Pfluger 2003.

Clinical features and settings	Inclusion period: five years and nine months for all studies (including follow‐up and MRI). Patient population: 28 patients with suspected or histologically proven neuroblastoma and a total of 50 ¹²³I‐MIBG scans and 50 MRI examinations Inclusion criteria: suspected or histologically proven neuroblastoma and a maximum time frame of 30 days between ¹²³I‐MIBG scintigraphy and MRI. Suspect tumour lesions were included only if they were in the field of view on images from both modalities. Exclusion criteria were not reported. Image analyses were performed on a lesion‐related basis. A total of 115 lesions were evaluated. Consecutive series: n.r. Diagnostic work‐up: ¹²³I‐MIBG scintigraphy and MRI examinations. Time spans symptoms‐index test, symptoms‐reference standard and index test‐reference standard: n.r. Treatment between index test‐reference standard: n.r.
Participants	Included patients: 22 children with neuroblastoma and a ¹²³I‐MIBG scan at first diagnosis. Median age at diagnosis: n.r. for these 22 included patients; for all 28 patients: mean age of 3.2 years (range 1 week to 11 years). Sex distribution: n.r. for these 22 included patients; for all 28 patients:18 boys (64%), 10 girls (36%). INSS stage: n.r.
Study design	Case series with pathologically proven neuroblastoma (histopathology not known at the time of MIBG‐scintigraphy).
Target condition and reference standard(s)	Target condition: newly diagnosed neuroblastoma. Reference standard: histopathology. For patients with stage 4 neuroblastoma, histologic verification of all metastases is impossible. Therefore, on follow‐up control examinations, a minimum of six months was used for verification of lesions. In these cases, a lesion was classified as a false‐positive finding if it disappeared without tumour therapy during the observation period. A lesion was classified as a true‐positive finding if it persisted or progressed during follow‐up or if it showed clear regression under specific therapy.
Index and comparator tests	Assessed primary objective 1.1: to determine the diagnostic accuracy of ¹²³I‐MIBG (SPECT‐CT) scintigraphy for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old. Index test: ¹²³I‐MIBG scintigraphy. Radiofarmacon: ¹²³I‐MIBG. Dose: 3.7 MBq/kg. Collimator: medium energy. Matrix: 256 × 256. Acquisition protocol: anterior and posterior images of the WB and SPECT. Acquisition time: 24 hours after injection. Acquisition duration: n.r. Interfering medication: n.r. Thyroid prophylaxis: supersaturated potassium iodide one day before the examination and for three days. Positive test result: non‐physiologic focal uptake. Number and expertise of observers: ¹²³I‐MIBG scans were interpreted by two experienced observers with knowledge of clinical data, but blinded for the results on the MRI. Interobserver concordance: On both ¹²³I‐MIBG scans and MRI scans, each lesion was judged either positive or negative with regard to neuroblastoma involvement. For observers to reach a decision about lesions with discrepant results on both modalities, a diagnostic confidence score of three levels was established for each modality: 1. both observers were uncertain about a positive or negative finding; 2. one observer was uncertain and one observer was certain; and 3. both observers were certain. This diagnostic confidence score was assigned to each suspect lesion on ¹²³I‐MIBG scintigraphy and MRI separately. For lesions with discrepant findings on both modalities, the finding of the modality with the higher diagnostic confidence score was accepted. If results from both modalities were discrepant and had the same diagnostic confidence score value, the lesion was judged positive. Interobserver concordance was unclear for the 22 participants; for all 115 lesions (28 patients) the mean diagnostic confidence score was 2.7 with a SD of 0.6.
Follow‐up	n.r.; follow‐up of a minimum of six months was used for verification of lesions.
Notes
Table of Methodological Quality
Item	Authors' judgement	Description
Representative spectrum? All tests	Unclear	Distribution of stage n.r.
Acceptable reference standard? All tests	Yes	Histopathology.
Acceptable delay between tests? All tests	Unclear	n.r.
Partial verification avoided? All tests	No	For patients with stage 4 neuroblastoma, histological verification of all metastases is impossible. Therefore, on follow‐up control examinations, a minimum of 6 months was used for verification of lesions. In these cases, a lesion was classified as a false‐positive finding if it disappeared without tumour therapy during the observation period.
Differential verification avoided? All tests	No	For patients with stage 4 neuroblastoma, histologic verification of all metastases is impossible. Therefore, on follow‐up control examinations, a minimum of 6 months was used for verification of lesions. In these cases, a lesion was classified as a false‐positive finding if it disappeared without tumour therapy during the observation period.
Incorporation avoided? All tests	Yes	Index test was not a part of the reference test.
Reference standard results blinded? All tests	Unclear	n.r.
Index test results blinded? All tests	Unclear	n.r.
Relevant clinical information? All tests	Yes	Analysis was performed with knowledge of clinical data.
Uninterpretable results reported? All tests	Yes	For observers to reach a decision about lesions with discrepant results on both modalities, a diagnostic confidence score of three levels was established for each modality: 1. both observers were uncertain about a positive or negative finding; 2. one observer was uncertain and one observer was certain; and 3. both observers were certain. This diagnostic confidence score was assigned to each suspect lesion on MIBG scintigraphy separately.
Withdrawals explained? All tests	Unclear	n.r.
Selection criteria clearly described? All tests	Yes	Inclusion criteria: suspected or proven neuroblastoma; maximum time frame of 10 days between ¹²³I‐MIBG scan and MRI scan.
Sufficient detail for replication index test? All tests	Yes	¹²³I‐MIBGscans were acquired 24 hours after injection of tracer with an administered activity of 3.7 MBq/kg. SPECT images were acquired at intervals of 24 hours only. The dual‐headed gamma camera was equipped with a medium‐energy collimator, 256 × 256 matrix]. MIBG scans were reviewed on a Hermes workstation.
Sufficient detail for replication reference test? All tests	No	n.r.
Clear definition of positive result index test? All tests	Yes	Non‐physiological focal uptake.
Interobserver variation reported and acceptable? All tests	Unclear	n.r.