SUN-136 Clinico-Pathological Features, Treatment Modalities and Survival of Patients with Malignant Insulinoma: A Multicenter Study

Introduction: management of malignant insulinoma is challenging due to the need to control both hypoglycemic syndrome and tumor growth. Literature data is limited to small series.

Aim of the study: to analyze clinical-pathological characteristics, treatment modalities and prognosis of patients with malignant insulinoma.

Materials and methods: Multicenter retrospective study on 31 patients (M 61.3%) diagnosed between 1988 and 2017.

Results: The mean age at diagnosis was 48 ± 15 years. In 5 cases (16.1%) the hypoglycemic syndrome occurred after 46 ± 35 months from the diagnosis of NET, in 26 (83.9%) cases it led to the diagnosis of NET, of which 11 cases (42.3%) with mean diagnostic delay of 32.7 ± 39.8 months. The majority ​​of the NET were G2 (70.8 %) and in the pancreatic body-tail (78.6%). The mean NET diameter was 41 ± 31 mm. Metastases were widespread in 40.7%, only hepatic in 37%, only lymph nodal in 18.5%..Surgical treatment was performed in 21/31 (67.7%) with hypoglycemic control in 42.9%. Except for 2 patients with curative surgery, the others underwent further different lines of therapies including somatostatin analogues (SA), Peptide Receptor Radionuclide Therapy (PRRT), everolimus, chemotherapy, TAE/TACE/RFA, radiotherapy. PRRT was performed in 14/31 (45.1%) with complete (42.9 %) or partial (50%) syndrome control.

The median follow-up was 60 months. The 5-year survival rate was 62%. The median overall survival (OS) was 40 months. No significant difference in OS was observed according to the site of primary tumour and its dimension. A trend towards increased survival was found according to grading (5-year OS 100% for G1, 77% for G2, 33% for G3). Patients with Ki-67 ≤ 10% had a significant higher survival rate compared to patient with Ki-67 >10% (5-year OS rate 87% vs 43%, p: 0.03). As regards the type of treatment, patients who underwent surgery had a higher survival rate than those who did not (5-year OS 76% vs 31.7%, p= 0.006). Moreover, patients receiving PRRT as II line treatment had a better prognosis than those who underwent it in further lines, although the 5-year OS was not significantly different (80% vs 25% respectively, p=0.057).

Conclusions: Our study includes the largest series of patients with malignant insulinomas up to now reported. The hypoglycemic 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 seems to be promising in the control of hypoglycemic syndrome.