Frederik A. Verburg

To examine success rates in strictly defined high risk differentiated thyroid cancer (DTC) patients who received a high activity (≥5550 MBq) adjuvant post-operative I-131 therapy and compare these to the rates found in highest risk and low risk patients. Retrospective database study We examined 377 DTC patients who received I-131 ablation. Patients with distant metastases were classified as very high risk. Patients with primary tumours >4 cm, extensive extrathyroidal invasion (pT4a or pT4b in accordance with the 7^th edition of the TNM system), patients with ≥5 lymph node metastases or any lateral compartment lymph node metastases were considered high risk. All other patients were considered low risk. Ablation success rate at first TSH stimulated follow-up. the ablation success rate was 72.6% in low risk patients, 51.7% in high risk patients and 13.8% in highest risk patients (all differences p<0.001) In none of the groups a significant difference in the initial I-131 activity was found between patients with successful and unsuccessful ablation (low risk: p=0.16, high risk: p=0.91 and highest risk: p=0.48). Furthermore there was no difference in ablation success between patients who received <5550 MBq and those who received ≥5550 Mbq (low risk: p=0.31, high risk: p=0.69 and highest risk: p=0.22). high risk DTC patients have a significantly reduced I-131 ablation success rate compared to low risk ones in spite of high initial I-131 activities. As successful ablation is prognostically important, efforts should be made to improve outcome in these patients.

The procedure guideline for radioiodine therapy of differentiated thyroid cancer (version 4) was developed in the consensus of a representative expert group. This fulfils the level S1 (first step) within the AWMF classification of Clinical Practice Guidelines (AWMF, Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, Germany). This procedure guideline completed the guideline for surgical management of thyroid cancer (level S2) with the aspects from nuclear medicine. Controversies over ablative radioiodine therapy in small papillary thyroid cancers and in minimally invasive follicular cancer without angioinvasion, over empirical standard doses for ablative radioiodine therapy, and over the kind of TSH-stimulation were described and the guideline formulated a corridor of good clinical practice. The text has included the recent results from the National Cancer database and the SEER database (both from the USA), indicating that the ablative radioiodine therapy has improved the survival rate even in low risk patients. Such a statistically significant benefit can be detected only by a national cancer registry with long-term follow-up data.

There is no clinically relevant difference between reconstruction of PET images based on ceCT or neCT in FCH-PET/CT in patients with prostate cancer. Small quantitative differences exist, but do not lead to clinically relevant differences in visual quality or clinical assessment of patients. Therefore, CT scan may be used for attenuation correction.

To examine the relationship between the extent of disease determined by [⁶⁸Ga]PSMA-HBED-CC-PET/CT and the important clinical measures prostate-specific antigen (PSA), PSA doubling time (PSAdt) and Gleason score.

Based on a single older study it is established dogma that TSH levels should be ≥30 mU/l at the time of postoperative ¹³¹I ablation in differentiated thyroid cancer (DTC) patients. We sought to determine whether endogenous TSH levels, i.e. after levothyroxine withdrawal, at the time of ablation influence ablation success rates, recurrence-free survival and DTC-related mortality. A total of 1,873 patients without distant metastases referred for postoperative adjuvant ¹³¹I therapy were retrospectively included from 1991 onwards. Successful ablation was defined as stimulated Tg p = 0.34), recurrence-free survival (p = 0.29) or DTC -elated mortality (p = 0.82), but established risk factors such as T-stage, lymph node metastases and age were. Ablation was successful in 230 of 275 patients (83.6 %) with TSH p = 0.55). Of the whole group of 1,873 patients, 21 had recurrent disease. There were no significant differences in recurrence rates between patients with TSH p = 0.16). Ten of the 1,873 patients died of DTC. There were no significant differences in DTC-specific survival between patients with TSH p = 0.53). The precise endogenous TSH levels at the time of ¹³¹I ablation are not related to the ablation success rates, recurrence free survival and DTC related mortality. The established dogma that TSH levels need to be ≥30 mU/l at the time of ¹³¹I ablation can be discarded.

