Asphericity of Tumor FDG Uptake in Non-Small Cell Lung Cancer: Reproducibility and Implications for Harmonization in Multicenter Studies

Abstract Background Asphericity (ASP) of the primary tumor’s metabolic tumor volume (MTV) in FDG-PET/CT is independently predictive for survival in patients with non-small cell lung cancer (NSCLC). However, comparability between PET systems may be limited. Therefore, reproducibility of ASP was evaluated at varying image reconstruction and acquisition times to assess feasibility of ASP assessment in multicenter studies. Methods Retrospective study of 50 patients with NSCLC (female, 20; median age, 69 years) undergoing pretherapeutic FDG-PET/CT (median, 3.7 MBq/kg; 180 s/bed position). Reconstruction used OSEM with TOF4/16 (iterations, 4; subsets, 16; in-plane filter, 2.0, 6.4 or 9.5 mm), TOF4/8 (4 it; 8 ss; filter, 2.0/6.0/9.5 mm), PSF + TOF2/17 (2 it; 17 ss; filter, 2.0/7.0/10.0 mm) or Bayesian penalized likelihood (Q.Clear; beta, 600/1750/4000). Resulting reconstructed spatial resolution (FWHM) was determined from hot sphere inserts of a NEMA IEC phantom. Data with approx. 5 mm FWHM were retrospectively smoothed to achieve 7 mm FWHM. List mode data were rebinned for acquisition times of 120/90/60 s. Threshold-based delineation of primary tumor MTV was followed by evaluation of relative ASP/SUVmax/MTV differences between datasets and resulting proportions of discordantly classified cases. Results Reconstructed resolution for narrow/medium/wide in-plane filter (or low/medium/high beta) was approx. 5/7/9 mm FWHM. Comparing different pairs of reconstructed resolution between TOF4/8, PSF + TOF2/17, Q.Clear and the reference algorithm TOF4/16, ASP differences were lowest at FWHM of 7 vs. 7 mm. Proportions of discordant cases (ASP > 19.5% vs. ≤19.5%) were also lowest at 7 mm (TOF4/8, 2%; PSF + TOF2/17, 4%; Q.Clear, 10%). Smoothing of 5 mm data to 7 mm FWHM significantly reduced discordant cases (TOF4/8, 38% reduced to 2%; PSF + TOF2/17, 12–4%; Q.Clear, 10–6%) resulting in proportions comparable to original 7 mm data. Shorter acquisition time only increased proportions of discordant cases at < 90 s. Conclusions ASP differences were mainly determined by reconstructed spatial resolution, and multicenter studies should aim at comparable FWHM (e.g., 7 mm; determined by in-plane filter width). This reduces discordant cases (high vs. low ASP) to an acceptable proportion for TOF and PSF + TOF of < 5% (Q.Clear: 10%). Data with better resolution (i.e. lower FWHM) could be retrospectively smoothed to the desired FWHM resulting in a comparable number of discordant cases.