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Background: Thyroid nodules are common yet remain a diagnostic challenge. While ultrasound and Thyroid Imaging Reporting and Data Systems (TIRADS) are accepted as standard, the use of thyroid scintigraphy in euthyroid patients is debated. The European Association of Nuclear Medicine advocates it, whereas the American Thyroid Association and European Thyroid Association do not. However, it has not been evaluated whether scintigraphy adds value to TIRADS in a multimodal approach. Our study addresses this gap by assessing the impact of integrated pertechnetate scintigraphy on TIRADS accuracy. Methods: The diagnostic performance of ACR-TIRADS, EU-TIRADS, pertechnetate scintigraphy, and multimodal models were retrospectively analyzed for 322 nodules (231 benign, 91 malignant) in 208 euthyroid patients with histopathology as a reference. Generalized estimating equations were used for statistical analysis. Results: On scintigraphy, 210 nodules were hypofunctional, 99 isofunctional, and 13 hyperfunctional. The AUC for thyroid scintigraphy, ACR-TIRADS, and EU-TIRADS were 0.6 (95% CI: 0.55-0.66), 0.83 (95% CI: 0.78-0.88), and 0.78 (95% CI: 0.72-0.83). Integrating scintigraphy with ACR-TIRADS and EU-TIRADS slightly increased diagnostic accuracy (AUC 0.86 vs. 0.83, p = 0.039 and AUC 0.80 vs. 0.78, p = 0.008) and adjusted the malignancy probability for intermediate risk TIRADS categories, with iso- or hyperfunctioning nodules in ACR-TIRADS-TR4 or EU-TIRADS-4 showing comparable malignancy probabilities as hypofunctioning nodules in TR3 or EU-TIRADS-3, respectively. Conclusions: Integrating thyroid scintigraphy with ACR- or EU-TIRADS moderately improves diagnostic performance, potentially benefiting management, especially in complex cases like multinodular goiter or indeterminate FNA. Further research is warranted to validate these findings and explore their clinical implications.

[ 18 F]tetrafluoroborate ([ 18 F]TFB) is an emerging PET tracer with excellent properties for human sodium iodide symporter (NIS)-based imaging in patients with differentiated thyroid cancer (DTC). The aim of this study was to compare [ 18 F]TFB PET with high-activity posttherapeutic [ 131 I]iodine whole-body scintigraphy and SPECT/CT in recurrent DTC and with [ 18 F]FDG PET/CT in suspected dedifferentiation. Methods: Twenty-six patients treated with high-activity radioactive [ 131 I]iodine therapy (range, 5.00-10.23 GBq) between May 2020 and November 2022 were retrospectively included. Thyroid-stimulating hormone was stimulated by 2 injections of recombinant thyroid-stimulating hormone (0.9 mg) 48 and 24 h before therapy. Before treatment, all patients underwent [ 18 F]TFB PET/CT 40 min after injection of a median of 321 MBq of [ 18 F]TFB. To study tracer kinetics in DTC lesions, 23 patients received an additional scan at 90 min. [ 131 I]iodine therapeutic whole-body scintigraphy and SPECT/CT were performed at a median of 3.8 d after treatment. Twenty-five patients underwent additional [ 18 F]FDG PET. Two experienced nuclear medicine physicians evaluated all imaging modalities in consensus. Results: A total of 62 suspected lesions were identified; of these, 30 lesions were [ 131 I]iodine positive, 32 lesions were [ 18 F]TFB positive, and 52 were [ 18 F]FDG positive. Three of the 30 [ 131 I]iodine-positive lesions were retrospectively rated as false-positive iodide uptake. Tumor-to-background ratio measurements at the 40- and 90-min time points were closely correlated (e.g., for the tumor-to-background ratio for muscle, the Pearson correlation coefficient was 0.91; P < 0.001; n = 49). We found a significant negative correlation between [ 18 F]TFB uptake and [ 18 F]FDG uptake as a potential marker for dedifferentiation (Pearson correlation coefficient, -0.26; P = 0.041; n = 62). Conclusion: Pretherapeutic [ 18 F]TFB PET/CT may help to predict the positivity of recurrent DTC lesions on [ 131 I]iodine scans. Therefore, it may help in the selection of patients