Evolving management strategies in head and neck paragangliomas: A single‐centre experience with 147 patients over a 60‐year period

•Paragangliomas of the head and neck (HNPGLs) are rare, slow-growing and usually benign tumours that arise in the paraganglion tissue associated with the autonomic nervous system. •Management strategies and outcome of 147 patients with a total of 289 HNPGLs in a 60-year period were evaluated. •In HNPGLs patients, the clinician should be aware of variable clinical manifestations, such as the risk of multifocality, associated sympathetic PGL, concurrent pheochromocytoma, catecholamine excess and risk of metastatic disease. •A decreasing number of HNPGLs were surgically resected. Increasingly, an active surveillance strategy has become the treatment of choice. •The genetic predisposition, a key factor in the clinical risk profile (phenotype) of HNPGL patient subgroups, in combination with a better understanding of the natural course of HNPGLs, has resulted in a more conservative management of HNPGL patients. This article is protected by copyright. All rights reserved.


| MATERIAL S AND ME THODS
Patients visiting the department between 1956 and 2017, with at least one HNPGL were included. Patient characteristics including genetic status (if available), gender, family history, age at diagnosis, number and localisation of HNPGLs, concurrent sPGL, PHEO, metastatic disease, management strategy and outcome were recorded.
The duration of follow-up was defined as the period between the date of HNPGL diagnosis (on imaging) and the most recent outpatient clinic visit. The diagnosis of HNPGL was based on patient and family history, otolaryngology examination including otoscopy and laryngoscopy, and/or computed tomography (CT) imaging, and/ or magnetic resonance (MR) imaging and/or an angiography of the head and neck region including the skull base. Since 2003, HNPGL patients (and family members at risk) have been offered genetic counselling and DNA testing. Biochemical screening including the measurement of (nor)adrenaline, vanillylmandelic acid (VMA), dopamine, (nor)metanephrine and/or 3-methoxytyramine (3-MT) in two 24-h urinary samples and/or plasma-free (nor)metanephrine was offered to HNPGL patients. In case of excessive catecholamine secretion, additional radiological assessment by MR imaging or CT scans of thorax, abdomen and pelvis and/or 123 I-metaiodobenzylguanidine (MIBG)-scan, and/or positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose (18F-FDG PET)-scans/ 18F-L-dihydroxyphenylalanine (18F-DOPA) PET scans were performed to identify potential sources of excessive catecholamine production outside the head and neck region. In SDHB mutation carriers, MR imaging of the thorax, abdomen and pelvis was performed as standard routine. Active surveillance (also called "wait and scan policy" or "watchful waiting"), radiotherapy, surgical resection or combinations were possible treatment strategies and were This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. The material in this manuscript is original research, has not been previously published and has not been submitted for publication elsewhere. multidisciplinary discussed, weighing potential risks and benefits of each treatment strategy per tumour and per patient. Active surveillance, and postoperative and post-irradiation follow-up comprised of regular MR imaging and clinical evaluation by an endocrinologist and ENT surgeon. The interval was determined by several factors, such as tumour size, tumour progression rate, tumour localisation, symptoms and treatment modality, and thus differed per tumour and per patient. IBM SPSS Statistics version 20.0 (SPSS) was used for data analysis.

| Clinical characteristics
One hundred and forty-seven patients, 47 male (32%) and 100 female (68%), with a total of 289 HNPGLs were diagnosed in a 60-year period.
Multiple synchronous or metachronous HNPGLs were found in 79 of 147 patients (54%), up to a maximum of six metachronous HNPGL.

| Management
Since 1956, an increasing number of HNPGLs have been diagnosed   Imaging studies not available. A surgical approach is still the treatment option of choice in the majority of carotid body and tympanic tumours, tumours that can generally be surgically resected with limited surgical risk. Growing insight into the usually indolent natural course of HNPGL has resulted in a more conservative approach of tumours in which surgery would infer considerable risk to cranial nerves, that is, vagal and jugular PGL ( Figure 1). This approach has been supported by several cohort studies, describing stable or slowly progressive tumours in a large proportion of HNPGL patients (42%-79%).2012,2015 In the Netherlands, therapeutic options (ie surgical resection, radiotherapy or surveillance) are multidisciplinary discussed, weighing potential risks and benefits of each treatment strategy per tumour and per patient.

| D ISCUSS I ON
Moving forward, more research is necessary to accurately predict the clinical behaviour of specific HNPGL tumours of individual patients, allowing for even more tailor-made management strategies, not only with regard to the natural course of the disease, but also with regard to the short-and long-term effects of possible interventions. As tumour eradication is not always possible or necessary, quality of life should be the dominant outcome parameter.
F I G U R E 1 Management of head and neck paragangliomas. A, Number of diagnosed head and neck paragangliomas (HNPGLs). B, Percentage of HNPGLs that was surgically resected. C, Percentage of HNPGLs that was treated with radiotherapy. D, Percentage of HNPGL followed an active surveillance policy