Open Access

Purpose: (i) To examine the criterion taller-than-wide (TTW) for the sonographic assessment of thyroid nodules in areas of iodine deficiency in terms of frequency, anatomical distribution within the thyroid gland and risk of malignancy. (ii) To develop a model for nodule growth in the thyroid gland. Methods: German multicenter study consisting of two parts. In the prospective part, thyroid nodules were sonographically measured in all three dimensions, location within the thyroid gland and contact to a protrusion-like formation (horn) in the dorsal position of thyroid gland was noted. In addition, further sonographic features such as the composition, echogenity, margins and calcifications were investigated. All nodules from the prospective part were assessed for malignancy as part of clinical routine at the decision of the treating physician adhering to institutionally based algorithms. In the retrospective part, only nodules with fine needle aspiration and/or histology were included. The risk of malignancy in TTW nodules was determined by correlating them with cyotological and histological results. Results: Prospective part: out of 441 consecutively evaluated thyroid nodules, 6 were found to be malignant (1.4%, 95% CI 0.6–2.7%). Among the 74 TTW nodules (17%), 1 was malignant (1%, 95% CI 0–4%). TTW nodules were more often located in the dorsal half of the thyroid than non-TTW nodules (factor 2.3, p = 0.01, 95% CI 2.1–2.5) and more often located in close proximity to a horn than non-TTW nodules (factor 3.0, p = 0.01, 95% CI 2.4–3.8). Retrospective part: out of 1315 histologically and/or cytologically confirmed thyroid nodules, 163 TTW nodules were retrieved and retrospectively analyzed. A TTW nodule was 1.7 times more often benign when it was dorsal (95% CI 1.1–2.5) and 2.5 times more often benign when it was associated with a horn (95% CI 1.2–5.3). The overall probability of malignancy for TTW nodules was 38% (95% CI 30–46%) in this highly preselected patient group. Conclusion: TTW nodules are common in iodine deficient areas. They are often located in the dorsal half of the thyroid gland and are frequently associated with a dorsal protrusion-like formation (horn) of the thyroid. Obviously, the shape of benign nodules follows distinct anatomical preconditions within the thyroid gland. The frequency of TTW nodules and their predominant benignity can be explained by a pole concept of goiter growth. The difference between the low malignancy risk of TTW nodules found on a prospective basis and the high risk found retrospectively may be the result of a positive preselection in the latter.

Background: Myelosuppression is a potential dose-limiting factor in radioligand therapy (RLT). This study aims to investigate occurrence, severity and reversibility of hematotoxic adverse events in patients undergoing RLT with 177Lu-PSMA-617 for metastatic castration-resistant prostate cancer (mCRPC). The contribution of pretreatment risk factors and cumulative treatment activity is taken into account specifically. Methods: RLT was performed in 140 patients receiving a total of 497 cycles. A mean activity of 6.9 ± 1.3 GBq 177Lu-PSMA-617 per cycle was administered, and mean cumulative activity was 24.6 ± 15.9 GBq. Hematological parameters were measured at baseline, prior to each treatment course, 2 to 4 weeks thereafter and throughout follow-up. Toxicity was graded based on Common Terminology Criteria for Adverse Events v5.0. Results: Significant (grade ≥ 3) hematologic adverse events occurred in 13 (9.3%) patients, with anemia in 10 (7.1%), leukopenia in 5 (3.6%) and thrombocytopenia in 6 (4.3%). Hematotoxicity was reversible to grade ≤ 2 through a median follow-up of 8 (IQR 9) months in all but two patients who died from disease progression within less than 3 months after RLT. Myelosuppression was significantly more frequent in patients with pre-existing grade 2 cytopenia (OR: 3.50, 95%CI 1.08–11.32, p = 0.04) or high bone tumor burden (disseminated or diffuse based on PROMISE miTNM, OR: 5.08, 95%CI 1.08–23.86, p = 0.04). Previous taxane-based chemotherapy was associated with an increased incidence of significant hematotoxicity (OR: 4.62, 95%CI 1.23–17.28, p = 0.02), while treatment with 223Ra-dichloride, cumulative RLT treatment activity and activity per cycle were not significantly correlated (p = 0.93, 0.33, 0.29). Conclusion: Hematologic adverse events after RLT have an acceptable overall incidence and are frequently reversible. High bone tumor burden, previous taxane-based chemotherapy and pretreatment grade 2 cytopenia may be considered as risk factors for developing clinically relevant myelosuppression, whereas cumulative RLT activity and previous 223Ra-dichloride treatment show no significant contribution to incidence rates.

