Zusammenfassung In Deutschland wird bei etwa 6000 Patienten pro Jahr die Diagnose eines differenzierten Schilddrüsenkarzinoms (PTC und FTC) gestellt. Das differenzierte Schilddrüsenkarzinom gilt als eine Tumorentität mit überwiegend guter Prognose. Die Behandlung besteht meistens in einer Kombination aus Operation und Radioiodtherapie. Die „richtige“ Behandlung wird dabei international kontrovers diskutiert. Besonders die Indikation zur Radioiodtherapie wird in den U.S.A. bei Patienten mit niedrigem Rezidivrisiko in Frage gestellt, was sich u.a. aus der geringen Zahl prospektiv randomisierter Studien ergibt. Die vorliegende Arbeit fasst die Sichtweise der deutschen S3-leitlinie zusammen und soll Hilfestellung bei der Indikationsstellung zur Radioiodtherapie bei Patienten mit differenziertem Schilddrüsenkarzinom geben.

The ESTIMABL2-trial demonstrated non-inferiority of avoiding radioiodine therapy in low-risk differentiated thyroid cancer (DTC, i.e. papillary- and follicular thyroid cancer (PTC, FTC)). Yet, follow-up duration was limited and FTC were underrepresented. We therefore assessed long-term relative survival by comparing observed and expected cancer-free survival. This robust measure of net survival was used to evaluate the long-term effects of radioiodine therapy, including in previously underrepresented histological subgroups. Using the SEER-database, we identified 18,645 patients with DTC according to the criteria in the ESTIMABL2-trial (low risk PTC and FTC with pT1am-pT1b, N0-NX). Long-term relative survival (> 10 years) was analysed retrospectively, subdivided based on histology (PTC and FTC) and TNM-status, and additionally in 5,171 patients with lymph node involvement (N1). Relative survival was compared at 3 -, 5 -, and 10-years follow-up with and without radioiodine. Radioiodine therapy was associated with higher long-term relative survival in specific subgroups: Among FTC patients, relative survival was higher with radioiodine after 5- and, 10-years by 0.3

BACKGROUND/AIM:The question of whether sentinel lymph node (SLN) marking depends on the injection site on the vulva warrants further elucidation. This issue emerges in circumstances where, after the surgical excision of a vulvar tumor, a malignancy is identified microscopically, yet lymph node removal was not initially implemented. In such cases, during subsequent surgical operations for lymph node staging, the injection of a tracer near the tumor becomes impossible, as the tumor has already been removed. In order to elucidate this issue, an investigation was conducted into the marking behavior of inguinal SLNs in dual marking with two different tracers and injections at different sites on the vulva in patients with squamous cell vulvar cancer. PATIENTS AND METHODS:Twenty-seven groins of 15 patients with squamous cell carcinoma of the vulva who underwent SLN resection between 2016 and 2022 at the University Hospital of Cologne, Germany, were analyzed in this retrospective cohort study. As part of SLN marking, a mark was made at various points on the vulva using technetium and indocyanine green (ICG). RESULTS:SLNs could be harvested from all groins. All radioactively labeled SLNs also showed ICG labeling. After removal of the radioactively labeled SLN, no ICG-labeled lymph nodes were detectable intraoperatively. Three groins in two patients had tumor-infiltrated lymph nodes. CONCLUSION:All excised SLNs of the patients with squamous cell carcinoma of the vulva successfully demonstrated uptake of both tracers (technetium and indocyanine green), despite being administered at different injection sites. In this study, the stainability of the inguinal SLN was independent of the respective injection site. This is experimental evidence that, when SLN marking is performed after removal of a vulvar tumor, the same lymph nodes will stain as would be the case if marking were performed during tumor removal.

