PET/CT Scanner and Bone Marrow Biopsy in Detection of Bone Marrow Involvement in Diffuse Large B-Cell Lymphoma.

Evaluation of bone marrow involvement (BMI) is paramount in diffuse large B-cell lymphoma (DLBCL) for prognostic and therapeutic reasons. PET/CT scanner (PET) is now a routine examination for the staging of DLBCL with prognostic and therapeutic implications. This study evaluates the role of PET for detecting marrow involvement compared to bone marrow biopsy (BMB). This monocentric study included 54 patients diagnosed with DLBCL between 2009 and 2013 and who had FDG PET/CT in a pre-treatment setting. A correlation analysis of the detection of BMI by PET and BMB was performed. A prognostic evaluation of BMI by BMB and/or PET/CT and correlation with an overall 2-year survival were analyzed. PET was more sensitive for the detection of BMI than BMB (92.3% vs. 38.5%). It can be considered a discriminatory Pre-BMB test with a negative predictive value of 97.6%. In addition, BMI by PET had a prognostic value with strong correlation with progression-free survival (PFS) (HR = 3.81; p = 0.013) and overall survival (OS) (HR = 4.12; p = 0.03) while the BMB had not. PET shows superior performance to the BMB for the detection of marrow involvement in DLBCL. It may be considered as the first line examination of bone marrow instead of the biopsy

Immune-Related Adverse Events Induced by Immune Checkpoint Inhibitors and CAR-T Cell Therapy: A Comprehensive Imaging-Based Review.

Immunotherapy has revolutionized oncology care, improving patient outcomes in several cancers. However, these therapies are also associated with typical immune-related adverse events due to the enhanced inflammatory and immune response. These toxicities can arise at any time during treatment but are more frequent within the first few months. Any organ and tissue can be affected, ranging from mild to life-threatening. While some manifestations are common and more often mild, such as dermatitis and colitis, others are rarer and more severe, such as myocarditis. Management depends on the severity, with treatment being held for >grade 2 toxicities. Steroids are used in more severe cases, and immunosuppressive treatment may be considered for non-responsive toxicities, along with specific organ support. A multidisciplinary approach is mandatory for prompt identification and management. The diagnosis is primarily of exclusion. It often relies on imaging features, and, when possible, cytologic and/or pathological analyses are performed for confirmation. In case of clinical suspicion, imaging is required to assess the presence, extent, and features of abnormalities and to evoke and rule out differential diagnoses. This imaging-based review illustrates the diverse system-specific toxicities associated with immune checkpoint inhibitors and chimeric antigen receptor T-cells with a multidisciplinary perspective. Clinical characteristics, imaging features, cytological and histological patterns, as well as the management approach, are presented with insights into radiological tips to distinguish these toxicities from the most important differential diagnoses and mimickers-including tumor progression, pseudoprogression, inflammation, and infection-to guide imaging and clinical specialists in the pathway of diagnosing immune-related adverse events

Signature of survival: a ¹⁸F-FDG PET based whole-liver radiomic analysis predicts survival after ⁹⁰Y-TARE for hepatocellular carcinoma.