Bone-seeking 223Radium-dichloride (223Ra) is an established treatment prolonging survival and reducing morbidity in selected patients with metastatic castration-resistant prostate cancer (mCRPC) with skeletal involvement. Radioligand therapy with 177Lutetium-PSMA-617 (177Lu-PSMA-617) has been increasingly implemented in patients with mCRPC failing conventional treatment options. In this study, the safety and efficacy of 177Lu-PSMA-617 in patients with progressive bone involvement under treatment with 223Ra was assessed. Twenty-eight men (median age 73 years, range 63–89 years) with progressive mCRPC, who started 177Lu-PSMA-617 within 8 weeks after the last 223Ra administration, received a median of 4 (IQR 3–6) and a total of 120 cycles of 223Ra and a median of 4 (IQR 2–7) cycles 177Lu-PSMA-617 with a mean treatment activity of 6.5 ± 1.2 GBq per cycle, reaching a mean cumulative activity of 30.7 ± 23.4 GBq. A PSA response (≥50% PSA decline 12 weeks after the first 177Lu-PSMA-617 cycle) was observed in 18/28 (64.3%) patients and imaging-based partial remission (PR) was observed in 11/28 (39.3%) patients. Median imaging-based progression-free survival (PFS) was 10 (95% CI, 6–14) months and median overall survival (OS) was 18 (95% CI, 14–22) months. Patients with low bone tumor burden (2–20 lesions) had a significantly longer OS (28 vs. 14 months, p < 0.045) compared to patients with a high tumor burden (>20 lesions). Grade ≥ 3 hematological toxicity was observed in six patients after their last treatment cycle with anemia, leukopenia and thrombocytopenia in 5/28 (17.9%), 4/28 (14.3%) and 6/28 (21.4%) patients, respectively. In progressive bone-metastatic mCRPC patients, prompt initiation of 177Lu-PSMA-617 after failing 223Ra is effective with an acceptable toxicity profile.

Aim: Radioiodine therapy (RIT) may trigger the development of Graves’ ophthalmopathy (GO) or exacerbate pre-existing subclinical GO. Therefore, glucocorticoid administration is recommended for patients with pre-existing GO. Aim of this study was to analyze the influence of glucocorticoid therapy with methylprednisolone on intratherapeutic effective half-life (EHL) of radioiodine-131 in patients with Graves’ disease (GD) as recent studies showed an effect for prednisolone. Methods: In a retrospective study, 264 patients with GD who underwent RIT without any additional antithyroid medication were evaluated. Intrathyroidal EHL was determined pre- and intratherapeutically. Patients with co-existing GO (n = 43) received methylprednisolone according to a fixed scheme starting 1 day prior to RIT, patients without GO (n = 221) did not receive any protective glucocorticoid medication. The ratios of EHL during RIT and during radioiodine uptake test (RIUT) were compared. Results: Patients receiving methylprednisolone showed a slight decrease of the mean EHL from 5.63 d (RIUT) to 5.39 d (RIT) (p > 0.05). A comparable result was obtained in patients without glucocorticoids (5.71 d (RIUT) to 5.47 d (RIT); p > 0.05). The ratios of the EHL between RIT and RIUT failed to show a significant difference between the two groups. EHL is therefore not significantly influenced by an additional protective treatment with methylprednisolone. Conclusions: In the present study a decreased intrathyroidal EHL under glucocorticoid medication with methylprednisolone could not be detected. Therefore, co-medication with methylprednisolone in patients with GO may be preferred to avoid an intratherapeutic decrease of EHL by accompanying protective glucocorticoides.