@article{BasilePuglisiAltierietal.2021,
  author    = {Basile, Vittoria and Puglisi, Soraya and Altieri, Barbara and Canu, Letizia and Lib{\`e}, Rossella and Ceccato, Filippo and Beuschlein, Felix and Quinkler, Marcus and Calabrese, Anna and Perotti, Paola and Berchialla, Paola and Dischinger, Ulrich and Megerle, Felix and Baudin, Eric and Bourdeau, Isabelle and Lacroix, Andr{\´e} and Loli, Paola and Berruti, Alfredo and Kastelan, Darko and Haak, Harm R. and Fassnacht, Martin and Terzolo, Massimo},
  title     = {What is the optimal duration of adjuvant mitotane therapy in adrenocortical carcinoma? An unanswered question},
  series = {Journal of Personalized Medicine},
  volume    = {11},
  journal   = {Journal of Personalized Medicine},
  number    = {4},
  issn      = {2075-4426},
  doi       = {10.3390/jpm11040269},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236507},
  year      = {2021},
  abstract  = {A relevant issue on the treatment of adrenocortical carcinoma (ACC) concerns the optimal duration of adjuvant mitotane treatment. We tried to address this question, assessing whether a correlation exists between the duration of adjuvant mitotane treatment and recurrence-free survival (RFS) of patients with ACC. We conducted a multicenter retrospective analysis on 154 ACC patients treated for ≥12 months with adjuvant mitotane after radical surgery and who were free of disease at the mitotane stop. During a median follow-up of 38 months, 19 patients (12.3\%) experienced recurrence. We calculated the RFS after mitotane (RFSAM), from the landmark time-point of mitotane discontinuation, to overcome immortal time bias. We found a wide variability in the duration of adjuvant mitotane treatment among different centers and also among patients cared for at the same center, reflecting heterogeneous practice. We did not find any survival advantage in patients treated for longer than 24 months. Moreover, the relationship between treatment duration and the frequency of ACC recurrence was not linear after stratifying our patients in tertiles of length of adjuvant treatment. In conclusion, the present findings do not support the concept that extending adjuvant mitotane treatment over two years is beneficial for ACC patients with low to moderate risk of recurrence.},
  language  = {en}
}
@article{WernerBundschuhHiguchietal.2018,
  author    = {Werner, Rudolf A. and Bundschuh, Ralph A. and Higuchi, Takahiro and Javadi, Mehrbod S. and Rowe, Steven P. and Zs{\´o}t{\´e}r, Norbert and Kroiss, Matthias and Fassnacht, Martin and Buck, Andreas K. and Kreissl, Michael C. and Lapa, Constantin},
  title     = {Volumetric and Texture Analysis of Pretherapeutic \(^{18}\)F-FDG PET can Predict Overall Survival in Medullary Thyroid Cancer Patients Treated with Vandetanib},
  series = {Endocrine},
  journal   = {Endocrine},
  issn      = {1355-008X},
  doi       = {10.1007/s12020-018-1749-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167910},
  year      = {2018},
  abstract  = {Purpose: The metabolically most active lesion in 2-deoxy-2-(\(^{18}\)F)fluoro-D-glucose (\(^{18}\)F-FDG) PET/CT can predict progression-free survival (PFS) in patients with medullary thyroid carcinoma (MTC) starting treatment with the tyrosine kinase inhibitor (TKI) vandetanib. However, this metric failed in overall survival (OS) prediction. In the present proof of concept study, we aimed to explore the prognostic value of intratumoral textural features (TF) as well as volumetric parameters (total lesion glycolysis, TLG) derived by pre-therapeutic \(^{18}\)F-FDG PET. Methods: Eighteen patients with progressive MTC underwent baseline \(^{18}\)F-FDG PET/CT prior to and 3 months after vandetanib initiation. By manual segmentation of the tumor burden at baseline and follow-up PET, intratumoral TF and TLG were computed. The ability of TLG, imaging-based TF, and clinical parameters (including age, tumor marker doubling times, prior therapies and RET (rearranged during transfection) mutational status) for prediction of both PFS and OS were evaluated. Results: The TF Complexity and the volumetric parameter TLG obtained at baseline prior to TKI initiation successfully differentiated between low- and high-risk patients. Complexity allocated 10/18 patients to the high-risk group with an OS of 3.3y (vs. low-risk group, OS=5.3y, 8/18, AUC=0.78, P=0.03). Baseline TLG designated 11/18 patients to the high-risk group (OS=3.5y vs. low-risk group, OS=5y, 7/18, AUC=0.83, P=0.005). The Hazard Ratio for cancer-related death was 6.1 for Complexity (TLG, 9.5). Among investigated clinical parameters, the age at initiation of TKI treatment reached significance for PFS prediction (P=0.02, OS, n.s.). Conclusions: The TF Complexity and the volumetric parameter TLG are both independent parameters for OS prediction.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@article{ArltBiehlTayloretal.2011,
