Faculty Bibliography

BACKGROUND:Advances in systemic therapy for advanced hepatocellular carcinoma (HCC) have fuelled a growing interest in evaluating these therapies in earlier stages of disease. However, trial design remains challenging due to the marked clinical and biological heterogeneity of early-stage and intermediate-stage HCC. OBJECTIVE:A multidisciplinary group of cancer experts was convened by the HCC-Live Consortium to discuss inclusion criteria, risk stratification, treatment arms and appropriate endpoints of trials evaluating perioperative and combination therapies in patients with HCC. DESIGN/METHODS:Consensus statements were defined as those obtaining >70% approval by panellists. RESULTS:The panel achieved consensus regarding nine consensus statements for neoadjuvant or perioperative systemic therapy and nine statements for combination locoregional plus systemic therapy. Statements emphasised recruiting carefully selected patient populations, employing treatment strategies and duration that balance efficacy with safety and using clinically relevant endpoints. Trials evaluating neoadjuvant/perioperative approaches should include patients at the highest risk of recurrence, with a recommended primary outcome of 2-year event-free survival using restricted mean survival time. Trials evaluating combination therapies should include a homogeneous patient population and use an appropriate comparator arm that aligns with clinical practice. Specifically, systemic therapy was the recommended comparator arm for patients with larger tumour burden and locally advanced disease. The recommended primary outcome for combination trials was progression-free survival and overall survival, with an alpha-recycling strategy. Secondary endpoints are essential to inform clinical applicability. CONCLUSION/CONCLUSIONS:Optimal design of HCC trials is important to rigorously evaluate the role of systemic therapy in patients undergoing surgical resection or in combination with locoregional therapy.

Disparities in deceased donor liver transplantation (DDLT) may be due to geographic imbalances of organ supply-to-demand ratios and/or center organ acceptance practices. We evaluated the relative contribution of centers versus broader geographic units (DSAs/States/OPTN regions/census divisions) to variability of DDLT rate. Using SRTR data on adult, first-time, non-Status1A, period-prevalent waitlist candidates, we conducted multilevel Poisson regression with center-level and donor service area (DSA)-level intercepts to model DDLT rates across three eras: pre-acuity circles (AC)(5/1/2017-4/30/2019), initial post-AC (2/4/2020-2/3/2022), and recent post-AC (02/04/2022-12/31/2024), adjusting for candidate factors. We calculated center-level and DSA-level median incidence rate ratios (MIRRs) and their relative contributions to total geographic variation. DSA-level MIRR declined from _1.471.52_1.58 to _1.321.37_1.42 to _1.171.23_1.28 from pre-AC to initial post-AC to recent post-AC. The center-level, within-DSA MIRR increased from _1.561.61_1.64 to _1.761.82_1.84 to _1.921.96_2.05 across eras. The DSA-level contribution to total center-level variation declined from 43.7% to 21.5% to 8.4% across eras. Similarly, the contribution of other broad, geographic units (States/OPTN regions/census divisions) to total geographic variation in DDLT rates decreased after AC. Further allocation changes are unlikely to substantially reduce geographic disparities because DDLT rate variation is predominantly driven by center-level differences, which were associated with highly variable advanced preservation practices.

As hepatitis C virus (HCV) infection is now curable, HCV-positive donor organs have expanded the deceased donor pool. Using OPTN data, we identified adult kidney, liver, heart, and lung candidates listed between 2016-2025 and evaluated rates of consent to accept HCV antibody-positive (Ab+) and HCV viremic (NAT+) organs. Temporal trends were described, and multilevel modified Poisson regression with center-level random effects was used to estimate adjusted risk ratios for candidate factors and quantify center variation using median incidence rate ratios (MIRR). Rates of consent to accept both HCV Ab+ and NAT+ organs rose over time. By the end of follow-up, consent rates for HCV Ab+ organs were 63.1% for kidney, 80.6% for liver, 73.3% for heart, and 72.1% for lung candidates, and consent rates for NAT+ organs were 44.9%, 70.7%, 50.5%, and 46.1%, respectively. Associations between candidate characteristics and consent were small after adjustment for center, whereas center effects were large. For HCV Ab+ organs, MIRRs were 6.31 (kidney), 2.48 (liver), 2.90 (heart), and 4.36 (lung); for NAT+ organs, MIRRs were even higher, 9.65, 3.19, 4.00, and 7.30, respectively, indicating marked between-center variability. Our analyses suggest that access to HCV-positive organs is influenced more by center practices than patient characteristics.

