Determinants of disease-specific survival in patients with and without metastatic pheochromocytoma and paraganglioma

Christina Pamporaki; Tamara Prodanov; Leah Meuter; Annika M A Berends; Nicole Bechmann; Georgiana Constantinescu; Felix Beuschlein; Hanna Remde; Andrzej Januszewicz; Michiel N Kerstens; Henri J L M Timmers; David Taïeb; Mercedes Robledo; Jacques W M Lenders; Karel Pacak; Graeme Eisenhofer

doi:10.1016/j.ejca.2022.03.032

Determinants of disease-specific survival in patients with and without metastatic pheochromocytoma and paraganglioma

Christina Pamporaki^*, Tamara Prodanov, Leah Meuter, Annika M A Berends, Nicole Bechmann, Georgiana Constantinescu, Felix Beuschlein, Hanna Remde, Andrzej Januszewicz, Michiel N Kerstens, Henri J L M Timmers, David Taïeb, Mercedes Robledo, Jacques W M Lenders, Karel Pacak, Graeme Eisenhofer

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

BACKGROUND: Pheochromocytomas and paragangliomas (PPGLs) have a heterogeneous prognosis, the basis of which remains unclear. We, therefore, assessed disease-specific survival (DSS) and potential predictors of progressive disease in patients with PPGLs and head/neck paragangliomas (HNPGLs) according to the presence or absence of metastases.

METHODS: This retrospective study included 582 patients with PPGLs and 57 with HNPGLs. DSS was assessed according to age, location and size of tumours, recurrent/metastatic disease, genetics, plasma metanephrines and methoxytyramine.

RESULTS: Among all patients with PPGLs, multivariable analysis indicated that apart from older age (HR = 5.4, CI = 2.93-10.29, P < 0.0001) and presence of metastases (HR = 4.8, CI = 2.41-9.94, P < 0.0001), shorter DSS was also associated with extra-adrenal tumour location (HR = 2.6, CI = 1.32-5.23, P = 0.0007) and higher plasma methoxytyramine (HR = 1.8, CI = 1.11-2.85, P = 0.0170) and normetanephrine (HR = 1.8, CI = 1.12-2.91, P = 0.0160). Among patients with HNPGLs, those with metastases presented with longer DSS compared to patients with metastatic PPGLs (33.4 versus 20.2 years, P < 0.0001) and only plasma methoxytyramine (HR = 13, CI = 1.35-148, P = 0.0380) was an independent predictor of DSS. For patients with metastatic PPGLs, multivariable analysis revealed that apart from older age (HR = 6.2, CI = 3.20-12.20, P < 0.0001), shorter DSS was associated with the presence of synchronous metastases (HR = 4.9, CI = 2.78-8.80, P < 0.0001), higher plasma methoxytyramine (HR = 2.4, CI = 1.44-4.14, P = 0.0010) and extensive metastatic burden (HR = 2.1, CI = 1.07-3.79, P = 0.0290).

CONCLUSIONS: DSS among patients with PPGLs/HNPGLs relates to several presentations of the disease that may provide prognostic markers. In particular, the independent associations of higher methoxytyramine with shorter DSS in patients with HNPGLs and metastatic PPGLs suggest the utility of this biomarker to guide individualized management and follow-up strategies in affected patients.

Original language	English
Pages (from-to)	32-41
Number of pages	10
Journal	European Journal of Cancer
Volume	169
Early online date	29-Apr-2022
DOIs	https://doi.org/10.1016/j.ejca.2022.03.032
Publication status	Published - Jul-2022

Keywords

Pheochromocytoma
Paraganglioma
Metastases
Predictors
Survival
Methoxytyramine
MALIGNANT PHEOCHROMOCYTOMA
DOPAMINE
METHOXYTYRAMINE
HIF2-ALPHA
BEHAVIOR
UTILITY
HEAD

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Determinants of disease-specific survival in patients with and without metastatic pheochromocytoma and paragangliomaFinal publisher's version, 883 KBLicence: CC BY-NC-ND

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Pamporaki, C., Prodanov, T., Meuter, L., Berends, A. M. A., Bechmann, N., Constantinescu, G., Beuschlein, F., Remde, H., Januszewicz, A., Kerstens, M. N., Timmers, H. J. L. M., Taïeb, D., Robledo, M., Lenders, J. W. M., Pacak, K., & Eisenhofer, G. (2022). Determinants of disease-specific survival in patients with and without metastatic pheochromocytoma and paraganglioma. European Journal of Cancer, 169, 32-41. https://doi.org/10.1016/j.ejca.2022.03.032

