The asphericity of the metabolic tumour volume in NSCLC: correlation with histopathology and molecular markers.

PURPOSE: Asphericity (ASP) is a tumour shape descriptor based on the PET image. It quantitates the deviation from spherical of the shape of the metabolic tumour volume (MTV). In order to identify its biological correlates, we investigated the relationship between ASP and clinically relevant histopathological and molecular signatures in non-small-cell lung cancer (NSCLC). METHODS: The study included 83 consecutive patients (18 women, aged 66.4 ± 8.9 years) with newly diagnosed NSCLC in whom PET/CT with 18F-FDG had been performed prior to therapy. Primary tumour resection specimens and core biopsies were used for basic histopathology and determination of the Ki-67 proliferation index. EGFR status, VEGF, p53 and ALK expression were obtained in a subgroup of 44 patients. The FDG PET images of the primary tumours were delineated using an automatic algorithm based on adaptive thresholding taking into account local background. In addition to ASP, SUVmax, MTV and some further descriptors of shape and intratumour heterogeneity were assessed as semiquantitative PET measures. RESULTS: SUVmax, MTV and ASP were associated with pathological T stage (Kruskal-Wallis, p = 0.001, p < 0.0005 and p < 0.0005, respectively) and N stage (p = 0.017, p = 0.003 and p = 0.002, respectively). Only ASP was associated with M stage (p = 0.026). SUVmax, MTV and ASP were correlated with Ki-67 index (Spearman's rho = 0.326/p = 0.003, rho = 0.302/p = 0.006 and rho = 0.271/p = 0.015, respectively). The latter correlations were considerably stronger in adenocarcinomas than in squamous cell carcinomas. ASP, but not SUVmax or MTV, showed a tendency for a significant association with the extent of VEGF expression (p = 0.058). In multivariate Cox regression analysis, ASP (p < 0.0005) and the presence of distant metastases (p = 0.023) were significantly associated with progression-free survival. ASP (p = 0.006), the presence of distant metastases (p = 0.010), and Ki-67 index (p = 0.062) were significantly associated with overall survival. CONCLUSION: The ASP of primary NSCLCs on FDG PET images is associated with tumour dimensions and molecular markers of proliferation and angiogenesis.

Dual time point imaging for F18-FDG-PET/CT does not improve the accuracy of nodal staging in non-small cell lung cancer patients.

OBJECTIVES: To analyze the diagnostic performance of dual time point imaging (DTPI) for pre-therapeutic lymph node (LN) staging in non-small cell lung cancer (NSCLC). METHODS: This was a retrospective analysis of 47 patients with NSCLC who had undergone DTPI by PET (early + delayed) using F18-fluorodeoxyglucose (FDG). PET raw data were reconstructed iteratively (point spread function + time-of-flight). LN uptake in PET was assessed visually (four-step score) and semi-quantitatively (SUVmax, SUVmean, ratios LN/primary, LN/liver, and LN/mediastinal blood pool). DTPI analyses included retention indices (RIs), Δ-ratios and changes in visual score. Histology or cytology served as standards of reference. Accuracy was determined based on ROC analyses. RESULTS: Thirty-six of 155 LNs were malignant. DTPI accuracy was low for all measures (visual assessment, 24.5%; RI SUVmax, 68.4%; RI SUVmean, 65.8%; Δ-ratios, 63.9-76.1%) and significantly inferior to early PET. Accuracies of early (range, 86.5-92.9%) and delayed PET (range, 85.2-92.9%) were comparable. At early PET, accuracy of the visual score (92.9%) was similar or superior to semi-quantitative analyses (range, 86.5-92.3%). CONCLUSIONS: Using a modern PET/CT device and novel image reconstruction, neither additional delayed PET nor DTPI analyses improved the accuracy of PET-based LN staging. Dedicated visual assessment criteria performed very well. KEY POINTS: • DTPI did not improve accuracy of PET-based LN staging in NSCLC. • Analyzed SUV ratios were not superior to LN SUVmax or SUVmean. • A four-step visual score may allow highly accurate, standardized LN assessment.

Standardized visual reading of F18-FDG-PET in patients with non-small cell lung cancer scheduled for preoperative thoracic lymph node staging.

OBJECTIVES: Routine visual assessment of positron emission tomography (PET) for thoracic lymph node (LN) staging in patients with non-small cell lung cancer (NSCLC) is limited by a lack of reliable assessment criteria. This study evaluates the accuracy and inter-rater agreement of a standardized approach with unified windowing and a PET-based visual score. MATERIALS AND METHODS: This retrospective analysis included pretherapeutic FDG-PET data of 86 patients with NSCLC. After standardized windowing (threshold: 2×liver SUVmean) the LN uptake was assessed visually by three independent readers with varying levels of experience using a 4-step score (1, LN uptake≤mediastinal blood pool structures (MBPS); 2, MBPS3). The inexperienced (n=1), advanced (n=1), and expert readers (n=1) achieved similar accuracies of 93.5%, 91.4% and 92.1%, respectively (P>0.05 each). Cohen's κ ranged from 0.92 to 0.96 and Fleiss' κ was 0.93. ROC-analyses showed no significant differences between attendant readers within any subgroup (AUC, 0.92-0.96). CONCLUSION: Applying unified windowing, the introduced PET-score achieved highly accurate and robust LN assessment. This approach may shorten learning curves of inexperienced readers, facilitate multicenter trials, and improve comparability of future studies.