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  - Merzenich, Hiltrud
A1  - Baaken, Dan
A1  - Schmidt, Marcus
A1  - Bekes, Inga
A1  - Schwentner, Lukas
A1  - Janni, Wolfgang
A1  - Woeckel, Achim
A1  - Bartkowiak, Detlef
A1  - Wiegel, Thomas
A1  - Blettner, Maria
A1  - Wollschläger, Daniel
A1  - Schmidberger, Heinz
T1  - Cardiac late effects after modern 3D-conformal radiotherapy in breast cancer patients: a retrospective cohort study in Germany (ESCaRa)
JF  - Breast Cancer Research and Treatment
N2  - Purpose
Radiotherapy (RT) was identified as a risk factor for long-term cardiac effects in breast cancer patients treated until the 1990s. However, modern techniques reduce radiation exposure of the heart, but some exposure remains unavoidable. In a retrospective cohort study, we investigated cardiac mortality and morbidity of breast cancer survivors treated with recent RT in Germany.

Methods
A total of 11,982 breast cancer patients treated between 1998 and 2008 were included. A mortality follow-up was conducted until 06/2018. In order to assess cardiac morbidity occurring after breast cancer treatment, a questionnaire was sent out in 2014 and 2019. The effect of breast cancer laterality on cardiac mortality and morbidity was investigated as a proxy for radiation exposure. We used Cox Proportional Hazards regression analysis, taking potential confounders into account.

Results
After a median follow-up time of 11.1 years, there was no significant association of tumor laterality with cardiac mortality in irradiated patients (hazard ratio (HR) for left-sided versus right-sided tumor 1.09; 95% confidence interval (CI) 0.85–1.41). Furthermore, tumor laterality was not identified as a significant risk factor for cardiac morbidity (HR = 1.05; 95%CI 0.88–1.25).

Conclusions
Even though RT for left-sided breast cancer on average incurs higher radiation dose to the heart than RT for right-sided tumors, we found no evidence that laterality is a strong risk factor for cardiac disease after contemporary RT. However, larger sample sizes, longer follow-up, detailed information on individual risk factors and heart dose are needed to assess clinically manifest late effects of current cancer therapy.
KW  - breast cancer
KW  - 3D-conformal radiotherapy
KW  - cardiac mortality
KW  - cardiac morbidity
KW  - cohort study
KW  - survival
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-308606
SN  - 0167-6806
SN  - 1573-7217
VL  - 191
IS  - 1
ER  -