Applying 177Lu-DOTATATE for hereditary neuroendocrine tumours: the role in MEN1.

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is the most common genetic syndrome causing neuroendocrine tumours (NETs) with metastatic duodenopancreatic NETs (dpNETs) 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 dpNETs. As MEN1 loss of function has been associated with potential radiosensitizing effects, this retrospective study evaluated outcomes of patients with germline MEN1-associated NET after treatment with 177Lu-DOTATATE. This is a retrospective cohort study in patients with MEN1 and metastatic NETs treated with 177Lu-DOTATATE compared with a control group of patients with advanced sporadic pancreatic NETs (panNETs). Survival outcomes, response rates and adverse events after the initiation of 177Lu-DOTATATE were evaluated. A total of nineteen MEN1 patients with dpNETs 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. MEN1 patients with advanced dpNETs benefit equally from 177Lu-DOTATATE treatment as those with sporadic panNETs in terms of survival and response. These findings support the use of PRRT in MEN1-associated dpNETs similar to sporadic cases.