Tumor hypoxia is associated with radiation resistance and can be longitudinally monitored by ¹⁸F-fluoromisonidazole (¹⁸F-FMISO)-PET/CT. Our study aimed at evaluating radiomics dynamics of ¹⁸F-FMISO-hypoxia imaging during chemo-radiotherapy (CRT) as predictors for treatment outcome in head-and-neck squamous cell carcinoma (HNSCC) patients. We prospectively recruited 35 HNSCC patients undergoing definitive CRT and longitudinal ¹⁸F-FMISO-PET/CT scans at weeks 0, 2 and 5 (W0/W2/W5). Patients were classified based on peritherapeutic variations of the hypoxic sub-volume (HSV) size (increasing/stable/decreasing) and location (geographically-static/geographically-dynamic) by a new objective classification parameter (CP) accounting for spatial overlap. Additionally, 130 radiomic features (RF) were extracted from HSV at W0, and their variations during CRT were quantified by relative deviations (∆_RF). Prediction of treatment outcome was considered statistically relevant after being corrected for multiple testing and confirmed for the two ¹⁸F-FMISO-PET/CT time-points and for a validation cohort. HSV decreased in 64% of patients at W2 and in 80% at W5. CP distinguished earlier disease progression (geographically-dynamic) from later disease progression (geographically-static) in both time-points and cohorts. The texture feature low grey-level zone emphasis predicted local recurrence with AUC_W2 = 0.82 and AUC_W5 = 0.81 in initial cohort (N = 25) and AUC_W2 = 0.79 and AUC_W5 = 0.80 in validation cohort. Radiomics analysis of ¹⁸F-FMISO-derived hypoxia dynamics was able to predict outcome of HNSCC patients after CRT.

Purpose: The value of O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-positron emission tomography (PET)-radiomics in the outcome assessment of patients with recurrent glioblastoma (rGBM) has not been evaluated until now. The aim of this study was to evaluate whether a prognostic model based on FET-PET radiomics features (RF) is feasible and can identify rGBM patients that would most benefit from re-irradiation. Methods: We prospectively recruited rGBM patients who underwent FET-PET before re-irradiation (GLIAA-Pilot trial, DRKS00000633). Tumor volume was delineated using a semi-automatic method with a threshold of 1.8 times the standardized-uptake-value of the background. 135 FET-RF (histogram parameters, shape and texture features) were extracted. The analysis involved the characterization of tumor and non-tumor tissue with FET-RF and the evaluation of the prognostic value of FET-RF for time-to-progression (TTP), overall survival (OS) and recurrence location (RL). Results: Thirty-two rGBM patients constituted our cohort. FET-RF discriminated significantly between tumor and non-tumor. The texture feature Small-Zone-Low-Gray-Level-Emphasis (SZLGE) showed the best performance for the prediction of TTP (p = 0.001, satisfying Bonferroni-multiple-test significance level). Additionally, two radiomics signatures could predict TTP (TTP-radiomics-signature, p = 0.001) and OS (OS-radiomics-signature, p = 0.038). SZLGE and the TTP-radiomics-signature additionally predicted RL. Specifically, high values for TTP-radiomics-signature and for SZLGE indicated not only earlier progression, but also a RL within the initial FET-PET active volume. Conclusion: Our findings suggest that FET-PET radiomics could contribute to the prognostic assessment and selection of rGBM-patients benefiting from re-irradiation. Trial registration DRKS00000633. Registered on 8th of December in 2010. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00000633.

A major source of error in quantitative PET/CT scans of lung cancer tumors is respiratory motion. Regarding the variability of PET texture features (TF), the impact of respiratory motion has not been properly studied with experimental phantoms. The primary aim of this work was to evaluate the current use of PET texture analysis for heterogeneity characterization in lesions affected by respiratory motion. Twenty-eight heterogeneous lesions were simulated by a mixture of alginate and ¹⁸ F -fluoro-2-deoxy-D-glucose (FDG). Sixteen respiratory patterns were applied. Firstly, the TF response for different heterogeneous phantoms and its robustness with respect to the segmentation method were calculated. Secondly, the variability for TF derived from PET image with (gated, G-) and without (ungated, U-) motion compensation was analyzed. Finally, TF complementarity was assessed. In the comparison of TF derived from the ideal contour with respect to TF derived from 40%-threshold and adaptive-threshold PET contours, 7/8 TF showed strong linear correlation (LC) ( p < 0.001, r > 0.75), despite a significant volume underestimation. Independence of lesion movement (LC in 100% of the combined pairs of movements, p < 0.05) was obtained for 1/8 TF with U-image (width of the volume-activity histogram, WH) and 4/8 TF with G-image (WH and energy (ENG), local-homogeneity (LH) and entropy (ENT), derived from the co-ocurrence matrix). Their variability in terms of the coefficient of variance ( C V ) resulted in C V (WH) = 0.18 on the U-image and C V (WH) = 0.24, C V (ENG) = 0.15, C V (LH) = 0.07 and C V (ENT) = 0.06 on the G-image. Apart from WH ( r > 0.9, p < 0.001), not one of these TF has shown LC with C _max . Complementarity was observed for the TF pairs: ENG–LH, CONT (contrast)–ENT and LH–ENT. In conclusion, the effect of respiratory motion should be taken into account when the heterogeneity of lung cancer is quantified on PET/CT images. Despite inaccurate volume delineation, TF derived from 40% and COA contours could be reliable for their prognostic use. The TF that exhibited simultaneous added value and independence of lesion movement were ENG and ENT computed from the G-image. Their use is therefore recommended for heterogeneity quantification of lesions affected by respiratory motion.