Ziel: Beantwortung der Frage, ob drei Monate nach ¹³¹I-Ablation als zu früh für eine diagnostische Radioiod-Ganzkörperszintigraphie (dxWBS) bei Patienten mit einem differenzierten Schilddrüsenkarzinom (DTC) anzusehen sind. Patienten, Material, Methode: Daten von 462 DTC-Patienten, die in unserem Klinikum behandelt worden waren, wurden analysiert. Alle Patienten wurden thyreoid ektomiert. Von 129 Patienten waren folgende Daten verfügbar a) eine dxWBS mit gleichzeitiger TSH-stimulierter Thyreoglobulin-Messung, die innerhalb von vier Monaten (max. 120 Tage) nach ¹³¹I-Ablation durchgeführt wurde ohne weitere therapeutische Maßnahmen zwischen Ablation und dxWBS, b) eine zweite dxWBS oder ¹³¹I-Therapie (rxWBS), die innerhalb von 1,5 Jahren nach Ablation durchgeführt wurde. Ergebnisse: Bei 25/129 Patienten stimmten die Ergebnisse der initialen und weiteren Scans nicht überein: Bei 15 von 54 Patienten (27%) mit einem positiven initialen dxWBS widersprachen diese Ergebnisse dem zweiten dxWBS oder rxWBS. Neue Läsionen wurden bei 10/74 (14%) Patienten mit einem initial negativen dxWBS entdeckt. Eine Diskordanz zwischen dem ersten und weiteren in der Nachsorge gemessenen stimulierten Tg-Werten wurde in 5/129 (4%) der Patienten gefunden: Bei 2/90 (2%) Patienten mit einer negativen ersten stimulierten Tg-Bestimmung wurde nachfolgend ein positives Ergebnis gefunden. Bei 3/29 (10%) Patienten mit einer positiven ersten Bestimmung wurde bei der zweiten Untersuchung ein negatives Ergebnis festgestellt. Schlussfolgerung: Weniger als vier Monate nach ¹³¹I-Ablation ist zu früh für eine diagnostische Radioiod-Ganzkörperszintigraphie mit zeitgleich TSH-stimulierter Tg-Messung. Die Ermittlung des richtigen späteren Zeitpunkts erfordert weitere Untersuchungen. Das Zeitintervall zwischen 131I Ablation und diagnostischer Ganzkörperszintigraphie bei Patienten mit differenziertem Schilddrüsenkarzinom Weniger als vier Monate nach Ablation dürfte zu früh sein Aim: to determine whether the first three months after ¹³¹I ablation is too early to perform radioiodine diagnostic whole body scintigraphy (dxWBS) in differentiated thyroid carcinoma patients. Patients, material, methods: The files of 462 patients who were treated for DTC in our hospital were reviewed. All patients underwent surgical thyroidectomy. 146 patients had data available on a. a dxWBS which was performed less than four months (max 120 days) after ¹³¹I ablation with concurrent stimulated TSH stimulated thyroglobulin (Tg) measurement without further therapeutic measures between ablation and dxWBS and b. a second dxWBS or ¹³¹I therapy (rxWBS) within 1.5 years after ablation. Results: A discordance between the initial and follow-up scan was found in 25/129 (19%) patients: of 54 patients with a positive initial dxWBS, scan results of a second dxWBS or rxWBS obtained with a suitable distance to the initial scan contradicted the initial one in 15 patients (27%). New lesions were discovered in 10/74 negative first dxWBS cases (14%). A discordance between the initial and follow-up stimulated Tg was found in 5/129 (4%) patients: 2/90 (2%) of patients with a negative stimulated Tg at initial dxWBS subsequently showed a positive results whereas 3/29 (10%) patients with an initially positive Tg showed a negative Tg level at the second procedure. Conclusion: Less than four months after ¹³¹I ablation is too early to perform radioiodine diagnostic whole body scintigraphy with concurrent TSH stimulated Tg measurement. The identification of the right, later, timepoint however requires further research.

Fatty acid synthase (FASN) is crucial to de novo long-chain fatty acid synthesis, needed to meet cancer cells’ increased demands for membrane, energy, and protein production. We investigated FASN overexpression as a therapeutic and chemosensitization target in ovarian cancer tissue, cell lines, and primary cell cultures. FASN expression at mRNA and protein levels was determined by quantitative real-time polymerase chain reaction and immunoblotting and immunohistochemistry, respectively. FASN inhibition’s impact on cell viability, apoptosis, and fatty acid metabolism was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide assay, cell death detection enzyme-linked immunosorbent assay, immunoblotting, and 18 F-fluoromethylcholine uptake measurement, respectively. Relative to that in healthy fallopian tube tissue, tumor tissues had 1.8-fold average FASN protein overexpression; cell lines and primary cultures had 11-fold–100-fold mRNA and protein overexpression. In most samples, the FASN inhibitor cerulenin markedly decreased FASN expression and cell viability and induced apoptosis. Unlike concomitant administration, sequential cerulenin/cisplatin treatment reduced cisplatin’s half maximal inhibitory concentration profoundly (up to 54%) in a cisplatin-resistant cell line, suggesting platinum (re)sensitization. Cisplatin-resistant cells displayed lower 18 F-fluoro-methylcholine uptake than did cisplatin-sensitive cells, suggesting that metabolic imaging might help guide therapy. FASN inhibition induced apoptosis in chemosensitive and platinum-resistant ovarian cancer cells and may reverse cisplatin resistance.