Introduction d The objective of this systematic review and meta-analysis was to determine the diagnostic accuracy of nonattenuation-corrected (NAC) and attenuation-corrected (AC) FDG-PET in oncological patients. We studied the effects of attenuation correction for both FR-PET and dual-head coincidence PET (DH-PET), and as a function of different body locations (head/neck, chest, abdomen/pelvis). Materials and Methods Literature Search Appendix 1 Study Selection From the list of retrieved articles, articles were initially evaluated for eligibility on the basis of title and abstract by two independent reviewers (UJ, PR). If there was uncertainty as to whether an article was eligible for inclusion, the entire article was reviewed. Inclusion criteria were (1) clinical studies evaluating FDG imaging with and without attenuation correction in oncology patients; (2) study population of at least ten patients; (3) sufficient detail to reconstruct a 2 × 2 contingency table expressing FDG imaging results by disease status, or sufficient detail to reconstruct relative lesion detection measurement of AC vs. NAC imaging; and (4) studies utilizing FR-PET and/or DH-PET. We excluded abstracts, editorials, and reviews, although the latter two categories were used for cross-referencing. Methodological Quality Assessment 1 2 Table 1 Methodological assessment of individual diagnostic studies: criteria Test Criteria A. Internal study validity   Al. Valid reference test Histology, AC FR or DH coincidence PET  A2. Blind measurement of reference test(s) without knowledge of index test Assessment of reference test independent of index test(s) results  A3. Avoidance of verification bias Choice of patients assessed by reference test independent of index test result  A4. Index test(s) interpreted independently of all clinical information Mentioned in publication  A5. Prospective study Mentioned in publication B. External study validity   B1. Spectrum of diseases Localization of disease described (selected or general)  B2. Demographic information Age and sex given  B3. Inclusion criteria described Mentioned in publication  B4. Exclusion criteria described Mentioned in publication  B5. Avoidance of selection bias Consecutive series of patients  B6. Standardized execution of index test(s) Described technical aspects of index test(s) C. Reproducibility described Mentioned in publication Data Extraction and Quantitative Analysis In addition to methodological quality assessment, data related to the type of camera, the FDG dose, the time interval between injection and imaging, the transmission and emission acquisition protocols, the reconstruction protocol, and the interpretation protocol were independently extracted from each study by each reviewer. For studies where it was possible, a contingency 2 × 2 table was constructed. Disagreements were solved by consensus. For studies using an independent gold standard (histopathology), we determined the sensitivity and specificity of the index tests using the number of true positive, false positive, true negative, and false negative results from the 2 × 2 contingency table. Furthermore, we calculated the “relative lesion detection,” defined as the percentage of lesions scoring equally positive or negative with NAC vs. AC images. We performed a subgroup analysis for different locations of lesions and analyzed sensitivity, specificity, or relative lesion detection of NAC vs. AC for lesion location in the head and neck region, the chest, and the abdominopelvic region. In cases of discrepancy of relative lesion detection between NAC and AC, we extracted data to analyze whether this was related to lesion size and/or intensity. p All statistical analyses were performed with the SPSS 11.0.01 program for Windows (version 11.0.1., SPSS, Chicago, IL, USA). Results 3 12 13 14 15 16 27 2 Table 2 Quality assessment of included studies Study Year A1 A2 A3 A4 A5 B1 B2 B3 B4 B5 B6 C Bleckmann 1999 + + + + − + − + − − + − Chan 2001 + − + − − + + + − − + − Delbeke 2001 + − + − + + + + − − + − Even-Sapir 2004 + − + − + + + + − + + − Kotzerke 1999 + − + − − + + + − + + + Lonneux 1999 + − + − + + + − − + + + Nakamoto 2002 + + + + + + + + − − + + Reinhardt 2005 + − + − − + + + + − + − Schauwecker 2003 + − − − − + + + − − + + Weber 1999 + − + − + + + + − − + − Zimny 1999 + + + + − + + + − − + − Zimny 2003 + − + + + + + + − − + − Meta-Analysis 22 24 25 n 22 24 25 n 27 1 n n n n Fig. 1 Pooled lesion detection of NAC vs. AC images for FR-PET and DH-PET.  20 21 23 26 17 18 26 n n n p p 3 16 23 25 18 22 24 Table 3 Evaluation of discrepant lesions between AC and NAC images with respect to lesion size and intensity Study Camera type Number of discrepant lesions Size range Intensity (semiquantitative or qualitative) Bleckmann et al. FR-PET 5 <1 cm Not given a FR-PET 1 1.8 cm Not given Reinhardt et al. FR-PET 6 0.5–1.1 cm 79/174 lesions demonstrated discrepancy in qualitative lesion intensity: 72/174 lesions demonstrating higher intensity (i.e., better visibility) on NAC images a FR-PET 4 3 1.8–2.6 (SUVmax) Weber et al. FR-PET 1 0.8 cm Not given Delbeke et al. DH-PET 2 1.0–3.0 cm “Mild uptake” at AC, “equivocal uptake” at NAC a Discussion The cumulated evidence summarized in this systematic review of oncological FDG imaging studies suggests that the accuracy of attenuation and nonattenuation corrected FR-PET are similar. However, with DH coincidence imaging NAC images detect 12% less lesions than AC images, without prominent differences between body areas. 28 29 16 23 2 We were surprised by the limited number of good comparative studies evaluating the value of attenuation correction. It appears that attenuation correction has been accepted as the standard of practice without sound scientific evidence to support it. 5 30 45 23 Conclusions In this meta-analysis, we found no significant difference in sensitivity, specificity, or relative lesion detectability between AC and NAC FR FDG PET. However, attenuation correction improved lesion detection for DH coincidence imaging.