Our findings contribute to the evidence that the addition of omics in prognostic models can improve ML interpretability.

The accuracy of cardiac structure delineation has been correlated with cardiotoxicity in radiation therapy, and thus plays a significant role in treatment decisions and outcome of care. In an attempt to improve cardiac substructure contouring, two auto-segmentation approaches based on in-house models that feature atlas-based automatic contouring (ABAC) and fully convolution neural network (FCNN) have been studied. A total of 469 NRG RTOG 0617 cases with complete clinical and image data were included in the present study. CT cardiac substructures (pericardium, ventricles, and atria) from RTOG 0617 repository were independently re-contoured by experienced radiation oncologists using a consistent contouring guideline. ABAC library was created using manually contoured cardiac substructures of 100 patients. For the rest of the patients, the library was used to automatically generate cardiac contours. Similarly, CT images of 100 patients were selected as a training set to adjust the FCNN parameters, and the remaining patients' CT images were used to evaluate the model's performance. Using the Dice similarity coefficient (DSC) and Hausdorff distances (HD), the quantitative agreement of the automatically generated contours with the manually drawn contours was evaluated. For dosimetric comparison, fractional volume dose factors were calculated for all the cardiac structures. The variations in geometric contouring were then associated with dosimetric differences, making it possible to analyze toxicity. The DSC values of the ABAC contours were compared with the manual contours for pericardium and evaluated at 0.90 ± 0.014, ventricles at 0.84 ± 0.08 and atria at 0.73 ± 0.06; whereas those of FCNN were 0.93 ± 0.05 for pericardium, 0.91 ± 0.03 for ventricles and 0.81 ± 0.02 for atria. These DSC results generally indicate that only minor edits were required. The maximum HD for all structures were 28.06 ± 1.86 mm for ABAC and 21.96 ± 2.58 mm for FCNN. The relative dose volume differences, V5Gy (%), V20Gy (%), V30Gy (%), V50Gy (%) between the two models and manually delineated cardiac contours were evaluated and were consistently lower for FCNN (< 1 %). Investigations show that while ABAC achieve sufficient contouring for cardiac structures, FCNN achieved better agreement of dosimetric parameters with the manual contours, enabling better prediction of cardiac toxicity.

Patients with early stage non-small cell lung cancer (ES-NSCLC) treated with stereotactic body radiation therapy (SBRT) have excellent local control rates although they have a relatively high rate of regional and distant recurrences. Recently, patients with elevated pre-treatment (pre-RT) circulating tumor cells (CTCs) or persistently detectable post-treatment (post-RT) CTCs were found to have significantly increased risk of regional and distant recurrence outside the treatment volume. Knowledge about radiomics biomarkers associated with CTCs may have additional value in predicting these recurrences. This study aims to evaluate the predictability of radiomic phenotypes of intratumoral heterogeneity for pre- and post-RT CTCs in ES-NSCLC patients treated with SBRT. A total of 56 patients with stage I NSCLC treated with SBRT underwent 18F-FDG-PET/CT imaging pre-SBRT and post-SBRT (median, 5 months; range, 3 to 10 months). For each patient, CTCs were assessed via a telomerase-based assay before ("pre") and within 3 months after SBRT ("post"), and dichotomized at 5 and 1.3 CTCs/mL. Pre-RT, post-RT and delta radiomics features were extracted from the gross tumor volume of the original, wavelet-filtered, Laplacian of Gaussian-filtered PET/CT images, each of which included 1,562 CT and 1,548 PET radiomics features that consisted of shape, first-order, second-order, higher-order local gray-level statistics and global texture features. CT and PET radiomics features were considered different omics data types. Two (CT and PET)-block radiomics-based data integration analysis for biomarker discovery using latent components (DIABLO) was performed to seek for common information between CT and PET radiomics data types through feature selection, while discriminating CTC levels. ROC AUC value and 20-repeated 5-fold cross-validation (CV) were used to evaluate the prediction performance of the DIABLO models. CV prediction scores between one class vs the other were compared using the Wilcoxon rank sum test. For predicting pre-SBRT CTCs, a pre-SBRT radiomics-derived DIABLO model showed the CV AUC of 0.841 (p = 0.018) with two global texture features from wavelet-filtered CT and PET. For predicting post-RT CTCs, post-RT and delta radiomics-derived DIABLO models showed the CV AUCs of 0.794 (p = 0.018) with four global texture features from wavelet-filtered CT and original PET, and 0.799 (p = 0.013) with three first-order features from wavelet-filtered PET and a single second-order texture feature from wavelet-filtered CT. Radiomics signatures that reflect intratumoral anatomic and metabolic heterogeneities derived by maximizing common information between CT and PET may reveal surrogate biomarkers for pre-RT and post-RT CTCs.

