Purpose Concern is growing about long-term side effects of differentiated thyroid cancer treatment, most notably radioactive iodine (RAI) therapy. However, published studies on the subject have had heterogeneous cohorts and conflicting results. This review seeks to provide an updated evaluation of published evidence, and to elucidate the risk of second primary malignancies (SPMs), especially secondary hematologic malignancies (SHMs), attributable to RAI therapy. Methods An extensive literature search was performed in Ovid MEDLINE, Ovid MEDLINE and In-Process & Other Non-Indexed Citations, Ovid MEDLINE Epub Ahead of Print, Cochrane Central Register of Controlled Trials (CENTRAL) and PubMed. Studies regarding RAI-induced SPMs or a dose–response relationship between RAI therapy and SPMs were identified, 10 of which were eligible for the analysis. We evaluated risk of bias in each study and judged quality of evidence (QOE) across all studies using the Grading of Recommendations, Assessment, Development and Evaluations approach. Results For the outcome “SPM”, the relative effect (relative risk, hazard ratio, or odds ratio) of RAI vs. no RAI ranged from 1.14 to 1.84 across studies, but most results were not statistically significant. For the outcome “SHM”, reported relative effects ranged from 1.30 to 2.50, with 2/3 of the studies presenting statistically significant results. In 7/8 of the studies, increased risk for SPM was shown with increasing cumulative RAI activity. QOE was “very low” regarding SPM after RAI and regarding a dose–response relationship, and “low” for SHM after RAI. Conclusion Based on low quality evidence, an excess risk for the development of SPM cannot be excluded but is expected to be small.

Several studies have demonstrated an expression of the prostate-specific membrane antigen (PSMA) in the cancer-related neovasculature of thyroid malignancies. Due to the poor prognosis and limited therapeutic options for patients with anaplastic (ATC) and poorly differentiated (PDTC) thyroid carcinoma, the aim of our study was to investigate the theranostic approach of PSMA expression in these patients. The PSMA uptake on Gallium-68 (68Ga)-PSMA-positron emission tomography/computed tomography (PET/CT) and glucose uptake on F-18-Fluordeoxyglucose (18F-FDG)-PET/CTs were analysed in two ATC and six PDTC patients. The PSMA expression in corresponding patients’ tissue samples was detected by immunohistochemistry. In addition, various tissue sections from 22 ATC and six PDTC patients were examined concerning PSMA expression. 68Ga-PSMA-PET/CT showed heterogeneous PSMA expression among patients and lesions. Six of the eight analyzed patients (two ATC, four PDTC) showed increased glucose metabolism without increased PSMA uptake after PET/CT. In one patient (PDTC), 18F-FDG-PET/CT tracer uptake was positive and 68Ga-PSMA-PET/CT showed heterogeneous results. Another patient (PDTC) evidenced only PSMA-positive lesions and received two cycles of Lutetium-177 (177Lu)-PSMA therapy, which kept his disease stable for seven months. There was a correlation between immunohistochemical PSMA expression and uptake on 68Ga-PMSA-PET/CT in three of the examined patients. Twenty-seven of the analyzed 39 ATC and 13 of the analyzed 22 PDTC tissue sections showed a strong PSMA expression. Considering the rarity of PDTC and ATC, which is the reason for the small patient population we studied, the findings of this study confirm the high diagnostic sensitivity and superiority of 18F-FDG-PET/CT in comparison to 68Ga-PSMA-PET/CT in the diagnosis of ATC and PDTC. However, it can be suggested that 68Ga-PMSA-PET/CT can be considered as a beneficial adjunct to the well-established 18F-FDG-PET/CT for a few individual selected patients with ATC and PDTC to detect lesions not discovered by 18F-FDG-PET/CT and to determine patients’ eligibility for a radioligand therapy. Radiolabelled PSMA-ligands may, in the future, represent a theranostic approach with only minor side effects for a few individual selected patients with ATC and PDTC who need alternative treatment options in case of progression when established therapies are no longer effective. However, due to the small sample size of our collective, larger studies are needed to allow for a final evaluation on the significance of PSMA-targeted diagnostic and therapy for ATC and PDTC.

