Despite advances in surgery, chemotherapy, and radiation treatments for pancreatic ductal adenocarcinoma (PDAC), 5-year survival rates remain at nearly 11%. Cholangiocarcinoma, while not as severe, also possesses similar survival rates. Fewer than 20% of patients are surgical candidates at time of diagnosis; therefore, it is imperative that alternative therapies are effective for non-surgical patients. There are several thermal ablative techniques, including radiofrequency ablation (RFA), high-intensity focused ultrasound (HIFU), microwave ablation (MWA), alcohol ablation, stereotactic body radiotherapy (SBRT), cryoablation, irreversible electroporation (IRE), biliary intraluminal brachytherapy, and biliary photodynamic therapy (PDT). Emerging literature in animal models and human patients has demonstrated that endoscopic ultrasound (EUS)-guided RFA (EUS-RFA) prevents tumor progression through coagulative necrosis, protein denaturation, and activation of anticancer immunity in local and distant tumor tissue (abscopal effect). RFA treatment has been shown to not only reduce tumor-associated immunosuppressive cells but also increase functional T cells in distant tumor cells not treated with RFA. The remarkable ability to reduce tumor progression and promote tumor microenvironment (TME) remodeling makes RFA a very promising non-surgical therapy technique that has the potential to reduce mortality in this patient population. EUS-RFA offers superior precision and safety compared to other ablation techniques for pancreatic and biliary cancers, due to real-time imaging capabilities and minimally invasive nature. Future research should focus on optimizing RFA protocols, exploring combination therapies with chemotherapy or immunotherapy, and expanding its use in patients with metastatic disease. This review article will explore the current data and underlying pathophysiology of EUS-RFA while also highlighting the role of ablative therapies as a whole in immune activation response.

Objectives: Many patients with cancer receive chemotherapy alongside glucagon-like peptide-1 receptor agonists (GLP-1 RA) to manage type 2 diabetes or obesity. However, both GLP-1 RA and platinum-based chemotherapies can cause upper gastrointestinal (GI) adverse effects (AE) such as nausea and vomiting. This study aimed to evaluate the impact of GLP-1 RA use in patients receiving platinum-based chemotherapy, focusing on GI AE incidence, risk factors, and treatment outcomes. Methods: This single-center study retrospectively reviewed patients who were treated with a platinum-based therapy and concurrent GLP-1 RA and developed symptoms of upper GI AE. Results: The study included 200 patients. Upper GI adverse events occurred in 126 patients. Compared with patients without GI AE, patients with GI AE received fewer doses of platinum therapy (median: 2.5 vs. 5, P <0.0001) and had higher all-cause mortality (40.5% vs. 25.7%, P =0.034), shorter follow-up (median: 1.5 vs. 2.7 y, P <0.0001), and a higher rate of hypothyroidism (35.1% vs. 20.6%, P =0.025). GI AEs were treated with 5-HT3 receptor antagonists in 123 (99.2%) patients and corticosteroids in 5 (4.0%). GI AE symptoms lasted a median of 42.5 days; 92.7% achieved clinical remission of GI AE. Twenty-one (16.7%) patients required hospitalization for GI AE, of whom 4 required rehospitalization. Platinum analogs were discontinued in 72 (57.1%) patients and resumed in 57 (79.2%). GLP-1 RA was discontinued in 11 (8.7%) patients. Conclusions: Most patients receiving GLP-1 RA and platinum-based chemotherapy developed mild GI AE that responded to conservative management.