  author    = {Arlt, Wiebke and Biehl, Michael and Taylor, Angela E. and Hahner, Stefanie and Lib{\´e}, Rossella and Hughes, Beverly A. and Schneider, Petra and Smith, David J. and Stiekema, Han and Krone, Nils and Porfiri, Emilio and Opocher, Giuseppe and Bertherat, Jer{\^o}me and Mantero, Franco and Allolio, Bruno and Terzolo, Massimo and Nightingale, Peter and Shackleton, Cedric H. L. and Bertagna, Xavier and Fassnacht, Martin and Stewart, Paul M.},
  title     = {Urine Steroid Metabolomics as a Biomarker Tool for Detecting Malignancy in Adrenal Tumors},
  series = {The Journal of Clinical Endocrinology \& Metabolism},
  volume    = {96},
  journal   = {The Journal of Clinical Endocrinology \& Metabolism},
  number    = {12},
  doi       = {10.1210/jc.2011-1565},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154682},
  pages     = {3775 -- 3784},
  year      = {2011},
  abstract  = {Context: Adrenal tumors have a prevalence of around 2\% in the general population. Adrenocortical carcinoma (ACC) is rare but accounts for 2-11\% of incidentally discovered adrenal masses. Differentiating ACC from adrenocortical adenoma (ACA) represents a diagnostic challenge in patients with adrenal incidentalomas, with tumor size, imaging, and even histology all providing unsatisfactory predictive values. Objective: Here we developed a novel steroid metabolomic approach, mass spectrometry-based steroid profiling followed by machine learning analysis, and examined its diagnostic value for the detection of adrenal malignancy. Design: Quantification of 32 distinct adrenal derived steroids was carried out by gas chromatography/mass spectrometry in 24-h urine samples from 102 ACA patients (age range 19-84 yr) and 45 ACC patients (20-80 yr). Underlying diagnosis was ascertained by histology and metastasis in ACC and by clinical follow-up [median duration 52 (range 26-201) months] without evidence of metastasis in ACA. Steroid excretion data were subjected to generalized matrix learning vector quantization (GMLVQ) to identify the most discriminative steroids. Results: Steroid profiling revealed a pattern of predominantly immature, early-stage steroidogenesis in ACC. GMLVQ analysis identified a subset of nine steroids that performed best in differentiating ACA from ACC. Receiver-operating characteristics analysis of GMLVQ results demonstrated sensitivity = specificity = 90\% (area under the curve = 0.97) employing all 32 steroids and sensitivity = specificity = 88\% (area under the curve = 0.96) when using only the nine most differentiating markers. Conclusions: Urine steroid metabolomics is a novel, highly sensitive, and specific biomarker tool for discriminating benign from malignant adrenal tumors, with obvious promise for the diagnostic work-up of patients with adrenal incidentalomas.},
  language  = {en}
}
@article{DischingerHasingerKoenigsraineretal.2021,
  author    = {Dischinger, Ulrich and Hasinger, Julia and K{\"o}nigsrainer, Malina and Corteville, Carolin and Otto, Christoph and Fassnacht, Martin and Hankir, Mohamed and Seyfried, Florian Johannes David},
  title     = {Toward a Medical Gastric Bypass: Chronic Feeding Studies With Liraglutide + PYY\(_{3-36}\) Combination Therapy in Diet-Induced Obese Rats},
  series = {Frontiers in Endocrinology},
  volume    = {11},
  journal   = {Frontiers in Endocrinology},
  issn      = {1664-2392},
  doi       = {10.3389/fendo.2020.598843},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223113},
  year      = {2021},
  abstract  = {Background Combination therapies of anorectic gut hormones partially mimic the beneficial effects of bariatric surgery. Thus far, the effects of a combined chronic systemic administration of Glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine 3-36 (PYY\(_{3-36}\)) have not been directly compared to Roux-en-Y gastric bypass (RYGB) in a standardized experimental setting. Methods High-fat diet (HFD)-induced obese male Wistar rats were randomized into six treatment groups: (1) RYGB, (2) sham-operation (shams), (3) liraglutide, (4) PYY\(_{3-36}\), (5) PYY\(_{3-36}\)+liraglutide (6), saline. Animals were kept on a free choice high- and low-fat diet. Food intake, preference, and body weight were measured daily for 4 weeks. Open field (OP) and elevated plus maze (EPM) tests were performed. Results RYGB reduced food intake and achieved sustained weight loss. Combined PYY\(_{3-36}\)+liraglutide treatment led to similar and plateaued weight loss compared to RYGB. Combined PYY\(_{3-36}\)+liraglutide treatment was superior to PYY\(_{3-36}\) (p ≤ 0.0001) and liraglutide (p ≤ 0.05 or p ≤ 0.01) mono-therapy. PYY\(_{3-36}\)+liraglutide treatment and RYGB also reduced overall food intake and (less pronounced) high-fat preference compared to controls. The animals showed no signs of abnormal behavior in OF or EPM. Conclusions Liraglutide and PYY\(_{3-36}\) combination therapy vastly mimics reduced food intake, food choice and weight reducing benefits of RYGB.},