BACKGROUND:As a 6-month waiting period is required to receive exception points to prioritize patients with hepatocellular carcinoma (HCC) for liver transplantation, prompt addition to the waitlist is critical in access to LT. METHODS:Using Epic Cosmos data on patients with HCC referred for LT 1/2018-10/2024, we used modified Poisson regression to calculate rates of waitlisting. Center-level and individual (socioeconomic, geographic, and insurance) factors were measured among those who progressed. RESULTS:Among 11,422 HCC patients referred for LT at 70 centers, with median age 63 [IQR: 58, 68], 71.5% initiated evaluation and, of those who began evaluation, 57.6% were waitlisted for LT. Of those referred, patients who were older (age 70+ vs. 51-60; RR 0.77, 95% CI: 0.65-0.90, p < 0.001), on Medicaid (0.83, 95% CI: 0.71-0.97, p = 0.02), never-married (0.82, 95% CI: 0.73-0.91, p < 0.001), or low SES (Q4: 0.87, 95% CI: 0.77-0.97, p = 0.002) had lower rates of waitlisting. Among waitlisted patients, median time from referral was 3.3 months [IQR: 2.0, 5.3]. Despite adjustment for patient level covariates, there was high center-level variation in rate of waitlisting within 12 months; 13% of centers listed patients at a rate ≥ 20% below the national median. CONCLUSION/CONCLUSIONS:Only a fraction of referred patients with HCC are waitlisted for LT. High variation in access to waitlisting based on non-clinical factors suggests barriers to waitlisting that must be addressed. Centers should focus on interventions to reduce barriers to waitlisting in patients with HCC.

BACKGROUND:Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality. Optimal treatment decisions are challenging, and existing treatment allocation frameworks may not fully reflect the evolving therapeutic landscape or contemporary clinical practices in North America. METHODS:Using a modified Delphi process, a multidisciplinary panel of 20 North American experts in hepatology, medical oncology, surgery, radiology, and radiation oncology developed a consensus-based treatment framework for HCC, termed the BEACON-HCC system. The framework was informed by current evidence and expert opinion through iterative discussion and voting. In a pilot study using 29 real-world patient cases, we assessed concordance between external expert recommendations and BEACON-HCC recommendations and Barcelona Clinic Liver Cancer (BCLC) 2025 treatment recommendations. RESULTS:The BEACON-HCC treatment allocation framework diverges from prior frameworks by incorporating nuanced clinical features such as degree of intrahepatic tumor burden and vascular invasion, and adverse tumor prognostic markers, to align treatment allocation with tumor biology and therapeutic potential. Key innovations include the incorporation of emerging modalities such as external beam radiation therapy (EBRT), transarterial radioembolization (TARE), and systemic-locoregional combination therapies. In the pilot exercise, expert treatment decisions showed 96.6% concordance with BEACON-HCC recommendations and 72.4% concordance with BCLC recommendations. CONCLUSIONS:BEACON-HCC is a consensus-based framework for treatment allocation that incorporates the expanding range of therapeutic options available to patients in the North American HCC population. Expert treatment decisions showed a high concordance with the BEACON-HCC system; further validation using empiric clinical data is planned through the HCC-Live Consortium.

The clinical management of hepatocellular carcinoma (HCC) has evolved significantly over the past decade. Key advances include the introduction of immune-based treatment options, which now serve as the foundation for systemic therapies. Additionally, innovations in surgical techniques, such as robotic surgery, have broadened the scope of resection to include selected patients previously deemed unsuitable due to factors like tumor location or the presence of portal hypertension. HCC downstaging has also gained recognition as a viable strategy in appropriately selected patients, demonstrating outcomes comparable to those achieved under conventional listing criteria. Consequently, the management of HCC has become increasingly complex, underscoring the critical importance of multidisciplinary collaboration and shared decision-making. In this review, we provide a concise overview of practical recommendations for HCC management, encompassing aspects such as risk stratification, early detection, diagnosis, and treatment strategies.

