Fig 1.
Flow chart of patient selection.
Abbreviations: NSCLC = non-small cell lung cancer, EGFR = epidermal growth factor receptor, PET = positron emission tomography, CT = computed tomography.
Fig 2.
Schematic flow of textural analysis.
(A) FDG-PET/CT scan acquisition. (B) Placement of a volume of interest on the primary tumor. (C) Tumor segmentation by isocontour with SUV of 3.5 (D) Gray scale resampling and texture feature extraction in global, local, and regional scales. Abbreviations: Co = Co-occurrence, NID = Neighborhood intensity difference, VA = Voxel alignment, ISZ = intensity size zone.
Fig 3.
Spearman’s rank correlation coefficients of textural parameters compared to the value of co-occurrence entropy.
Abbreviations are listed in S1 Table.
Table 1.
Characteristics of the study population.
Fig 4.
Representative images from the exploratory dataset (200 x 200 matrix).
Representative images of two patients who had metabolic volumes with different heterogeneity textural parameters. Patients with increased intratumoral heterogeneity by textural parameters showed poor progression free survival. Panel A & B. A 51-year-old woman with 4.7 months of progression free survival. (A) Pre-treatment FDG-PET/CT images (SUVmax 34.1, metabolic volume 109.3 cm3) EGFR exon 19 micro-deletion mutation; Co entropy: -82302; Co homogeneity: 6951; VA intensity variability: 299; VA short run emphasis: 0.458; NID busyness: 1.170; NID contrast: 4.85 x 10–5; ISZ intensity variability: 964.0; and ISZ high intensity zone emphasis: 472.1. (B) Post-treatment FDG-PET/CT images after 4.7 months (SUVmax 36.7, metabolic volume 358.5 cm3) Panel C & D. A 71-year-old woman with 15.4 months of progression free survival. (C) Pre-treatment FDG-PET/CT images (SUVmax 16.0, metabolic volume 95.1 cm3) EGFR exon 19 micro-deletion mutation; Co entropy: -53663; Co homogeneity: 5156; VA intensity variability: 680; VA short run emphasis: 0.387; NID busyness: 1.012; NID contrast: 7.98 x 10–5; ISZ intensity variability: 603.8; ISZ high intensity zone emphasis: 530.2. (D) Post-treatment FDG-PET/CT images after 2.8 months (SUVmax: 6.0, metabolic volume: 4.2 cm3). Abbreviations: Co = co-occurrence,VA = voxel alignment, NID = neighbor intensity-difference, ISZ = intensity size-zone.
Table 2.
Cox proportional regression analysis of the optimal cutoff value calculated from the exploratory dataset.
Table 3.
Incremental predictive value of textural parameters for EGFR TKI failure.
Fig 5.
Kaplan-Meier curves of progression free survival via representative textural parameters from the validation dataset (n = 21).
Binary distribution with the cutoff of the upper third value in parameter Co heterogeneity (HR: 1.65, 95% CI 0.56–4.83), VA intensity variability (HR 1.63, 95% CI 0.56–4.75), NID busyness (HR: 2.41, 95% CI 0.82–7.10), and ISZ intensity variability (HR: 3.80, 95% CI 1.24–11.6); and with the cutoff of the lower third value in parameter Co entropy (HR: 1.65, 95% CI 0.56–4.83), VA short run emphasis (HR: 1.99, 95% CI 0.66–6.02), NID contrast (HR: 1.77, 95% CI 0.60–5.18), ISZ high intensity zone emphasis (HR: 2.36, 95% CI 0.77–7.24). Abbreviations: Co = co-occurrence, VA = voxel alignment, NID = neighbor intensity-difference, ISZ = intensity size-zone.