For patients with differentiated thyroid cancer (DTC), that is, papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC), the American Thyroid Association and European Thyroid Association generally recommend radioactive iodine (RAI) therapy after surgery only for high-risk patients. For intermediate-risk patients, RAI therapy is recommended only as a should-be-considered option. For low-risk patients, RAI therapy is not routinely recommended. Other countries, such as Germany, are more in favor of using RAI. Thus, RAI therapy remains a matter of controversial debate, because prospective long-term data on survival are scarce. Methods: We retrospectively compared long-term relative survival in DTC cohorts treated with and without RAI. From the Surveillance, Epidemiology, and End Results Program database, 101,087 patients harboring DTC were identified between 2000 and 2020. Patient cohorts were subdivided based on histology (classical PTC, aggressive variants of PTC, FTC, and minimally invasive FTC). These cohorts were stratified into the following categories: very low risk, low risk, intermediate risk, and high risk. Relative survival was determined for each subgroup. Statistics included a z-test specifically developed for comparison of relative survival, testing the long-term effect of RAI therapy (3, 5, and 10 y). Results: The relative survival rate is higher or tends to be higher in most subgroups undergoing RAI therapy than in subgroups not undergoing RAI therapy. Even for low-risk minimally invasive FTC, the 10-y relative survival rate tends to be higher by 2.0% (P = 0.055). For larger tumor size or lymph node involvement in classical PTC, a 10-y relative survival benefit of 1.3%-2.0% (P = 0.045) in the RAI subgroup prevails. In high-risk DTC, benefits in relative survival of up to 30.9% (P < 0.05) were observed. Relative survival is not negatively affected in any RAI subgroup. Conclusion: In patients with DTC, depending on histology subtype, a benefit in relative survival prevails in low-, intermediate-, and high-risk subgroups that underwent RAI therapy compared with patients who did not undergo RAI therapy. Even in low-risk minimally invasive FTC, a clear trend toward higher survival rates is observed. For PTC, a survival benefit prevails in the presence of lymph node involvement, larger tumor size, or distant metastasis.

OBJECTIVES:Tumor volume in prostate-specific membrane antigen (PSMA-TV)-PET/computed tomography (CT) has shown an emerging impact for prognosis and response evaluation in patients with prostate cancer. We evaluated the robustness of different PSMA-TV delineation methods. MATERIALS AND METHODS:A total of 40 18 F-JK-7-PSMA-PET/CT performed on the same scanner were analyzed. PSMA-TV measurements were performed using a standardized uptake value of 4.0 as a fixed threshold (T1), 41% of the single hottest voxel as an adaptive threshold (T2), and a liver-specific threshold (T3) for delineation in two reconstruction methods [four iterations and 12 subsets (R1) and three iterations and 21 subsets while applying a point spread function and a time-of-flight algorithm (R2)]. Differences between the segmentation thresholds in R1 and R2 were gathered and tested for statistical significance. RESULTS:PSMA-TV differed significantly between R1Tx and R2Tx for individual segmentation thresholds, with PSMA-TV in R2 being significantly smaller than in R1 using the same segmentation method. Comparing the differences in PSMA-TV between R1 and R2 reconstruction between the three separate segmentation thresholds showed significantly larger absolute volume differences for T2 compared with T3 and significantly larger relative volume differences for T2 compared with T1 and T3. CONCLUSION:Reconstruction settings greatly influence the measurement of PSMA-TV, regardless of the segmentation threshold chosen; however, our results indicate that the fixed thresholds (T1 and T3) are less susceptible to reconstruction-induced volumetry effects than a relative threshold.

Graves’ disease and hyperthyroidism in women with childbearing potential are a challenge in pre-conceptional counseling. The non-surgical alternatives are radioiodine therapy or antithyroid drugs. Here, we focus on the TSH receptor antibody (TRAb) level—without or after radioiodine therapy—and the probability of fetal or neonatal hyperthyroidism. This immunological effect should be weighed against the risk of congenital malformation taking propylthiouracil during pregnancy. For up to 2 years after radioiodine therapy for Graves’ disease, TRAb levels may remain above the pre-therapeutic level. The time of conception after radioiodine therapy and a high TRAb level are associated with the likelihood of neonatal hyperthyroidism: 8.8% probability if conception occurred 6–12 months after radioiodine therapy, with a 5.5% probability for 12–18 months, and 3.6% probability for 18–24 months. The TRAb value above 10 U/L in the third trimester is the main risk factor for neonatal hyperthyroidism. If a woman does not wish to postpone her family planning, the pre-conceptional counseling has to describe the risk of propylthiouracil, thiamazole, or of an uncontrolled hyperthyroidism. According to some national cohort studies (Danish, Swedish, Korean), the risk for fetal malformations (ear, urinary tract) under propylthiouracil is increased by 1.1–1.6%, in addition to the spontaneous risk for unexposed pregnant women. For thiamazole, the additional risk for fetal malformation was about 2–3%, depending on the dose of thiamazole. Propylthiouracil has posed a lower risk for congenital malformation than an uncontrolled hyperthyroidism. To minimize the risk for the newborn, women with Graves’ disease and hyperthyroidism should offer a definitive therapy strategy (e.g., radioiodine therapy) long before planning a pregnancy.

