Added value of baseline ¹⁸F-FDG uptake in serial ¹⁸F-FDG PET for evaluation of response of solid extracerebral tumors to systemic cytotoxic neoadjuvant treatment: A meta-analysis

The purpose of this study was to test the hypothesis that the level of baseline ¹⁸F-FDG uptake in the primary tumor adds value to its relative change in ¹⁸F-FDG uptake in serial PET scans in predicting the histopathologic response to systemic cytotoxic neoadjuvant treatment of patients with solid extracerebral tumors. Methods: We performed a literature search from January 1995 through November 2008 using PubMed and Embase. Two reviewers independently selected eligible studies for possible inclusion in the meta-analysis by reviewing titles and abstracts. Inclusion criteria were at least 10 patients, ¹⁸F-FDG PET before and after therapy, ¹⁸F-FDG PET performed with the intention of monitoring the response of solid extracerebral tumors in humans to cytotoxic neoadjuvant systemic therapy, attenuation-corrected ¹⁸F-FDG PET studies, and studies presenting individual patient data (PET results and histopathologic reference test after treatment). Multilevel logistic regression was used to assess the effect of relative change of ¹⁸F-FDG uptake ([baseline - end]/baseline) and baseline ¹⁸F-FDG uptake value with type of tumor and type of treatment as level 1 covariates. Results: Nineteen studies (all observational; a total of 438 patients [median, 23 patients per study; range, 10-40]) were included, aiming at the accuracy of PET versus histopathology. To quantify PET, maximum standardized uptake value (SUV) was used in 6 studies, mean SUV in 7, SUV (subtype unclear) in 1, tumor-to-background ratio in 3, and dose uptake ratio in 1. The average overall histopathologic response rate was 0.47 (median, 0.50), ranging from 0.17 to 0.88. The relative change in ¹⁸F-FDG uptake was the strongest indicator (P < 0.0001) for tumor response. Baseline ¹⁸F-FDG was not significantly associated as a main factor; however, a significant interaction of baseline uptake and relative change after therapy was observed (P < 0.001). Conclusion: Relative change in ¹⁸F-FDG uptake was the strongest indicator for tumor response, but the level of baseline ¹⁸F-FDG uptake in the primary tumor provided additional information about prediction of response to therapy. These data corroborate and extend the need for standardization, quality assurance, and control of PET studies quantifying ¹⁸F-FDG in oncologic treatment monitoring.