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Uveal melanoma, a rare subset of melanoma, is the most common primary intraocular malignancy in adults. Despite effective primary therapy, nearly 50% of patients will develop metastatic disease. Outcomes for those with metastatic disease remain dismal due to a lack of effective therapies. The unique biology and immunology of uveal melanoma necessitates the development of dedicated management and treatment approaches. Ongoing efforts seek to optimize the efficacy of targeted therapy and immunotherapy in both the adjuvant and metastatic setting. This review provides a comprehensive, updated overview of disease biology and risk stratification, the management of primary disease, options for adjuvant therapy, and the current status of treatment strategies for metastatic disease.

Background Metastatic uveal melanoma (mUM) has a poor prognosis, with liver metastases typically presenting a therapeutic challenge. Melphalan/Hepatic Delivery System (Melphalan/HDS) is a drug/medical device combination used for liver-directed treatment of unresectable mUM patients. This study assessed efficacy and safety of Melphalan/HDS versus best alternative care (BAC). Methods Eligible patients with unresectable mUM were randomized (1:1) to receive Melphalan/HDS (3 mg/kg ideal body weight) once every 6 to 8 weeks for a maximum of 6 cycles or BAC. Due to slow enrollment and patient reluctance to receive BAC treatment, the study design was amended to a single-arm Melphalan/HDS study, and all efficacy analyses of the randomized study were treated as exploratory. Results The study enrolled 85 patients. Eligible patients were randomized to receive Melphalan/HDS ( n = 43) or BAC ( n = 42), and 72 patients received study treatment (Melphalan/HDS [ n = 40]; BAC [ n = 32]). Exploratory analyses of efficacy endpoints showed numerical differences consistently favoring the Melphalan/HDS arm versus BAC (median overall survival: 18.5 vs. 14.5 months; median progression-free survival: 9.1 vs. 3.3 months; objective response rate: 27.5% vs. 9.4%; and disease control rate: 80.0% vs. 46.9%). Serious adverse events (SAEs) occurred in 51.2% of Melphalan/HDS and in 21.9% of BAC patients. The most common (>5%) SAEs included thrombocytopenia (19.5%), neutropenia (9.8%), leukopenia (9.8%) and febrile neutropenia (7.3%) in Melphalan/HDS patients and cholecystitis, nausea and vomiting (6.3% each) in BAC patients. No treatment-related deaths were observed. Conclusion Treatment with Melphalan/HDS shows clinically meaningful efficacy and demonstrates a favorable benefit-risk profile in patients with unresectable mUM as compared to BAC.

Hepatocellular carcinoma (HCC) represents a significant contributor to cancer-related morbidity and mortality with increasing incidence in both developing and developed countries. Embolotherapy as a locoregional therapeutic strategy consists of trans-arterial or “bland” embolization (TAE), trans-arterial chemoembolization (TACE), and selective internal radiotherapy (SIRT). Trans-catheter arterial therapies can be applied along all stages of HCC, either as an alternative or neoadjuvant to surgical resection/transplantation in very early and early stage HCC or as a palliative option for local disease control in unresectable and advanced stage HCC. In advanced stage HCC, SIRT did not demonstrate superiority in comparison to systemic treatment options in several recent large prospective trials, though for carefully selected patients, may confer improved tolerability with similar disease control rates. The latest embolotherapeutic techniques and literature as they pertain to the management of HCC, as well as future directions, are reviewed in this article.

Locoregional treatments (LRT) continue to advance for hepatocellular carcinoma (HCC). Selective internal radiation therapy (SIRT) or transarterial radioembolization (TARE) with radioactive 90 Yttrium (Y90) microspheres is currently widely accepted, and external beam and stereotactic body radiation (EBRT/SBRT) are increasingly used as LRT 1–5 . Assessment of treatment response after these radiation-based therapies can be challenging, given that the adjacent liver also undergoes treatment related changes, inflammatory changes occur, and there is a variable time for response to develop. In 2017, the liver imaging reporting and data system (LI-RADS) workgroup initially developed a single algorithm for the imaging assessment of treatment response encompassing all types of locoregional therapies, the LI-RADS treatment response (LR-TR) algorithm. Recognizing that response and imaging patterns differ between radiation and non-radiation based therapies, the LR-TR working group recently updated the algorithm to reflect the unique characteristics of tumor response for therapies involving radiation. This article aims to elucidate the changes in the new version of the LI-RADS TR, with a guide for algorithm utilization and illustration of expected and unexpected findings post liver directed therapies for HCC.

