Poster Presentation ESA-SRB 2023 in conjunction with ENSA

Peptide receptor radionuclide therapy (PRRT) for management of ectopic Cushing’s syndrome due to metastatic gastroenteropancreatic neuroendocrine neoplasia (GEPNEN): A single centre experience (#241)

Emma Boehm 1 , Terry Hung 1 , Tim Akhurst 1 , Anthony Cardin 1 , Ramin Alipour 1 , Cherie Chiang 1 , Rod Hicks 2 , Michael Hofman 1 , Michael Michael 1 , Nirupa Sachithanandan 1 , Javad Saghebi 1 , Grace Kong 1
  1. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  2. St Vincent's Hospital, Melbourne, Vic, Aus

AIM: Metastatic GEPNEN can cause ectopic Cushing’s syndrome (ECS) due to secretion of ACTH or CRH. ECS is highly morbid and challenging to control with medical therapy(1). Bilateral adrenalectomy carries perioperative risk and long-term morbidity. Patients who are unsuitable for surgery have dismal outcomes(2). We describe the biochemical and clinical outcomes of patients with metastatic GEPNEN and ECS treated with PRRT in our centre.

METHODS: Single-centre, retrospective analysis of the molecular imaging, biochemistry, and clinical outcomes of 7 consecutive patients with ECS caused by metastatic GEPNEN treated with radionuclide therapy (PRRT) from 2006-2023.

RESULTS: See table 1 for cohort demographic and clinical details. The primary site of disease was pancreas (5/7) and rectum (2/7). Prior to PRRT all patients had high somatostatin receptor (SSTR)-expressing and FDG-avid imaging phenotype of positron emission tomography (PET) scans. All patients (except one who had bilateral adrenalectomy performed prior to PRRT) were on medical therapy for ECS prior to PRRT. Five patients had clinical and biochemical flare of ECS within one week of the first cycle of PRRT.  Following PRRT, five of seven patients had complete biochemical resolution of ECS (four ongoing at last follow-up; one ECS recurrence after 14 months); bilateral adrenalectomy was avoided in three and delayed in two patients (17 and 9months respectively). Following PRRT, three patients had a complete metabolic response (CMR) on FDG-PET imaging, two had a partial metabolic response, two progressed. Biochemical and imaging responses were durable, the longest ECS regression and CMR is ongoing at 14 years.

CONCLUSION: PRRT is effective in controlling ECS caused by metastatic SSTR-positive GEPNEN. PRRT may avoid or delay adrenalectomy and lead to durable biochemical responses. Careful multidisciplinary management to consider treatment sequencing and management of post treatment Cushing’s flare is required.

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  1. 1. Davi MV, Cosaro E, Piacentini S, et al. Prognostic factors in ectopic Cushing's syndrome due to neuroendocrine tumors: a multicenter study. Eur J Endocrinol. 2017;176(4):453-461
  2. 2. Landry JP, Clemente-Gutierrez U, Pieterman CRC, et al. Management of adrenocorticotropic hormone-secreting neuroendocrine tumors and the role of bilateral adrenalectomy in ectopic Cushing syndrome. Surgery. 2022;172(2):559-566