Pamporaki Christina, Prodanov Tamara, Meuter Leah, Berends Annika M A, Bechmann Nicole, Constantinescu Georgiana, Beuschlein Felix, Remde Hanna, Januszewicz Andrzej, Kerstens Michiel N, Timmers Henri J L M, Taïeb David, Robledo Mercedes, Lenders Jacques W M, Pacak Karel, Eisenhofer Graeme
Department of Medicine ΙΙI, University Hospital Carl Gustav Carus at the TU Dresden, Dresden, Germany.
National Institutes of Health (NIH), Bethesda, USA.
Eur J Cancer. 2022 Jul;169:32-41. doi: 10.1016/j.ejca.2022.03.032. Epub 2022 Apr 29.
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.
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.
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).
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.
嗜铬细胞瘤和副神经节瘤（PPGLs）的预后存在异质性，其基础尚不清楚。因此，我们根据有无转移情况，评估了PPGLs和头颈部副神经节瘤（HNPGLs）患者的疾病特异性生存率（DSS）及疾病进展的潜在预测因素。
这项回顾性研究纳入了582例PPGLs患者和57例HNPGLs患者。根据年龄、肿瘤位置和大小、复发/转移疾病、遗传学、血浆甲氧基肾上腺素和甲氧基酪胺评估DSS。
在所有PPGLs患者中，多变量分析表明，除了年龄较大（HR = 5.4，CI = 2.93 - 10.29，P < 0.0001）和存在转移（HR = 4.8，CI = 2.41 - 9.94，P < 0.0001）外，较短的DSS还与肾上腺外肿瘤位置（HR = 2.6，CI = 1.32 - 5.23，P = 0.0007）以及较高的血浆甲氧基酪胺（HR = 1.8，CI = 1.11 - 2.85，P = 0.0170）和去甲肾上腺素（HR = 1.8，CI = 1.12 - 2.91，P = 0.0160）有关。在HNPGLs患者中，有转移的患者与有转移的PPGLs患者相比，DSS更长（33.4年对20.2年，P < 0.0001），且只有血浆甲氧基酪胺（HR = 13，CI = 1.35 - 148，P = 0.0380）是DSS的独立预测因素。对于有转移的PPGLs患者，多变量分析显示，除了年龄较大（HR = 6.2，CI = 3.20 - 12.20，P < 0.0001）外，较短的DSS还与同时存在转移（HR = 4.9，CI = 2.78 - 8.80，P < 0.0001）、较高血浆甲氧基酪胺（HR = 2.4，CI = 1.44 - 4.14，P = 0.0010）和广泛转移负担（HR = 2.1，CI = 1.07 - 3.79，P = 0.0290）有关。
PPGLs/HNPGLs患者的DSS与该疾病的多种表现相关，这些表现可能提供预后标志物。特别是，较高的甲氧基酪胺与HNPGLs和转移性PPGLs患者较短的DSS之间的独立关联表明，这种生物标志物有助于指导对受影响患者的个体化管理和随访策略。