Since 2013, North American Neuroendocrine Tumor Society (NANETS) consensus-guidelines have endorsed consideration of surgical intervention for pancreatic- neuroendocrine tumors (PNET) with liver metastases. Patients with non-functional PNET with liver only metastases from 2010 to 2019 were identified from the National Cancer Database. 34.7% underwent surgical intervention (13% PNET resection, 2.1% surgical management of liver metastases (SMLM), 19.5% PNET resection ​+ ​SMLM). In multivariable analysis, government insurance, year of diagnosis>2013, increasing primary tumor size were associated with lower rate of surgical intervention. Receiving treatment at an academic center (OR 3.59, 95%CI 1.81–7.11; P ​< ​0.001) or integrated cancer network (OR 3.21, 95%CI 1.57–6.54; P ​= ​0.001) was associated with a higher rate of surgical intervention. The overall rate of surgical intervention decreased from 45.7% in 2010 to 23.0% in 2019. Despite guideline recommendations and the suggested survival benefits, only one-third of patients underwent surgical intervention, potentially influenced by the rising utilization of systemic therapy in the past decade. •One-third of patients with PNET and liver metastases received surgical intervention.•Overall rate of surgical intervention for patients with PNET +liver metastases decreased from 45.7% in 2010 to 23.0% in 2019.•Treatment in community centers compared to academic centers was associated with lower chance of surgical intervention.•5-year OS non-surgical patients 40.4%, vs. PNET resection 74.4% vs. both SMLM and PNET resection 75.9%.

Background A growing number of centers offer hepatic artery infusion pump (HAIP) chemotherapy for advanced liver malignancies. While small series have demonstrated feasibility of robotic HAIP placement, comparison of outcomes with open placement is lacking. We compared outcomes after robotic versus open HAIP placement. Methods We retrospectively reviewed HAIP placement without concurrent hepatectomy at Memorial Sloan Kettering Cancer Center from 1 January 2011 to 15 September 2022, and Duke Health from 1 November 2018 to 18 May 2023. Patients with prior liver surgery or who required catheterization of a non-standard vessel were excluded. Propensity score matching weights (PSMW) were calculated using age, sex, race, body mass index, American Society of Anesthesiologists class, neoadjuvant chemotherapy, colorectal procedure, and institution. Survey-weighted generalized linear models assessed the relationship between approach and outcomes. Results Of 2002 consecutive HAIP placements, 819 (645 open/174 robotic) met the inclusion criteria. A higher proportion of open procedures involved combined colorectal procedures; other patient characteristics were similar. Overall, 15% of patients experienced an HAIP-specific complication and 12% required re-intervention; 2.7% had HAIP failure ≤ 90 days. After PSMW, the robotic approach had a longer operative time ( β  = 68 min, 95% confidence interval [CI] 55–81, p  < 0.001) but shorter length of stay ( β  = − 1.8 days, 95% CI − 2.3 to 1.3, p  < 0.001). The robotic approach was associated with increased HAIP-specific complications (odds ratio [OR] 1.72, p  = 0.025) and re-intervention (OR 2.33, p  < 0.001), with no difference in time to initiation of HAIP chemotherapy or HAIP failure. Conclusions Robotic HAIP placement was associated with increased postoperative complications and significantly shorter length of stay, with similar time to initiation of HAIP therapy. There was no difference in the rate of early HAIP failure versus the open approach. These results suggest robotic HAIP placement is feasible and effective.

Surgical resection is the only treatment known to provide durable disease-free survival in patients with intrahepatic cholangiocarcinoma (iCCA). Many with iCCA are not candidates for resection because of tumor size, location, or comorbid disease. The efficacy of newer forms of liver directed therapy (LDT) relative to resection has not been defined. We compare outcomes for patients undergoing LDT for clinical stage I to IVa iCCA in our healthcare system between 2010 and 2024 to those undergoing resection. Multivariable regression (MVR), Cox modeling and Kaplan-Meier Analysis were used to identify factors associated with resection, overall (OS) and disease-specific (DSS) survival. 77 (48.7 ​%) patients underwent treatment for localized iCCA; 39 (50.6 ​%) underwent LDT, 38 (49.4 ​%) resection. On MVR, patients of advanced age were less likely to undergo resection (AOR 0.92, p ​< ​0.01). On Cox modeling, compromised performance status (ECOG ≥1: HR 2.59, p ​= ​0.011) was associated with decreased OS; systemic therapy (HR 0.27, p ​< ​0.01) and resection (HR 0.71, p ​< ​0.01) were associated with increased OS. On Kaplan-Meyer analysis, there was no significant difference in OS or DSS between treatment cohorts (p ​> ​0.05). LDT offers local disease control comparable to resection and may be considered definitive local treatment in appropriately selected patients with iCCA. •Liver directed therapy (LDT) may offer definitive local treatment for intrahepatic cholangiocarcinoma (iCCA) for non-surgical candidates.