Radioiodine therapy (RAI) is usually a standard procedure performed after thyroidectomy in differentiated thyroid cancer (DTC). While the indication for RAI in high-risk patients has been established in various national and international guidelines, there is an ongoing discussion with regard to intermediate-risk patients. In addition to the inconsistent definition of this risk category, the absence of large multinational prospective randomized controlled trials forms the basis of the debate. In this context, the actual pattern of care and national guidelines in the country where the patient is living plays an important role with respect to regional iodine supply and goiter prevalence, preoperative diagnostics (fine needle aspiration biopsy), and corresponding surgical strategies. Participatory decision-making between physician and informed patient, which is demanded in principle today anyway, is of particular importance in this situation. This article will discuss the approach of shared decision making for radioiodine therapy in intermediate-risk DTC.

Introduction Few available data indicate that a mutation-based “neoadjuvant” therapy in advanced anaplastic thyroid carcinoma (ATC) might convert an initially unresectable primary tumor to resectable and optimize local tumor control. We evaluated a preoperative short-term “neoadjuvant” therapy with a BRAF-directed therapy or, in case of BRAF non-mutated tumors, an mKI/checkpoint inhibitor combination in three patients with ATC stage IVB and C. Methods In the context of preoperative diagnostics, immunohistochemistry (IHC) assessment and genetic analysis was started as soon as possible. The antiangiogenetic therapy with lenvatinib was immediately after diagnosis of ATC started as bridging therapy. In case of a BRAF-mutated ATC, a combination therapy of dabrafenib and trametinib, in case of BRAF-wildtype ATC a combination of pembrolizumab and lenvatinib was given for 4 weeks. If re-staging has shown a significant therapy response due to a decrease in size of > 50%, surgical resection was reconsidered. A primary tumor resection was performed first. As a second step, limited distant metastasis have been resected approximately 4 weeks after thyroid surgery. After postoperative recovery, the targeted systemic therapy was continued. Patients Two patients presented with BRAF-wildtype ATC stage IVC, one with BRAF-mutated ATC stage IVB. All patients were evaluated by surgery, nuclear medicine and oncology upon diagnosis of ATC. Results In all three cases, the “neoadjuvant” therapy induced a dramatic response and led to local resectability in primarily non-resectable ATC stage IVB or C. We have chosen for the first time a short-term “neoadjuvant” treatment period to reduce the risk of bleeding and/or fistula due to potential rapid tumor shrinkage. The results of surgery after only short-term “neoadjuvant” therapy showed two R0 und one R1 resections. Postoperative histopathological findings confirmed an extent of tumor necrosis or regressive fibrotic tissue between 60 and > 95% in our patients. Conclusions A short-term mutation-based “neoadjuvant” therapy can achieve local resectability in initially unresectable ATC stage IVB or C. A neoadjuvant treatment period of about 4 weeks seems to show similar response as a treatment duration of at least 3 months.

Purpose The interdisciplinary “Martinique-Principles” of four international professional societies concerned with the patient management of differentiated thyroid cancer (DTC) patients were agreed upon. Differences in perioperative diagnostics can lead to differences in clinical decision founding regarding the treatment of thyroid carcinoma. Our aim was to analyze the perioperative diagnostics of patients referred for postoperative I-131 therapy of DTC. Methods We retrospectively examined the data of 142 patients who were referred to our center for the first course of postsurgical I-131 therapy. We extracted data on perioperative diagnostics. Results Fine-needle biopsy (FNB) was performed in 27/142 patients. In 17 patients, FNB yielded findings suspicious of malignancy, in 3 patients a follicular lesion was reported. An intraoperative frozen section analysis was performed in 79/142 patients. 5/63 patients showed already a cytologically proven malignancy. In 10/79 patients, the frozen section had a nonmalignant result, although DTC was found on final assessment. In 2/79 patients, frozen section analysis was indecisive, although the final report confirmed DTC. In the remaining 67 patients, frozen section yielded DTC. Conclusions There is room for improvement in perioperative diagnostics surrounding thyroid surgery, currently many procedures are performed without adequate information on potential presence of thyroid cancer. More frequent use of FNB might be able to decrease the number of unnecessary thyroid surgeries, increased use of frozen section might decrease the number of second operations and might contribute to less discordance between experts in the field of DTC treatment.