The clinical course of neuroblastoma is more heterogeneous than any other malignant disease. Many low-risk patients experience regression after limited or even no chemotherapy. However, more than half of high-risk patients die from disease despite intensive multimodal treatment. Precise disease characterization for each patient at diagnosis is key for risk-adapted treatment. The guidelines presented here incorporate results from national and international clinical trials to produce recommendations for diagnosing and treating neuroblastoma patients in German hospitals outside of clinical trials.

Osseous metastases are a common finding in prostate cancer, usually affecting the central skeleton. Metastases in the peripheral skeleton are less frequent but can occur as isolated findings as well. Therefore, imaging protocols limited to the trunk may miss such lesions and extended range (total-body) PSMA-PET/CT may be helpful for comprehensive evaluation, especially when peripheral metastases are suspected, for example, due to clinical symptoms.

Preliminary studies on a radioactive antibody against the neural cell adhesion molecule (NCAM) demonstrated a significant accumulation of [131I]I-ERIC1 in neuroblastoma tumor cells in mice. This study aims to validate the therapeutic efficacy and potential adverse effects of these radioactive immunoconjugates (RICs) in neuroblastoma-bearing mice. To determine the highest tolerated dose, healthy SCID mice received 1 to 22 MBq of [131I]I-ERIC1, with the survival time measured. Tumor response was evaluated by administering 0.8 to 22 MBq of [131I]I-ERIC1 to neuroblastoma-bearing mice and assessing tumor size and systemic toxicity through body weight, blood counts, and survival. It was observed that doses up to approximately 3 MBq per animal (150 MBq/kg) were well tolerated, whereas higher doses resulted in systemic toxicity and death. The neuroblastomas exhibited a dose-dependent response, with optimal therapeutic efficacy achieved at 1.8–2.5 MBq per animal (90–125 MBq/kg), significantly extending survival by a factor of five. The antibody ERIC1 is a promising vehicle for the transport of beta emitters into NCAM-positive tumor tissue. An optimal dosage of the [131I]I-ERIC1 antibody can be established with a balance of tumor-static effects and adverse effects, resulting in a marked extension of survival time.

Background:Frozen section (FS) analysis is strongly influenced by the experience of surgeons and pathologists. We analyzed its performance in a secondary care hospital with surgical and pathologic experience transferred from a university hospital.Methods:Indications, results, and consequences of all thyroid FS performed between January 1, 2021 and December 31, 2022 were critically reviewed.Results:FS was performed in 90 (26.5%) of 340 procedures. Indications consisted in a suspicious fine needle biopsy in 28 (31.1%) cases, (99m) Technetium-Methoxy-Isobutyl-Isonitrile (MIBI) retaining hypofunctional nodules in 25 (27.8%), the intraoperative appearance in 18 (20%), the sonographic appearance in 18 (20%) and a positron emission tomography (PET) positive result in 1 case (1.1%). Malignancy was diagnosed in 21 (23.3%) and confirmed by final histology in all cases (100%). In the remaining 69 (76.7%) FS displaying no positive malignancy criteria, final histology delivered benign in 62 (89.8%) and malignant diagnoses in 7 cases (10.1%). 25% of thyroid carcinomas could not be diagnosed by FS. FS sensitivity was consequently 75% (95% CI: 55.1-89.3%). All missed malignancies were papillary thyroid carcinomas of follicular variant (fvPTC). FS sensitivity was lowest in MIBI positive hypofunctional nodules (33%) and Bethesda III (50%) as opposed to Bethesda V (92.9%) and to those cases with suspicious sonographic or intraoperative appearance (71.4%). Two-staged surgery was necessary in 10 (15.8%) of carcinomas.Conclusions:Sensitivity of FS in a secondary care hospital offering surgical and pathologic experience from a specialized university center is 75% and mainly reduced by the prevalence of fvPTC. Omitting FS in Bethesda III and MIBI positive hypofunctional nodules might improve FS performance.