TABLE 3

Methodologic Quality Criteria Guidelines*

Guideline	Criteria for adherence evaluation
Guideline 1: description of study design and patient selection criteria
1. Study design	Type of study conducted must be clearly presented.
2. Patient selection criteria	Inclusion criteria, especially particular specifications, should be explained.
3. Exclusion of patients from study’s final analysis	Exclusion of patients from study’s final analysis should be explained, as this can affect study results.
Guideline 2: characteristics of patient population finally studied
1. Mean age with range and sex	Ideally, age and sex of all patients included must be described, as this will allow comparisons of patient populations of different studies.
2. Comorbid conditions	Presence or absence should be stated, as this can affect interpretation.
3. Diabetes mellitus	Patient description should include presence or absence of diabetes mellitus.^†
4. Localization of metastasis of UPT	Localization of metastasis of UPT should be clearly stated for every patient included in study, together with histopathologic findings.
5. Special institution characteristics	Institution characteristics should be described or stated in published article, as it can be useful for defining study population.
Guideline 3: patient indications leading to use of ¹⁸F-FDG PET
1. Reasons for use of ¹⁸F-FDG PET	Results of previous diagnostic procedures and clinical situations used to refer patient for further evaluation with ¹⁸F-FDG PET must be clearly explained.
2. Reasons for use of ¹⁸F-FDG PET correlated with specific ¹⁸F-FDG PET findings	Reasons for patient referral to ¹⁸F-FDG PET and results of ¹⁸F-FDG PET scan should be stated for every patient included in study analysis.
3. Extent of metastatic disease in every patient	If patients present several metastatic lesions from UPT, localization and extent of every lesion should be clearly stated.
Guideline 4: details of technologies used during study and image-interpretation issues
1. Imaging techniques used in study and resolution	All imaging techniques used, together with their resolutions, should be stated.
2. Patient preparation	Patient preparation should follow Society Nuclear Medicine guidelines (27).
3. Minimum 4-h fasting before ¹⁸F-FDG injection	Minimum 4-h fasting before ¹⁸F-FDG administration should be carried out in every patient and clearly stated.
4. Blood glucose level checked before ¹⁸F-FDG injection	Blood glucose level should be checked before ¹⁸F-FDG administration in every patient and clearly stated.
5. Attenuation correction (AC)	If AC is performed, it is scored A. If AC is not performed, but this is correctly stated, it is scored P. N score is given when this issue is not addressed.
6. Explanation of special characteristics of interpreters	No. of interpreters and their experience in reading ¹⁸F-FDG PET scans should be clearly stated.
7. Definition of positive and negative ¹⁸F-FDG PET findings	Characteristics that defined imaging findings as positive or negative should be clearly explained, as these aspects represent study’s threshold.
8. Additional scans	Additional imaging procedures performed in patients should be stated.
Guideline 5: final diagnostic confirmation
1. Final confirmation	Diagnostic procedures used as reference standards must be described.
2. Association between specific ¹⁸F-FDG PET finding and final confirmation technique used	If different confirmation methods are used, correspondence between each specific imaging finding and specific confirmation method used should be clearly described.
3. Histopathologic confirmation	Although histopathologic confirmation is considered the gold standard, technique used (surgery, biopsy, fine-needle aspiration cytology) must be stated, as diagnostic accuracy can vary between techniques.
4. Nonhistopathologic confirmation	When histopathologic confirmation is not possible, other techniques used for confirmation should be explained and amount of time of follow-up stated.
5. Patients lost to clinical follow-up confirmation	Patients lost to clinical follow-up confirmation should be described together with clear statement of their inclusion (or not) in study’s final analysis.
Guideline 6: sensitivity and specificity data
1. Description of TP, FP, TN, and FN	True-positive (TP), false-positive (FP), true-negative (TN), and false-negative (FN) values should be quantitatively described for all imaging methods analyzed in study and clearly presented.
2. Qualitative explanation of FP and FN	Errors made by imaging modality (FP, FN) need to be explained.
3. Specific region studied by ¹⁸F-FDG PET	When study performs whole-body ¹⁸F-FDG PET scans and this is clearly stated, score is A. When ¹⁸F-FDG PET scan includes only 1 region of body and it is clearly stated, score is P. When region studied by ¹⁸F-FDG PET is not clearly stated, score is N.
4. Location and no. of primary tumors and other metastatic lesions detected by ¹⁸F-FDG PET	All lesions detected by ¹⁸F-FDG PET must be described in every patient. Localization of primary tumors and metastatic lesions detected by PET must be clearly presented.
5. Confidence intervals	Confidence intervals of values reported should be included.
6. Equivocal ¹⁸F-FDG PET findings	When equivocal ¹⁸F-FDG PET findings exist, it should be clear how findings were defined in final analysis of study.
7. Data reported in patients and in corresponding lesions	Studies should report data both for patients and for lesions detected.
Guideline 7: change-in-management information
1. ¹⁸F-FDG PET-directed change in management	Management changes that are consequence of ¹⁸F-FDG PET should be clearly stated. When study does not analyze change-in-management information, an N/A score is assigned (to most or all items in guideline 7).
2. Diagnostic tool used to make initial treatment decision	Diagnostic tool used and its results that were used to make initial treatment decision must be clearly described, allowing comparisons with results of ¹⁸F-FDG PET scan.
3. Diagnostic tool used to make final treatment decision	Diagnostic tool used and its results that were used to make final treatment decision must be clearly described.
4. Medical treatment made both initially and after ¹⁸F-FDG PET	Changes in medical treatment must be stated, allowing evaluation of management changes induced by ¹⁸F-FDG PET.
5. Correct or incorrect ¹⁸F-FDG PET-directed management change	Clear statement of correct or incorrect ¹⁸F-FDG PET-directed management change must be presented.
6. Upstaging and downstaging	Extent of disease diagnosed before and after ¹⁸F-FDG PET scan must be presented.
7. ¹⁸F-FDG PET in management algorithm	Management data presented in study must be discussed and conclusion on benefits of ¹⁸F-FDG PET and moment of management algorithm in which to perform ¹⁸F-FDG PET scan must be clearly presented.

↵* Methodologic quality criteria guidelines formulated by Huebner et al. (25) and adapted for review of studies of patients with UPT in which ¹⁸F-FDG PET is performed to detect primary tumor.
↵^† Patients with diabetes mellitus (DM) can present high levels of blood glucose, especially when DM is poorly controlled with treatment. During hyperglycemic states, uptake of ¹⁸F-FDG by tumor can be reduced due to competitive effect between excess plasma glucose and ¹⁸F-FDG. As a consequence, ¹⁸F-FDG PET image quality is reduced and sensitivity decreases. Studies should describe in all patients: presence or absence of DM and blood glucose level during ¹⁸F-FDG administration.
A = adequate adherence; P = partial adherence; N = not addressed; N/A = not applicable; TP = true-positive; FP = false-positive; TN = true-negative; FN = false-negative.