Dokument: Detektion und Bewertung von Lungenrundherden im initialen Staging von Brustkrebspatientinnen mittels PET/MRT
| Titel: | Detektion und Bewertung von Lungenrundherden im initialen Staging von Brustkrebspatientinnen mittels PET/MRT | |||||||
| Weiterer Titel: | Lung nodules missed in initial staging of breast cancer patients in PET/MRI – clinically relevant? | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=67552 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20241127-110249-9 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Deutsch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Bruckmann, Charlotte Johanna [Autor] | |||||||
| Dateien: |
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| Beitragende: | Kirchner, Julian [Gutachter] Dr. Flügen, Georg [Gutachter] | |||||||
| Stichwörter: | PET/MRT, Lungenrundherde, MRT, CT, Mammakarzinom | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibungen: | Die kombinierte Positronenemissions-Magnetresonanztomographie mit [18F] Fluordesoxyglucose ([18F]FDG-PET/MRT) ist insbesondere bei Patientinnen mit Hochrisiko-Mammakarzinom eine vielversprechende Ganzkörper-Staging-Methode. Die Computertomographie (CT) stellt aktuell den Goldstandard in der Diagnostik der Lunge dar und ist der Magnetresonanztomographie (MRT) bei der Erkennung von Lungenrundherden überlegen. Vorherige Arbeiten legen den Verdacht nahe, dass diese Überlegenheit bei Tumorpatienten keinen relevanten klinischen Einfluss hat. Ziel dieser Studie war es daher, die klinische Relevanz von nicht detektierten Lungenrundherden beim Primärstaging von Brustkrebspatientinnen mittels [18F]FDG-PET/MRT im Vergleich zur CT zu untersuchen.
152 Frauen mit neu diagnostiziertem Mammakarzinom wurden in diese Studie eingeschlossen. Alle Patientinnen erhielten zum initialen Staging eine Ganzkörper-[18F]FDG-PET/MRT und eine thorakoabdominelle CT. Die Nachsorge erfolgte mittels Ganzkörper-MRT und/oder einer Thorax-CT im Zeitraum von bis zu einem Jahr. Die mittels der primären MRT-VIBE und MRT-HASTE Sequenz im Vergleich zur CT verpassten Lungenrundherde wurden in Anlehnung an die Fleischner-Kriterien definiert und charakterisiert (Referenzstandard I). Zur endgültigen klinischen Einschätzung wurden alle im initialen Staging verpassten Rundherde im Follow-up erneut charakterisiert (Referenzstandard II). Basierend auf dieser Einschätzung wurde zwischen „klinisch relevanten“ und „klinisch nicht relevanten“ verpassten Rundherden differenziert. Die Datenanalyse wurde sowohl patientenbezogen als auch läsionsbezogen durchgeführt. Die deskriptiven Statistiken wurden mit SPSS erstellt. Die Unterschiede bei der Abgrenzung von Lungenrundherden in der MRT-VIBE und der -HASTE Sequenz wurden mit dem McNemar-Test auf statistische Signifikanz untersucht. Die läsionsbasierte Analyse ergab, dass mittels VIBE Sequenz 96 Rundherde im Vergleich zur CT verpasst wurden, von diesen waren 4 Metastasen (4 %). Mittels HASTE Sequenz wurden insgesamt 138 Rundherde verpasst, von denen 8 Metastasen waren (6 %). Die patientenbasierte Analyse ergab, dass insgesamt eine Patientin mit Lungenmetastasen basierend auf der HASTE Sequenz verpasst wurde. Basierend auf den Ergebnissen der VIBE Sequenz wurden alle Patientinnen mit pulmonalen Metastasen detektiert. In der VIBE Sequenz wurden 67/163 (41 %) und in der HASTE Sequenz 25/163 (15 %) der Lungenrundherde detektiert. Der Unterschied war