TY  - JOUR
A1  - Koehler, Viktoria Florentine
A1  - Adam, Pia
A1  - Fuss, Carmina Teresa
A1  - Jiang, Linmiao
A1  - Berg, Elke
A1  - Frank-Raue, Karin
A1  - Raue, Friedhelm
A1  - Hoster, Eva
A1  - Knösel, Thomas
A1  - Schildhaus, Hans-Ulrich
A1  - Negele, Thomas
A1  - Siebolts, Udo
A1  - Lorenz, Kerstin
A1  - Allelein, Stephanie
A1  - Schott, Matthias
A1  - Spitzweg, Christine
A1  - Kroiss, Matthias
T1  - Treatment of RET-positive advanced medullary thyroid cancer with multi-tyrosine kinase inhibitors — a retrospective multi-center registry analysis
JF  - Cancers
N2  - Background: RET (rearranged during transfection) variants are the most prevalent oncogenic events in medullary thyroid cancer (MTC). In advanced disease, multi-tyrosine kinase inhibitors (MKIs) cabozantinib and vandetanib are the approved standard treatment irrespective of RET status. The actual outcome of patients with RET-positive MTC treated with MKIs is ill described. Methods: We here retrospectively determined the RET oncogene variant status with a targeted DNA Custom Panel in a prospectively collected cohort of 48 patients with advanced MTC treated with vandetanib and/or cabozantinib at four German referral centers. Progression-free survival (PFS) and overall survival (OS) probabilities were estimated using the Kaplan-Meier method. Results: In total, 44/48 (92%) patients had germline or somatic RET variants. The M918T variant was found in 29/44 (66%) cases. In total, 2/32 (6%) patients with a somatic RET variant had further somatic variants, while in 1/32 (3%) patient with a germline RET variant, additional variants were found. Only 1/48 (2%) patient had a pathogenic HRAS variant, and no variants were found in 3 cases. In first-line treatment, the median OS was 53 (95% CI (95% confidence interval), 32–NR (not reached); n = 36), and the median PFS was 21 months (12–39; n = 33) in RET-positive MTC patients. In second-line treatment, the median OS was 18 (13–79; n = 22), and the median PFS was 3.5 months (2–14; n = 22) in RET-positive cases. Conclusions: RET variants were highly prevalent in patients with advanced MTC. The treatment results in RET-positive cases were similar to those reported in unselected cohorts.
KW  - medullary thyroid cancer
KW  - rearranged during transfection
KW  - variant
KW  - multi-tyrosine kinase inhibitor
KW  - survival
KW  - treatment outcome
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-281776
SN  - 2072-6694
VL  - 14
IS  - 14
ER  - 
TY  - JOUR
A1  - Werner, R.A.
A1  - Schmid, J.S.
A1  - Muegge, D.O.
A1  - Lückerath, K.
A1  - Higuchi, T.
A1  - Hänscheid, H.
A1  - Grelle, I.
A1  - Reiners, C.
A1  - Herrmann, K.
A1  - Buck, A.K.
A1  - Lapa, C.
T1  - Prognostic value of serum tumor markers in medullary thyroid cancer patients undergoing vandetanib treatment
JF  - Medicine
N2  - Tyrosine kinase inhibitors (TKIs) such as vandetanib have shown clinical effectiveness in advanced medullary thyroid cancer (MTC). During TKI treatment, fluctuations in the tumor markers carcinoembryonic antigen (CEA) and calcitonin (CTN) are frequently observed. Their role for treatment monitoring and the decision-making process has not been fully elucidated yet.
Twenty-one patients (male, 16, female, 5; mean age, 49±13 years) with progressive MTC receiving vandetanib (300mg orally per day) were considered. Tumor restaging was performed every 3 months including contrast-enhanced computed tomography (CT). Response was assessed according to recent criteria (Response Evaluation Criteria in Solid Tumors, RECIST 1.1). Additionally, CEA and CTN were measured at the day of CT imaging and alterations observed in tumor markers were compared to respective imaging findings (partial response, PR; stable disease, SD; progressive disease, PD).
During long-term follow-up (510±350 days [range, 97-1140 days]), CTN and CEA levels initially dropped in 71.4% and 61.9% of the patients followed by fluctuations in serum marker levels. A rise in CTN ≥39.5% between 2 subsequent measurements (defined by ROC analysis) had a sensitivity of 70.6% and a specificity of 83.2% in predicting PD with an accuracy of 82.0% (area under the curve (AUC), 0.76). Oscillations in CEA levels were not predictive for PD.
Whereas tumor marker fluctuations in MTC patients undergoing TKI treatment are a frequent phenomenon, a significant rise in CTN ≥40% turns out to as an early indicator of tumor progression.
KW  - follow-up
KW  - kinase inhibitor
KW  - carcinoma
KW  - calcitonin
KW  - trial
KW  - medullary thyroid cancer
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-145154
VL  - 94
IS  - 45
ER  -