  language  = {en}
}
@article{PaschkeLinckeMuelleretal.2015,
  author    = {Paschke, Ralf and Lincke, Thomas and M{\"u}ller, Stefan P. and Kreissl, Michael C. and Dralle, Henning and Fassnacht, Martin},
  title     = {The Treatment of Well-Differentiated Thyroid Carcinoma},
  series = {Deutsches {\"A}rzteblatt International},
  volume    = {112},
  journal   = {Deutsches {\"A}rzteblatt International},
  doi       = {10.3238/arztebl.2015.0452},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151636},
  pages     = {452 -- 458},
  year      = {2015},
  abstract  = {Background: Recent decades have seen a rise in the incidence of well-differentiated (mainly papillary) thyroid carcinoma around the world. In Germany, the age-adjusted incidence of well-differentiated thyroid carcinoma in 2010 was 3.5 per 100 000 men and 8.7 per 100 000 women per year. Method: This review is based on randomized, controlled trials and multicenter trials on the treatment of well-differentiated thyroid carcinoma that were retrieved by a selective literature search, as well as on three updated guidelines issued in the past two years. Results: The recommended extent of surgical resection depends on whether the tumor is classified as low-risk or high-risk, so that papillary microcar cinomas, which carry a highly favorable prognosis, will not be overtreated. More than 90\% of localized, well-differentiated thyroid carcinomas can be cured with a combination of surgery and radioactive iodine therapy. Radio active iodine therapy is also effective in the treatment of well-differentiated thyroid carcinomas with distant metastases, yielding a 10-year survival rate of 90\%, as long as there is good iodine uptake and the tumor goes into remission after treatment; otherwise, the 10-year survival rate is only 10\%. In the past two years, better treatment options have become available for radioactive-iodine-resistant thyroid carcinoma. Phase 3 studies of two different tyrosine kinase inhibitors have shown that either one can markedly prolong progression-free survival, but not overall survival. Their more common clinically significant side effects are hand-foot syndrome, hypertension, diarrhea, proteinuria, and weight loss. Conclusion: Slow tumor growth, good resectability, and susceptibility to radioactive iodine therapy lend a favorable prognosis to most cases of well-differentiated thyroid carcinoma. The treatment should be risk-adjusted and interdisciplinary, in accordance with the current treatment guidelines. Even metastatic thyroid carcinoma has a favorable prognosis as long as there is good iodine uptake. The newly available medical treatment options for radioactive-iodine-resistant disease need to be further studied.},
  language  = {en}
}
@article{LippertFassnachtRonchi2022,
  author    = {Lippert, Juliane and Fassnacht, Martin and Ronchi, Cristina L.},
  title     = {The role of molecular profiling in adrenocortical carcinoma},
  series = {Clinical Endocrinology},
  volume    = {97},
  journal   = {Clinical Endocrinology},
  number    = {4},
  doi       = {10.1111/cen.14629},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258382},
  pages     = {460-472},
  year      = {2022},
  abstract  = {Adrenocortical carcinoma (ACC) is a rare, aggressive cancer with still partially unknown pathogenesis, heterogenous clinical behaviour and no effective treatment for advanced stages. Therefore, there is an urgent clinical unmet need for better prognostication strategies, innovative therapies and significant improvement of the management of the individual patients. In this review, we summarize available studies on molecular prognostic markers and markers predictive of response to standard therapies as well as newly proposed drug targets in sporadic ACC. We include in vitro studies and available clinical trials, focusing on alterations at the DNA, RNA and epigenetic levels. We also discuss the potential of biomarkers to be implemented in a clinical routine workflow for improved ACC patient care.},
  language  = {en}
}
@article{GelbrichMorbachDeutschbeinetal.2023,
  author    = {Gelbrich, G{\"o}tz and Morbach, Caroline and Deutschbein, Timo and Fassnacht, Martin and St{\"o}rk, Stefan and Heuschmann, Peter U.},
  title     = {The population comparison index: an intuitive measure to calibrate the extent of impairments in patient cohorts in relation to healthy and diseased populations},
  series = {International Journal of Environmental Research and Public Health},
  volume    = {20},
  journal   = {International Journal of Environmental Research and Public Health},
  number    = {3},
  issn      = {1660-4601},
  doi       = {10.3390/ijerph20032168},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304933},
