 expression and was accompanied by LC3B and p62 accumulation and elevated cleaved caspase-3. Inhibition of p38 partially restored cell viability and reduced apoptosis.Conclusion RTA-408 suppresses HCC cell survival through a p38-dependent stress response associated with NRF2 activation and LC3B/p62 accumulation.
The treatment paradigm of hepatocellular carcinoma (HCC) has evolved with the emergence of immune checkpoint inhibitors (ICIs). Two ICI-based regimens have gained regulatory approval worldwide in unresectable HCC as first line treatment based on the IMBrave150 and HIMALAYA trial. Other regimens such as camrelizumab-rivoceranib and ipilimumab-nivolumab also demonstrated improvement in overall survival as compared to multi-targeted agents in recent phase III clinical trials. With the growing amount of evidence, it is imperative for clinicians to decide the most suitable ICI therapy for each patient based on their disease status and tolerability. Furthermore, ICI in combination with locoregional treatment such as transarterial chemoembolization (TACE) has been shown to prolong the progression-free survival as compared to TACE alone. In early-stage HCC, the role of ICI has been studied in both the adjuvant and neoadjuvant setting. In this narrative review, we will highlight the major advancement of ICI in different stages of HCC and their implication in real world practice. The unmet need in the special population of liver cancer patients and the management of immune-related hepatitis will also be addressed.
Aim The present study aimed to explore the patient experience in advanced and/or metastatic hepatocellular carcinoma (HCC).Materials & methods A multi-phase research design was followed that included a targeted literature review (TLR), interviews with clinicians, and interviews with patients. Patient interviews were analyzed using an iterative, thematic analysis approach. An assessment of the conceptual saturation of all spontaneously patient-reported signs and symptoms was conducted.Results Ten patient-centric qualitative studies were identified in the TLR. Five United States (US) clinicians and 15 US patients participated in semi-structured interviews, conducted via video conferencing, lasting approximately 60 minutes each. The five most commonly reported symptoms were fatigue, weight loss, weakness, reduction in appetite, and sleep disturbance. Furthermore, HCC impacted all aspects of patients’ lives, including physical functioning, social and family functioning, emotional functioning, physical activities, and activities of daily living. The concepts were mostly similar across the different data sources. A patient-centric conceptual model was developed based on the TLR and patient interviews.Conclusion The study provides an in-depth description of signs/symptoms and impacts in advanced and/or metastatic HCC that can support the identification of suitable patient-reported outcome measures. Separate investigation is needed to distinguish between disease impacts and treatment impacts.
