@article{KoehlerAdamFussetal.2022,
  author    = {Koehler, Viktoria Florentine and Adam, Pia and Fuss, Carmina Teresa and Jiang, Linmiao and Berg, Elke and Frank-Raue, Karin and Raue, Friedhelm and Hoster, Eva and Kn{\"o}sel, Thomas and Schildhaus, Hans-Ulrich and Negele, Thomas and Siebolts, Udo and Lorenz, Kerstin and Allelein, Stephanie and Schott, Matthias and Spitzweg, Christine and Kroiss, Matthias},
  title     = {Treatment of RET-positive advanced medullary thyroid cancer with multi-tyrosine kinase inhibitors — a retrospective multi-center registry analysis},
  series = {Cancers},
  volume    = {14},
  journal   = {Cancers},
  number    = {14},
  issn      = {2072-6694},
  doi       = {10.3390/cancers14143405},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-281776},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}
@article{BaurBuentemeyerMegerleetal.2017,
  author    = {Baur, Johannes and B{\"u}ntemeyer, Tjark-Ole and Megerle, Felix and Deutschbein, Timo and Spitzweg, Christine and Quinkler, Marcus and Nawroth, Peter and Kroiss, Matthias and Germer, Christoph-Thomas and Fassnacht, Martin and Steger, Ulrich},
  title     = {Outcome after resection of Adrenocortical Carcinoma liver metastases: a retrospective study},
  series = {BMC Cancer},
  volume    = {17},
  journal   = {BMC Cancer},
  number    = {522},
  doi       = {10.1186/s12885-017-3506-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159409},
  year      = {2017},
  abstract  = {Background: Metastatic Adrenocortical Carcinoma (ACC) is a rare malignancy with a poor 5-year-survival rate (<15\%). A surgical approach is recommended in selected patients if complete resection of distant metastasis can be achieved. To date there are only limited data on the outcome after surgical resection of hepatic metastases of ACC. Methods: A retrospective analysis of the German Adrenocortical Carcinoma Registry was conducted. Patients with liver metastases of ACC but without extrahepatic metastases or incomplete tumour resection were included. Results: Seventy-seven patients fulfilled these criteria. Forty-three patients underwent resection of liver metastases of ACC. Complete tumour resection (R0) could be achieved in 30 (69.8\%). Median overall survival after liver resection was 76.1 months in comparison to 10.1 months in the 34 remaining patients with unresected liver metastases (p < 0.001). However, disease free survival after liver resection was only 9.1 months. Neither resection status (R0/R1) nor extent of liver resection were significant predictive factors for overall survival. Patients with a time interval to the first metastasis/recurrence (TTFR) of greater than 12 months or solitary liver metastases showed significantly prolonged survival. Conclusions: Liver resection in the case of ACC liver metastases can achieve long term survival with a median overall survival of more than 5 years, but disease free survival is short despite metastasectomy. Time to recurrence and single versus multiple metastases are predictive factors for the outcome.},
  language  = {en}
}
@article{AdamKircherSbieraetal.2021,
  author    = {Adam, Pia and Kircher, Stefan and Sbiera, Iuliu and Koehler, Viktoria Florentine and Berg, Elke and Kn{\"o}sel, Thomas and Sandner, Benjamin and Fenske, Wiebke Kristin and Bl{\"a}ker, Hendrik and Smaxwil, Constantin and Zielke, Andreas and Sipos, Bence and Allelein, Stephanie and Schott, Matthias and Dierks, Christine and Spitzweg, Christine and Fassnacht, Martin and Kroiss, Matthias},
  title     = {FGF-Receptors and PD-L1 in Anaplastic and Poorly Differentiated Thyroid Cancer: Evaluation of the Preclinical Rationale},
  series = {Frontiers in Endocrinology},
  volume    = {12},
  journal   = {Frontiers in Endocrinology},
  issn      = {1664-2392},
  doi       = {10.3389/fendo.2021.712107},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244653},
  year      = {2021},
  abstract  = {Background Treatment options for poorly differentiated (PDTC) and anaplastic (ATC) thyroid carcinoma are unsatisfactory and prognosis is generally poor. Lenvatinib (LEN), a multi-tyrosine kinase inhibitor targeting fibroblast growth factor receptors (FGFR) 1-4 is approved for advanced radioiodine refractory thyroid carcinoma, but response to single agent is poor in ATC. Recent reports of combining LEN with PD-1 inhibitor pembrolizumab (PEM) are promising. Materials and Methods Primary ATC (n=93) and PDTC (n=47) tissue samples diagnosed 1997-2019 at five German tertiary care centers were assessed for PD-L1 expression by immunohistochemistry using Tumor Proportion Score (TPS). FGFR 1-4 mRNA was quantified in 31 ATC and 14 PDTC with RNAscope in-situ hybridization. Normal thyroid tissue (NT) and papillary thyroid carcinoma (PTC) served as controls. Disease specific survival (DSS) was the primary outcome variable. Results PD-L1 TPS≥50\% was observed in 42\% of ATC and 26\% of PDTC specimens. Mean PD-L1 expression was significantly higher in ATC (TPS 30\%) than in PDTC (5\%; p<0.01) and NT (0\%, p<0.001). 53\% of PDTC samples had PD-L1 expression ≤5\%. FGFR mRNA expression was generally low in all samples but combined FGFR1-4 expression was significantly higher in PDTC and ATC compared to NT (each p<0.001). No impact of PD-L1 and FGFR 1-4 expression was observed on DSS. Conclusion High tumoral expression of PD-L1 in a large proportion of ATCs and a subgroup of PDTCs provides a rationale for immune checkpoint inhibition. FGFR expression is low thyroid tumor cells. The clinically observed synergism of PEM with LEN may be caused by immune modulation.},
  language  = {en}
}