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.
AIM:Our aim was to examine two-way increased-risk associations between hepatobiliary cancers and malignancies that develop before/after them. PATIENTS AND METHODS:Data of USA from Surveillance, Epidemiology, and End Results (SEER), 17 registries (2000-2021) were analyzed using different statistical methods. RESULTS:Overall, 5,574,604 cancer cases were identified, which included hepatocellular carcinoma (HCC) (59,764), cancer of bile duct (including Ampulla of Vater) (22,735), cancer of gallbladder (10,155), and other malignancies (5,481,950). We found two-way increased-risk associations for the following eight cancer pairs: HCC-upper aerodigestive tract, HCC-esophagus, HCC-stomach, HCC-anus, HCC-bile duct, HCC-lung/bronchus, HCC-non-Hodgkin lymphoma, and bile duct-stomach. After HCC or bile duct cancer, the standardized incidence ratios (SIRs) (95% CI) of the corresponding second primary malignancies (SPMs) were 1.88 (1.61-2.18), 1.46 (1.07-1.96), 1.59 (1.25-2.00), 3.53 (2.31-5.18), 3.98 (3.15-4.97), 1.54 (1.41-1.69), 2.2 (1.92-2.52), and 2.30 (1.59-3.21), respectively. In reverse order (i.e. HCC or bile duct cancer as SPM), the SIRs (95% CI) were 1.48 (1.34-1.62), 1.43 (1.06-1.90), 1.49 (1.22-1.79), 1.76 (1.27-2.36), 1.62 (1.03-2.44), 1.39 (1.27-1.53), 1.31 (1.19-1.44), and 1.73 (1.31-2.24), respectively. CONCLUSION:The major shared etiologic factors for the identified cancer pairs were life-style (smoking, alcohol use, and excess body weight), chronic infections (hepatitis B and C viruses), and genetic risks.
Hepatocellular carcinoma (HCC) is a highly morbid malignancy that is a leading cause of death in patients with cirrhosis or chronic hepatitis B. Liver transplantation is considered a curative therapy for HCC, with 5-year survival rates exceeding 75%. Current allocation policy in the US restricts transplant to patients with early HCC, and priority for transplant is granted after 6 months on the waitlist, thus patients often require therapies for cancer control while awaiting liver transplantation. The most commonly applied therapies for HCC in patients awaiting liver transplantation are locoregional therapies, including ablative, radiation, and arterial based therapies. Using these therapies patient can be effectively bridged or downstaged to liver transplantation, however there are risks of progressive liver decompensation with locoregional therapies in patients with portal hypertension. There are emerging data for the use of immune checkpoint inhibitor-based immunotherapies in the treatment of HCC. While there has been concern for rejection with the administration of immunotherapy prior to liver transplantation, early data suggest that the risk can be minimized with sufficient washout time prior to liver transplantation. Herein we aim to review management strategies for patients with HCC awaiting liver transplantation.
AIM:Real-world outcomes in early-stage hepatocellular carcinoma (eHCC) are not well characterized. We aimed to evaluate treatment patterns and long-term outcomes in patients with eHCC treated with resection or ablation in the United States. MATERIALS AND METHODS:We conducted a retrospective study with Optum's de-identified Market Clarity Data. Patient characteristics, treatment patterns, and overall survival (OS) were assessed in adults with eHCC treated with resection or ablation between July 2016 and March 2021. RESULTS:Of 649 patients who met inclusion criteria, 59.3%, 37.3%, and 3.4% underwent ablation only, resection only, or both, as their initial treatment, respectively. Median age was 64.0 years; most patients were male (72.9%) and White (65.5%). Subsequent treatment was received in 47.1% of patients. The median (quartile 1-3) time to first subsequent treatment was 216 (89.3-414.3) days. The most common subsequent treatments included embolization (22.7%) and ablation (15.6%). In total, 35.7% of patients died post-index. Median OS was 67.7 (95% CI: 56.4-not estimable) months. Estimated 24-month OS was 79.0% (95% CI: 75.0-82.0). CONCLUSIONS:Our results highlight the need for post-treatment surveillance and the potential role for neoadjuvant and/or adjuvant treatments to improve outcomes in patients with eHCC treated with resection or ablation.
