New hybrid approach intensifies treatment for liver tumor metastases

Combining intraarterial and intravenous administration of peptide receptor radionuclide therapy (PRRT) can selectively intensify treatment for liver-dominant metastatic neuroendocrine tumors (NETs) while still effectively delivering treatment throughout the whole body. This hybrid approach safely delivered over three times more radiation directly to liver metastases, resulting in encouraging tumor responses among patients. This research was published online in The Journal of Nuclear Medicine.

Once considered rare, gastroenteropancreatic NETs now show increasing incidence and prevalence. Diagnosis often occurs late, usually with liver metastases, making surgery-the only curative option-unfeasible. Current liver-directed (or hepatic) therapies, such as systemic agents, chemotherapy, and PRRT, offer symptom and tumor control, with a median progression-free survival of approximately 1.5 years.

Research has shown that standard intravenous PRRT may not deliver enough radiation to these lesions. Our study explored a personalized hybrid approach-delivering the first treatments directly through hepatic arteries, followed by intravenous therapy-and sought to determine if this treatment method was feasible, safe, and effective."

Lisa Bodei, MD, PhD, attending physician, member, and director, RadioTheranostics Section, Molecular Imaging and Theranostics Service, Department of Radiology, Memorial Sloan Kettering Cancer Center and professor of radiology, Weill Cornell Medical College, Cornell University, New York

The prospective pilot study included 10 patients with progressive, liver-dominant metastatic gastroenteropancreatic NETs. The patients received four cycles of ¹⁷⁷Lu-DOTATATE administered every two months: two initial intraarterial cycles followed by two intravenous cycles. Safety monitoring, radiation protection, and dosimetry comparisons between intraarterial and intravenous routes were performed and preliminary efficacy was evaluated.

The intraarterial administration procedure was feasible in 100 percent of patients. Radiation exposure to staff and patients remained within regulatory limits, with no contamination events. Dosimetry analysis indicated that intraarterial administration delivered a greater than three-fold higher radiation dose to liver metastases compared with the intravenous route.

Furthermore, ⁶⁸Ga-DOTATATE PET imaging revealed an 86 percent increase in median liver lesion uptake with intraarterial administration. Efficacy analysis showed partial response rates in 67 percent of patients at the first follow-up three months after treatment completion, improving to 87 percent at the second follow-up six months after treatment completion.

"The novelty of this research is not simply that liver-directed intraarterial PRRT increases hepatic uptake; rather, it evaluates a clinically integrated, personalized hybrid strategy that links delivery, dosimetry, safety, and response within the same prospective study," said Bodei. "For patients, this could translate into better tumor control and a more effective, individualized treatment option."