PURPOSE:CD19-targeting chimeric antigen receptor T-cell (CART) therapy has emerged as a promising treatment for relapsed/refractory aggressive B-cell lymphoma (r/rABL), culminating in 2 US Food and Drug Administration-approved therapies: tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel). Following leukapheresis and in preparation for CART infusion, contemporary bridging and lymphodepletion regimens rely mostly on cytotoxic chemotherapy. Here, in a cohort of patients treated with commercial tisa-cel and axi-cel, we show that bridging-RT may offer a supplemental approach. METHODS AND MATERIALS:Thirty-one patients receiving commercial tisa-cel (n = 13) or axi-cel (n = 18) between August 2018 and February 2019 for r/rABL were retrospectively reviewed. Patients were categorized into 2 groups: (1) bridging-RT within 30 days of CART infusion or (2) nonbridging-RT (NBRT), in which patients received either remote RT greater than 30 days before CART infusion or no prior RT. RESULTS:Five patients received bridging-RT within 30 days of CART infusion. Median bridging-RT dose was 37.5 Gy and was completed a median of 13 days before infusion. No grade 3 (G3) or higher RT-toxicities occurred. No patients in the bridging-RT group experienced G3 or higher CART-related toxicities (CRS or neurotoxicity), and 23% (n = 6) and 15% (n = 4) experienced G3-5 CRS and G3-5 neurotoxicity in the NBRT group, respectively. Overall treatment response in the bridging-RT and NBRT groups was 80% and 64%, respectively. The axi-cel CART product was associated with CRS (odds ratio [OR] = 26.67, P = .001) and CRS correlated with neurotoxicity (OR = 12.22, P = .028). There was a trend toward an association for CRS with metabolic tumor volume (OR = 1.06/mL, P = .141) and TLG (OR = 1.01/mL x standard uptake value, P = .099). CONCLUSIONS:Bridging-RT before commercial CART does not appear to increase the risk for CART-related toxicities or negatively affect outcomes in r/rABL patients. No G3 or higher RT-toxicities occurred in this series. Pretreatment metabolic tumor burden may be associated with CART-associated CRS; however, larger patient numbers are required to elucidate significant associations. Future work to prospectively assess the value of bridging-RT is warranted.

Purpose: The main objective of the present study was to integrate F-18-FDG-PET/CT radiomics with multiblock discriminant analysis for predicting circulating tumor cells (CTCs) in early-stage non-small cell lung cancer (ES-NSCLC) treated with stereotactic body radiation therapy (SBRT). Methods: Fifty-six patients with stage I NSCLC treated with SBRT underwent F-18-FDG-PET/CT imaging pre-SBRT and post-SBRT (median, 5 months; range, 3-10 months). CTCs were assessed via a telomerase-based assay before and within 3 months after SBRT and dichotomized at 5 and 1.3 CTCs/ mL. Pre-SBRT, post-SBRT, and delta PET/CT radiomics features (n Z 1548 x 3/1562 x 3) were extracted from gross tumor volume. Seven feature blocks were constructed including clinical parameters (n Z 12). Multiblock data integration was performed using block sparse partial least squares- discriminant analysis (sPLS-DA) referred to as Data Integration Analysis for Biomarker Discovery Using Latent Components (DIABLO) for identifying key signatures by maximizing common information between different feature blocks while discriminating CTC levels. Optimal input blocks were identified using a pairwise combination method. DIABLO performance for predicting pre-SBRT and post-SBRT CTCs was evaluated using combined AUC (area under the curve, averaged across different blocks) analysis with 20 x 5-fold cross-validation (CV) and compared with that of concatenation-based sPLS-DA that consisted of combining all features into 1 block. CV prediction scores between 1 class versus the other were compared using the Wilcoxon rank sum test. Results: For predicting pre-SBRT CTCs, DIABLO achieved the best performance with combined pre-SBRT PET radiomics and clinical feature blocks, showing CVAUC of 0.875 (P = .009). For predicting post-SBRT CTCs, DIABLO achieved the best performance with combined post-SBRT CT and delta CT radiomics feature blocks, showing CV AUCs of 0.883 (P = .001). In contrast, all single-block sPLS-DA models could not attain CV AUCs higher than 0.7. Conclusions: Multiblock integration with discriminant analysis of F-18-FDG-PET/CT radiomics has the potential for predicting pre-SBRT and post-SBRT CTCs. Radiomics and CTC analysis may complement and together help guide the subsequent management of patients with ES-NSCLC. (C) 2021 Elsevier Inc. All rights reserved.