Aims Hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin plus raltitrexed showed a promising response rate in patients with unresectable hepatocellular carcinoma (HCC) in a phase 2 trial. Here, we report the updated 3-year survival data after enrollment.Methods In this prospective trial, we enrolled patients with intermediate and advanced unresectable HCC. The treatment was HAIC with raltitrexed plus oxaliplatin.Results The objective responses were achieved in 19 (48.7%) of 39 patients in the intention-to-treat population. The median overall survival and progress-free survival were 11.2 and 6.5 months, respectively.Conclusion The 3-year survival update confirmed the antitumor activity and long-term survival benefit of HAIC with oxaliplatin plus raltitrexed in patients with unresectable HCC.Clinical trial registration www.chictr.org.cn identifier is ChiCTR-OOC-17014182.
This was a narrative review of select studies published through September of 2024. We review the shift toward multi-dimensional scores such as HCC early detection screening (HES), GALAD, ASAP, and mt-HBT represents a significant advancement in biomarker research for hepatocellular carcinoma (HCC) detection. Unlike single biomarker approaches, these scores integrate various clinical and biochemical factors to enhance predictive accuracy by reflecting different complementary aspects of disease progression and HCC oncogenesis. Proper testing and validation of biomarker scores in phase 3 biomarker studies is essential before wide use can be recommended. We also review the comparative performance of biomarker scores in phase 3 studies. The new version of HES (HES V2.0) which includes AFP, AFP L3, DCP, and changes in their levels the past one year, if available, in addition to age, platelets, albumin, ALT and underlying liver disease etiology outperforms GALAD in detecting early-stage HCC with overall 6.7% higher sensitivity, and ASAP with 13.4%-18.0% higher sensitivity, both at fixed 90% specificity. HES V2.0 is a leading candidate biomarker score for prospective testing in clinical studies of early HCC detection.
Hepatocellular carcinoma (HCC) remains a health concern characterized by heterogeneity and high mortality. Surgical resection, radiofrequency ablation, trans-arterial chemoembolization, and liver transplantation offer potentially curative treatments for early-stage disease, but recurrence remains high. Most patients present with advanced-stage HCC, where locoregional therapies are less effective, and systemic treatments-primarily multi-kinase inhibitors and immune checkpoint inhibitors-often yield limited responses. Precision medicine aims to tailor therapy to molecular and genetic profiles, yet its adoption in HCC is hindered by inter-/intra-tumoral heterogeneity and limited biopsy availability. Advances in molecular diagnostics support reintroducing tissue sampling to better characterize genetic, epigenetic, and immunological features. Liquid biopsy offers a minimally invasive method for capturing real-time tumor evolution, overcoming spatial and temporal heterogeneity. Artificial intelligence and machine learning are revolutionizing biomarker discovery, risk stratification, and treatment planning by integrating multi-omics data. Immunological factors such as tumor-infiltrating lymphocytes, natural killer cells, macrophages, and fibroblasts have emerged as determinants of HCC progression and treatment response. Conversion therapy-combining systemic agents with locoregional treatments-has showndemonstrated promise in downstaging unresectable HCC. Ongoing efforts to refine biomarker-driven approaches and optimize multi-modality regimens underscore precision medicine's potential to improve outcomes. PubMed (January 2002-February 2025) was searched for relevant studies.
Precision medicine has emerged as a cornerstone in cancer treatment revolutionizing our approach across malignancies. Molecular profiling of biliary tract cancers (BTCs) has changed the treatment landscape positively by prolonging survival in an aggressively fatal malignancy in its advanced stages. The acquisition of tissue tumor DNA for genomic analysis in BTC is often anatomically challenging, limited by quantity and quality. In response, ctDNA has emerged as a noninvasive means of molecular profiling. The utility of both plasma and bile ctDNA has been explored in several studies demonstrating the high mutation detection rates and the ability to isolate targetable mutations when present. In addition, the concordance between plasma and tissue DNA provides validity in utilizing ctDNA results to infer treatment decisions. Analysis of ctDNA in BTC has also provided prognostic information and facilitated evaluation of clonal evolution with ease of serial measurements. Insight into novel mechanisms of resistance to targeted therapies are being uncovered in ctDNA. As research endeavors continue to deepen our understanding in the field particularly in the space of ctDNA surveillance after curative intent, the tremendous progress made so far has enabled integration of ctDNA into the clinical practice of BTCs.