statistisch signifikant (p < 0.01). In der patientenbasierten Analyse konnten alle Patientinnen mit Lungenmetastasen mittels der [18F]FDG-PET/MRT unter Verwendung der VIBE Sequenz detektiert werden. Dies zeigt die hohe diagnostische Aussagekraft einer Ganzkörper [18F]FDG-PET/MRT Untersuchung für Patientinnen mit fortgeschrittenem Mammakarzinom. Darüber hinaus könnte aufgrund der guten Sensitivität der MRT-VIBE Sequenz im Rahmen des Screenings von Lungenrundherden auf die HASTE Sequenz des Thorax verzichtet und hierdurch eine Zeitersparnis in der klinischen Screening-Routine erreicht werden.Combined positron emission magnetic resonance imaging with [18F] fluorodeoxyglucose ([18F]FDG-PET/MRI) is a promising whole-body staging method, especially for patients with high-risk breast cancer. Computed tomography (CT) is the current goldstandard in lung imaging and is superior to magnetic resonance imaging (MRI) in the detection of pulmonary nodules. However, previous work has shown that this superiority does not seem to have a relevant clinical impact in patients with known malignancies. Therefore, the aim of this study was to evaluate the clinical relevance of undetected pulmonary nodules in primary staging of breast cancer patients using [18F]FDG-PET/MRI compared to CT. 152 women with newly diagnosed breast cancer were included in this study. All patients underwent whole-body [18F]FDG-PET/MRI and thoracoabdominal CT for initial staging. Follow-up was performed approximately one year later by whole-body MRI and/or thoracic CT. Pulmonary nodules missed by the primary MRI-VIBE and MRI-HASTE sequence when compared to CT were defined and characterised according to the Fleischner criteria (reference standard I). For final clinical assessment, all lesions missed in the initial staging were re-characterised in the follow-up (reference standard II). Based on this assessment, a differentiation was made between "clinically relevant" and "clinically non-relevant" missed nodules. The data analysis was performed both patient-based and lesion-based. Descriptive statistics were performed using SPSS. Differences in the discrimination of lung nodules in the MRI-VIBE and -HASTE sequences were tested for statistical significance using the McNemar test. In a lesion-based analysis 4/96 (VIBE) and 8/138 (HASTE) missed lung nodules had signs of malignancy and were therefore clinically relevant. The patient-based analysis showed that all patients with pulmonary metastases were detected based on the VIBE sequence results. Subsequently, none of the in 84 patients missed lung nodules in the VIBE sequence referring to the initial CT were clinically relevant. With regard to the HASTE sequence one patient with lung metastases was missed. In VIBE 67/163 (41 %) and in HASTE 25/163 (15 %) pulmonary nodules were detected. The difference was statistically relevant (p < 0.01). In the patient-based analysis, all patients with pulmonary metastases were detected by [18F]FDG-PET/MRI using the VIBE sequence. This demonstrates the high diagnostic value of a whole-body [18F]FDG-PET/MRI examination for patients with advanced breast cancer. Furthermore, due to the good sensitivity of the MRI-VIBE sequence, the HASTE sequence could be omitted in the screening of pulmonary nodules, thus saving time in the clinical screening routine. | |||||||
| Quelle: | 1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394-424.
