Pancreatic neuroendocrine tumors, also called PNETs or PanNETs, are the second most common type of pancreatic cancer after pancreatic ductal adenocarcinomas or PDACs. While PDACs arise from ductal or exocrine cells that make up the pancreas, PNETs arise from the hormone producing islets or endocrine cells. Though PDACs account for more than 90% of pancreatic cancers, the incidence of PNETs have been increasing due to increased awareness and advances in imaging. PNETs tend to be more localized and slow-growing than PDACs and therefore have better prognoses; a 5-year survival rate of 83%. Since less than 30% of patients have metastatic disease, resection surgery is commonly recommended for patients with localized disease as it is potentially curative. However, resection surgery can be quite extensive, leaving only a small portion of the pancreas and frequently resulting in diabetes and pancreatic enzyme insufficiency.
To address this, we funded a 2024 PNET Grant towards Tamas Gonda, MD, Professor, Department of Medicine at NYU Grossman School of Medicine and Director of the Pancreatic Disease Program at NYU. Dr. Gonda is a physician-scientist specializing in advanced endoscopy and pancreatic diseases. His research focuses on developing and refining minimally invasive therapies for pancreatic tumors, with the goal of reducing patient risk while maintaining effective disease control.
Dr. Gonda’s work has focused on maximizing the efficacy of endoscopic ultrasound guided radiofrequency ablation (EUS RFA) for PNETs. This technique uses thermal energy to destroy tumor tissue in a minimally invasive and localized manner. Dr. Gonda has set out to understand the efficacy of EUS RFA for PNETs, define the optimal treatment strategy and radiographic features to monitor response and surveillance for progression. Here we provide an update to the work being supported by The Hirshberg Foundation on this project.
In the largest cohort of EUS RFA treated PNET patients with non-functioning islets, Dr. Gonda and his team evaluated tumor response and treatment-related risks over time. They saw a 60% complete response as well as a 31.1% partial response rate combining for a 91% overall response. While 15% of patients did experience some adverse events, most were mild indicating the safety of the procedure. These findings suggest that EUS RFA can offer strong tumor control with a favorable safety profile.
Further analysis showed that traditional predictors such as tumor size, grade, or specific procedural techniques did not reliably determine treatment success. Instead, the number of ablation sites was associated with higher complete response rates, providing actionable insight into how the procedure can be optimized. This work has been presented at the American Pancreas Association (APA) and Digestive Disease Week (DDW) meetings and a manuscript for publication is currently undergoing revisions.
Unlike surgery, ablative therapies trigger gradual biological changes that evolve over months. This study revealed that tumor response continues to improve well beyond the initial follow-up period. Following a single ablation, the group found that follow-up at 2-4 months didn’t adequately capture the total number of patients who would go on to have complete responses and this took up to 12 months to fully capture. Long term follow-up showed that additional response did not develop beyond 12 months suggesting 12 months is the optimal time period to follow up and potentially reassess for repeat ablation. These findings offer critical guidance for both physicians and patients, setting clearer expectations and supporting more precise treatment planning.
The research team also examined how tumors appear on advanced imaging before and after EUS RFA, focusing on contrast enhancement and PET DOTATATE uptake. The group is also working to identify biomarkers that could predict response to EUS RFA to identify which patients would benefit from this procedure and which patients may need different interventions. This imaging-based insight moves the field closer to personalized treatment algorithms, allowing care teams to tailor follow-up and next steps based on early response signals.
To further this research, the group seeks to build models to increase the understanding of PNET development and to aid in treatment decisions based on potential outcomes. Due to the slow growth of PNETs, understanding the risk of progression for small tumors could allow for the stratification of patients who may be able to forgo treatment for surveillance or benefit from this new localized treatment and define patients who may need a more aggressive resection for optimal response.
This work and its continuation will represent meaningful progress in providing treatment for PNET patients. Dr. Gonda and his team are hoping to shift treatment for pancreatic neuroendocrine tumors toward safer, more targeted approaches. By generating high-quality evidence and clear clinical guidance, the Hirshberg Foundation is supporting research that transforms innovation into real-world benefit for patients.