Aim: The present study aimed to compare the long-term survival outcomes of hepatic resection (HR) and radiofrequency ablation (RFA) in patients with single small (<= 2 cm) hepatocellular carcinoma (HCC). Materials & methods: This retrospective study enrolled patients with a single small HCC measuring 2 cm or smaller underwent HR or RFA as their initial treatment. Results: Overall survival (OS) was significantly higher in the HR group than in the RFA group, while no significant difference was observed in recurrence free survival (RFS) between the two groups. However, after propensity score matching, both OS and RFS in the HR group were significantly higher than in the RFA group. Multivariate analysis showed that patients with hepatitis B virus infection, elevated prothrombin-induced by vitamin K absence or antagonist-II, and albumin-bilirubin (ALBI) grade 2/3 before treatment had poorer OS. Patients with ALBI grade 1 in the HR group demonstrated the highest OS. Conclusion: HR showed significantly better long-term OS and RFS compared with RFA in patients with as a single HCC (<= 2 cm). Moreover, the ALBI grade may help identify patients who would benefit from HR or RFA.
Aim: To investigate the role of immunotherapy in the overall survival (OS) of gastrointestinal cancer patients who have liver metastases at the time of the primary site cancer diagnosis. Materials & methods: Survival outcome was compared between groups with immunotherapy and groups without immunotherapy. Results: Chemoimmunotherapy was associated with improved OS (hazard ratio [HR] 0.768; 95% CI 0.739-0.800; p < 0.001) compared with chemotherapy alone. Radiotherapy to the primary site plus chemoimmunotherapy was also associated with improved OS (HR 0.796; 95% CI 0.705-0.898; p < 0.001) compared to chemoradiation. Chemoimmunotherapy with radiotherapy to metastatic sites (except liver) was associated with improved OS (HR 0.771; 95% CI 0.706-0.842; p < 0.001) compared to chemoradiation. Conclusion: Immunotherapy plus chemotherapy or chemoradiation was associated with improved OS compared with chemotherapy or chemoradiation without immunotherapy.
Aim: The aim of this study was to assess the utility of weighted amide proton transfer (APTw) MRI in three different rodent models of hepatocellular carcinoma (HCC).Methods: APTw MRI was evaluated in models of diethylnitrosamine (DEN) induced HCC, N1S1 syngeneic orthotopic xenograft and human HepG2 ectopic xenograft.Results: All models of HCC showed a higher APTw signal over the surrounding normal tissues. In the DEN model, the APTw signal could differentiate HCC lesions from benign nodules. Intra-arterial administration of low-density lipoprotein docosahexaenoic acid (LDL-DHA) nanoparticles to N1S1 xenografts rapidly lowered the tumor APTw signal within 72 h. Direct injections of LDL-DHA nanoparticles into HepG2 xenografts also showed similar therapeutic responses.Conclusion: We have demonstrated the utility of APTw imaging in the diagnostic/therapeutic management of HCC.
Aim: To assess real-world management of patients diagnosed with hepatocellular carcinoma (HCC) within an integrated delivery network. Materials & methods: A retrospective cohort analysis of adults newly diagnosed with HCC from January 2014 to March 2019. Overall survival and treatment journey were assessed over the entire available follow-up period per patient. Results: Of the 462 patients, 85% had ≥1 treatment. The 24-month overall survival rate (95% CI) from first treatment was 77% (72–82%). Majority of Child-Pugh class A (71%) and B (60%) patients received locoregional therapy first. Half (53.6%) of the patients with liver transplantation first were Child-Pugh class C patients. Sorafenib was the predominant systemic therapy. Conclusion: This integrated delivery network data analysis offers a comprehensive insight into the real-world management of HCC.
Aim:This study examined treatment patterns, survival outcomes and healthcare costs related to hepatocellular carcinoma (HCC) in British Columbia.Methods:The study utilized data from two physician databases (HCC and MOTION) and the provincial British Columbia transplant database.Results:The analysis revealed diverse treatment approaches and identified the varying treatment journeys of patients. Liver transplant and systemic therapies demonstrated improved survival rates. However, there was a scarcity of Canadian-specific cost data.Conclusion:The research emphasizes the complexities of managing HCC and underscores the need for personalized treatment strategies to enhance patient outcomes. These findings contribute valuable insights into HCC management and provide a foundation for future studies and interventions aimed at optimizing care and resource allocation.
