Purpose: Restoration of iodine incorporation (redifferentiation) by MAPK inhibition was achieved in previously radioiodine-refractory, unresectable thyroid carcinoma (RR-TC). However, results were unsatisfactory in BRAFV600E-mutant (BRAF-MUT) RR-TC. Here we assess safety and efficacy of redifferentiation therapy through genotype-guided MAPK-modulation in patients with BRAF-MUT or wildtype (BRAF-WT) RR-TC. Patients and Methods: In this prospective single-center, two-arm phase II study, patients received trametinib (BRAF-WT) or trametinib + dabrafenib (BRAF-MUT) for 21 ± 3 days. Redifferentiation was assessed by 123I-scintigraphy. In case of restored radioiodine uptake, 124I-guided 131I therapy was performed. Primary endpoint was the redifferentiation rate. Secondary endpoints were treatment response (thyroglobulin, RECIST 1.1) and safety. Parameters predicting successful redifferentiation were assessed using a receiver operating characteristic analysis and Youden J statistic. Results: Redifferentiation was achieved in 7 of 20 (35%) patients, 2 of 6 (33%) in the BRAF-MUT and 5 of 14 (36%) in the BRAF-WT arm. Patients received a mean (range) activity of 300.0 (273.0–421.6) mCi for 131I therapy. Any thyroglobulin decline was seen in 57% (4/7) of the patients, RECIST 1.1 stable/partial response/progressive disease in 71% (5/7)/14% (1/7)/14% (1/7). Peak standardized uptake value (SUVpeak) < 10 on 2[18F]fluoro-2-deoxy-D-glucose (FDG)-PET was associated with successful redifferentiation (P = 0.01). Transient pyrexia (grade 3) and rash (grade 4) were noted in one patient each. Conclusions: Genotype-guided MAPK inhibition was safe and resulted in successful redifferentiation in about one third of patients in each arm. Subsequent 131I therapy led to a thyroglobulin (Tg) decline in more than half of the treated patients. Low tumor glycolytic rate as assessed by FDG-PET is predictive of redifferentiation success. See related commentary by Cabanillas et al., p. 4164

PURPOSE: We conducted a post hoc analysis of the vandetanib phase III trial involving patients with advanced medullary thyroid cancer (MTC) to assess the efficacy and safety of vandetanib in patients with progressive and symptomatic MTC. The primary objective of the analysis was to determine progression-free survival (PFS) of these patients. PATIENTS AND METHODS: Eligible patients from the ZETA trial were divided into 4 disease severity subgroups: progression and symptoms, symptoms only, progression only, and no progression and no symptoms assessed at baseline. PFS, determined from objective tumor measurements performed by the local investigator, overall survival (OS), time to worsening of pain (TWP), and objective response rate (ORR) were evaluated. RESULTS: Of the 331 patients in this trial, 184 had symptomatic and progressive disease at baseline. In this subgroup, results were similar in magnitude to those observed in the overall trial for PFS (hazard ratio [HR], 0.43; 95% CI, 0.28 to 0.64; P < .0001), OS (HR, 1.08; 95% CI, 0.72 to 1.61; P = .71), and TWP (HR, 0.67; 95% CI, 0.43 to 1.04; P = .07), and the observed adverse events were consistent with the known safety profile of vandetanib. In this subgroup, the ORR was 37% in the treatment arm versus 2% in the placebo arm. CONCLUSION: Vandetanib demonstrated clinical benefit—specifically, increased PFS—in patients with symptomatic and progressive MTC.

Merkel cell carcinoma (MCC) is a rare cutaneous neoplasm with increasing incidence, aggressive behavior and poor prognosis. Somatostatin receptors (SSTR) are expressed in MCC and represent a potential target for both imaging and treatment.

Germany has a long history of insufficient iodine supply and thyroid nodules occur in over 30% of the adult population, the vast majority of which are benign. Non-invasive diagnostics remain challenging, and ultrasound-based risk stratification systems are essential for selecting lesions requiring further clarification. However, no recommendation can yet be made about which system performs the best for iodine deficiency areas. In a German multicenter approach, 1211 thyroid nodules from 849 consecutive patients with cytological or histopathological results were enrolled. Scintigraphically hyperfunctioning lesions were excluded. Ultrasound features were prospectively recorded, and the resulting classifications according to five risk stratification systems were retrospectively determined. Observations determined 1022 benign and 189 malignant lesions. The diagnostic accuracies were 0.79, 0.78, 0.70, 0.82, and 0.79 for Kwak Thyroid Imaging Reporting and Data System (Kwak-TIRADS), American College of Radiology (ACR) TI-RADS, European Thyroid Association (EU)-TIRADS, Korean-TIRADS, and American Thyroid Association (ATA) Guidelines, respectively. Receiver Operating Curves revealed Areas under the Curve of 0.803, 0.795, 0.800, 0.805, and 0.801, respectively. According to the ATA Guidelines, 135 thyroid nodules (11.1%) could not be classified. Kwak-TIRADS, ACR TI-RADS, and Korean-TIRADS outperformed EU-TIRADS and ATA Guidelines and therefore can be primarily recommended for non-autonomously functioning lesions in areas with a history of iodine deficiency.

The classification of thyroid nodules using ultrasound (US) imaging is done using the Thyroid Imaging Reporting and Data System (TIRADS) guidelines that classify nodules based on visual and textural characteristics. These are composition, shape, size, echogenicity, calcifications, margins, and vascularity. This work aims to reduce subjectivity in the current diagnostic process by using geometric and morphological (G-M) features that represent the visual characteristics of thyroid nodules to provide physicians with decision support. A total of 27 G-M features were extracted from images obtained from an open-access US thyroid nodule image database. 11 significant features in accordance with TIRADS were selected from this global feature set. Each feature was labeled (0 = benign and 1 = malignant) and the performance of the selected features was evaluated using machine learning (ML). G-M features together with ML resulted in the classification of thyroid nodules with a high accuracy, sensitivity and specificity. The results obtained here were compared against state-of the-art methods and perform significantly well in comparison. Furthermore, this method can act as a computer aided diagnostic (CAD) system for physicians by providing them with a validation of the TIRADS visual characteristics used for the classification of thyroid nodules in US images.

Due to the widespread use of ultrasound, small thyroid nodules (TNs) ≤ 10 mm are common findings. Standardized approaches for the risk stratification of TNs with Thyroid Imaging Reporting and Data Systems (TIRADS) were evaluated for the clinical routine. With TIRADS, the risk of malignancy in TNs is calculated by scoring the number or combination of suspicious ultrasound features, leading to recommendations for further diagnostic steps. However, there are only scarce data on the performance of TIRADS for small TNs. The aim was to compare three different TIRADS for risk stratification of small TNs in routine clinical practice. We conducted a retrospective cohort analysis of TNs ≤ 10 mm and their available histology. Nodules were classified according to three different TIRADS. In the study, 140 patients (n = 113 female) with 145 thyroid nodules (n = 76 malignant) were included. Most of the malignant nodules were papillary carcinoma (97%), and the remaining 3% were medullary carcinoma. For all tested TIRADS, the prevalence of malignancy rose with increasing category levels. The highest negative predictive value was found for ACR TI-RADS and the highest positive predictive value for Kwak-TIRADS. All tested variants of TIRADS showed comparable diagnostic performance for the risk stratification of small TNs. TIRADS seems to be a promising tool to reliably assess the risk of malignancy of small TNs.