Applying 177Lu-Dotatate for Hereditary Neuroendocrine Tumours: The Role in MEN1

Abstract Introduction Multiple endocrine neoplasia type 1 (MEN1) is the most common genetic syndrome causing neuroendocrine tumours (NET) with metastatic duodenopancreatic NET (dpNET) forming the predominant cause of MEN1-related mortality. Peptide receptor radionuclide therapy with [177Lu]Lu-[DOTA0,Tyr3]-octreotate (177Lu-Dotatate) is an established treatment for advanced dpNET. As MEN1 loss-of-function has been associated with potential radiosensitising effects, this retrospective study evaluated outcomes of patients with germline MEN1-associated NET after treatment with 177Lu-Dotatate. Methods This is a retrospective cohort study in patients with MEN1 and metastatic NET treated with 177Lu-Dotatate compared to a control group of patients with advanced sporadic pancreas NET (panNET). Survival outcomes, response rates and adverse events after the initiation of 177Lu-Dotatate were evaluated. Results A total of nineteen MEN1 patients with dpNET and fifty-seven sporadic panNET controls were included. No significant difference in median progression-free survival with 39.6 months (95%CI 13.7-65.5) in the MEN1 group versus 45.0 months (95%CI 35.7-54.3) in the control group was seen, with a hazard ratio of 1.086 (95%CI 0.60-1.98). Overall survival was similar between groups with 97.8 months (95%CI 36.3-159.3) and 89.3 months (95%CI 54.6-123.9), respectively, and a hazard ratio of 0.883 (95%CI 0.43-1.82). There were no significant differences in objective radiological response (44.4% in the MEN1 group versus 35.2% in the control group) or in grade ≥ 3 toxicity. Conclusion MEN1 patients with advanced dpNET benefit equally from 177Lu-Dotatate treatment as those with sporadic panNET in terms of survival and response. These findings support the use of PRRT in MEN1-associated dpNET similar to sporadic cases.