Veit‐Haibach 2009.

Study characteristics
Patient sampling	Design: within‐person comparison; prospective Country: Germany Data collection: NR Inclusion criteria: any primary MM referred for PET‐CT Excluded if insufficient FU
Patient characteristics and setting	Presentation: primary (any); any primary MM referred for PET‐CT Number patients: 56 Number primary lesions: 56 Number LNBs/metastases: NR Stage of disease: presentation stage I or II 44, 79%; stage III or IV 12, 21% Mean age: 62 years; Median age: NR; Range: 23 to 86 years Male: 27 (48.2%) Primary lesion site: trunk 26, 46%; upper extremities 10, 18%; lower extremity 18, 32%; HN 2, 4% Breslow/Clark: NR Ulceration: NR Other: NR
Index tests	CT: CE; 2‐slice Machine: Biograph Duo PET/CT System (Siemens Molecular Imaging, Hoffman Estates, IL); integrates a dual‐slice CT scanner (Somatom Emotion, Siemens Medical Solutions, Forchheim, Germany) and a full‐ring, BGO‐based PET Tomograph (Siemens Molecular Imaging) Scan coverage: WB; no further detail, just states caudocranial direction Contrast: dual‐phase injection of 140 mL of 300 mmol/mL iodinated contrast agent (90 mL at a rate of 3 mL/s, and 50 mL at a rate of 1.5 mL/s; dual‐phase used to ensure fully diagnostic (portal venous phase) CT data in the abdomen) CT parameters: NR Breath hold: NR Threshold: nodal mets ‐ lesion size and central necrosis for malignancy; fatty hilum and calcifications for benign. For size: short‐axis diameter threshold of 1.5 cm for jugulodigastric and pre‐carinal LNs and threshold of 1 cm for all other LNs of the neck, thorax, and abdomen. Distant mets ‐ detection of soft tissue masses (or focal cutaneous thickening) with contrast enhancement # PET‐CT: full‐ring CT (CE; 2‐slice) Machine: Biograph Duo PET/CT System (Siemens Molecular Imaging, Hoffman Estates, IL); integrates a dual‐slice CT scanner (Somatom Emotion, Siemens Medical Solutions, Forchheim, Germany) and a full‐ring, BGO‐based PET tomograph (Siemens Molecular Imaging) Scan coverage: WB; no further detail, just states caudocranial direction Contrast: 140 mL of 300 mmol/mL iodinated contrast agent CT parameters: NR FDG: 330 to 350 MBq Breath hold: NR CT used for: attenuation correction Reconstruction: reconstructed iteratively (FORE‐OSEM, 2 iterations, 8 subsets, 128×128 matrix with 5‐mm gaussian smoothing) Threshold: nodal mets ‐ increased glucose metabolism and independent of size. Diatant mets ‐ qualitative + SUV; detection of soft tissue masses (or focal cutaneous thickening) with contrast enhancement in different body compartments and in conjunction with focally increased glucose metabolism above the surrounding tissue level on FDG PET/ CT; supported by SUVmax ≥ 1.5 for cutaneous lesions, ≥ 2.5 for other extrahepatic lesions, and ≥ 3.5 for intrahepatic lesions # Number observers: 2 Qualification (experience): radiologists and and nuclear medicine specialist for PET‐CT (NR) Diagnosis (single, consensus, etc.): consensus of 2 Info provided during test interpretation: clinical ‐ provided patient‐specific clinical background (first diagnosis of melanoma, postsurgical resection status, location of resection site) but blinded to clinical exam and histopathology of primary tumour; other tests ‐ blinded to other imaging procedures
Target condition and reference standard(s)	Histology/FU Histological detail (n, %): all patients with suspected metastases on imaging, histopathological evaluation of at least 1 metastatic site served as the standard of reference for both N‐stage and M‐stage during the clinical course. Total of 14 patients had SLNB within 4 weeks of the initial PET‐CT procedure (unclear; 14 with SLNB, 25%). Histopathologist: NR FNAC (n, %): N/A (0) Follow‐up (n, %): imaging, tumour markers, physical examination (56, 100%) FU schedule: NR FU duration: mean 780 days (range 102 to 1390 days); roughly equivalent to 25.6 months (3.3 to 45.7 months) Reference blinding: N/A # Target condition Data: per pt Definition: nodal; Prevalence: 13/56 = 23% Definition: distant; Prevalence: 12/56 = 21% (no breakdown by anatomical site) Metastases: 12 patients with nodal and/or distant mets reported as detected on initial staging; 4 patients with nodal mets (stage III) and 8 with distant (stage IV). PET‐CT correctly classified 6/12 and CT correctly classified 3/12. A further 6 patients had metastases detected on follow‐up for a total of 18 patients with any metastases Of the 8 FNs on PET‐CT and 10 FNs on CT alone, 2 were micro‐metastases identified by SLNB
Flow and timing	Index to histology interval: 4 weeks for SLNB Index to FU interval: NR Exclusions: n = 0
Comparative	(1) Blinded to other imaging procedures (2) Same scanner (3) All referred for PET‐CT
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Does the study report results for participants at the same point in the clinical pathway and who would be eligible for imaging in normal practice?	Yes
Did the study report data on a per patient rather than per lesion basis?	Yes
		Low	Low
DOMAIN 2: Index Test CT
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
Was the imaging test applied and interpreted in a clinically applicable manner?	No
Were thresholds or criteria for diagnosis reported in sufficient detail to allow replication?	Yes
Was the test interpreted by an experienced examiner?	Yes
		Low	High
DOMAIN 2: Index Test PET‐CT
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
Was the imaging test applied and interpreted in a clinically applicable manner?	No
Were thresholds or criteria for diagnosis reported in sufficient detail to allow replication?	Yes
Was the test interpreted by an experienced examiner?	Yes
		Low	High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Unclear
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Were the reference standard results based on patient follow‐up interpreted without knowledge of the original imaging test result?	Unclear
Does the study use the same definition of disease positive as the primary review question (i.e. any mets) OR is it possible to disaggregate or regroup data such that data matching the review question can be extracted?	No
Was histology or cytology interpretation carried out by an experienced histopathologist or by a dermatopathologist?	Unclear
		Unclear	High
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Unclear
Did all patients receive the same reference standard?	No
Were all patients included in the analysis?	Yes
		High
DOMAIN 5: Comparative
1) was each index test result interpreted without knowledge of the results of other index tests or testing strategies?	Yes
2) Was the interval between application of index tests	Yes
3) Was it predetermined that all index tests should be given to all study participants?	Yes
		Low