  year      = {2023},
  abstract  = {We assume that a specific health constraint, e.g., a certain aspect of bodily function or quality of life that is measured by a variable X, is absent (or irrelevant) in a healthy reference population (Ref0), and it is materially present and precisely measured in a diseased reference population (Ref1). We further assume that some amount of this constraint of interest is suspected to be present in a population under study (SP). In order to quantify this issue, we propose the introduction of an intuitive measure, the population comparison index (PCI), that relates the mean value of X in population SP to the mean values of X in populations Ref0 and Ref1. This measure is defined as PCI[X] = (mean[X|SP] - mean[X|Ref0])/(mean[X|Ref1] - mean[X|Ref0]) × 100[\%], where mean[X|.] is the average value of X in the respective group of individuals. For interpretation, PCI[X] ≈ 0 indicates that the values of X in the population SP are similar to those in population Ref0, and hence, the impairment measured by X is not materially present in the individuals in population SP. On the other hand, PCI[X] ≈ 100 means that the individuals in SP exhibit values of X comparable to those occurring in Ref1, i.e., the constraint of interest is equally present in populations SP and Ref1. A value of 0 < PCI[X] < 100 indicates that a certain percentage of the constraint is present in SP, and it is more than in Ref0 but less than in Ref1. A value of PCI[X] > 100 means that population SP is even more affected by the constraint than population Ref1.},
  language  = {en}
}
@article{SbieraKunzWeigandetal.2019,
  author    = {Sbiera, Silviu and Kunz, Meik and Weigand, Isabel and Deutschbein, Timo and Dandekar, Thomas and Fassnacht, Martin},
  title     = {The new genetic landscape of Cushing's disease: deubiquitinases in the spotlight},
  series = {Cancers},
  volume    = {11},
  journal   = {Cancers},
  number    = {11},
  issn      = {2072-6694},
  doi       = {10.3390/cancers11111761},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193194},
  pages     = {1761},
  year      = {2019},
  abstract  = {Cushing's disease (CD) is a rare condition caused by adrenocorticotropic hormone (ACTH)-producing adenomas of the pituitary, which lead to hypercortisolism that is associated with high morbidity and mortality. Treatment options in case of persistent or recurrent disease are limited, but new insights into the pathogenesis of CD are raising hope for new therapeutic avenues. Here, we have performed a meta-analysis of the available sequencing data in CD to create a comprehensive picture of CD's genetics. Our analyses clearly indicate that somatic mutations in the deubiquitinases are the key drivers in CD, namely USP8 (36.5\%) and USP48 (13.3\%). While in USP48 only Met415 is affected by mutations, in USP8 there are 26 different mutations described. However, these different mutations are clustering in the same hotspot region (affecting in 94.5\% of cases Ser718 and Pro720). In contrast, pathogenic variants classically associated with tumorigenesis in genes like TP53 and BRAF are also present in CD but with low incidence (12.5\% and 7\%). Importantly, several of these mutations might have therapeutic potential as there are drugs already investigated in preclinical and clinical setting for other diseases. Furthermore, network and pathway analyses of all somatic mutations in CD suggest a rather unified picture hinting towards converging oncogenic pathways.},
  language  = {en}
}
@article{WernerSayehliHaenscheidetal.2023,
  author    = {Werner, Rudolf A. and Sayehli, Cyrus and H{\"a}nscheid, Heribert and Higuchi, Takahiro and Serfling, Sebastian E. and Fassnacht, Martin and Goebeler, Maria-Elisabeth and Buck, Andreas K. and Kroiss, Matthias},
  title     = {Successful combination of selpercatinib and radioiodine after pretherapeutic dose estimation in RET-altered thyroid carcinoma},
  series = {European Journal of Nuclear Medicine and Molecular Imaging},
  volume    = {50},
  journal   = {European Journal of Nuclear Medicine and Molecular Imaging},
  number    = {6},
  doi       = {10.1007/s00259-022-06061-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324435},
  pages     = {1833-1834},
  year      = {2023},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{FassnachtJohanssenAllolio2011,
  author    = {Fassnacht, Martin and Johanssen, Sarah and Allolio, Bruno},
  title     = {Statements Cannot Be Substantiated : In Reply},
  series = {Deutsches {\"A}rzteblatt International},
  volume    = {108},
  journal   = {Deutsches {\"A}rzteblatt International},
  number    = {19},
  doi       = {10.3238/arztebl.2011.0339b},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142597},
  pages     = {339-340},
  year      = {2011},
  abstract  = {No abstract available.},
  language  = {en}
}