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In uveal melanoma patients, short-term evaluation of treatment response to hepatic artery infusion chemotherapy (HAIC) using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria is challenging due to the diffuse metastatic spread. As liver enlargement can frequently be observed, this study aims to compare RECIST 1.1 and liver volumetry (LV) for the evaluation of HAIC treatment response. Treatment response was evaluated in 143 patients (mean age 65.1 ± 10.9 years, 54% female) treated by HAIC by RECIST 1.1 and LV on CT imaging performed before and after HAIC. In LV, different increases in liver volume were evaluated to set an effective threshold to distinguish between stable disease (SD) and progressive disease (PD). Overall survival (OS) was calculated as the time from first HAIC to patient death using Kaplan-Meier test and multivariate analysis was performed for RECIST 1.1 and LV. In the overall population, median OS (mOS) was 13.5 months (95% CI 11.2–15.8 months). In LV, a threshold of 10% increase in liver volume was suited to identify patients with significantly reduced OS (SD: 103/143 patients, mOS 15.9 months; PD: 40/143 patients, 6.6 months; p < 0.001). Compared to RECIST 1.1, LV was the only significant prognostic factor that was able to identify a decreased OS. In uveal melanoma patients with liver metastases, LV with a threshold for liver volume increase of 10% was suitable to evaluate treatment response and would be able to be used as a valuable add-on or even alternative to RECIST 1.1. [ABSTRACT FROM AUTHOR]

Approximately every second patient with uveal melanoma develops distant metastases, with the liver as the predominant target organ. While the median survival after diagnosis of distant metastases is limited to a year, yet‐to‐be‐defined subgroups of patients experience a more favorable outcome. Therefore, prognostic biomarkers could help identify distinct risk groups to guide patient counseling, therapeutic decision‐making, and stratification of study populations. To this end, we retrospectively analyzed a cohort of 101 patients with newly diagnosed hepatic metastases from uveal melanoma by using Cox‐Lasso regression machine learning, adapted to a high‐dimensional input parameter space. We show that substantial binary risk stratification can be performed, based on (i) clinical and laboratory parameters, (ii) measures of quantitative overall hepatic tumor burden, and (iii) radiomic parameters. Yet, combining two or all three domains failed to improve prognostic separation of patients. Additionally, we identified highly relevant clinical parameters (including lactate dehydrogenase, thrombocyte counts, aspartate transaminase, and the metastasis‐free interval) at first diagnosis of metastatic disease as predictors for time‐to‐treatment failure and overall survival. Taken together, the risk stratification models, built by our machine‐learning algorithm, identified a comparable and independent prognostic value of clinical, radiological, and radiomic parameters in uveal melanoma patients with hepatic metastases. [ABSTRACT FROM AUTHOR]

Introduction: In uveal melanoma (UM) patients with hepatic metastases, hepatic artery infusion chemotherapy (HAIC) is a viable, palliative treatment option. To evaluate the impact of two histomorphological patterns (spindle cell vs. epithelioid) of liver metastases on median overall survival (mOS) in UM patients undergoing HAIC. Methods: A retrospective analysis with 60 UM patients (29 females, mean age: 61.6 ± 12.1 years) with hepatic metastases was performed. Histomorphological patterns in metastases were analysed and classified as either predominant spindle cell or epithelioid pattern. mOS between both patient groups was analysed using Kaplan–Meier curves and the log‐rank test. Results: In 73.3% (44/60) of the metastases, a predominant epithelioid pattern, in 21.7% (13/60) a predominant spindle cell pattern, and in 5% (3/60) other patterns were found. No significant differences between patients with an epithelioid (mOS: 14.2 months, 95% CI: 8.8–19.6) and a spindle cell pattern (mOS: 14.4 months, 95% CI: 4.3–24.5) were detected by the log‐rank test, χ2(2) = 0.22, P = 0.881. Conclusion: Histomorphological patterns of UM metastases do not seem to be a predictor for mOS in UM patients undergoing HAIC. [ABSTRACT FROM AUTHOR]

Simple Summary: Tebentafusp has recently been approved for the treatment of metastatic uveal melanoma (mUM). We performed a retrospective, multicenter study to analyze the outcomes and safety of tebentafusp therapy in 78 patients with mUM. Patients treated with tebentafusp had a median PFS of 3 months (95% CI 2.7 to 3.3) and a median OS of 22 months (95% CI 10.6 to 33.4). In contrast to a published Phase 3 study, our cohort had a higher rate of patients with elevated LDH (65.4% vs. 35.7%) and included patients with prior systemic and local ablative therapies. In patients treated with tebentafusp following ICI, there was a trend for a longer median OS (28 months, 95% CI 26.9 to 29.1) compared to the inverse treatment sequence (24 months, 95% CI 13.0 to 35.0, p = 0.257). The most common treatment-related adverse events were cytokine release syndrome in 71.2% of patients, which was managed with antipyretic drugs (66.1%), intravenous fluids (28.6%) and systemic corticosteroids or tocilizumab (5.4%), and skin toxicity in 53.8%, which was managed with topical corticosteroids (38.1%) or antihistamines (45.2%). Background: Tebentafusp has recently been approved for the treatment of metastatic uveal melanoma (mUM) after proving to have survival benefits in a first-line setting. Patients and Methods: This retrospective, multicenter study analyzed the outcomes and safety of tebentafusp therapy in 78 patients with mUM. Results: Patients treated with tebentafusp had a median PFS of 3 months (95% CI 2.7 to 3.3) and a median OS of 22 months (95% CI 10.6 to 33.4). In contrast to a published Phase 3 study, our cohort had a higher rate of patients with elevated LDH (65.4% vs. 35.7%) and included patients with prior systemic and local ablative therapies. In patients treated with tebentafusp following ICI, there was a trend for a longer median OS (28 months, 95% CI 26.9 to 29.1) compared to the inverse treatment sequence (24 months, 95% CI 13.0 to 35.0, p = 0.257). The most common treatment-related adverse events were cytokine release syndrome in 71.2% and skin toxicity in 53.8% of patients. Tumor lysis syndrome occurred in one patient. Conclusions: Data from this real-life cohort showed a median PFS/OS similar to published Phase 3 trial data. Treatment with ICI followed by tebentafusp may result in longer PFS/OS compared to the inverse treatment sequence. [ABSTRACT FROM AUTHOR]