Presacral neuroendocrine tumors associated with the Currarino syndrome.

Currarino syndrome (CS) is an autosomal dominant syndrome caused by mutations in MNX1 and characterized by anorectal abnormalities, partial sacral agenesis, and presacral masses. The presacral masses are typically benign; however, malignant degeneration can occur, and presacral neuroendocrine tumors (NETs) have been reported in six cases. We report three individuals from two families affected by CS in which multiple individuals developed presacral NETs. The first family, 491, had six members with features of CS, including two siblings who presented with presacral, Grade 2 NETs, one of which had metastasized to bone and lymph nodes. A germline c.874C>T (p.Arg292Trp) mutation was found in a highly conserved region of MNX1 in three affected members who underwent sequencing. A second somatic variant/deletion in MNX1 was not detected in either patient's tumor. In the second family, 342, the proband presented with an incidentally discovered presacral NET. The proband's father had previously undergone resection of a presacral NET, and so genetic testing was performed, which did not reveal an MNX1 mutation or copy number variants. The lack of a second, somatic mutation in the tumors from family 491 argues against MNX1 acting as a tumor suppressor, and the absence of a germline MNX1 mutation in family 342 suggests that other genetic and anatomic factors contribute to the development of presacral NETs. These cases highlight the variable presentation of CS, and the potential for malignancy in these patients.

Abnormal Pretreatment Liver Function Tests Are Associated with Discontinuation of Peptide Receptor Radionuclide Therapy in a U.S.-Based Neuroendocrine Tumor Cohort.

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) is effective for treating midgut neuroendocrine tumors (NETs); however, incorporation of PRRT into routine practice in the U.S. is not well studied. Herein we analyze the first year of PRRT implementation to determine tolerance of PRRT and factors that increase risk of PRRT discontinuation. MATERIALS AND METHODS: Medical records were reviewed and data were abstracted on all patients with NETs scheduled for PRRT during the first year of PRRT implementation at a U.S. NET referral center (August 2018 through July 2019). Logistic regression was used to identify factors associated with PRRT discontinuation. RESULTS: Fifty-five patients (56% male) were scheduled for PRRT over the study period. The most common primary NET location was small bowel (47%), followed by pancreas (26%), and 84% of the NETs were World Health Organization grade 1 or 2. The cohort was heavily pretreated with somatostatin analog (SSA) therapy (98%), non-SSA systemic therapy (64%), primary tumor resection (73%), and liver-directed therapy (55%). At the time of analysis, 52 patients completed at least one PRRT treatment. Toxicities including bone marrow suppression and liver function test (LFT) abnormalities were comparable to prior publications. Eleven patients (21%) prematurely discontinued PRRT because of toxicity or an adverse event. Pretreatment LFT abnormality was associated with increased risk of PRRT cancellation (odds ratio: 12; 95% confidence interval: 2.59-55.54; p < .001). CONCLUSION: PRRT can be administered to a diverse NET population at a U.S. NET referral center. Baseline liver function test abnormality increases the likelihood of PRRT discontinuation. IMPLICATIONS FOR PRACTICE: Peptide receptor radionuclide therapy (PRRT) can be successfully implemented at a U.S. neuroendocrine tumor (NET) referral center in a NET population that is diverse in tumor location, grade, and prior treatment history. Toxicity and adverse effects of PRRT are comparable to prior reports; however, 21% of individuals prematurely discontinued PRRT. Patients with baseline liver function test abnormalities were more likely to discontinue PRRT than patients with normal liver function tests, which should be taken into consideration when selecting treatment options for NETs.