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Open Access Research article

The size of the primary tumor and age at initial diagnosis are independent predictors of the metastatic behavior and survival of patients with SDHB-related pheochromocytoma and paraganglioma: a retrospective cohort study

Jan Schovanek12, Victoria Martucci1, Robert Wesley3, Tito Fojo4, Jaydira del Rivero1, Thanh Huynh1, Karen Adams1, Electron Kebebew5, Zdenek Frysak2, Constantine A Stratakis6 and Karel Pacak1*

Author Affiliations

1 Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health & Human Development, NIH, Building 10, CRC, Room 1E-3140, 10 Center Drive MSC-1109, Bethesda, Maryland 20892-1109, USA

2 Department of Internal Medicine III – Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic

3 Warren G. Magnuson Clinical Center, NIH, Bethesda, MD, USA

4 Medical Oncology Branch, National Cancer Institute, NIH, Bethesda, MD, USA

5 Endocrine Oncology Branch, National Cancer Institute, NIH, Bethesda, MD, USA

6 Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health & Human Development, NIH, Bethesda, MD, USA

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BMC Cancer 2014, 14:523  doi:10.1186/1471-2407-14-523

Published: 21 July 2014

Abstract

Background

Succinate dehydrogenase subunit B (SDHB) mutations are associated with aggressive pheochromocytoma (PHEO)/paraganglioma (PGL) behavior, often resulting in metastatic disease and fatal outcomes. These tumors are often larger, extra-adrenal, and contain lower catecholamine concentrations than other hereditary PHEOs/PGLs. This study evaluated the size and age at diagnosis of primary SDHB-related PHEOs/PGLs as independent predictors of their metastatic behavior and outcome (survival).

Methods

One hundred six patients with SDHB mutation-related PHEO/PGL were included in this retrospective study. The recorded largest diameters, locations, and patient ages at initial diagnosis of SDHB-related primary tumors were analyzed in the context of time to metastasis and patient survival.

Results

First, the development of metastatic disease in patients with primary tumors ≥4.5 cm was significantly earlier than in patients with smaller tumors (P = 0.003). Second, patients with primary tumors larger than 5.5 cm also had worse overall survival than patients with smaller tumors (P = 0.008). Third, age at initial diagnosis was found to be an independent predictor of patient survival (PHEOs: P = 0.041; PGLs: P < 0.001). Fourth, we did not observe a significant difference in survival based on the specific SDHB mutations or patient sex.

Conclusion

Receiver operating characteristic curves established 4.5 cm as the best value to dichotomize the primary SDHB-related PHEO/PGL in order to evaluate the development of metastatic disease and 5.5 cm as the best value for survival prediction. Subsequently, the size of the primary tumor was found as an age-independent predictor of patient survival and metastases development in PGL. In both PHEO and PGL, age at diagnosis was found to be a size-independent predictor of patient survival. No significant difference was found in metastases development or patient survival between males and females or among specific SDHB mutations. This data further extends and supports previous recommendations that carriers with SDHB mutations must undergo early and regular evaluations to detect PHEO/PGL in order to achieve the best clinical outcome.

Keywords:
Pheochromocytoma; Paraganglioma; Size; Age; SDHB; Metastatic; Survival