2. Caspritz S, Christ M, Ernst A, et al. Mundhöle und Rachen.; 2015. 3. Krebs in Deutschland für 2017/2018. 2018. 4. Sinn HP, Kreipe H. A brief overview of the WHO classification of breast tumors, 4th edition, focusing on issues and updates from the 3rd edition. Breast Care. 2013;8:149-154. 5. Fischer U, Baum F. Diagnostik und Therapie des Mammakarzinoms. Thieme Verlag KG; 2014. 6. Gerber D. Diagnostik und Therapie früher und fortgeschrittener Mammakarzinome Optionen der primären Prävention : Veränderbare Lifestyle-Faktoren Prävention Version 2022 : 2022. 7. Fasching P, Rhiem K. Diagnostik und Therapie früher und fortgeschrittener Mammakarzinome: Brustkrebsrisiko und Prävention. 2020. 8. Badve SS, Beitsch PD, Bose S, et al. 8th AJCC breast cancer staging.; 2017. 9. Giuliano AE, Kirgan DM, Guenther JM, Morton DL. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg. 1994;220:391-401. 10. Parkes A, Clifton K, Al-Awadhi A, et al. Characterization of bone only metastasis patients with respect to tumor subtypes. npj Breast Cancer. 2018;4:2. 11. Coleman RE, Rubens RD. The clinical course of bone metastases from breast cancer. Br J Cancer. 1987;55:61-66. 12. Liede A, Jerzak KJ, Hernandez RK, Wade SW, Sun P, Narod SA. The incidence of bone metastasis after early-stage breast cancer in Canada. Breast Cancer Res Treat. 2016;156:587-595. 13. Brockton NT, Gill SJ, Laborge SL, et al. The Breast Cancer to Bone (B2B) Metastases Research Program: A multi-disciplinary investigation of bone metastases from breast cancer. BMC Cancer. 2015;15:512. 14. Jung SY, Rosenzweig M, Sereika SM, Linkov F, Brufsky A, Weissfeld JL. Factors associated with mortality after breast cancer metastasis. Cancer Causes Control. 2012;23:103-112. 15. Bruckmann NM, Kirchner J, Umutlu L, et al. Prospective comparison of the diagnostic accuracy of 18F-FDG PET/MRI, MRI, CT, and bone scintigraphy for the detection of bone metastases in the initial staging of primary breast cancer patients. Eur Radiol. 2021;31:8714-8724. 16. Liu T, Cheng T, Xu W, Yan WL, Liu J, Yang HL. A meta-analysis of 18FDG-PET, MRI and bone scintigraphy for diagnosis of bone metastases in patients with breast cancer. Skeletal Radiol. 2011;40:523-31. 17. Wöckel A, Kreienberg R. Interdisziplinäre S3-Leitlinie „Früherkennung, Diagnostik, Therapie und Nachsorge des Mammakarzinoms“. Gynakologe. 2018;51:510-513. 18. D`Orsi CJ, Sickles EA, Mendelson EB, et al. ACR BI-RADS-Atlas der Mammadiagnostik Richtlinien zu Befundung, Handlungsempfehlungen und Monitoring. 5th ed. (Walthers D med. EM, ed.). Springer-Verlag Berlin Heidelberg 2016; 2013. 19. Nelson HD, Pappas M, Cantor A, Griffin J, Daeges M, Humphrey L. Harms of breast cancer screening: Systematic review to update the 2009 U.S. Preventive services task force recommendation. Ann Intern Med. 2016;164:256-267. 20. Alkadhi H, Leschka S, Stolzmann P, Scheffel H. Wie funktioniert CT? Springer Medizin Verlag Heidelberg; 2011. 21. Weishaupt D, Köchli VD, Marincek B. Wie funktioniert MRI? Eine Einführung in Physik und Funktionsweise der Magnetresonanzbildgebung. 6.Auflage. Springer Medizin Verlag Heidelberg; 2009. 22. Lin, Eugene, Alavi A. PET and PET/CT: A Clinical Guide. 3rd Editio. New York: Thieme; 2019. 23. Moses WW. Fundamental Limits of Spatial Resolution in PET. Nucl instruments methods Phys Res Sect A, Accel spectrometers, Detect Assoc Equip. 2011;648 Supple:S236-S240. 