Baseline PET radiomics outperforms the IPI risk score for prediction of outcome in diffuse large B-cell lymphoma.

The objective of this study is to externally validate the clinical positron emission tomography (PET) model developed in the HOVON-84 trial and to compare the model performance of our clinical PET model using the international prognostic index (IPI). In total, 1195 patients with diffuse large B-cell lymphoma (DLBCL) were included in the study. Data of 887 patients from 6 studies were used as external validation data sets. The primary outcomes were 2-year progression-free survival (PFS) and 2-year time to progression (TTP). The metabolic tumor volume (MTV), maximum distance between the largest lesion and another lesion (Dmaxbulk), and peak standardized uptake value (SUVpeak) were extracted. The predictive values of the IPI and clinical PET model (MTV, Dmaxbulk, SUVpeak, performance status, and age) were tested. Model performance was assessed using the area under the curve (AUC), and diagnostic performance, using the positive predictive value (PPV). The IPI yielded an AUC of 0.62. The clinical PET model yielded a significantly higher AUC of 0.71 (P < .001). Patients with high-risk IPI had a 2-year PFS of 61.4% vs 51.9% for those with high-risk clinical PET, with an increase in PPV from 35.5% to 49.1%, respectively. A total of 66.4% of patients with high-risk IPI were free from progression or relapse vs 55.5% of patients with high-risk clinical PET scores, with an increased PPV from 33.7% to 44.6%, respectively. The clinical PET model remained predictive of outcome in 6 independent first-line DLBCL studies, and had higher model performance than the currently used IPI in all studies.

Cost-Effectiveness of Shortening Treatment Duration Based on Interim PET Outcome in Patients With Diffuse Large B-cell Lymphoma.

BACKGROUND: Guideline recommendations for diffuse large-B-cell lymphoma (DLBCL) treatment are shifting from long to short treatment duration, although it is still unclear whether shortening treatment duration does not cause any harm. As interim PET (I-PET) has high negative predictive value for progression, we evaluated the cost-effectiveness of shortening treatment duration dependent on I-PET result. MATERIALS AND METHODS: We developed a Markov cohort model using the PET Re-Analysis (PETRA) database to evaluate a long treatment duration (LTD) strategy, ie 8x R-CHOP or 6x R-CHOP plus 2 R, and a short treatment duration (STD) strategy, ie 6x R-CHOP. Strategies were evaluated separately in I-PET2 positive and I-PET2 negative patients. Outcomes included total costs and quality-adjusted life-years (QALYs) per patient (pp) from a societal perspective. Net monetary benefit (NMB) per strategy was calculated using a willingness-to-pay threshold of €50,000/QALY. Robustness of model predictions was assessed in sensitivity analyses. RESULTS: In I-PET2 positive patients, shortening treatment duration led to 50.4 additional deaths per 1000 patients. The STD strategy was less effective (-0.161 [95%CI: -0.343;0.028] QALYs pp) and less costly (-€2768 [95%CI: -€8420;€1105] pp). Shortening treatment duration was not cost-effective (incremental NMB -€5281). In I-PET2 negative patients, shortening treatment duration led to 5.0 additional deaths per 1000 patients and a minor difference in effectiveness (-0.007 [95%CI: -0.136;0.140] QALY pp). The STD strategy was less costly (-€5807 [95%CI: -€10,724;-€2685] pp) and led to an incremental NMB of €5449, indicating that it is cost-effective to shorten treatment duration. Robustness of these findings was underpinned by deterministic and probabilistic sensitivity analyses. CONCLUSION: Treatment duration should not be shortened in I-PET2 positive patients whereas it is cost-effective to shorten treatment duration in I-PET2 negative patients.

Optimal timing and criteria of interim PET in DLBCL: a comparative study of 1692 patients.