Background: The Compton camera is increasingly becoming the subject of investigation for possible implementa- tion in nuclear medical imaging. It is likely to have advantages over Anger camera in medical imaging. However, very little has been done to characterize its performance for specific medical imaging techniques. There is therefore a need to fill in the gaps in knowledge relating to realistic evaluation of the viability of the camera for nuclear medical imaging.

We present a study on the effects of detector material, radionuclide source and source position on the Compton camera aimed at realistic characterization of the camera's performance in multitracer imaging as it relates to brain imaging. The GEANT4 Monte Carlo simulation software was used to model the physics of radiation transport and interactions with matter. Silicon (Si) and germanium (Ge) detectors were evaluated for the scatterer, and cadmium zinc telluride (CZT) and cerium-doped lanthanum bromide (LaBr(3):Ce) were considered for the absorber. Image quality analyses suggest that the use of Si as the scatterer and CZT as the absorber would be preferred. Nevertheless, two simulated Compton camera models (Si/CZT and Si/LaBr(3):Ce Compton cameras) that are considered in this study demonstrated good capabilities for multitracer imaging in that four radiotracers within the nuclear medicine energy range are clearly visualized by the cameras. It is found however that beyond a range difference of about 2 cm for (113m)In and (18)F radiotracers in a brain phantom, there may be a need to rotate the Compton camera for efficient brain imaging.

We study the performance of a Si/LaBr3:Ce Compton camera model for scintimammography, and compare it with a Si/NaI(Tl) model of similar geometry. The GEANT4 simulation toolkit was used to study the behaviour of the cameras at 511keV. Certain simulation steps, such as the modelling of radionuclide decay times, scintillation photon transport and interactions with photomultipliers, as well as detector dead time corrections were included to make the modelling of the cameras more realistic than previous studies. The Si/LaBr3:Ce Compton camera shows superior efficiency of 2.0×10−3 and resolution of 5.3mm over the Si/NaI(Tl) Compton camera model which has the efficiency of 1.6×10−3 and resolution of 6.9mm at a source-to-scatterer distance of interest, 2.5cm. A similar result sequence is obtained for two breast tumours of 5mm diameter embedded in the medial region of an average-size breast phantom of thickness 5cm. Notably, the signal-to-noise ratios (SNR) obtained for the Si/LaBr3:Ce camera are 9.7 and 3.4 for tumour/background radiation uptakes of 10:1 and 6:1, whereas 6.8 and 2.4 were obtained for the Si/NaI(Tl) camera model for the same tumour/background radiation uptakes respectively. It is therefore envisioned that with lower cost, LaBr3:Ce could replace NaI(Tl) as the Compton camera absorber.

We present a quantitative study on the performance of cadmium zinc telluride (CZT), thallium-doped sodium iodide (NaI(Tl)) and germanium (Ge) detectors as potential Compton camera absorbers. The GEANT4 toolkit was used to model the performance of these materials over the nuclear medicine energy range. CZT and Ge demonstrate the highest and lowest efficiencies respectively. Although the best spatial resolution was attained for Ge, its lowest ratio of single photoelectric to multiple interactions suggests that it is most prone to inter-pixel cross-talk. In contrast, CZT, which demonstrates the least positioning error due to multiple interactions, has a comparable spatial resolution with Ge. Therefore, we modelled a Compton camera system based on silicon (Si) and CZT as the scatterer and absorber respectively. The effects of the detector parameters of our proposed system on image resolution were evaluated and our results show good agreement with previous studies. Interestingly, spatial resolution which accounted for the least image degradation at 140.5 keV became the dominant degrading factor at 511 keV, indicating that the absorber parameters play some key roles at higher energies. The results of this study have validated the predictions by An et al. which state that the use of a higher energy gamma source together with reduction of the absorber segmentation to sub-millimetre could achieve the image resolution of 5 mm required in medical imaging.

