Predictors of malignancy and survival in patients with pheochromocytoma and paraganglioma.

person Hector Raul Gonzalez-Sanchez Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico info_outline Hector Raul Gonzalez-Sanchez, Alejandro Aranda-Gutierrez, Andres Meraz-Brenez, Haydee Cristina Verduzco-Aguirre, Roberto De la Peña-Lopez

Authors person Hector Raul Gonzalez-Sanchez Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico info_outline Hector Raul Gonzalez-Sanchez, Alejandro Aranda-Gutierrez, Andres Meraz-Brenez, Haydee Cristina Verduzco-Aguirre, Roberto De la Peña-Lopez Organizations Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico Abstract Disclosures Research Funding No funding sources reported Background: Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors for which the definitive diagnosis of malignancy hinges on the detection of metastatic disease, rather than histological features, making prognostication particularly challenging. Consequently, identifying reliable clinical predictors for both malignancy and survival is of utmost importance. Methods: We retrospectively analyzed records of patients with biopsy-proven PCC or PGL treated at a single center in Mexico City from 2008 to 2022. Patients with follow-up > =12 months were eligible. Data was collected from electronic medical records. Independent-samples T-test and X 2 and Fisher’s exact tests were used to evaluate associations between variables. We used the Kaplan-Meier method to calculate disease-free survival (DFS) and overall survival (OS) rates, and utilized the log-rank test to compare these outcomes across clinicopathological features. Cox regression analysis was used to determine survival hazard ratios (HR). Results: Among 60 patients, the mean age at diagnosis was 41 years, 37 (62%) had PCC, and 12 (20%) had malignant disease (6 distant recurrences and 6 de novo metastatic cases). Clinicopathological features according to disease type (i.e. benign or malignant) are shown in Table 1. Patients with malignant disease were more likely to have PGL (67% vs. 31%, p = 0.024) and have a body mass index of > =30 kg/m 2 at diagnosis (67% vs. 8%, p < 0.01). With a median follow-up of 42 months (95% CI 35-49), 8 recurrences (2 local and 6 distant) and 6 deaths were recorded, yielding 3-year DFS and OS rates of 92% and 91%, respectively. In a multivariate analysis including factors associated with DFS and OS in univariate analyses (i.e. obesity status and hypertension at diagnosis), only obesity (HR 4.93, 95% CI 1.02 - 23.79; p = 0.047) remained associated with a worse DFS, with no influence on OS. Conclusions: This study highlights obesity as a significant predictor of malignancy and recurrence in patients with PCC and PGL, marking a novel finding in the literature on these tumors. Further research is warranted to explore the underlying mechanisms linking obesity with more aggressive disease in PCC and PGL. Disease type Benign Malignant p- value n (%) 48 (80) 12 (20) Mean age (SD) 43 (17) 39 (12) 0.431 Sex Female Male 16 (33) 32 (67) 3 (25) 9 (75) 0.735 Tumor type Pheochromocytoma Paraganglioma 33 (69) 15 (31) 4 (33) 8 (67) 0.024 Obesity (BMI > =30 kg/m 2 ) No Yes 44 (92) 4 (8) 4 (33) 8 (67) < 0.01 Hypertension at diagnosis No Yes 9 (19) 39 (81) 4 (36) 7 (64) 0.237 Catecholamine secretion No Yes 10 (21) 38 (79) 4 (33) 8 (67) 0.360