Personalized Dosimetry Used to Guard Against Liver Disease in Novel NET Protocol

In an interview with Targeted Oncology at the 2025 North American Neuroendocrine Tumor Society (NANETS) Symposium, Michael Soulen, MD, addresses the specific safety profile and adverse events (AEs) observed during the clinical trials of the combined systemic chemotherapy and Lutetium-177 dotatate protocol for neuroendocrine tumors (NETs).

The major toxicity seen in both the phase 1 and ongoing phase 2 trials is cytopenia, specifically a drop in platelet count. This hematological toxicity is attributed primarily to the systemic chemotherapy component, temozolomide and Cap/Tem, and remains within the expected spectrum for that drug dosage. This underscores the rationale for modifying the treatment schedule to allow for adequate bone marrow recovery between cycles.

The biggest safety concern for patients undergoing any liver-directed therapy, including this combined approach, is the risk of radiation-induced liver disease (RILD), which Soulen refers to as "real or renormalization" liver disease. This is a known risk for any patient receiving radiation to the liver. To mitigate this, a sophisticated personalized dosimetry approach is employed. Soulen reassures that meticulous planning prevents over-irradiation of the liver, ensuring patient safety while maintaining therapeutic efficacy.