Interim 18F-fluorodeoxyglucose positron emission tomography (Interim-18F-FDG-PET, hereafter I-PET) has the potential to guide treatment of patients with diffuse large B-cell lymphoma (DLBCL) if the prognostic value is known. The aim of this study was to determine the optimal timing and response criteria for evaluating prognosis with I-PET in DLBCL. Individual patient data from 1692 patients with de novo DLBCL were combined and scans were harmonized. I-PET was performed at various time points during treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Scans were interpreted using the Deauville score (DS) and change in maximum standardized uptake value (ΔSUVmax). Multilevel Cox proportional hazards models corrected for International Prognostic Index (IPI) score were used to study the effects of timing and response criteria on 2-year progression-free survival (PFS). I-PET after 2 cycles (I-PET2) and I-PET4 significantly discriminated good responders from poor responders, with the highest hazard ratios (HRs) for I-PET4. Multivariable HRs for a PET-positive result at I-PET2 and I-PET4 were 1.71 and 2.95 using DS4-5, 4.91 and 6.20 using DS5, and 2.93 and 4.65 using ΔSUVmax, respectively. ΔSUVmax identified a larger proportion of poor responders than DS5 did. For all criteria, the negative predictive value was >80%, and positive predictive values ranged from 30% to 70% at I-PET2 and I-PET4. Unlike I-PET1, I-PET3 discriminated good responders from poor responders using DS4-5 and DS5 thresholds (HRs, 2.94 and 4.67, respectively). I-PET2 and I-PET4 predict good response equally during R-CHOP therapy in DLBCL. Optimal timing and response criteria depend on the clinical context. Good response at I-PET2 is suggested for de-escalation trials, and poor response using ΔSUVmax at I-PET4 is suggested for randomized trials that are evaluating new therapies.

EFSA's OpenFoodTox: An open source toxicological database on chemicals in food and feed and its future developments.

Since its creation in 2002, the European Food Safety Authority (EFSA) has produced risk assessments for over 5000 substances in >2000 Scientific Opinions, Statements and Conclusions through the work of its Scientific Panels, Units and Scientific Committee. OpenFoodTox is an open source toxicological database, available both for download and data visualisation which provides data for all substances evaluated by EFSA including substance characterisation, links to EFSA's outputs, applicable legislations regulations, and a summary of hazard identification and hazard characterisation data for human health, animal health and ecological assessments. The database has been structured using OECD harmonised templates for reporting chemical test summaries (OHTs) to facilitate data sharing with stakeholders with an interest in chemical risk assessment, such as sister agencies, international scientific advisory bodies, and others. This manuscript provides a description of OpenFoodTox including data model, content and tools to download and search the database. Examples of applications of OpenFoodTox in chemical risk assessment are discussed including new quantitative structure-activity relationship (QSAR) models, integration into tools (OECD QSAR Toolbox and AMBIT-2.0), assessment of environmental footprints and testing of threshold of toxicological concern (TTC) values for food related compounds. Finally, future developments for OpenFoodTox 2.0 include the integration of new properties, such as physico-chemical properties, exposure data, toxicokinetic information; and the future integration within in silico modelling platforms such as QSAR models and physiologically-based kinetic models. Such structured in vivo, in vitro and in silico hazard data provide different lines of evidence which can be assembled, weighed and integrated using harmonised Weight of Evidence approaches to support the use of New Approach Methodologies (NAMs) in chemical risk assessment and the reduction of animal testing.

FNA indication according to ACR-TIRADS, EU-TIRADS and K-TIRADS in thyroid incidentalomas at 18F-FDG PET/CT.

OBJECTIVE: Focal thyroid incidentaloma (TI) occurs in a 2% of 18F-FDG PET/CT and about one-third of TIs is cancer. Due to the lack of evidence on the optimal management of TI, current guidelines suggest performing fine-needle aspiration cytology (FNA). The study aim was to evaluate the reliability of ACR-TIRADS, EU-TIRADS, and K-TIRADS in indicating FNA in TIs. DESIGN: We retrospectively reviewed 18F-FDG PET/CT TIs recorded during the period 2016-2019. Enrolled were TIs with histologic outcome and autonomous nodules. Cases with uncertain matching between 18F-FDG PET/CT, US/scintiscan and histology were excluded. RESULTS: Eighty TIs at 18F-FDG PET/CT (median size 17 mm, median SUVmax 7.85) were included; a 26.2% was cancer. The percentage of nodules classified as high risk according to ACR-TIRADS, EU-TIRADS, and K-TIRADS was 20%, 30%, and 29.8%, respectively. The cancer prevalence in high-risk class was 56.2%, 66.7%, and 65.2% in ACR-TIRADS, EU-TIRADS, and K-TIRADS, respectively. ACR-TIRADS had the lowest number of cases with FNA indication (48%) and the K-TIRADS, the highest one (75%). Evaluating the reliability of the three systems in indicating FNA, we found a 100% sensitivity and NPV for EU-TIRADS and K-TIRADS; while all the three systems showed poor specificity and PPV. CONCLUSION: All TIRADSs were reliable to stratify the risk of cancer in focal TI. Comparing their reliability in indicating FNA, we found a good performance of EU-TIRADS and K-TIRADS. Considering the high cancer percentage expected in this setting of patients, those TIRADS with higher propensity to indicate FNA should be preferred.

