Poor Response to Checkpoint Immunotherapy in Uveal Melanoma Highlights the Persistent Need for Innovative Regional Therapy Approaches to Manage Liver Metastases

Uveal melanoma is a cancer that develops from melanocytes in the posterior uveal tract. Metastatic uveal melanoma is an extremely rare disease that has a poor long-term prognosis, limited treatment options and a strong predilection for liver metastasis. Median overall survival has been reported to be 6 months and 1 year mortality of 80%. Traditional chemotherapy used in cutaneous melanoma is ineffective in uveal cases. Surgical resection and ablation is the preferred therapy for liver metastasis but is often not feasible due to extent of disease. In this review, we will explore treatment options for liver metastases from uveal melanoma, with a focus on isolated hepatic perfusion (IHP). IHP offers an aggressive regional therapy approach that can be used in bulky unresectable disease and allows high-dose chemotherapy with melphalan to be delivered directly to the liver without systemic effects. Long-term median overall survival has been reported to be as high as 27 months. We will also highlight the poor responses associated with checkpoint inhibitors, including an overview of the biological rationale driving this lack of immunotherapy effect for this disease. The persistent failure of traditional treatments and immunotherapy suggest an ongoing need for regional surgical approaches such as IHP in this disease.

The lines of loco-regional therapies received and the healthcare economic burden of patients newly diagnosed with hepatocellular carcinoma in the United States.

286 Background: Hepatocelluar carcinoma (HCC) is one of the fastest growing causes of cancer-related deaths in the US. The objectives of this study were to examine the lines of loco-regional therapies received and the healthcare economic burden of patients newly diagnosed with HCC in the US. Methods: Patients (≥18 years of age) diagnosed with HCC who received ≥1 loco-regional therapy (index date) after diagnosis were identified from the MarketScan Commercial and Medicare Supplemental databases (July 1, 2013-May 31, 2018). Patients were required to have ≥6 months of continuous insurance enrollment before the index date and ≥1 month after (follow-up period). The follow-up period was censored when patients received any systemic therapy. During the follow-up periods, the number of patients who received radiation therapy, ablative therapy, and embolization procedures (transarterial embolization/chemoembolization [TAE] and radioembolization [TARE]) were examined. All-cause and HCC-related healthcare costs (total and patient out-of-pocket [OOP] payments per patient per month [PPPM]) were also measured. Results: Among the 2,101 patients newly diagnosed with HCC who received ≥1 loco-regional therapy, median age was 64 years and 75.0% were male; the mean follow-up duration was 11.5 months. During the follow-up periods, 28.1% (n = 590) received radiation therapy, 27.3% (n = 574) ablative therapy, and 77.3% (n = 1,623) embolization therapy (TAE: 68.7% [n = 1,443]; TARE: 20.7% [n = 434]); 30.9% of patients received multiple loco-regional therapies. During the follow-up periods, total all-cause healthcare costs were a mean of $20,316 (OOP: $378) PPPM, of which 70.7% ($14,359; OOP: $227 PPPM) were HCC-related. The breakdown of healthcare costs is shown in the table. Conclusions: According to the findings of this large-scale real-world analysis of patients newly diagnosed with HCC in the US, a vast majority received at least one embolization procedure. The monthly healthcare economic burden of patients with HCC treated with local-regional therapies is relatively high. [Table: see text]

Cepharanthine as a Potential Novel Tumor-Regional Therapy in Treating Cutaneous Melanoma: Altering the Expression of Cathepsin B, Tumor Suppressor Genes and Autophagy-Related Proteins

The incidence of primary cutaneous melanoma continues to increase annually and is one of the most aggressive malignancies in humans and need to develop more novel non-surgical therapies. Autophagy and cathepsin B targeted therapy was reported to improve melanoma treatment. Cepharanthine (CEP), a natural alkaloid extracted from the genus Cephalophyllum has been reported to have the function of inhibiting cancers. We found that CEP inhibited human primary cutaneous melanoma cells viability and proliferation in 24 h in vitro, and topical application or intra-tumoral injection of CEP decreased the growth of cutaneous melanoma in mice within 4 weeks. CEP preparations below 50% concentration did not induce skin irritation and allergy reaction on human skin in vivo. Primary cutaneous melanoma cells incubated with CEP, the expression of cathepsin B was decreased and the LC3-I and LC3-II expression changed in a dose-dependent manner, while p53, p21Cip1p, and p16Inka gene expression was up-regulated. We demonstrated the effects of CEP as a novel tumor-regional therapy for cutaneous melanoma and provided a preliminary research basis for future clinical treatment researches and the exploration of integrated treatments with systemic therapy, radiotherapy, and surgery for human primary cutaneous melanoma.