Morecroft, Renee A

Introduction Approximately 50% of patients with uveal melanoma develop metastatic disease, most commonly involving the liver, and prognosis remains poor. Immunoembolization (IE) is an established liver-directed therapy for patients with liver-dominant metastatic uveal melanoma (mUM), though comparative data with other regional therapies remain limited. We present a single-center retrospective analysis of IE in hepatic mUM and compare outcomes with those reported in the Phase 3 FOCUS trial evaluating melphalan via percutaneous hepatic perfusion. Methods All patients with liver-dominant mUM treated with IE between 2010 and 2023 at our institution were included. Clinical records were reviewed for demographics, tumor characteristics, treatment details, and outcomes. The primary endpoint was disease control rate (DCR), defined as complete response (CR), partial response (PR), or stable disease (SD). Secondary endpoints included progression-free survival (PFS) and overall survival (OS), with subgroup analyses based on prior systemic therapy exposure. Descriptive statistics were used for analysis. Results Forty-three patients (62.8% female; median age 62 years; all Caucasian) underwent 249 IE procedures (mean 5.8 procedures per patient) over a median treatment duration of 9.1 months. Choroidal primaries accounted for 95.3% of cases, and 90.7% had liver-only metastases. The overall DCR was 27.9% (CR 4.7%, PR 20.9%, SD 2.3%), while 62.8% experienced disease progression. Median PFS was 0.85 months, and median OS was 32.7 months. One- and two-year OS rates were 69.8% and 55.8%, respectively. In subgroup analysis, patients who had received prior systemic therapy (n=12) demonstrated improved outcomes compared with treatment-naïve patients, with longer median PFS (29.9 vs. 7.2 months) and higher 2-year OS (60.0% vs. 47.0%). Compared with outcomes reported in the FOCUS trial, IE demonstrated shorter median PFS (0.85 vs. 9.0 months) and lower DCR (27.9% vs. 73.6%), but longer median OS (32.7 vs. 20.5 months). Discussion IE produced overall survival outcomes comparable to hepatic melphalan delivery despite lower radiographic response rates. Notably, patients previously treated with systemic therapy experienced improved outcomes, suggesting a potential sequencing effect. These findings support IE as a viable liver-directed therapy for liver-dominant mUM. Prospective, multicenter trials are warranted to clarify optimal sequencing strategies and enhance therapeutic outcomes.

Localized cutaneous squamous cell carcinoma (cSCC) has a favorable prognosis, unlike advanced disease, especially with clinical perineural invasion (PNI), which poses substantial management challenges due to aggressivity and higher recurrence, metastasis, and mortality risks. PNI, a high-risk staging feature, has worse outcomes, particularly when clinically evident rather than incidental. Clinical PNI (cPNI) is evident by clinical symptoms (such as pain, paresthesia, or motor deficits) or radiologic findings, whereas incidental PNI (iPNI) is identified only histologically without associated symptoms or radiologic evidence. PNI remains a novel area with varying practice patterns across institutions. Improving risk stratification and tailoring multidisciplinary approaches are critical for optimizing outcomes. Our review outlines clinical practice patterns at our institution, providing insights into managing cSCC with PNI, focusing on diagnosis, imaging, staging, and emerging immunotherapies. A structured search was conducted using the terms “perineural invasion,” “cutaneous squamous cell carcinoma,” and “immunotherapy.” cPNI has a poor prognosis and requires nuanced clinical decision-making. Surgery and radiation remain central to management. Adjuvant therapy offers substantial survival benefit in cSCC with PNI, with improved disease-free and overall survival compared with surgery alone, supporting its use in appropriately selected high-risk patients. Traditional systemic therapies, including cisplatin and cetuximab, remain foundational but have shown only moderate response rates and limited durability in advanced or neurotropic cSCC. In contrast, immunotherapy—now preferred for advanced or unresectable cases—has transformed management, with programmed cell death protein-1 (PD-1) inhibitors showing promising results (up to 69% response rate) and disease stabilization. Neoadjuvant immunotherapy may enable tumor downstaging, improve radiation planning, and reduce surgical morbidity. Imaging for squamous cell carcinoma (SCC) with PNI aids staging and surveillance, but symptoms remain key for detecting recurrence. Our multidisciplinary approach emphasizes personalized care. Larger trials are needed to define the optimal role and sequencing of immunotherapy in this high-risk patient population.

e21600 Background: Uveal melanoma (UM), the most common intraocular malignancy in the U.S., metastasizes in 50% of patients, frequently to the liver (~90%) with poor prognosis (median overall survival [mOS] 1 year). Metastatic UM (mUM) literature is limited (due to its rarity/complexity) and management remains challenging, as standard therapies—liver-directed approaches (e.g. transarterial chemoembolization [TACE]) and systemic therapy with tebentafusp (limited to HLA-A*02:01-positivity)—offer limited efficacy, with no durable responses or significant survival benefits. Interestingly, Delcath’s recent FOCUS Phase 3 trial demonstrated the efficacy of the melphalan/Hepatic Delivery System for unresectable mUM, with an objective response rate (ORR) of 36.3%, 1-year OS of 80%, and median progression-free survival (PFS) of 9 months. Here, we present a large retrospective study of liver-predominant mUM treated with immunoembolization (IE) at a tertiary academic center. This study provides valuable data to the underreported mUM literature. We also compare our findings with Delcath’s trial to contextualize results and identify clinical factors influencing treatment response and prognosis. Methods: We retrospectively reviewed charts of mUM patients treated with IE (age ≥18 years, 2010–2023). Data collected included demographics, clinical/pathology/molecular details, and management/outcomes. Subgroup analysis on prior systemic therapy use was performed (similar to Delcath). The primary outcome was OS at 12 and 24 months. Results: 43 patients were included (100% White, 62.8% female, median age 62). Most had choroidal type (95.3%), hepatic-only metastases (90.7%), and were treatment-naïve before IE (72.1%). Across 249 IE procedures (5.8 per patient, mean duration 9.1 months), we observed median PFS and OS of 9.2 and 23 months, respectively - comparable to Delcath’s trial (9 and 20.5 months). Despite higher disease progression in our study (62.8% vs. 25.3%) and lower best clinical response (27.9% vs. 73.7%), 1-year (67% vs. 80%) and 2-year OS rates (49% vs. 43%) were similar. Subgroup analysis revealed better outcomes in previously treated patients (n = 12) compared to treatment-naïve patients (n = 31), with improved median PFS (29.9 vs. 7.2 months) and 1- and 2-year OS (75% vs. 65% and 58.3% vs. 41.9%, respectively). This contrasts with Delcath’s findings, where prior therapy did not significantly affect PFS or OS. Median PFS was comparable in treatment-naïve groups (7.2 vs. 9 months) but markedly improved in our previously treated group (29.9 vs. 9.2 months). Conclusions: We highlight IE’s comparable efficacy to Delcath’s melphalan/Hepatic Delivery System regarding mUM PFS and OS, with added benefits for previously treated patients. While our findings advance understanding of mUM management, more prospective studies are needed to improve therapeutic strategies/patient outcomes.