24. Townsend DW. Combined positron emission tomography-computed tomography: the historical perspective. Semin Ultrasound CT MR. 2008;29:232-235. 25. Antoch G, Stattaus J, Nemat AT, et al. Non-Small Cell Lung Cancer: Dual-Modality PET/CT in Preoperative Staging. Radiology. 2003. 26. Antoch G, Vogt FM, Freudenberg LS, et al. Whole-Body Dual-Modality PET/CT and Whole-Body MRI for Tumor Staging in Oncology. J Am Med Assoc. 2003;290:3199-206. 27. Bar-Shalom R, Yefremov N, Guralnik L, et al. Clinical performance of PET/CT in evaluation of cancer: additional value for diagnostic imaging and patient management. J Nucl Med. 2003;44:1200-1209. 28. Lardinois D, Weder W, Hany TF, et al. Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography. N Engl J Med. 2003;348:2500-2507. 29. Brix G, Nosske D, Lechel U. Radiation exposure of patients undergoing whole-body FDG-PET/CT examinations: an update pursuant to the new ICRP recommendations. Nuklearmedizin. 2014;53:217-220. 30. Hahn K, Pfluger T. Is PET/CT necessary in paediatric oncology? Against. Eur J Nucl Med Mol Imaging. 2006;33:966-968. 31. Magometschnigg HF, Baltzer PA, Fueger B, et al. Diagnostic accuracy of (18)F-FDG PET/CT compared with that of contrast-enhanced MRI of the breast at 3 T. Eur J Nucl Med Mol Imaging. 2015;42:1656-1665. 32. Fukui MB, Blodgett TM, Snyderman CH, et al. Combined PET-CT in the head and neck: part 2. Diagnostic uses and pitfalls of oncologic imaging. Radiogr a Rev Publ Radiol Soc North Am Inc. 2005;25:913-930. 33. Gu P, Pan L-L, Wu S-Q, Sun L, Huang G. CA 125, PET alone, PET-CT, CT and MRI in diagnosing recurrent ovarian carcinoma: a systematic review and meta-analysis. Eur J Radiol. 2009;71:164-174. 34. Khalil HI, Patterson SA, Panicek DM. Hepatic lesions deemed too small to characterize at CT: prevalence and importance in women with breast cancer. Radiology. 2005;235:872-878. 35. Antoch G, Bockisch A. Combined PET/MRI: A new dimension in whole-body oncology imaging? Eur J Nucl Med Mol Imaging. 2009. 36. Buchbender C, Heusner TA, Lauenstein TC, Bockisch A, Antoch G. Oncologic PET/MRI, part 1: Tumors of the brain, head and neck, chest, abdomen, and pelvis. J Nucl Med. 2012;53:928-38. 37. Buchbender C, Heusner TA, Lauenstein TC, Bockisch A, Antoch G. Oncologic PET/MRI, part 2: Bone tumors, soft-tissue tumors, melanoma, and lymphoma. J Nucl Med. 2012;53:1244-52. 38. Quick HH. Integrated PET/MR. J Magn Reson Imaging. 2014;39:243-58. 39. Kirchner J. Onkologische Diagnosik mittels hybrider Bildgebung.; 2020. 40. Beuthien-Baumann B. [PET/MRI]. Radiologe. 2018;58:211-217. 41. Martinez-Moller A, Souvatzoglou M, Delso G, et al. Tissue classification as a potential approach for attenuation correction in whole-body PET/MRI: Evaluation with PET/CT data. J Nucl Med. 2009;50:520-6. 42. Kim JH, Lee JS, Song I-C, Lee DS. Comparison of segmentation-based attenuation correction methods for PET/MRI: evaluation of bone and liver standardized uptake value with oncologic PET/CT data. J Nucl Med. 2012;53:1878-1882. 43. Heusch P, Buchbender C, Beiderwellen K, et al. Standardized uptake values for [18F] FDG in normal organ tissues: Comparison of whole-body PET/CT and PET/MRI. Eur J Radiol. 2013;82:870-6. 44. Sawicki LM, Grueneisen J, Buchbender C, et al. Evaluation of the Outcome of Lung Nodules Missed on 18F-FDG PET/MRI Compared with 18F-FDG PET/CT in Patients with Known Malignancies. J Nucl Med. 2016;57:15-20. 