for [ 131 I]iodine therapy. Future prospective trials for iodine therapy guidance are warranted. Lesion [ 18 F]TFB uptake seems to be inversely correlated with [ 18 F]FDG uptake and therefore might serve as a dedifferentiation marker in DTC., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Natural killer (NK) cells are key effectors in cancer immunosurveillance and posttransplant immunity, but deficiency of environmental signals and insufficient tumor recognition may limit their activity. We hypothesized that the antibody-mediated anchoring of interleukin-2 (IL-2) to a spliced isoform of the extracellular matrix (ECM) glycoprotein tenascin-C would potentiate NK-cell-mediated antibody-dependent cellular cytotoxicity against leukemic blasts. In this novel-novel combination, dose-escalation, phase 1 trial, we enrolled patients with posttransplant acute myeloid leukemia (AML) relapse to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary activity of the antibody-cytokine fusion F16IL2 (10 × 106 to 20 × 106 IU IV; days 1, 8, 15, and 22 of each 28-day cycle) in combination with the anti-CD33 antibody BI 836858 (10-40 mg IV, 2 days after each F16IL2 infusion). Among the 15 patients (median [range] age, 50 [20-68] years) treated across 4 dose levels (DLs), 6 (40%) had received 2 or 3 prior transplantations. The most frequent adverse events were pyrexia, chills, and infusion-related reactions, which were manageable, transient and of grade ≤2. One dose-limiting toxicity occurred at each of DLs 3 (pulmonary edema) and 4 (graft-versus-host disease). Three objective responses were observed among 7 patients treated at the 2 higher DLs, whereas no responses occurred at the 2 starting DLs. Combination therapy stimulated the expansion and activation of NK cells, including those expressing the FcγRIIIA/CD16 receptor. ECM-targeted IL-2 combined with anti-CD33 immunotherapy represents an innovative approach associated with acceptable safety and encouraging biologic and clinical activity in posttransplant AML relapse. This trial was registered at EudraCT as 2015-004763-37., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Multimodal therapies are the standard of care for advanced adenocarcinomas of the oesophagus and gastro-oesophageal junction (AEG Types I and II). Only three randomised trials have compared preoperative chemotherapy with and without radiation. The results showed a small benefit for combined chemoradiation. In the meantime, newer therapy protocols are available., Aim: In a propensity-score matched study, we analysed patients with locally advanced AEG type I or II, treated with chemotherapy (FLOT-protocol) or chemoradiation (CROSS-protocol), followed by oesophagectomy, in a single high-volume centre., Patients and Methods: Between 2011 and 2015, 137 patients with advanced (cT3NxcM0) adenocarcinoma received pre-operative therapy; 70% had chemoradiation (CROSS-protocol) and 30% had chemotherapy (FLOT-protocol). After propensity-score matching, 40 patients from the CROSS-group were selected for analysis. Postoperative histopathological response and prognosis were analysed., Results: The two groups were comparable according to the matching criteria age, gender, tumour location, and year of surgery. R0-resection was achieved in 97% of patients in the CROSS-group and 85% of the FLOT-group (p = 0.049). Major response of the primary tumour was evident more often in the CROSS-group (17/40 pts. 43%) versus FLOT-group (11/40 pts. 27%) as well no lymph node metastasis (ypN0 = 68% versus ypN0 = 40%) (p = 0.014). Prognosis were not significantly different between the two groups. In multivariate analysis, only ypN-category was an independent prognostic factor., Conclusion: Compared to FLOT-chemotherapy, neoadjuvant chemoradiotherapy with the CROSS-protocol in locally advanced adenocarcinoma AEG types I and II resulted in better response by the primary tumour and less lymph node metastasis but without superior survival., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)