To generate a predictive whole-liver radiomics scoring system for progression-free survival (PFS) and overall survival (OS) in patients undergoing transarterial radioembolization using Yttrium-90 ( <sup>90</sup> Y-TARE) for unresectable hepatocellular carcinoma (uHCC). The generated pPET-RadScores were significantly correlated with survival for PFS (median of 11.4 mo [95% confidence interval CI: 6.3-16.5 mo] in low-risk group [PFS-pPET-RadScore < 0.09] vs. 4.0 mo [95% CI: 2.3-5.7 mo] in high-risk group [PFS-pPET-RadScore > 0.09]; <i>P</i> = 0.0004) and OS (median of 20.3 mo [95% CI: 5.7-35 mo] in low-risk group [OS-pPET-RadScore < 0.11] vs. 7.7 mo [95% CI: 6.0-9.5 mo] in high-risk group [OS-pPET-RadScore > 0.11]; <i>P</i> = 0.007). The multivariate analysis confirmed PFS-pPET-RadScore ( <i>P</i> = 0.006) and OS-pPET-RadScore ( <i>P</i> = 0.001) as independent negative predictors. Pretreatment <sup>18</sup> F-FDG PET whole-liver radiomics signature appears as an independent negative predictor for PFS and OS in patients undergoing <sup>90</sup> Y-TARE for uHCC. Pretreatment <sup>18</sup> F-FDG PET of 47 consecutive patients undergoing <sup>90</sup> Y-TARE for uHCC (31 resin spheres, 16 glass spheres) were retrospectively analyzed. For each patient, based on PET radiomics signature from whole-liver semi-automatic segmentation, PFS and OS predictive PET-radiomics scores (pPET-RadScores) were obtained using LASSO Cox regression. Using X-tile software, the optimal score to predict PFS (PFS-pPET-RadScore) and OS (OS-pPET-RadScore) served as cutoff to separate high and low-risk patients. Survival curves were estimated using the Kaplan-Meier method. The prognostic value of PFS and OS-pPET-RadScore, Barcelona-Clinic Liver Cancer staging system and serum alpha-fetoprotein level was analyzed to predict PFS and OS in multivariate analysis

Automatic Head and Neck Tumor segmentation and outcome prediction relying on FDG-PET/CT images: Findings from the second edition of the HECKTOR challenge.

By focusing on metabolic and morphological tissue properties respectively, FluoroDeoxyGlucose (FDG)-Positron Emission Tomography (PET) and Computed Tomography (CT) modalities include complementary and synergistic information for cancerous lesion delineation and characterization (e.g. for outcome prediction), in addition to usual clinical variables. This is especially true in Head and Neck Cancer (HNC). The goal of the HEad and neCK TumOR segmentation and outcome prediction (HECKTOR) challenge was to develop and compare modern image analysis methods to best extract and leverage this information automatically. We present here the post-analysis of HECKTOR 2nd edition, at the 24th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2021. The scope of the challenge was substantially expanded compared to the first edition, by providing a larger population (adding patients from a new clinical center) and proposing an additional task to the challengers, namely the prediction of Progression-Free Survival (PFS). To this end, the participants were given access to a training set of 224 cases from 5 different centers, each with a pre-treatment FDG-PET/CT scan and clinical variables. Their methods were subsequently evaluated on a held-out test set of 101 cases from two centers. For the segmentation task (Task 1), the ranking was based on a Borda counting of their ranks according to two metrics: mean Dice Similarity Coefficient (DSC) and median Hausdorff Distance at 95th percentile (HD95). For the PFS prediction task, challengers could use the tumor contours provided by experts (Task 3) or rely on their own (Task 2). The ranking was obtained according to the Concordance index (C-index) calculated on the predicted risk scores. A total of 103 teams registered for the challenge, for a total of 448 submissions and 29 papers. The best method in the segmentation task obtained an average DSC of 0.759, and the best predictions of PFS obtained a C-index of 0.717 (without relying on the provided contours) and 0.698 (using the expert contours). An interesting finding was that best PFS predictions were reached by relying on DL approaches (with or without explicit tumor segmentation, 4 out of the 5 best ranked) compared to standard radiomics methods using handcrafted features extracted from delineated tumors, and by exploiting alternative tumor contours (automated and/or larger volumes encompassing surrounding tissues) rather than relying on the expert contours. This second edition of the challenge confirmed the promising performance of fully automated primary tumor delineation in PET/CT images of HNC patients, although there is still a margin for improvement in some difficult cases. For the first time, the prediction of outcome was also addressed and the best methods reached relatively good performance (C-index above 0.7). Both results constitute another step forward toward large-scale outcome prediction studies in HNC

68Ga-NODAGA-RGDyK PET/CT Imaging in Esophageal Cancer: First-in-Human Imaging.