45. Sawicki LM, Grueneisen J, Buchbender C, et al. Comparative Performance of 18F-FDG PET/MRI and 18F-FDG PET/CT in Detection and Characterization of Pulmonary Lesions in 121 Oncologic Patients. J Nucl Med. 2016;57:582-586. 46. Gould MK, Donington J, Lynch WR, et al. Evaluation of individuals with pulmonary nodules: when is it lung cancer? Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143:e93S-e120S. 47. MacMahon H, Naidich DP, Goo JM, et al. Guidelines for Management of Incidental Pulmonary Nodules Detected on CT Images: From the Fleischner Society 2017. Radiology. 2017;284:228-243. 48. Henschke CI, Yankelevitz DF, Mirtcheva R, McGuinness G, McCauley D, Miettinen OS. CT screening for lung cancer: frequency and significance of part-solid and nonsolid nodules. AJR Am J Roentgenol. 2002;178:1053-1057. 49. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310:2191-2194. 50. Kirchner J, Grueneisen J, Martin O, et al. Local and whole-body staging in patients with primary breast cancer: a comparison of one-step to two-step staging utilizing 18F-FDG-PET/MRI. Eur J Nucl Med Mol Imaging. 2018;45:2328-2337. 51. Rausch I, Quick HH, Cal-Gonzalez J, Sattler B, Boellaard R, Beyer T. Technical and instrumentational foundations of PET/MRI. Eur J Radiol. 2017;94:A3-A13. 52. Blumhagen JO, Ladebeck R, Fenchel M, Scheffler K. MR-based field-of-view extension in MR/PET: B0 homogenization using gradient enhancement (HUGE). Magn Reson Med. 2013;70:1047-57. 53. Jannusch K, Bruckmann NM, Geuting CJ, et al. Lung Nodules Missed in Initial Staging of Breast Cancer Patients in PET/MRI-Clinically Relevant? Cancers (Basel). 2022;14. 54. Cardoso F, Paluch-Shimon S, Senkus E, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020;31:1623-1649. 55. National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and treatment | 1-Guidance | Guidance and guidelines | NICE. NICE Guidance. 56. Jin L, Han B, Siegel E, Cui Y, Giuliano A, Cui X. Breast cancer lung metastasis: Molecular biology and therapeutic implications. Cancer Biol Ther. 2018;19:858-868. 57. Jiang B, Liu H, Zhou D. Diagnostic and clinical utility of dynamic contrast-enhanced MR imaging in indeterminate pulmonary nodules: a metaanalysis. Clin Imaging. 2016;40:1219-1225. 58. Li B, Li Q, Chen C, Guan Y, Liu S. A systematic review and meta-analysis of the accuracy of diffusion-weighted MRI in the detection of malignant pulmonary nodules and masses. Acad Radiol. 2014;21:21-29. 59. Cronin P, Dwamena BA, Kelly AM, Bernstein SJ, Carlos RC. Solitary pulmonary nodules and masses: a meta-analysis of the diagnostic utility of alternative imaging tests. Eur Radiol. 2008;18:1840-1856. 60. Liu H, Chen R, Tong C, Liang XW. MRI versus CT for the detection of pulmonary nodules: A meta-analysis. Medicine (Baltimore). 2021;100:e27270. 61. Kumar S, Rai R, Stemmer A, et al. Feasibility of free breathing Lung MRi for Radiotherapy using non-Cartesian k-space acquisition schemes. Br J Radiol. 2017;90:20170037. 62. Sommer G, Koenigkam-Santos M, Biederer J, Puderbach M. Role of MRI for detection and characterization of pulmonary nodules. Radiologe. 2014;54:470-7. 63. Sawicki LM, Grueneisen J, Buchbender C, et al. Comparative performance of 18F-FDG PET/MRI and 18F-FDG PET/CT in detection and characterization of pulmonary lesions in 121 oncologic patients. J Nucl Med. 2016;57:582-586. 64. Biondetti P, Vangel MG, Lahoud RM, et al. PET/MRI assessment of lung nodules in primary abdominal malignancies: sensitivity and outcome analysis. Eur J Nucl Med Mol Imaging. 