Comparing [18F]FDG PET/CT response criteria in melanoma and lung cancer patients treated with immunotherapy: a systematic review

Purpose: To compare the predictive value of new immunotherapy-specific fluorine-18-labeled glucose Positron Emission Tomography/Computed Tomography ([18F]FDG PET/CT) response criteria to conventional PET/CT criteria for overall survival (OS) in melanoma and lung cancer patients treated with immunotherapy. Methods: MEDLINE (Ovid), Embase, Scopus, Web of Science and the Cochrane Library databases were searched until June 4, 2021, in line with the PRISMA statement. Two reviewers independently screened resulting records. Quality assessment was performed according to Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and/or Quality in Prognostic Studies (QUIPS) criteria. PET/CT response assessment was divided in immunotherapy PET/CT response criteria, conventional PET/CT response criteria, and individual Δ[18F]FDG/PET CT metrics. The main outcome measure extracted was the univariate hazard ratio (HR) for OS. Results: Fifteen studies (n = 565) were included, with ten studies (225 NSCLC, 178 melanoma cases) reporting on PET/CT response criteria and five studies (126 NSCLC, 36 melanoma cases) on individual Δ[18F]FDG PET/CT metrics. Until 2016, conventional criteria: EORTC and PERCIST1.0 were applied; since then, several new, modified criteria emerged: imPERCIST, PERCIMT, PECRIT and iPERCIST. For both NSCLC and melanoma, univariate HRs did not show substantial differences between immunotherapy and conventional PET/CT response criteria, with overlapping confidence intervals. No individual Δ[18F]FDG PET/CT metric can yet be recommended. ΔTMTV in melanoma and ΔSUVmax in NSCLC showed the highest univariate HRs. Conclusion: There is insufficient evidence to decide whether the predictive value of immunotherapy PET/CT criteria is superior to conventional ones for OS, in melanoma and lung cancer treated with immunotherapy. A different research strategy is needed to reach the answer: PET/CT research should focus on directly comparing (modifications of) immunotherapy and conventional PET/CT criteria within a homogenous population with standardized PET timing, immunotherapy categories and OS definition. A consortium-based comprehensive database with individual patient data could be the solution.