A Monte Carlo approach was used to study the effects of Doppler energy broadening on Compton camera performance. The GEANT4 simulation toolkit was used to model the radiation transport and interactions with matter in a simulated Compton camera. The low energy electromagnetic physics model of GEANT4 incorporating Doppler broadening developed by Longo et al. was used in the simulations. The camera had a 9 × 9 cm scatterer and a 10 × 10 cm absorber with a scatterer to-absorber separation of 5 cm. Modelling was done such that only the effects of Doppler broadening were taken into consideration and effects of scatterer and absorber thickness and pixelation were not taken into account, thus a 'perfect' Compton camera was assumed. Scatterer materials were either silicon or germanium and the absorber material was cadmium zinc telluride. Simulations were done for point sources 10 cm in front of the scatterer. The results of the simulations validated the use of the low energy model of GEANT4. As expected, Doppler broadening was found to degrade the Compton camera imaging resolution. For a 140.5 keV source the resulting full-width-at-half-maximum (FWHM) of the point source image without accounting for Doppler broadening and using a silicon scatterer was 0.58 mm. This degraded to 7.1 mm when Doppler broadening was introduced and degraded further to 12.3 mm when a germanium scatterer was used instead of silicon. But for a 511 keV source, the FWHM was better than for a 140 keV source. The FWHM improved to 2.4 mm for a silicon scatterer and 4.6 mm for a germanium scatterer. Our result for silicon at 140.5 keV is in very good agreement with that published by An et al.

We study the effects of energy threshold and dead time on the sensitivity and image resolution of the Compton camera. The simulation model includes the decay times, detection time jitters, energy threshold and detector dead time as well as basic detector parameters such as Doppler broadening, energy resolution and finite detector resolution. The GEANT4 toolkit was used to model the camera geometry and performance for two common nuclear medicine energies that correspond to 99mTc (140.5keV) and 18F (511keV) radiotracers. Results without the energy threshold and time effects show good agreement with previous studies. For 140.5keV, the inclusion of energy threshold improved image resolution from 10.7 to 9.5mm with a source-to-detector distance of 5cm, while the inclusion of time effects made no further difference on resolution. The energy threshold reduced the sensitivity by 48%, and subsequent inclusion of time effects further reduced the sensitivity by 17%. At 511keV, the application of energy threshold reduced the sensitivity by 6%, while the time effects dominated count rate losses with further reduction of 13%. However, the inclusion of the two effects had negligible impact on the resolution.

Thermoluminescent dosemeters (TLDs) have been used to measure the entrance surface doses (ESDs) of patients undergoing pelvis, abdomen and lumbar spine diagnostic X-ray examinations in Nigeria. A total of three public hospitals and 171 patients were included in this investigation. The ages of the patients involved were from 40 years to 85 years, while their weights ranged from 64 kg to 73 kg. Mean, median, first and third quartiles of ESDs are reported. The results showed that in most cases, for each of the examinations, the individual ESD values are found to be comparable with, and higher than, those from Ghana and Tanzania, respectively. The mean ESD values are also found to be within the range of mean ESD values that have been previously been reported from countries outside Africa. When compared with the European Community (EC) reference values, the mean ESDs were found to be below the reference values in only two of the hospitals. The ranges found in this work are high and this indicates more attention needs to be given to X-ray facilities in the country. This also suggests that radiographic departments need to review their radiographic practices in order to bring their doses to optimum levels. Effective doses were also calculated from the ESD values. The mean effective doses were found to be generally low when compared with those found in the literature from other countries including two African countries. The radiographic parameters used for all the patients were also compared with the European criteria. It is recommended that the tube filtration at one hospital be increased. The importance of good regulatory activities and trained personnel is stressed in this work. Apart from the fact that the data provided in this work will be useful for the formulation of national guidance levels, they also provide patient dosimetry information on healthcare level IV countries.