@article{b521ab36f11243828b8cdf6d20937608,

title = "Determinants of disease-specific survival in patients with and without metastatic pheochromocytoma and paraganglioma",

abstract = "BACKGROUND: Pheochromocytomas and paragangliomas (PPGLs) have a heterogeneous prognosis, the basis of which remains unclear. We, therefore, assessed disease-specific survival (DSS) and potential predictors of progressive disease in patients with PPGLs and head/neck paragangliomas (HNPGLs) according to the presence or absence of metastases.METHODS: This retrospective study included 582 patients with PPGLs and 57 with HNPGLs. DSS was assessed according to age, location and size of tumours, recurrent/metastatic disease, genetics, plasma metanephrines and methoxytyramine.RESULTS: Among all patients with PPGLs, multivariable analysis indicated that apart from older age (HR = 5.4, CI = 2.93-10.29, P < 0.0001) and presence of metastases (HR = 4.8, CI = 2.41-9.94, P < 0.0001), shorter DSS was also associated with extra-adrenal tumour location (HR = 2.6, CI = 1.32-5.23, P = 0.0007) and higher plasma methoxytyramine (HR = 1.8, CI = 1.11-2.85, P = 0.0170) and normetanephrine (HR = 1.8, CI = 1.12-2.91, P = 0.0160). Among patients with HNPGLs, those with metastases presented with longer DSS compared to patients with metastatic PPGLs (33.4 versus 20.2 years, P < 0.0001) and only plasma methoxytyramine (HR = 13, CI = 1.35-148, P = 0.0380) was an independent predictor of DSS. For patients with metastatic PPGLs, multivariable analysis revealed that apart from older age (HR = 6.2, CI = 3.20-12.20, P < 0.0001), shorter DSS was associated with the presence of synchronous metastases (HR = 4.9, CI = 2.78-8.80, P < 0.0001), higher plasma methoxytyramine (HR = 2.4, CI = 1.44-4.14, P = 0.0010) and extensive metastatic burden (HR = 2.1, CI = 1.07-3.79, P = 0.0290).CONCLUSIONS: DSS among patients with PPGLs/HNPGLs relates to several presentations of the disease that may provide prognostic markers. In particular, the independent associations of higher methoxytyramine with shorter DSS in patients with HNPGLs and metastatic PPGLs suggest the utility of this biomarker to guide individualized management and follow-up strategies in affected patients.",

keywords = "Pheochromocytoma, Paraganglioma, Metastases, Predictors, Survival, Methoxytyramine, MALIGNANT PHEOCHROMOCYTOMA, DOPAMINE, METHOXYTYRAMINE, HIF2-ALPHA, BEHAVIOR, UTILITY, HEAD",

author = "Christina Pamporaki and Tamara Prodanov and Leah Meuter and Berends, {Annika M A} and Nicole Bechmann and Georgiana Constantinescu and Felix Beuschlein and Hanna Remde and Andrzej Januszewicz and Kerstens, {Michiel N} and Timmers, {Henri J L M} and David Ta{\"i}eb and Mercedes Robledo and Lenders, {Jacques W M} and Karel Pacak and Graeme Eisenhofer",

year = "2022",

month = jul,

doi = "10.1016/j.ejca.2022.03.032",

language = "English",

volume = "169",

pages = "32--41",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "ELSEVIER SCI LTD",

}

Pamporaki, C, Prodanov, T, Meuter, L, Berends, AMA, Bechmann, N, Constantinescu, G, Beuschlein, F, Remde, H, Januszewicz, A, Kerstens, MN, Timmers, HJLM, Taïeb, D, Robledo, M, Lenders, JWM, Pacak, K & Eisenhofer, G 2022, 'Determinants of disease-specific survival in patients with and without metastatic pheochromocytoma and paraganglioma', European Journal of Cancer, vol. 169, pp. 32-41. https://doi.org/10.1016/j.ejca.2022.03.032

TY - JOUR

T1 - Determinants of disease-specific survival in patients with and without metastatic pheochromocytoma and paraganglioma