Ga-NODAGA-RGDyK(cyclic) and FDG PET/CT were performed in a 39-year-old man for the work-up of a moderately differentiated carcinoma of the gastro-esophageal junction within a clinical study protocol. Although FDG PET images showed intense, diffuse hypermetabolic lesion activity, NODAGA-RGDyK illustrated the neo-angiogenesis process with tracer uptake clearly localized in non-FDG-avid perilesional structures. Neo-angiogenesis is characterized by ανβ3 integrin expression at the lesion surface of newly formed vessels. This case supports evidence that angiogenesis imaging might therefore be a crucial step in early disease identification and localization, metastatization potential, and in monitoring the efficacy of antiangiogenic therapies

Diagnostic Performance of PET or PET/CT Using ¹⁸F-FDG Labeled White Blood Cells in Infectious Diseases: A Systematic Review and a Bivariate Meta-Analysis.

Diagnostic performance of positron emission tomography using white blood cells labeled with fluorine-18-fluorodeoxyglucose ( <sup>18</sup> F-FDG-WBC PET or PET/CT) in patients with suspicious infectious diseases has been evaluated in several studies; however, there is no consensus about the diagnostic accuracy of this method. Therefore, a systematic review and meta-analysis was carried out on this topic. A comprehensive computer literature search screening PubMed/MEDLINE, Embase and Cochrane library databases through March 2019 was performed. Pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), and diagnostic odds ratio (DOR) of <sup>18</sup> F-FDG-WBC PET or PET/CT in patients with infectious diseases were calculated. Eight studies on the use of <sup>18</sup> F-FDG-WBC PET or PET/CT in suspicious infectious diseases were discussed in the systematic review. The meta-analysis of seven studies (236 patients) provided these pooled results on a per patient-based analysis: sensitivity was 86.3% [95% confidence interval (95%CI) 75-92.9%], specificity 92% (95%CI 79.8-97.1%), LR+ 6.6 (95%CI: 3.1-14.1), LR- 0.2 (95%CI: 0.12-0.33), DOR 43.5 (95%CI: 12.2-155). A statistically significant heterogeneity was not detected. Despite limited literature data, <sup>18</sup> F-FDG-WBC PET or PET/CT demonstrated a good diagnostic accuracy for the diagnosis of infectious diseases; nevertheless, larger studies are needed

17 ways to say yes:Toward nuanced tone of voice in AAC and speech technology

People with complex communication needs who use speech-generating devices have very little expressive control over their tone of voice. Despite its importance in human interaction, the issue of tone of voice remains all but absent from AAC research and development however. In this paper, we describe three interdisciplinary projects, past, present and future: The critical design collection Six Speaking Chairs has provoked deeper discussion and inspired a social model of tone of voice; the speculative concept Speech Hedge illustrates challenges and opportunities in designing more expressive user interfaces; the pilot project Tonetable could enable participatory research and seed a research network around tone of voice. We speculate that more radical interactions might expand frontiers of AAC and disrupt speech technology as a whole

The Term Structure of Interest Rates and its Impact on the Liability Adequacy Test for Insurance Companies in Brazil

The Brazilian regulation for applying the Liability Adequacy Test (LAT) to technical provisions in insurance companies requires that the current estimate is discounted by a term structure of interest rates (hereafter TSIR). This article aims to analyze the LAT results, derived from the use of various models to build the TSIR: the cubic spline interpolation technique, Svensson's model (adopted by the regulator) and Vasicek's model. In order to achieve the objective proposed, the exchange rates of BM&FBOVESPA trading days were used to model the ETTJ and, consequently, to discount the cash flow of the insurance company. The results indicate that: (i) LAT is sensitive to the choice of the model used to build the TSIR; (ii) this sensitivity increases with cash flow longevity; (iii) the adoption of an ultimate forward rate (UFR) for the Brazilian insurance market should be evaluated by the regulator, in order to stabilize the trajectory of the yield curve at longer maturities. The technical provision is among the main solvency items of insurance companies and the LAT result is a significant indicator of the quality of this provision, as this evaluates its sufficiency or insufficiency. Thus, this article bridges a gap in the Brazilian actuarial literature, introducing the main methodologies available for modeling the yield curve and a practical application to analyze the impact of its choice on LAT.</p