Aim To evaluate the safety and efficacy of uncooled TATO microwave ablation (MWA) for primary and metastatic liver cancer. Materials & methods This was a retrospective study on percutaneous liver ablations performed with TATO MWA. Twenty-five ablations were performed; 11 (44%) were performed for hepatocellular carcinoma, 14 (56%) for colorectal carcinoma, gastric and pancreatic metastases. Results Adverse events were reported only in one (4%) ablation: an abscess that was observed in the ablated area and was resolved with a percutaneous drainage and antibiotic therapy. Local tumor control rate was 92% at the 3-month follow-up. Conclusion TATO MWA was safe and effective with high reproducibility in treating primary and secondary liver cancer with satisfactory technical and clinical outcomes.
Aim: The purpose of this study is to compare the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, fluorouracil and leucovorin (FOLFOX) plus lenvatinib and FOLFOX-HAIC alone in patients with unresectable cholangiocarcinoma. Patients & methods: Retrospective analysis of patients receiving FOLFOX-HAIC with or without lenvatinib. Results: Forty-one patients were included, with 22 patients receiving HAIC alone and 19 patients receiving HAIC plus lenvatinib. Combination treatment significantly prolonged overall survival and progression-free survival compared with HAIC alone. Grade 1-2 adverse events were more frequent in the combination group but manageable. No severe AEs or treatment-related deaths were reported. Conclusion: FOLFOX-HAIC plus lenvatinib has the potential to be a treatment option for unresectable cholangiocarcinoma. This study compared the effectiveness and safety of two treatments for unresectable cholangiocarcinoma (CCA), a type of liver cancer. The first treatment involved a combination of hepatic arterial infusion chemotherapy (FOLFOX-HAIC) and lenvatinib, a targeted therapy drug. The second treatment was FOLFOX-HAIC alone. The study included 41 patients with CCA, and the results showed that the group receiving FOLFOX-HAIC plus lenvatinib had significantly longer overall survival (32.0 months) and progression-free survival (20.0 months) compared with the group receiving FOLFOXHAIC alone. The combination treatment had manageable side effects, although some mild adverse events were more common in the combination group. The study suggests that FOLFOX-HAIC plus lenvatinib could be a potential treatment option for unresectable CCA. Combining FOLFOX-HAIC with lenvatinib improved the survival of patients with unresectable cholangiocarcinoma (CCA), and had manageable side effects. Therefore, the combined treatment shows promise as a treatment option for unresectable CCA.
Aim: To analyze the predictive value of biochemical liver tests in patients with malignant melanoma, breast, colorectal or lung cancers at the time of diagnosis of liver metastases. Methods: A retrospective review of patients with the above-mentioned solid tumors at MedStar Georgetown University Hospital from 2016–2020. Results: The highest optimal cutoff according to sensitivity and specificity for the presence of liver metastases was for AST ≥1.5 × ULN for melanoma, lung, and breast cancers and ≥2 × ULN for colorectal cancer, ALT ≥1.25 × ULN for melanoma, breast and colorectal cancers and ≥1.5 × ULN for lung cancer, and ALP ≥1.5 × ULN for melanoma, breast and colorectal cancers. Conclusion: Using thresholds of liver enzymes above the ULN may improve the diagnostic accuracy for the presence of liver metastases.
Aim: Many pivotal trials in advanced hepatocellular carcinoma (HCC) require participants to have Child-Pugh A disease. However, many patients in real-world practice are Child-Pugh B or C. This study examined treatment patterns and clinical outcomes in patients with advanced HCC treated with first-line systemic therapy. Materials & methods: In this retrospective study, patients with HCC treated with first-line systemic therapy (2010–2017) were identified from US Oncology Network records. Outcomes included overall survival and progression-free survival, by Child-Pugh Class and prior liver-directed therapy. Results: Of 352 patients, 78.7% were Child-Pugh A or B, 96.6% received first-line sorafenib, and 33.8% received first-line-prior liver-directed therapy. Survival outcomes were similar for Child-Pugh A or B, and longer after first-line prior liver-directed therapy. Conclusion: First-line systemic therapy is beneficial in patients with Child-Pugh A or B, and after first-line prior liver-directed therapy. These findings may help position systemic therapy in the community setting.
