Background. Lenvatinib has proven efficacy in progressive, radioiodine- (RAI-) refractory thyroid cancer (TC). Dose reductions are commonly performed due to decreased tolerability and adverse effects. This retrospective multicenter study analyzed overall survival (OS) and progression-free survival (PFS) and tolerability in the Austrian patient population treated with lenvatinib. Methods. Clinical data of 43 patients (25 males and 18 females) with a median age of 70 years (range: 39-91 years) and RAI-refractory TC with metastases to the lymph nodes (74%), lungs (86%), bone (35%), liver (16%), and brain (12%) were analyzed. The mean duration of treatment with lenvatinib was 26.6 +/- 15.4 months with dosage reductions required in 39 patients (91%). Results. PFS after 24 months was 71% (95% CI: 56-87), and overall survival (OS) was 74% (95% CI: 60-88), respectively. OS was significantly shorter (p=0.048) in patients with a daily maintenance dosage <= 10 mg (63%) (95% CI: 39-86) as compared to patients on >= 14 mg lenvatinib (82%) (95% CI: 66-98) daily. Dose reduction was noted in 39 patients (91%). Grade >= 3 toxicities (hypertension, diarrhea, weight loss, and palmar-plantar erythrodysesthesia syndrome) were most common leading to discontinuation of lenvatinib in 7 patients (16%). Conclusion. Lenvatinib showed sustained clinical efficacy in patients with metastatic RAI-refractory TC even with reduced maintenance dosages over years. The effects were comparable to the registration trial, although patients had a higher median age and, more commonly, dose reductions.

Tenascin C expression correlates with tumor grade and indicates worse prognosis in several tumors. Epidermal growth factor receptor (EGFR) plays an important role in driving proliferation in many tumors. Loss of E-cadherin function is associated with tumor invasion and metastasis. Thyroid transcription factor-1 (TTF-1) is involved in rearranged during transfection (RET) transcription in Hirschsprung’s disease. Tenascin C, EGFR, E-cadherin, TTF-1-expression, and their correlations with RET mutation status were investigated in 30 patients with medullary thyroid carcinoma (MTC) (n = 26) or C-cell hyperplasia (n = 4). Tenascin C was found in all, EGFR in 4/26, E-cadherin in 23/26, and TTF-1 in 25/26 MTC. Tenascin C correlated significantly with tumor proliferation (overall, r = 0.61, p < 0.005; RET-mutated, r = 0.81, p < 0.01). E-cadherin showed weak correlation, whereas EGFR and TTF-1 showed no significant correlation with tumor proliferation. EGFR, E-cadherin, and TTF-1 showed weak correlation with proliferation of RET-mutated tumors. Correlation between TTF-1 and tenascin C, E-cadherin, and EGFR was r = −0.10, 0.37, and 0.21, respectively. In conclusion, MTC express tenascin C, E-cadherin, and TTF-1. Tenascin C correlates significantly with tumor proliferation, especially in RET-mutated tumors. EGFR is low, and tumors expressing EGFR do not exhibit higher proliferation. TTF-1 does not correlate with RET mutation status and has a weak correlation with tenascin C, E-cadherin, and EGFR expression.

Objective: The comparison of 2-deoxy-2-[18F]fluoro-d-glucose (F-18 FDG) and 3′-deoxy-3′-[18F]fluorothymidine (F-18 FLT) imaging in patients with rectal cancer before and after neoadjuvant radiochemotherapy (RCT) in relation to histopathology and immunohistochemistry obtained from surgery. Methods: 20 consecutive patients (15 m, 5 f), mean age of 65 ± 10 years were included into this prospective study with a mean follow-up of 4.1 ± 0.8 years. Results: Among histopathological responders (n = 8 out of 20), posttreatment F-18 FLT and F-18 FDG scans were negative in 75 % (n = 6) and 38 % (n = 3), respectively. The mean response index (RI) was 61.0 % ± 14.0 % for F-18 FLT and 58.7 % ± 14.6 % for F-18 FDG imaging. Peritumoral lymphocytic infiltration (CD3 positive cells) was significantly related to posttreatment SUV_max in F-18 FDG but not F-18 FLT studies. Conclusion: A significant decrease of SUV_max in F-18 FDG and F-18 FLT studies could be seen after RCT. Negative posttreatment F-18 FLT studies identified more histopathological responders.

The accurate detection of hyperfunctioning parathyroid tissue (HFPT) is pivotal in the preoperative assessment of primary hyperparathyroidism (PHPT). PET/CT using [¹⁸F]fluorocholine ([¹⁸F]FCH) showed superior diagnostic performance compared to conventional functional imaging modalities. We aimed to evaluate the diagnostic performance of [¹⁸F]FCH PET/CT as a first-line functional imaging approach in patients with clinically diagnosed PHPT. The imaging and clinical data of 321 PHPT patients, including 271 overt PHPT and 50 mild PHPT, who underwent [¹⁸F]FCH PET/CT as first-line imaging were analysed in this retrospective study. Histopathology was the reference standard. In case of no available histopathology evaluation (conservative management), imaging and clinical follow-ups were considered reference standards. In the overt group (n = 271), [¹⁸F]FCH PET/CT showed sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 0.99, 0.91, 1.00, 0.80, and 0.99, respectively. Regarding the correlation of the index lesions and initial laboratory data, all [¹⁸F]FCH PET/CT parameters (SUVs, SULs, and mSAD) were significantly correlated with the serum iPTH level. Additionally, SUVmax, SULpeak, and mSAD were significantly associated with the serum calcium level. In the mild group (n = 50), [¹⁸F]FCH PET/CT showed a sensitivity, specificity, PPV, NPV, and accuracy of 0.93, 0.75, 0.95, 0.67, and 0.90. In conclusion, [¹⁸F]FCH PET/CT revealed high diagnostic performance in the detection of HFPTs and the potential to be considered as a first-line imaging modality in the assessment of PHPT, including both overt and mild types. However, its cost–benefit concerning the clinical impact of early PHPT detection should be investigated in future studies.

Background: We aimed to compare the established metabolic response criteria PERCIST and EORTC for their applicability and predictive value in terms of clinical response assessment early after the initiation of lenvatinib therapy in patients with metastatic radioiodine-refractory (RAI) thyroid cancer (TC). Methods: In 25 patients treated with lenvatinib, baseline and 4-month follow-up F-18 FDG PET/CT images were analyzed using PERCIST 1.0, modified PERCIST (using SUVpeak or SUVmax) and EORTC criteria. Two groups were defined: disease control (DC) and progressive disease (PD), which were correlated with PFS and OS. Results: PERCIST, mPERCIST, PERCISTmax and EORTC could be applied in 80%, 80%, 88% and 100% of the patients based on the requirements of lesion assessment criteria, respectively. With PERCIST, mPERCIST, PERCISTmax and EORTC, the patients classified as DC and PD ranged from 65 to 68% and from 32 to 35%, respectively. Patients with DC exhibited a longer median PFS than patients with PD for EORTC (p < 0.014) and for PERCIST and mPERCIST (p = 0.037), respectively. Conclusion: EORTC and the different PERCIST criteria performed equally regarding the identification of patients with PD requiring treatment changes. However, the applicability of PERCIST 1.0 using SULpeak seems restricted due to the significant proportion of small tumor lesions.