AU - Pamporaki, Christina

AU - Prodanov, Tamara

AU - Meuter, Leah

AU - Berends, Annika M A

AU - Bechmann, Nicole

AU - Constantinescu, Georgiana

AU - Beuschlein, Felix

AU - Remde, Hanna

AU - Januszewicz, Andrzej

AU - Kerstens, Michiel N

AU - Timmers, Henri J L M

AU - Taïeb, David

AU - Robledo, Mercedes

AU - Lenders, Jacques W M

AU - Pacak, Karel

AU - Eisenhofer, Graeme

PY - 2022/7

Y1 - 2022/7

N2 - BACKGROUND: Pheochromocytomas and paragangliomas (PPGLs) have a heterogeneous prognosis, the basis of which remains unclear. We, therefore, assessed disease-specific survival (DSS) and potential predictors of progressive disease in patients with PPGLs and head/neck paragangliomas (HNPGLs) according to the presence or absence of metastases.METHODS: This retrospective study included 582 patients with PPGLs and 57 with HNPGLs. DSS was assessed according to age, location and size of tumours, recurrent/metastatic disease, genetics, plasma metanephrines and methoxytyramine.RESULTS: Among all patients with PPGLs, multivariable analysis indicated that apart from older age (HR = 5.4, CI = 2.93-10.29, P < 0.0001) and presence of metastases (HR = 4.8, CI = 2.41-9.94, P < 0.0001), shorter DSS was also associated with extra-adrenal tumour location (HR = 2.6, CI = 1.32-5.23, P = 0.0007) and higher plasma methoxytyramine (HR = 1.8, CI = 1.11-2.85, P = 0.0170) and normetanephrine (HR = 1.8, CI = 1.12-2.91, P = 0.0160). Among patients with HNPGLs, those with metastases presented with longer DSS compared to patients with metastatic PPGLs (33.4 versus 20.2 years, P < 0.0001) and only plasma methoxytyramine (HR = 13, CI = 1.35-148, P = 0.0380) was an independent predictor of DSS. For patients with metastatic PPGLs, multivariable analysis revealed that apart from older age (HR = 6.2, CI = 3.20-12.20, P < 0.0001), shorter DSS was associated with the presence of synchronous metastases (HR = 4.9, CI = 2.78-8.80, P < 0.0001), higher plasma methoxytyramine (HR = 2.4, CI = 1.44-4.14, P = 0.0010) and extensive metastatic burden (HR = 2.1, CI = 1.07-3.79, P = 0.0290).CONCLUSIONS: DSS among patients with PPGLs/HNPGLs relates to several presentations of the disease that may provide prognostic markers. In particular, the independent associations of higher methoxytyramine with shorter DSS in patients with HNPGLs and metastatic PPGLs suggest the utility of this biomarker to guide individualized management and follow-up strategies in affected patients.

AB - BACKGROUND: Pheochromocytomas and paragangliomas (PPGLs) have a heterogeneous prognosis, the basis of which remains unclear. We, therefore, assessed disease-specific survival (DSS) and potential predictors of progressive disease in patients with PPGLs and head/neck paragangliomas (HNPGLs) according to the presence or absence of metastases.METHODS: This retrospective study included 582 patients with PPGLs and 57 with HNPGLs. DSS was assessed according to age, location and size of tumours, recurrent/metastatic disease, genetics, plasma metanephrines and methoxytyramine.RESULTS: Among all patients with PPGLs, multivariable analysis indicated that apart from older age (HR = 5.4, CI = 2.93-10.29, P < 0.0001) and presence of metastases (HR = 4.8, CI = 2.41-9.94, P < 0.0001), shorter DSS was also associated with extra-adrenal tumour location (HR = 2.6, CI = 1.32-5.23, P = 0.0007) and higher plasma methoxytyramine (HR = 1.8, CI = 1.11-2.85, P = 0.0170) and normetanephrine (HR = 1.8, CI = 1.12-2.91, P = 0.0160). Among patients with HNPGLs, those with metastases presented with longer DSS compared to patients with metastatic PPGLs (33.4 versus 20.2 years, P < 0.0001) and only plasma methoxytyramine (HR = 13, CI = 1.35-148, P = 0.0380) was an independent predictor of DSS. For patients with metastatic PPGLs, multivariable analysis revealed that apart from older age (HR = 6.2, CI = 3.20-12.20, P < 0.0001), shorter DSS was associated with the presence of synchronous metastases (HR = 4.9, CI = 2.78-8.80, P < 0.0001), higher plasma methoxytyramine (HR = 2.4, CI = 1.44-4.14, P = 0.0010) and extensive metastatic burden (HR = 2.1, CI = 1.07-3.79, P = 0.0290).CONCLUSIONS: DSS among patients with PPGLs/HNPGLs relates to several presentations of the disease that may provide prognostic markers. In particular, the independent associations of higher methoxytyramine with shorter DSS in patients with HNPGLs and metastatic PPGLs suggest the utility of this biomarker to guide individualized management and follow-up strategies in affected patients.

KW - Pheochromocytoma

KW - Paraganglioma

KW - Metastases

KW - Predictors

KW - Survival

KW - Methoxytyramine

KW - MALIGNANT PHEOCHROMOCYTOMA

KW - DOPAMINE

KW - METHOXYTYRAMINE

KW - HIF2-ALPHA

KW - BEHAVIOR

KW - UTILITY

KW - HEAD

U2 - 10.1016/j.ejca.2022.03.032

DO - 10.1016/j.ejca.2022.03.032

M3 - Article

C2 - 35500459

SN - 0959-8049

VL - 169

SP - 32

EP - 41

JO - European Journal of Cancer

JF - European Journal of Cancer

ER -

Determinants of disease-specific survival in patients with and without metastatic pheochromocytoma and paraganglioma

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Keywords

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