Chai 2012.

Study characteristics
Patient sampling	Design: non‐comparative; retrospective (Prosp. database: yes) Country: USA Data collection: Jun 2005 to Sep 2009 Inclusion criteria: node negative, BT > 0.76 mm or < 0.76 mm with high‐risk features such as ulceration, high mitotic rate, or positive deep margin
Patient characteristics and setting	Presentation: primary (pre‐SLNB) Number patients: 325 Number primary lesions: 325 Number LNBs/metastases: 347 LNBs Stage of disease: NR Mean age: NR; Median age: 58 years; Range: 18 to 86 years Male: 189 (58%) Primary lesion site: head and neck 34 (10.5%), trunk 129 (39.7%), upper extremity 101 (31.1%), lower extremity 61 (18.8%) Breslow/Clark: BT median (range) 1.78 (0.42 to 14.4); BT ≤ 1.00 56 (17.2%), 1.01 to 2.00 136 (41.8%), 2.01 to 4.00 88 (27.1%), 4.00 44 (13.5%), unknown 1 (0.3%) Clark level: III 24 (7.4%), IV 275 (84.6%), V 20 (6.2%), unknown 6 (1.8%) Ulceration: 97, 29.8%; unknown 16, 4.9% Other: regression present 26 (8.0%), unknown 15 (4.6%). Growth phase: radial 20 (6.2%), vertical 283 (87.1%), unknown 22 (6.7%) Angiolymphatic invasion: present 15 (4.6%), unknown 20 (6.2%) Mitotic rate: 0 9 (2.8%), C1 303 (93.2%), unknown 23 (7.1%)
Index tests	US: B mode; linear array Machine: NR Scan coverage: acc to primary MM site and discretion of attending surgeon (extremity melanomas ‐ ipsilateral groin or axilla, MM of hand or forearm also had epitrochlear US and of lower leg had popliteal US; HN MM ‐ ipsilateral neck, parotid, and supraclavicular US; MM on trunk according to Sappey’s line ‐ at or above the beltline included axillary ultrasound, at or below included groin ultrasound, lesions close to the midline had bilateral US) Contrast: N/A FNAC: If US performed the day before SLNB, US‐guided FNAC was offered; FNAC +ve proceeded to CLND, FNAC‐ to SLNB as planned Threshold: US ‐ classed as "abnormal," "suspicious," or "indeterminate ‐ recommending a short‐term follow‐up" were considered positive (criteria described in detail) Number observers: NR Qualification (experience): NR (NR) Diagnosis (single, consensus, etc.): NR Info provided during test interpretation: clinical NR; other tests NR
Target condition and reference standard(s)	Histology (CLND/SLNB) Histological detail (n, %): H&E (serial section); IHC (NR) (325, 100%). Histopathologist: NR FNAC (n, %): NR; all positive on CLND (6, 1.8%) Follow‐up (n, %): NR (NR; presume 100%) FU schedule: NR FU duration: NR; FU for SLNB negatives mentioned but no description given Reference blinding: NR Target condition Data: per pt Definition: nodal mets; Prevalence: 64/317 = 20%
Flow and timing	Index to histology interval: US performed either immediately or several days before LS Index to FU interval: NR Exclusions: n = 8; 1 patient had ultrasound of a non‐draining nodal basin, while the actual draining basin identified by lymphoscintigraphy was not examined with ultrasound; this patient was not included in further analysis for comparison between ultrasound and SLNB. Plus 7 SLN positive who did not get US
Comparative
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 Ultrasound (pre‐SLNB)
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?	Unclear
Were thresholds or criteria for diagnosis reported in sufficient detail to allow replication?	Yes
Was the test interpreted by an experienced examiner?	Unclear
		Low	Unclear
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
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?
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?	Yes
Was histology or cytology interpretation carried out by an experienced histopathologist or by a dermatopathologist?	Unclear
		Low	Unclear
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	No
		High