UTHealth Houston study on repeated radiofrequency ablation in combination with chemotherapy for pancreatic cancer supported with $3.3M HHS grant

A combination strategy of endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) with chemotherapy for pancreatic cancer will be studied at UTHealth Houston through a $3.3 million grant from the National Cancer Institute by the U.S. Department of Health and Human Services.

The survival rate of pancreatic adenocarcinoma, or pancreatic cancer, remains low, around 10%, because of its poor response to current chemotherapies.

The five-year grant will continue the established six-year clinical and translational research collaboration between Jennifer Bailey-Lundberg, PhD, assistant professor in the Department of Anesthesiology, Critical Care and Pain Medicine; and Nirav Thosani, MD, associate professor in the Department of Surgery, both with McGovern Medical School at UTHealth Houston.

Radiofrequency ablation therapy is the localized use of radio waves to destroy tumor tissues and reduce their growth. Shrinkage of the tumors can allow for them to be surgically removed.

The first aim of the project will evaluate the effects of chemotherapy with repeated EUS-RFA on tumor growth and long-term clinical outcomes such as survival and anti-tumor immunity mechanisms in patients with removable, or resectable, cancer of the pancreas. Researchers will build upon their published findings to follow patients already receiving the alternating standard chemotherapy and EUS-RFA versus chemotherapy treatment alone. Their evaluation will help create therapeutic potential and utility for the adoption of EUS-RFA treatment into clinical care.

“The EUS-guided radiofrequency ablation therapy is a minimally invasive and an extremely well-tolerated novel procedure that allows local control of the tumor and supports immune system response, which we hadn’t seen in any treatment before. This has the potential to change how we treat pancreatic cancer in the future,” said Thosani, who is also the Atilla Ertan, MD, Chair in Gastroenterology, Hepatology and Nutrition, and director of the Center for Interventional Gastroenterology with McGovern Medical School at UTHealth Houston.

The preclinical arm of the study aims to analyze the impact of repeated EUS-RFA treatment in sustaining immunity against tumors, and discover novel combination therapies that are targeting checkpoint blockade or immune suppression to amplify RFA-mediated anti-tumor responses.

Immune checkpoint inhibitors are cancer treatment drugs that block the binding of checkpoint proteins and their partner proteins, which are expressed on immune cells or cancer cells. Checkpoint proteins reduce the potency of cancer-fighting cells in the immune system.

Researchers will administer repeated RFA treatment to tumors in preclinical models, along with targeting immunotherapies to promote anti-tumor immune responses and tumor shrinkage. Anti-tumor immunity will be measured using comprehensive approaches to evaluate RFA and immunotherapy-dependent effects on primary tumors as well as tumors in areas of the body that did not receive direct local RFA therapy, a response called the abscopal effect.

“We want to determine if immunotherapy in combination with RFA can significantly reduce the growth rate of RFA-treated tumors and tumors in other parts of the body. In these studies, we want to enhance the RFA-dependent abscopal response to not only treat local disease, but also treat metastatic pancreatic cancer,” Bailey-Lundberg said.