Alpha DaRT Overcomes Anatomical Constraints in Inoperable Pancreatic Cancer

The therapeutic management of pancreatic adenocarcinoma is restricted by anatomical barriers and a high rate of advanced disease at presentation, according to Philip Blumenfeld, MD. Following the presentation of results from 2 clinical protocols evaluating Alpha DaRT (diffusing alpha-emitters radiation therapy) in pancreatic adenocarcinoma at Digestive Disease Week (DDW) 2026, CancerNetwork® spoke with Blumenfeld, the presenting study author and the director of the Advanced Radiotherapy Unit at the Sharett Institute of Oncology at Hadassah Medical Center, about the findings.

While external beam radiation therapy is an available modality for patients ineligible for surgical resection, its utility is limited in locally advanced disease. Clinicians are constrained by the extreme radiosensitivity of vital gastrointestinal structures surrounding the disease, which can make it difficult to escalate the radiation dose within the tumor.

Alpha DaRT utilizes radium-224 sources delivered directly into the malignancy via endoscopic ultrasound (EUS). Having already demonstrated efficacy in other malignancies, the successful integration of EUS-guided delivery provides a unique local treatment option. By circumventing the toxicities associated with conventional external beam radiation, Alpha DaRT may offer a safe and highly effective strategy to improve outcomes for a broader population of patients with localized, inoperable pancreatic cancer.

Transcript:

The unmet need in pancreatic adenocarcinoma is quite stark. Approximately 87% of patients with pancreatic adenocarcinoma are inoperable at diagnosis, and even for those patients, the therapeutic toolkit that we have is, essentially, systemic chemotherapy with modest survival benefit. External beam radiation has a defined role, but it is still limited to patients with locally advanced disease or patients requiring palliation. We’re essentially constrained by the radiosensitivity of the surrounding organs: the duodenum, stomach, bowel, kidneys, et cetera. We cannot reliably escalate [radiation] dose to the tumor. Again, we are essentially constrained by what we can deliver in terms of external beam [radiation].

Alpha DaRT is, from a mechanism standpoint, distinct. These are essentially radium-224 sources that we can deliver directly into the tumor. This essentially releases short-lived alpha-emitting daughter isotopes that diffuse throughout tumor tissue. Alpha particles deposit the energy with what we refer to as high linear energy transfer, and this causes direct double stranded DNA breaks that are independent of oxygen tension. This matters considerably due to the hypoxic microenvironment of pancreatic adenocarcinoma. The delivery is using endoscopic ultrasound, which is a procedure that gastroenterologists are already [using].

Reference

Blumenfeld P. Updated results of feasibility, safety, and tumor control in two first-in-human trials of a novel alpha-emitting radionuclide for pancreatic adenocarcinoma. Presented at: Digestive Disease Week 2026; May 2-5, 2026; Chicago, IL.