INTRODUCTION/BACKGROUND:Minimally invasive liver resection (MILR) is performed for other gastrointestinal applications. At our centre, all liver resections are systematically performed using a minimally invasive approach. This study aimed to describe our experience in minimising open surgery and emphasised the importance of minimally invasive surgery. PATIENTS AND METHODS/METHODS:We retrospectively reviewed 260 patients who underwent liver surgery and compared the surgical outcomes between the open and MILR groups. RESULTS:A total of 154 patients (68%) underwent MILR. The proportion of patients who underwent prior abdominal surgery and resection was higher in the open surgery group. However, the proportion of patients with liver cirrhosis was similar between the two groups. The MILR group was superior in terms of operative time, blood loss, Pringle manoeuvre rate and mean hospital stay. In addition, major complication and bile leak rates were lower in the MILR group. No significant differences in the tumour size, number of lesions or underlying liver pathology were observed between the two groups. CONCLUSION/CONCLUSIONS:Acceptable outcomes can be achieved even when the minimally invasive approach is considered the primary option for all patients who require liver resection. Minimally invasive tools are necessary for the modern practice of liver surgery; therefore, laparoscopic or robotic surgery should be included in the armamentarium of liver surgeons.

BACKGROUND:Liver transplantation for cancer indications has gained momentum in recent years. This review is intended to optimize the care setting of liver transplant candidates by highlighting current indications, technical aspects and barriers with available solutions to facilitate the guidance of available strategies for healthcare professionals in specialized centres. METHODS:A review of the most recent relevant literature was conducted for all the cancer indications of liver transplantation including colorectal cancer liver metastases, hilar cholangiocarcinoma, intrahepatic cholangiocarcinoma, neuroendocrine tumours, hepatocellular carcinoma and hepatic epitheloid haemangioendothelioma. RESULTS:Transplant benefit from the best available evidence, including SECA I, SECA II, TRANSMET studies for colorectal liver metastases, various preoperative protocols for cholangiocarcinoma patients, standard, extended selection criteria for hepatocellular carcinoma and neuroendocrine tumours, are discussed. Innovative approaches to deal with organ shortages, including machine-perfused deceased grafts, living donor liver transplantation and RAPID procedures, are also explored. CONCLUSION/CONCLUSIONS:Cancer indications for liver transplantation are here to stay, and the selection criteria among all cancer groups are likely to evolve further with improved prognostication of tumour biology using adjuncts such as radiomics, cancer genomics, and circulating DNA and RNA status. International prospective registry-based studies could overcome the limitations of smaller patient cohorts and lack of level 1 evidence.

BACKGROUND:Minimally invasive liver surgery (MILS) is superior to open surgery when considering decreased blood loss, fewer complications, shorter hospital stay, and similar or improved oncologic outcomes. However, operative limitations in laparoscopic hepatectomy have curved its applicability and momentum of complex minimally invasive liver surgery. Transitioning to robotic hepatectomy may bridge this complexity gap. METHODS:Retrospective cohort study conducted on comparable hepatectomies (open, laparoscopic, robotic) for benign or malignant diseases at Weill Cornell by three surgeons from 2017 to 2023. Case volume and Iwate difficulty scoring were examined over time by surgical approach. Outcome associations (operative time, estimated blood loss, length of stay, 90-day complications, open conversion, and resection margin) were analyzed using generalized estimating equations to account for the hierarchical data structure of different surgeons and controlled for clinical covariates. RESULTS:Among 353 hepatectomies, 112 were open (OH), 107 were laparoscopic (LH), and 134 were robotic (RH). OH patients were more likely to have malignant pathology (83% vs. LH 69%, RH 57%) and less likely to have cirrhosis (6% vs. LH 6%, RH 14%). OH and RH had similar case complexity (Median Iwate: OH 7 vs. RH 7). After adjustments, LH and RH had 39% and 43% shorter median lengths of stay, respectively, and 89% and 62% lower odds of complications compared to OH. RH had 87% lower odds of conversion to OH compared to LH. The odds of R0 resection were similar between LH, RH, and OH. These results remained consistent in high difficulty cases (Iwate 7-12). Over the study period, RH usage increased from 36 to 68%, while LH decreased from 39 to 9%. By 2023, RH was predominantly used over OH (74% vs.26%). CONCLUSION/CONCLUSIONS:The transition from laparoscopic to all-robotic approach resulted in increased case volume and complexity in MILS, largely improving perioperative outcomes in hepatectomy.