Purpose Tumoural portal vein thrombosis (PVT) is a major prognostic factor in hepatocellular carcinoma (HCC). The efficacy of sorafenib, the only treatment approved at an advanced stage, is limited. Based on previous data, selective internal radiation therapy (SIRT), or 90 Y radioembolization, seems an interesting option. We aimed to compare both treatments in this population. Methods We retrospectively compared patients treated in two centres for HCC with tumoural PVT. We compared overall survival (OS) between patients treated with SIRT and patients treated with sorafenib. Analyses were performed before and after 1:1 matching with a propensity score for controlling indication bias, using a Cox proportional hazards model. Results A total of 151 patients were analysed, 34 patients treated with SIRT and 117 patients treated with sorafenib only. In the whole population, SIRT was associated with a higher median OS as compared with sorafenib: 18.8 vs 6.5 months (log-rank p  < 0.001). There was an imbalance of baseline characteristics between patients treated by SIRT and sorafenib, which justified patient matching with use of a propensity score: 24 patients treated with SIRT could be matched with 24 patients treated with sorafenib. OS was estimated with a median of 26.2 vs 8.7 months in patients treated with SIRT vs sorafenib, respectively (log-rank p  = 0.054). Before and after patient matching, the adjusted hazard ratio related to treatment by SIRT was estimated at 0.62 [95 % confidence interval (CI) 0.39–0.97] ( p  = 0.037) and 0.40 (95 % CI 0.19–0.82) ( p  = 0.013), respectively. Conclusion SIRT seems more effective than sorafenib in patients presenting with HCC and tumoural PVT. This hypothesis is being tested in prospective randomized trials.

The increasing set of liver-directed therapies (LDT) have become an integral part of hepatocellular carcinoma (HCC) treatment. These range from percutaneous ablative techniques to arterial embolization, and varied radiotherapy strategies. They are now used for local disease control, symptom palliation, and bold curative strategies. The big challenge in the face of these innovative and sometimes overlapping technologies is to identify the best opportunity of use. In real practice, many patients may take benefit from LDT used as a bridge to curative treatment such as resection and liver transplantation. Varying trans-arterial embolization strategies are used, and comparison between established and developing technologies is scarce. Also, radioembolization utilizing yttrium-90 (Y-90) for locally advanced or intermediate-stage HCC needs further evidence of clinical efficacy. There is increasing interest on LDT-led changes in tumor biology that could have implications in systemic therapy efficacy. Foremost, additional to its apoptotic and necrotic properties, LDT could warrant changes in vascular endothelial growth factor (VEGF) expression and release. However, trans-arterial chemoembolization (TACE) used alongside tyrosine-kinase inhibitor (TKI) sorafenib has had its efficacy contested. Most recently, interest in associating Y-90 and TKI has emerged. Furthermore, LDT-led differences in tumor immune microenvironment and immune cell infiltration could be an opportunity to enhance immunotherapy efficacy for HCC patients. Early attempts to coordinate LDT and immunotherapy are being made. We here review LDT techniques exposing current evidence to understand its extant reach and future applications alongside systemic therapy development for HCC.

Uveal melanoma is the most common primary intraocular tumor in adults. It can arise from melanocytes in the anterior (iris) or posterior uveal tract (choroid and ciliary body). Uveal melanoma has a particular molecular pathogenesis, being characterized by specific chromosome alterations and gene mutations (e.g., GNAQ/GNA11; BAP1), which are considered promising targets for molecular therapy. Primary treatment of uveal melanoma includes radiotherapy (brachytherapy and charged-particle therapy), phototherapy (photocoagulation, transpupillary thermal therapy, and photodynamic therapy) and surgery (local resection, enucleation and exenteration). Approximately half of patients with uveal melanoma will, however, develop metastasis, especially in the liver. The treatment of metastatic uveal melanoma includes systemic chemotherapy, immunotherapy and molecular targeted therapy. Liver-directed therapies, such as resection, chemoembolization, immunoembolization, radioembolization, isolated hepatic perfusion and percutaneous hepatic perfusion, are also available to treat metastatic uveal melanoma. Several clinical trials are being developed to study new therapeutic options to treat uveal melanoma, mainly for those with identified liver metastases. The present work discusses the physiopathology and new in situ-specific therapies for the treatment of uveal melanoma.