The aim of this study is to identify clinically relevant image feature (IF) changes during chemoradiation and evaluate their efficacy in predicting treatment response. Patients with non-small-cell lung cancer (NSCLC) were enrolled in two prospective trials (STRIPE, PET-Plan). We evaluated 48 patients who underwent static (3D) and retrospectively-respiratory-gated 4D PET/CT scans before treatment and a 3D scan during or after treatment. Our proposed method rejects IF changes due to intrinsic variability. The IF variability observed across 4D PET is employed as a patient individualized normalization factor to emphasize statistically relevant IF changes during treatment. Predictions of overall survival (OS), local recurrence (LR) and distant metastasis (DM) were evaluated. From 135 IFs, only 17 satisfied the required criteria of being normally distributed across 4D PET and robust between 3D and 4D images. Changes during treatment in the area-under-the-curve of the cumulative standard-uptake-value histogram (δAUC_CSH) within primary tumor discriminated (AUC = 0.87, Specificity = 0.78) patients with and without LR. The resulted prognostic model was validated with a different segmentation method (AUC = 0.83) and in a different patient cohort (AUC = 0.63). The quantification of tumor FDG heterogeneity by δAUC_CSH during chemoradiation correlated with the incidence of local recurrence and might be recommended for monitoring treatment response in patients with NSCLC.

In lung cancer, quantification by positron emission tomography/computed tomography (PET/CT) imaging presents challenges due to respiratory movement. Our primary aim was to study the impact of motion compensation implied by retrospectively gated (4D)-PET/CT on the variability of PET quantitative parameters. Its significance was evaluated by comparison with the variability due to (i) the voxel size in image reconstruction and (ii) the voxel size in image post-resampling. The method employed for feature extraction was chosen based on the analysis of (i) the effect of discretization of the standardized uptake value (SUV) on complementarity between texture features (TF) and conventional indices, (ii) the impact of the segmentation method on the variability of image features, and (iii) the variability of image features across the time-frame of 4D-PET. Thirty-one PET-features were involved. Three SUV discretization methods were applied: a constant width (SUV resolution) of the resampling bin (method RW), a constant number of bins (method RN) and RN on the image obtained after histogram equalization (method EqRN). The segmentation approaches evaluated were 40 % of SUV _max and the contrast oriented algorithm (COA). Parameters derived from 4D-PET images were compared with values derived from the PET image obtained for (i) the static protocol used in our clinical routine (3D) and (ii) the 3D image post-resampled to the voxel size of the 4D image and PET image derived after modifying the reconstruction of the 3D image to comprise the voxel size of the 4D image. Results showed that TF complementarity with conventional indices was sensitive to the SUV discretization method. In the comparison of COA and 40 % contours, despite the values not being interchangeable, all image features showed strong linear correlations ( r > 0.91, p ≪ 0.001 ). Across the time-frames of 4D-PET, all image features followed a normal distribution in most patients. For our patient cohort, the compensation of tumor motion did not have a significant impact on the quantitative PET parameters. The variability of PET parameters due to voxel size in image reconstruction was more significant than variability due to voxel size in image post-resampling. In conclusion, most of the parameters (apart from the contrast of neighborhood matrix) were robust to the motion compensation implied by 4D-PET/CT. The impact on parameter variability due to the voxel size in image reconstruction and in image post-resampling could not be assumed to be equivalent.

Objectives: In lung cancer, one of the main limitations for the optimal integration of the biological and anatomical information derived from Positron Emission Tomography (PET) and Computed Tomography (CT) is the time and expertise required for the evaluation of the different respiratory phases. In this study, we present two open-source models able to automatically segment lung tumors on PET and CT, with and without motion compensation. Materials and methods: This study involved time-bin gated (4D) and non-gated (3D) PET/CT images from two prospective lung cancer cohorts (Trials 108237 and 108472) and one retrospective. For model construction, the ground truth (GT) was defined by consensus of two experts, and the nnU-Net with 5-fold cross-validation was applied to 560 4D-images for PET and 100 3D-images for CT. The test sets included 270 4D- images and 19 3D-images for PET and 80 4D-images and 27 3D-images for CT, recruited at 10 different centres. Results: In the performance evaluation with the multicentre test sets, the Dice Similarity Coefficients (DSC) obtained for our PET model were DSC(4D-PET) = 0.74 ± 0.06, improving 19% relative to the DSC between experts and DSC(3D-PET) = 0.82 ± 0.11. The performance for CT was DSC(4D-CT) = 0.61 ± 0.28 and DSC(3D-CT) = 0.63 ± 0.34, improving 4% and 15% relative to DSC between experts. Conclusions: Performance evaluation demonstrated that the automatic segmentation models have the potential to achieve accuracy comparable to manual segmentation and thus hold promise for clinical application. The resulting models can be freely downloaded and employed to support the integration of 3D- or 4D- PET/CT and to facilitate the evaluation of its impact on lung cancer clinical practice. Clinical relevance statement: We provide two open-source nnU-Net models for the automatic segmentation of lung tumors on PET/CT to facilitate the optimal integration of biological and anatomical information in clinical practice. The models have superior performance compared to the variability observed in manual segmentations by the different experts for images with and without motion compensation, allowing to take advantage in the clinical practice of the more accurate and robust 4D-quantification. Key Points: Lung tumor segmentation on PET/CT imaging is limited by respiratory motion and manual delineation is time consuming and suffer from inter- and intra-variability. Our segmentation models had superior performance compared to the manual segmentations by different experts. Automating PET image segmentation allows for easier clinical implementation of biological information.