Malignant pheochromocytoma and paraganglioma: A population level analysis of long‐term survival over two decades

Goffredo, Paolo; Sosa, Julie Ann; Roman, Sanziana A.

doi:10.1002/jso.23297

Cited by 91 publications

(72 citation statements)

References 19 publications

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“…We initially attributed this to the selected cut-off (5.5 cm), which was more representative of the size of primary PGLs (and divided them almost evenly) and divided the PHEOs quite unevenly. However, when we used 8 cm as a cutoff, the median size of PHEO primary tumors, there was again no survival difference in PHEOs between those with small vs. large tumors (P = 0.81) Significantly larger tumors in patients with PHEO than with PGL have been reported previously [24]. …”

Section: Discussionmentioning

confidence: 61%

“…A previous study, which did not classify the tumors based on genetic background, found overall survival to be significantly shorter in patients with PGLs than with PHEOs [19]. A different study, which also did not consider the genetic background of the disease and included only metastatic PHEO/PGL, reported better survival of PGLs [24]. Our study, including only patients with SDHB -related tumors, found that patients with PGLs had a better overall survival than patients with PHEOs.…”

Section: Discussionmentioning

confidence: 99%

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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

et al. 2014

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BackgroundSuccinate 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).MethodsOne 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.ResultsFirst, 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.ConclusionReceiver 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.

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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“…So far, 16 genes are known to be associated with PCCs/PGLs: SDHA, SDHB, SDHC, SDHD and SDHAF2 (together SDHx), VHL, RET, NF1, TMEM127, MAX, KIF1B, and PHD2, as well as the recently identified HIF2A (2, 4, 5, 6), HRAS (7), FH (8), and PHD1 (9). The identification of distant metastases is still the only proof of malignancy in PCCs/PGLs, and because treatment options are limited, finding an appropriate strategy poses a clinical challenge (10). A better mechanistic understanding of tumorigenesis, proliferation, and malignant behavior is therefore warranted.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical expression of stem cell markers in pheochromocytomas/paragangliomas is associated with SDHx mutations

Oudijk

Neuhofer

Lichtenauer

et al. 2015

European Journal of Endocrinology

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Objective: Pheochromocytomas (PCCs) are neuroendocrine tumors that occur in the adrenal medulla, whereas paragangliomas (PGLs) arise from paraganglia in the head, neck, thorax, or abdomen. In a variety of tumors, cancer cells with stem cell-like properties seem to form the basis of tumor initiation because of their ability to self-renew and proliferate. Specifically targeting this small cell population may lay the foundation for more effective therapeutic approaches. In the present study, we intended to identify stem cells in PCCs/PGLs. Design: We examined the immunohistochemical expression of 11 stem cell markers (SOX2, LIN28, NGFR, THY1, PREF1, SOX17, NESTIN, CD117, OCT3/4, NANOG, and CD133) on tissue microarrays containing 208 PCCs/PGLs with different genetic backgrounds from five European centers. Results: SOX2, LIN28, NGFR, and THY1 were expressed in more than 10% of tumors, and PREF1, SOX17, NESTIN, and CD117 were expressed in !10% of the samples. OCT3/4, NANOG, and CD133 were not detectable at all. Double staining for chromogranin A/SOX2 and S100/SOX2 demonstrated SOX2 immunopositivity in both tumor and adjacent sustentacular cells. The expression of SOX2, SOX17, NGFR, LIN28, PREF1, and THY1 was significantly associated with mutations in one of the succinate dehydrogenase (SDH) genes. In addition, NGFR expression was significantly correlated with metastatic disease. Conclusion: Immunohistochemical expression of stem cell markers was found in a subset of PCCs/PGLs. Further studies are required to validate whether some stem cell-associated markers, such as SOX2, could serve as targets for therapeutic approaches and whether NGFR expression could be utilized as a predictor of malignancy.

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“…We describe the demographic, clinical, and pathologic characteristics of A previous population-based study of 287 malignant pheochromocytomas diagnosed between 1988 and 2008 in the surveillance, epidemiology, and end results (SEER) database investigated predictors of overall mortality [25]. The 5-year overall survival rate was 58.1 %; presentation at diagnosis with distant metastases and failure to undergo surgery were factors independently associated with compromised survival.…”

Section: Discussionmentioning

confidence: 99%

Patterns of Use and Short‐Term Outcomes of Minimally Invasive Surgery for Malignant Pheochromocytoma: A Population‐Level Study

et al. 2015

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Malignant pheochromocytoma and paraganglioma: A population level analysis of long‐term survival over two decades

Abstract: Malignant PHEO has a more aggressive course than malignant PGL; long-term survival has not improved over the last two decades. Multi-institutional efforts should be pursued to seek novel treatments.

Cited by 91 publications

References 19 publications

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

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

Immunohistochemical expression of stem cell markers in pheochromocytomas/paragangliomas is associated with SDHx mutations

Patterns of Use and Short‐Term Outcomes of Minimally Invasive Surgery for Malignant Pheochromocytoma: A Population‐Level Study

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