Risk of bias assessment of included studies
| First author (year of publication) | Determination of exposure (SDHB or SDHD mutation) adequately reported | Adequate definition and assessment of metastatic paraganglioma | Adequate selection of patients | Adequate loss to follow-up |
|---|---|---|---|---|
| Astrom (2003)45 | Yes | Definition: no*, assessment: no† | Unclear | n.a. |
| Benn (2006)14 | Yes | Definition: yes, assessment: no‡ | Unclear | No |
| Boedeker (2007)46 | Yes | Definition: yes, assessment: yes | Unclear | n.a. |
| Hensen (2010)47 | Yes | Definition: yes, assessment: yes | Unclear | n.a. |
| Hensen (2011)12 | Yes | Definition: yes, assessment: yes | Unclear | n.a. |
| Mannelli (2009)48 | Yes | Definition: yes, assessment: yes | Unclear | n.a. |
| Neumann (2004)15 | Yes | Definition: yes, assessment: yes | Unclear | n.a. |
| Papaspyrou (2011)17 | No | Definition: yes, assessment: no§ | Unclear | n.a. |
| Peczkowska (2008)49 | Yes | Definition: yes, assessment: yes | Unclear | n.a. |
| Ricketts (2010)50 | Yes | Definition: yes, assessment: yes | Unclear | n.a. |
| Solis (2009)51 | Yes | Definition: yes, assessment: no¶ | Yes | n.a. |
| Srirangaligam (2008)52 | Yes | Definition: yes, assessment: yes | Unclear | No |
*The authors defined malignant paraganglioma as distant metastases or local invasion; the first meeting our eligibility criteria. However, it is not described as to who among the four patients with malignant disease in this study had distant metastases and who had local invasion.
†In this study, diagnostic work-up included self-reported clinical information. This information could be independently confirmed for 37 of 58 subjects through medical records or communications with physicians and genetic counsellors. However, it is not described if this confirmation also applies to the four patients with malignant paraganglioma.
‡In this study, for prevalence, diagnosis of malignancy is based on identification of distant metastases at first surgery. However, it is not described with what diagnostic tools these lesions have been identified. It is also not reported how distant metastases were diagnosed during follow-up.
§In this study, diagnostic work-up compromised only (18F)-DOPA-PET. It is unclear whether diagnosis of malignant PGL was based on (18F)-DOPA-PET imaging or had been made before patients were included in this study.
¶Diagnosis of malignancy in the one patient with malignant disease is based on family history reports from close relatives.
n.a., not applicable.