18F-FDG-PET/CT Imaging in Advanced Glottic Cancer: A Tool for Clinical Decision in Comparison with Conventional Imaging.

This study assessed the role of 18F-FDG PET-CT (PET/CT) to detect the cartilage and paraglottic infiltration in advanced glottic cancer comparing the results with those of conventional imaging (CI) (contrast-enhanced computed tomography and/or magnetic resonance). In addition, we assessed the prognostic value of quantitative parameters, measured on baseline PET/CT, in terms of event-free survival (EFS) and overall survival (OS). We retrospectively analyzed 27 patients with glottic squamous cell carcinoma stage III and IVA, treated in our institute between 2010 and 2016, comparing PET/CT, performed for staging and radiotherapy planning, and CI findings. Cohen's K was used to compare concordance between PET/CT and CI. Imaging findings were correlated with endoscopic evaluation and histological reports (gold standard (GS)). All lesions shown by CI were also detected by PET/CT imaging, and in 5 cases, a better definition of local infiltration was achieved with PET/CT than CI (5 CT). Sensitivity, specificity, and accuracy of PET/CT and CT were 95%, 86%, and 93% and 70%, 86%, and 74% for, respectively. MRI showed sensitivity and specificity of 100%. One false-negative (FN) cases and 1 false-positive (FP) case were observed with PET/CT with no difference compared to MRI (10 cases). Six FN cases and 1 FP case were observed with CT. Cohen's K was 0.60 (PET vs. CI) and 0.80 (PET vs. GS). Patients were followed-up for at least 24 months to calculate EFS and OS. 13 local recurrence and 7 deaths were recorded. Among quantitative PET parameters, baseline MTV was the most powerful predictor of outcome. Our data suggest a reliable sensitivity and accuracy of PET/CT in the evaluation of local extension, proving a useful method for initial local staging in addition to the well-established role in lymph-node and distant sites assessment. Furthermore, pretreatment MTV provides better prognostic information than other PET/CT parameters.

Additional value of integrated 18F-choline PET/4D contrast-enhanced CT in the localization of hyperfunctioning parathyroid glands and correlation with molecular profile.

PURPOSE: The localization of hyperfunctioning parathyroid gland(s) (HPTG) in patients with primary hyperparathyroidism (PHPT) with negative or inconclusive first-line imaging is a significant challenge. This study aimed to evaluate the role of integrated 18F-choline PET/4D contrast-enhanced computed tomography (4DCeCT) in these patients, compare its detection rate and sensitivity with those of 18F-choline PET/CT and (4DCeCT), and analyse the association between choline metabolism and morphological, biochemical and molecular parameters of HPTG. METHODS: We prospectively enrolled 44 PHPT patients with negative or inconclusive first-line imaging. 18F-Choline PET/CT and 4DCeCT were performed at the same time, and integrated 18F-choline PET/4DCeCT images were obtained after coregistration. Experienced physicians examined the images. The SUVratio and degree of contrast enhancement were recorded for each positive finding. Histopathology, laboratory and multidisciplinary follow-up were used as the standard of reference. Both the detection rates and sensitivities of the three imaging modalities were calculated retrospectively. Immunohistochemistry was performed to evaluate the molecular profile of HPTGs. RESULTS: 18F-Choline PET/4DCeCT was positive in 32 of 44 patients with PHPT (detection rate 72.7%), and 31 of 31 surgically treated patients (sensitivity 100%). These results were significantly (p < 0.05) better than those of 18F-choline PET/CT (56.8% and 80%, respectively) and those of 4DCeCT (54.5 and 74%, respectively). A significant correlation between SUV and calcium level was found. In a multivariate analysis, only calcium level was significantly associated with 18F-choline PET/4DCeCT findings. SUVratio and Ki67 expression were significantly correlated. CONCLUSION: Integrated 18F-choline PET/4DCeCT should be considered as an effective tool to detect PHPT in patients with negative or inconclusive first-line imaging. Choline metabolism is correlated with both calcium level and Ki67 expression in HPTG.

High-sensitive basal serum thyroglobulin 6-12 months after thyroid ablation is strongly associated with early response to therapy and event-free survival in patients with low-to-intermediate risk differentiated thyroid carcinomas.

