SUN-006 Successful Management of Metastatic Insulinoma with Capecitabine and Temozolomide Therapy

Abstract Disclosure: A. Arabi: None. T. Magee: None. M. Golagha: None. A. Naimian: None. A. Gupta: None. A. Rivero: None. K. Cooper: None. J. Del Rivero: None. Background: Metastatic insulinoma is an exceedingly rare type of neuroendocrine tumor with a poor prognosis. The incidence of metastatic insulinoma is estimated at 0.0-0.27 cases per million person-years. Due to its rarity, treatment remains challenging. In this case report, we present a patient with malignant insulinoma successfully treated with oral chemotherapy. Clinical Case: A 28-year-old female presented to the emergency room with altered mental status, nausea, and vomiting. Preliminary laboratory analyses revealed a blood glucose level of 38 mg/dL (normal 70-99 mg/dL). Initial computed tomography (CT) identified a large mass at the neck of the pancreas with numerous liver lesions. Further evaluation with a 72-hour supervised fasting test, revealed the following results: Insulin 41 µU/mL (6 – 24 µU /mL), pro-insulin 352 pmol/L (3.6-22 pmol/l) C-peptide 3.43 ng/mL (0.5 – 2.7 ng/mL), and beta-hydroxybutyrate 2 mg/dL (0.2 – 2.8 mg /dL), in the presence of a blood glucose level of 54 mg/dl mg/, consistent with hyperinsulinemic hypoglycemia. A sulfonylurea screen and insulin autoantibodies were negative. Further investigation using endoscopic ultrasound (EUS) identified two masses in the pancreatic neck and tail, as well as liver lesions and lymph node involvement. Ultrasound-guided Fine needle aspiration was performed on pancreatic lesions, and the biopsy confirmed grade 3 pancreatic neuroendocrine tumor (pNET) with a Ki-67 index of 23%. Tumor analysis revealed that protein 53 (P53) was wild-type, and both retinoblastoma protein 1 (RB-1) and Alpha Thalassemia/Mental Retardation Syndrome X-linked (ATRX) were retained, as indicated by immunohistochemistry (IHC). Additionally, genetic studies indicated that the O6-methylguanine-DNA methyltransferase (MGMT) Promoter was not methylated. A CU64 DOTATATE PET CT showed uptake in the pancreatic neck and tail, along with innumerable liver metastases, and several lymph nodes including the small aortopulmonary window lymph node, prevascular lymph node, left paraaortic lymph node (thoracic and abdominal), cardiophrenic lymph node, portocaval lymph node, and right aortocaval lymph node. The patient was started on diazoxide to manage hypoglycemia, followed by the administration of Lanreotide. After the second Lanreotide treatment, diazoxide was discontinued as normoglycemia was achieved. Given the disease burden, capecitabine and temozolomide (CAPTEM) therapy was initiated. At the 1-year follow-up, the patient exhibited a remarkable radiographic response to CAPTEM. Conclusion: Management of metastatic insulinoma is challenging. Treatment decisions are guided by a comprehensive evaluation of clinicopathologic criteria, including the primary tumor site, degree of differentiation, tumor grade, disease burden, patient functional status, and the extent of somatostatin receptor (SSTR) positivity. Presentation: Sunday, July 13, 2025