[18F] FDG Positron Emission Tomography (PET) Tumor and Penumbra Imaging Features Predict Recurrence in Non–Small Cell Lung Cancer

We identified computational imaging features on 18F-fluorodeoxyglucose positron emission tomography (PET) that predict recurrence/progression in non–small cell lung cancer (NSCLC). We retrospectively identified 291 patients with NSCLC from 2 prospectively acquired cohorts (training, n = 145; validation, n = 146). We contoured the metabolic tumor volume (MTV) on all pretreatment PET images and added a 3-dimensional penumbra region that extended outward 1 cm from the tumor surface. We generated 512 radiomics features, selected 435 features based on robustness to contour variations, and then applied randomized sparse regression (LASSO) to identify features that predicted time to recurrence in the training cohort. We built Cox proportional hazards models in the training cohort and independently evaluated the models in the validation cohort. Two features including stage and a MTV plus penumbra texture feature were selected by LASSO. Both features were significant univariate predictors, with stage being the best predictor (hazard ratio [HR] = 2.15 [95% confidence interval (CI): 1.56–2.95], p < 0.001). However, adding the MTV plus penumbra texture feature to stage significantly improved prediction (p = 0.006). This multivariate model was a significant predictor of time to recurrence in the training cohort (concordance = 0.74 [95% CI: 0.66–0.81], p < 0.001) that was validated in a separate validation cohort (concordance = 0.74 [95% CI: 0.67–0.81], p < 0.001). A combined radiomics and clinical model improved NSCLC recurrence prediction. FDG PET radiomic features may be useful biomarkers for lung cancer prognosis and add clinical utility for risk stratification

Simultaneous FDG-PET/MRI detects hippocampal subfield metabolic differences in AD/MCI.

The medial temporal lobe is one of the most well-studied brain regions affected by Alzheimer's disease (AD). Although the spread of neurofibrillary pathology in the hippocampus throughout the progression of AD has been thoroughly characterized and staged using histology and other imaging techniques, it has not been precisely quantified in vivo at the subfield level using simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI). Here, we investigate alterations in metabolism and volume using [18F]fluoro-deoxyglucose (FDG) and simultaneous time-of-flight (TOF) PET/MRI with hippocampal subfield analysis of AD, mild cognitive impairment (MCI), and healthy subjects. We found significant structural and metabolic changes within the hippocampus that can be sensitively assessed at the subfield level in a small cohort. While no significant differences were found between groups for whole hippocampal SUVr values (p = 0.166), we found a clear delineation in SUVr between groups in the dentate gyrus (p = 0.009). Subfield analysis may be more sensitive for detecting pathological changes using PET-MRI in AD compared to global hippocampal assessment

An Observational Study of Circulating Tumor Cells and ¹⁸F-FDG PET Uptake in Patients with Treatment-Naive Non-Small Cell Lung Cancer

<div><p>Introduction</p><p>We investigated the relationship of circulating tumor cells (CTCs) in non-small cell lung cancer (NSCLC) with tumor glucose metabolism as defined by ¹⁸F-fluorodeoxyglucose (FDG) uptake since both have been associated with patient prognosis.</p><p>Materials & Methods</p><p>We performed a retrospective screen of patients at four medical centers who underwent FDG PET-CT imaging and phlebotomy prior to a therapeutic intervention for NSCLC. We used an Epithelial Cell Adhesion Molecule (EpCAM) independent fluid biopsy based on cell morphology for CTC detection and enumeration (defined here as High Definition CTCs or “HD-CTCs”). We then correlated HD-CTCs with quantitative FDG uptake image data calibrated across centers in a cross-sectional analysis.</p><p>Results</p><p>We assessed seventy-one NSCLC patients whose median tumor size was 2.8 cm (interquartile range, IQR, 2.0–3.6) and median maximum standardized uptake value (SUV_max) was 7.2 (IQR 3.7–15.5). More than 2 HD-CTCs were detected in 63% of patients, whether across all stages (45 of 71) or in stage I disease (27 of 43). HD-CTCs were weakly correlated with partial volume corrected tumor SUV_max (r = 0.27, p-value = 0.03) and not correlated with tumor diameter (r = 0.07; p-value = 0.60). For a given partial volume corrected SUV_max or tumor diameter there was a wide range of detected HD-CTCs in circulation for both early and late stage disease.</p><p>Conclusions</p><p>CTCs are detected frequently in early-stage NSCLC using a non-EpCAM mediated approach with a wide range noted for a given level of FDG uptake or tumor size. Integrating potentially complementary biomarkers like these with traditional patient data may eventually enhance our understanding of clinical, <i>in vivo</i> tumor biology in the early stages of this deadly disease.</p></div

Clinical, CTC and FDG PET-CT Patient Characteristics by Center.

<p>SUMC = Stanford University Medical Center; UCSD =  University of California San Diego Moores Cancer Center, VAPAHCS = Veterans Affairs Health Palo Alto Health Care System; Billings = Billings Medical Center; NSCLC =  Non-small Cell Lung Cancer; AJCC = American Joint Committee on Cancer; 10 M WBC = 10 Million White Blood Cells. SUV = Standardized Uptake Value; PVC = Partial Volume Correction. DICOM = Digital Imaging and Communication in Medicine.</p>*<p>Variables are shown as median with interquartile range (IQR) for continuous variables and number with percent (%) for categorical or ordinal variables.</p>†<p>Significant differences (p-value <0.05) by center.</p>§<p>As measured on PET-VCAR, n = 62 (see methods).</p>¶<p>Range provided instead of IQR.</p>∧<p>n = 62.</p>≈<p>Clinically retrieved value was used for this calculation when extracted data (from PET-VCAR) was not available.</p

Non-small Cell Lung Cancer FDG PET-CT Imaging Features.

<p>A three dimensional, maximum intensity projection, whole body ¹⁸F-FDG PET-CT (left). Physiologic uptake is seen in the brain, heart and liver with excretion through the renal pelvis and bladder. This tumor showed an intense FDG uptake with SUV_max of 19, SUV_mean of 9.6, and TLG of 65.6 using a 50% SUV_max threshold (upper right). On CT, the lesion volume was estimated at 6.0 cm³ with a maximum diameter of 22 mm (lower right).</p

HD-CTC Scatter Plots for SUV_maxPVC and CT diameter*.

<p>Non-metastatic patients are highlighted in red (see methods for definition) and the axes are shown as log₂(x,y) for ease of interpretation. Increasing SUV_maxPVC (left) was weakly correlated (r = 0.27, p-value = 0.03) with increasing HD-CTC/10 M WBC count compared to tumor diameter on CT (right; r = 0.07, p-value = 0.60), which showed no correlation. *Shown for 62 of 71 patients with data extracted by PET-VCAR.</p

FDG Uptake and CTC Features Correlation Matrix*.

<p>TLG = Total Lesion Glycolysis; SUV = Standardized Uptake Value; PVC = Partial Volume Corrected; 10 M WBC = 10 Million White Blood Cells. Bolded numbers are significant by p-value <0.05. Half of the matrix only is presented since it is symmetric around one and correlations are shaded by the magnitude of correlation. *Spearman rank correlations are shown for 62 of 71 patients with data extracted by PET-VCAR.</p