Hepatic Oncology最新文献

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: 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.

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.

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.

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.

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.

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.

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.

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: 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.