Peptide receptor radionuclide therapy for ectopic Cushing’s syndrome caused by metastatic neuroendocrine neoplasia

Abstract

Background: Metastatic gastroenteropancreatic neuroendocrine neoplasia (GEPNEN) can cause ectopic Cushing’s syndrome (ECS). ECS is highly morbid and medical therapy is complex and can be ineffective. Patients unsuitable for bilateral adrenalectomy (BA) have dismal outcomes. Peptide receptor radionuclide therapy (PRRT) is a rational option for hormone and disease control in ECS caused by NEN with high somatostatin receptor (SSTR) expression. Aim: To describe characteristics and outcomes of patients with ECS treated with PRRT. Methods: Single-centre, retrospective analysis of imaging, biochemistry and outcomes of seven consecutive patients with ECS caused by metastatic GEPNEN treated with PRRT from 2006-2023. Results: Patients were aged 17–75 (female n=6). The primary site was pancreas (5/7) and rectum (2/7). Six patients were on medical therapy for ECS at baseline (one previous BA). A median of 34.4GBq of [177Lu]Lu-DOTA-octreotate was given. [90Y]Y-DOTA-octreotate (one patient) and [111In]In-octreotide (one patient) was also used. Five patients had radiosensitising chemotherapy. Five patients had a flare of ECS within one week of PRRT cycle 1 (PRRT-C1). Following PRRT-C1, 5/7 patients had complete biochemical resolution of ECS at 1.5–6 months (four ongoing; one recurred after 12 months and had elective BA at 18 months). Best metabolic response on [18F]F-FDG PET/CT: Four patients had a complete metabolic response (CMR), one had a partial metabolic response. PFS was 3–208 months. Two patients progressed at first follow-up. The longest ECS remission and CMR continues at >17 years. Conclusion: PRRT can be effective for ECS caused by metastatic SSTR-positive GEPNEN and should be considered in its treatment algorithm.