Peptide receptor radionuclide therapy in malignant insulinoma

The management of malignant insulinoma (MI) presents dual management challenges of hypoglycaemia and tumour control. This study aims to analyse long-term outcomes of PRRT for the treatment of MI. We retrospectively reviewed consecutive patients with MI treated with [177Lu]Lu-DOTATATE (LuTATE) at two Australian NET centres between 2004 and 2022. Follow-up for hypoglycaemia, molecular imaging, radiologic and biochemical responses, treatment-related side-effects, progression-free and overall survival were assessed. Of 15 patients (seven female; median age 60, range 26-82) treated for intractable hypoglycaemia, WHO grade (G) was known in 12 patients (three G1, six G2 and three G3). PRRT was administered in a median of seven cycles (range 1-15), with a median cumulative activity of 42 GBq (range 4-117 GBq) and radiosensitizing chemotherapy in 9/15 (60%) patients. Resolution of hypoglycaemia was observed in 14/15 (93%) patients after a median of 2.5 months (range 0.2-23.5), but recurred in 7/14 cases after a median of 17.7 months (range 7.6-48.3). Patients with recurrent hypoglycaemia had a longer time to hypoglycaemia resolution (median 3.0 vs 0.5 months), were more likely G3 (57 vs 0%) and experienced higher mortality (86 vs 29%). In all seven cases, PRRT re-treatment was successful. The mean duration of hypoglycaemia remission was 23.8 months (range 9.2-101). The median progression-free and overall survival was 17.9 months (95% CI, 8.5-43.2) and 50.1 months (95% CI, 23.0-ND), respectively. Side-effects included G3/4 myelosuppression in 4/15 patients and hypoglycaemia flare (hospitalisation >48 h) in 7/15 patients. PRRT provides durable hypoglycaemic and oncologic disease control of MI with manageable toxicity including hypoglycaemia flare requiring multidisciplinary care.