A Veltroni1, E Cosaro1, F Spada2, N Fazio2, A Faggiano3, A Colao4, S Pusceddu5, M C Zatelli6, D Campana7, A Piovesan8, A Pia9, E M Grossrubatscher10, A Filice11, A Bianchi12, P Razzore13, M Toaiari14, S Cingarlini15, L Landoni16, R Micciolo17, M V Davì1. 1. Section of Endocrinology, Department of Medicine, ENETS Center of Excellence, Verona University, Verona, Italy. 2. Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, ENETS Center of Excellence, European Institute of Oncology, IEO, IRCCS, Milan, Italy. 3. Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy. 4. Endocrinology Division, Department of Clinical Medicine and Surgery, ENETS Center of Excellence, University of Naples Federico II, Naples, Italy. 5. Fondazione IRCCS Istituto Nazionale Tumori, ENETS Center of Excellence, Milan, Italy. 6. Section of Endocrinology and Internal Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy. 7. Department of Medical and Surgical Sciences, ENETS Center of Excellence, University of Bologna, Bologna, Italy. 8. Oncological Endocrinology Unit, Department of Medical Sciences, University of Turin, Turin, Italy. 9. Internal Medicine, Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy. 10. S.C. Endocrinologia ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy. 11. Nuclear Medicine Azienda USL-IRCCS Reggio Emilia, Reggio Emilia, Italy. 12. Pituitary Unit, Fondazione Policlinico A. Gemelli IRCCS, Catholic University, ENETS Center of Excellence, School of Medicine, Rome, Italy. 13. Mauriziano Hospital, Turin, Italy. 14. Pederzoli Hospital, Peschiera del Garda, Italy. 15. Oncology, ENETS Center of Excellence, University of Verona, Verona, Italy. 16. Pancreatic Surgery, ENETS Center of Excellence, University of Verona, Verona, Italy. 17. Department of Psychology and Cognitive Sciences, University of Trento, Trento, Italy.
Abstract
INTRODUCTION: Management of malignant insulinomas is challenging due to the need to control both hypoglycaemic syndrome and tumor growth. Literature data is limited to small series. AIM OF THE STUDY: To analyze clinico-pathological characteristics, treatments and prognosis of patients with malignant insulinoma. MATERIALS AND METHODS: Multicenter retrospective study on 31 patients (male: 61.3%) diagnosed between 1988 and 2017. RESULTS: The mean age at diagnosis was 48 years. The mean NET diameter was 41 ± 31 mm, and 70.8% of NETs were G2. Metastases were widespread in 38.7%, hepatic in 41.9% and only lymph nodal in 19.4%. In 16.1% of the cases, the hypoglycaemic syndrome occurred after 46 ± 35 months from the diagnosis of originally non-functioning NET, whereas in 83.9% of the cases it led to the diagnosis of NET, of which 42.3% with a mean diagnostic delay of 32.7 ± 39.8 months. Surgical treatment was performed in 67.7% of the cases. The 5-year survival rate was 62%. Overall survival was significantly higher in patients with Ki-67 ≤10% (P = 0.03), insulin level <60 µU/mL (P = 0.015) and in patients who underwent surgery (P = 0.006). Peptide Receptor Radionuclide Therapy (PRRT) was performed in 45.1%, with syndrome control in 93% of patients. CONCLUSIONS: Our study includes the largest series of patients with malignant insulinoma reported to date. The hypoglycaemic syndrome may occur after years in initially non-functioning NETs or be misunderstood with delayed diagnosis of NETs. Surgical treatment and Ki67 ≤10% are prognostic factors associated with better survival. PPRT proved to be effective in the control of hypoglycaemia in majority of cases.
INTRODUCTION: Management of malignant insulinomas is challenging due to the need to control both hypoglycaemic syndrome and tumor growth. Literature data is limited to small series. AIM OF THE STUDY: To analyze clinico-pathological characteristics, treatments and prognosis of patients with malignant insulinoma. MATERIALS AND METHODS: Multicenter retrospective study on 31 patients (male: 61.3%) diagnosed between 1988 and 2017. RESULTS: The mean age at diagnosis was 48 years. The mean NET diameter was 41 ± 31 mm, and 70.8% of NETs were G2. Metastases were widespread in 38.7%, hepatic in 41.9% and only lymph nodal in 19.4%. In 16.1% of the cases, the hypoglycaemic syndrome occurred after 46 ± 35 months from the diagnosis of originally non-functioning NET, whereas in 83.9% of the cases it led to the diagnosis of NET, of which 42.3% with a mean diagnostic delay of 32.7 ± 39.8 months. Surgical treatment was performed in 67.7% of the cases. The 5-year survival rate was 62%. Overall survival was significantly higher in patients with Ki-67 ≤10% (P = 0.03), insulin level <60 µU/mL (P = 0.015) and in patients who underwent surgery (P = 0.006). Peptide Receptor Radionuclide Therapy (PRRT) was performed in 45.1%, with syndrome control in 93% of patients. CONCLUSIONS: Our study includes the largest series of patients with malignant insulinoma reported to date. The hypoglycaemic syndrome may occur after years in initially non-functioning NETs or be misunderstood with delayed diagnosis of NETs. Surgical treatment and Ki67 ≤10% are prognostic factors associated with better survival. PPRT proved to be effective in the control of hypoglycaemia in majority of cases.
Authors: Elina Peltola; Päivi Hannula; Heini Huhtala; Saara Metso; Juhani Sand; Johanna Laukkarinen; Mirja Tiikkainen; Jukka Sirén; Minna Soinio; Pirjo Nuutila; Leena Moilanen; David E Laaksonen; Tapani Ebeling; Johanna Arola; Camilla Schalin-Jäntti; Pia Jaatinen Journal: Eur J Endocrinol Date: 2021-09-01 Impact factor: 6.664