OBJECTIVE: High-sensitive thyroglobulin assays (hsTg) has decreased the need for stimulated Tg measurements in patients with differentiated thyroid carcinoma (DTC). However, multiple assays analyzing the same samples may report different values. Accordingly, appropriate assay-specific cut-off levels should be selected in representative patient series. Here, we evaluate the role of a new hsTg assay in low-to-intermediate risk DTC patients and select appropriate assay-specific clinical cut-off limits. DESIGN: This was a retrospective study. The response to treatment was assessed according to ATA. METHODS: Patients with low-to-intermediate risk DTC treated and regularly followed-up in our thyroid center. Tg was measured on the Kryptor Compact Plus Instrument (BRAHMS Thermo Fisher Scientific). RESULTS: The study series comprised 201 DTC patients and excellent response (ER) was demonstrated in 184 (91.5%). Optimized threshold of basal Tg (onT4-Tg) measured 6-12 months after initial treatment was set by ROC curves analysis at 0.28 ng/mL. Having onT4-Tg <0.28 ng/mL at 6-12 months after treatment was associated with longer disease-free survival of Kaplan-Meier (P < 0.001), ER at early follow-up (odds ratio (OR): 165, P < 0.001) and absence of relapse during follow-up (OR: 328, P = 0.0001). CONCLUSIONS: Patients with low- and intermediate-risk DTC could be considered cured when they have onT4-Tg levels <0.28 ng/mL coupled with negative imaging at their first post-ablation visit.

Pancreatic atypical mycobacteriosis evaluated by 18F-FDG-PET/CT / Micobacteriosis atípica pancreática evaluada con 18F-FDG PET/TC

No disponible

Molecular imaging with (99m)Tc-MIBI and molecular testing for mutations in differentiating benign from malignant follicular neoplasm: a prospective comparison.

PURPOSE: To compare mutation analysis of cytology specimens and (99m)Tc-MIBI thyroid scintigraphy for differentiating benign from malignant thyroid nodules in patients with a cytological reading of follicular neoplasm. METHODS: Patients ≥18 years of age with a solitary hypofunctioning thyroid nodule (≥10 mm), normal thyrotropin and calcitonin levels, and a cytological diagnosis of follicular neoplasm were prospectively enrolled. Mutation analysis and (99m)Tc-MIBI scintigraphy were performed and patients were subsequently operated on to confirm or exclude a malignant lesion. Mutations for KRAS, HRAS and NRAS and for BRAF and translocations of PAX8/PPARγ, RET/PTC1 and RET/PTC3 were investigated. Static thyroid scintigraphic images were acquired 10 and 60 min after intravenous injection of 200 MBq of (99m)Tc-MIBI and visually assessed. Additionally, the MIBI washout index was calculated using a semiquantitative method. RESULTS: In our series, 26 % of nodules with a follicular pattern on cytology were malignant with a prevalence of follicular carcinomas. (99m)Tc-MIBI scintigraphy was found to be significantly more accurate (positive likelihood ratio 4.56 for visual assessment and 12.35 for semiquantitative assessment) than mutation analysis (positive likelihood ratio 1.74). A negative (99m)Tc-MIBI scan reliably excluded malignancy. CONCLUSION: In patients with a thyroid nodule cytologically diagnosed as a follicular proliferation, semiquantitative analysis of (99m)Tc-MIBI scintigraphy should be the preferred method for differentiating benign from malignant nodules. It is superior to molecular testing for the presence of differentiated thyroid cancer-associated mutations in fine-needle aspiration cytology sample material.

A rare case of clear cell carcinoma of the breast evaluated by 18F-FDG PET/CT / Un caso poco frecuente de carcinoma de células claras de la mama evaluado con 18F-FDG PET/TC

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A rare case of adenoid cystic carcinoma of the breast detected by 18F-FDG PET/CT / Un caso poco frecuente de carcinoma adenoide quístico de mama detectado con 18F-FDG PET/TC

No disponible

A rare case of anaplastic large T-cell lymphoma of the lung evaluated by 18F-FDG PET/CT / Un caso poco frecuente de linfoma anaplásico de células grandes T en pulmón evaluado con 18F-FDG PET/TC

No disponible

Mesenteric lipogranuloma mimicking malignancy at 18F-FDG PET/CT in a patient with colon cancer / Lipogranuloma mesentérico que imita una neoplasia maligna en la 18F-FDG PET/TC de un paciente con carcinoma de colon

No disponible

A rare case of large cell neuroendocrine carcinoma of the urinary bladder evaluated by 18F-FDG-PET/CT / Un caso raro de carcinoma neuroendocrino de células grandes de la vejiga evaluado con 18F-FDG-PET/TC

No disponible