2021;48:1976-1986. 65. Chandarana H, Heacock L, Rakheja R, et al. Pulmonary nodules in patients with primary malignancy: Comparison of hybrid PET/MR and PET/CT imaging. Radiology. 2013;268:874-81. 66. Cistaro A, Lopci E, Gastaldo L, Fania P, Brach Del Prever A, Fagioli F. The role of 18F-FDG PET/CT in the metabolic characterization of lung nodules in pediatric patients with bone sarcoma. Pediatr Blood Cancer. 2012;59:1206-1210. 67. Groheux D, Quere G, Blanc E, et al. FDG PET-CT for solitary pulmonary nodule and lung cancer: Literature review. Diagn Interv Imaging. 2016;97:1003-1017. 68. Raad RA, Friedman KP, Heacock L, Ponzo F, Melsaether A, Chandarana H. Outcome of small lung nodules missed on hybrid PET/MRI in patients with primary malignancy. J Magn Reson Imaging. 2016;43:504-511. 69. Biederer J, Beer M, Hirsch W, et al. MRI of the lung (2/3). Why... when ... how? Insights Imaging. 2012;3:355-71. 70. Regier M, Kandel S, Kaul MG, et al. Detection of small pulmonary nodules in high-field MR at 3 T: Evaluation of different pulse sequences using porcine lung explants. Eur Radiol. 2007;17:1341-1351. 71. Schäfer JF, Vollmar J, Schick F, et al. [Detection of pulmonary nodules with breath-hold magnetic resonance imaging in comparison with computed tomography]. Rofo. 2005;177:41-49. 72. Biederer J, Hintze C, Fabel M. MRI of pulmonary nodules: Technique and diagnostic value. Cancer Imaging. 2008;8:125-30. 73. Biederer J, Ohno Y, Hatabu H, et al. Screening for lung cancer: Does MRI have a role? Eur J Radiol. 2017. 74. Bruckmann NM, Kirchner J, Morawitz J, et al. Free-breathing 3D Stack of Stars GRE (StarVIBE) sequence for detecting pulmonary nodules in (18)F-FDG PET/MRI. EJNMMI Phys. 2022;9:11. 75. Sanchez F, Tyrrell PN, Cheung P, et al. Detection of solid and subsolid pulmonary nodules with lung MRI: performance of UTE, T1 gradient-echo, and single-shot T2 fast spin echo. Cancer imaging Off Publ Int Cancer Imaging Soc. 2023;23:17. 76. Olthof S-C, Reinert C, Nikolaou K, et al. Detection of lung lesions in breath-hold VIBE and free-breathing Spiral VIBE MRI compared to CT. Insights Imaging. 2021;12:175. 77. Vermersch M, Emsen B, Monnet A, et al. Chest PET/MRI in Solid Cancers: Comparing the Diagnostic Performance of a Free-Breathing 3D-T1-GRE Stack-of-Stars Volume Interpolated Breath-Hold Examination (StarVIBE) Acquisition With That of a 3D-T1-GRE Volume Interpolated Breath-Hold Examination (VIBE. J Magn Reson Imaging. 2022;55:1683-1693. 78. Yilmaz F, Tastekin G. Sensitivity of (18)F-FDG PET in evaluation of solitary pulmonary nodules. Int J Clin Exp Med. 2015;8:45-51. 79. Colt HG, Murgu SD, Korst RJ, Slatore CG, Unger M, Quadrelli S. Follow-up and surveillance of the patient with lung cancer after curative-intent therapy: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143:e437S-e454S. 80. Saunders M, Sculier JP, Ball D, et al. Consensus: the follow-up of the treated patient. Lung Cancer. 2003;42 Suppl 1:S17-9. 81. Ettinger DS, Wood DE, Aisner DL, et al. Non-Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022;20:497-530. | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Bezug: | März 2022 bis Oktober 2024 | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät » Institute » Institut für Diagnostische Radiologie | |||||||
| Dokument erstellt am: | 27.11.2024 | |||||||
| Dateien geändert am: | 27.11.2024 | |||||||
| Promotionsantrag am: | 06.06.2024 | |||||||
| Datum der Promotion: | 22.10.2024 |
