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This work evaluates migration in breast cancer cell lines using an improved gap closure assay. Four cell lines (T47D, MDA-MB 361, MCF-7 and SkBr3) were irradiated with doses of 0, 2, 4 and 8 Gy. Migration, apoptosis and cell viability was analyzed. The cell line SkBr3 showed a statistically significant increase in migration in the 4 Gy and 8 Gy groups compared to sham irradiation. MCF-7 cells showed no statistically significant effect, but a tendency was observed. Significant changes in apoptosis or cell viability could not be detected (other than the expected results in the 8 Gy subgroup)., Diese Arbeit untersucht Migration von Brustkrebszelllinien mit einem verbesserten Gap-Closure-Assays. Vier Zelllinien (T47D, MDA-MB 361, MCF-7 und SkBr3) wurden mit Dosen von 0, 2, 4 und 8 Gy bestrahlt. Migration, Apoptose und Viabilität der Zellen wurden analysiert. Die Zelllinie SkBr3 zeigte eine statistisch signifikante Zunahme der Migration bei 4 Gy und 8 Gy. MCF-7-Zellen zeigten keinen statistisch signifikanten Effekt, jedoch eine Tendenz. Signifikante Veränderungen der Apoptose oder Viabilität konnten nicht festgestellt werden.

Bei der definitiven Radio(chemo-)therapie von Ösophaguskarzinomen kommt es sowohl bei der 3D-konformaler Bestrahlung, als auch bei der Volumetric modulated Arc Therapy (VMAT) zu einer hohen inzidentellen Dosisbelastung der regionalen Lymphabflusswege des Ösophagus, wobei diese partiell unter VMAT geringer ist. Diese Ergebnisse deuten darauf hin, dass auch bei der Verwendung moderner Bestrahlungstechnik eine involved field irradiation gegenüber einer elective nodal irradiation zu präferieren ist., In patients with esophageal cancer (EC) undergoing definitive chemo-radiotherapy (dCRT), the usage of both three-dimensional conformal radiotherapy and volumetric modulated arc therapy (VMAT) result in a high incidental irradiation to the regional lymphatic drainage pathways of the esophagus, although this is partially lower under VMAT. These results indicate that in dCRT of EC involved field irradiation is preferable to elective nodal irradiation, even when using modern radiation techniques.

Pancreatic cancer is characterized by high heterogeneity in resistance to radiotherapy. In this thesis the feasibility of pancreatic cancer patient-derived organoids as a radiobiological research platform for translational personalized radiooncology was analyzed. Radioresponse subgroups showed a correlation with multiple radiobiological markers as well as clinical overall survival. Additionally promising novel therapeutic targets to overcome radioresistance were identified., Das Pankreaskarzinom besitzt eine hohe Heterogenität in der Resistenz gegenüber Strahlentherapie. In dieser Arbeit wurde die Anwendbarkeit von Patienten-abgeleiteten Organoiden des Pankreaskarzinoms als radiobiologische Forschungsplattform für die translationale personalisierte Radioonkologie analysiert. Strahlensensitivitäts-Subgruppen zeigten eine Korrelation mit mehreren radiobiologischen Markern sowie dem klinischen Gesamtüberleben. Zusätzlich konnten neue Zielstrukturen zur Überwindung der Strahlenresistenz identifiziert werden.

Hochgradige Gliome (HGG) sind die häufigsten primär bösartigen Tumore des erwachsenen Gehirns und gehen mit einer schlechten Prognose einher. Die Behandlung rezidivierter HGG ist nicht einheitlich definiert. Scoring-Systeme können bei der Entscheidungsfindung ein hilfreiches Instrument darstellen. Ziel dieser Studie ist es, die Unterschiede fünf veröffentlichter Scoring-Systemen zur Vorhersage des Überlebens von Patienten mit rezidivierenden Gliomen zu bewerten., High-grade gliomas (HGG) are the most common primary malignant tumors of the adult brain and are associated with a poor prognosis. Treatment of recurrent HGG is not uniformly defined. Scoring systems can be a helpful tool in decision making. The aim of this study is to evaluate the differences of five published scoring systems for predicting survival of patients with recurrent glioma.

Untersucht wurde der Effekt ionisierender Strahlung an Strukturen des zentralen gustatorischen Systems auf den Blutzuckerspiegel bei Glioblastompatienten. Das Kollektiv umfasste 34 Patienten. Berücksichtigt wurden Strahlentherapieparameter, Steroidmedikation und Diabetesdiagnosen. Der durchschnittliche Blutzuckerwert stieg mit Beginn der Bestrahlung signifikant an. Die Strukturen des gustatorischen Systems sollten in der Bestrahlungsplanung berücksichtigt und geschont werden., The effect of ionising radiation on structures of the central gustatory system on blood glucose levels in glioblastoma patients was investigated. The collective comprised 34 patients. Radiation therapy parameters, steroid medication and diabetes diagnoses were taken into account. The average blood glucose level increased significantly with the start of radiation. The structures of the gustatory system should be considered and spared in radiation planning.

One aim of this study is to quantitatively analyze tumor shrinkage after fractionated stereotactic radiotherapy (FSRT) of pituitary adenomas by 3-D MRI. Exact evaluation of radiological tumor response to stereotactic radiotherapy seems to us of major importance in the subgroup of non-functioning pituitary adenomas N9FPAs), as compared to hormone secreting pituitary adenomas, where hormone levels are the main criteria to evaluate response to therapy, NFPAs lack this criteria for clinical evaluation of tumor control. The other aim of this study is to evaluate the role of FSRT (fractionated stereotactic radiotherapy) in the management of non-functioning and functioning pituitary adenomas in the postoperative setting, with respect to tumor control and side effects of radiotherapy.In conclusion, we think that volumetric evaluation of tumor size after radiotherapy of pituitary adenomas using 3D T1Gd-MRI is a highly precise method to measure tumor regression. In all pituitary adenomas a size reduction was detected, representing 100% radiological response.We report 26%, 47% and 62% reduction in tumor volume of NFPAs at < 36, 36 – 72 and > 72 months after radiotherapy, Etwa 90% der strahlentherapeutisch behandelten Hypophysenadenome zeigen ein Therapieansprechen (Remission oder stable disease). Es gibt nur wenige Daten über den Verlauf der Größenregredienz nach erfolgreicher stereotaktisch fraktionierter Strahlentherapie (SFS). Ziel dieser Untersuchung war die volumetrische Erfassung des Remissionsverhaltens von Hypophysenadenomen nach stereotaktischer Strahlentherapie. Methodisch basiert die vorliegende Arbeit auf der Volumetrie, die das jeweils aktuelle MRT mit dem Planungs-MRT vor Start der Strahlentherapie vergleicht.Die volumetrische Evaluation der Tumorgröße nach stereotaktischer Strahlentherapie von Hypophysenadenomen ist eine hochpräzise Messung bei der Ermittlung der exakten Größenregression der Resthypophysenadenome. Unsere Untersuchung zeigt, dass nach stereotaktisch fraktionierter Strahlentherapie bei den meisten Patienten eine Größenregression zu verzeichnen ist.

BACKGROUND Salvage radiation therapy (sRT) is often the sole curative option in patients with biochemical recurrence after radical prostatectomy. After sRT, we developed and validated a nomogram to predict freedom from biochemical failure. OBJECTIVE This study aims to evaluate prostate-specific membrane antigen-positron emission tomography (PSMA-PET)-based sRT efficacy for postprostatectomy prostate-specific antigen (PSA) persistence or recurrence. Objectives include developing a random survival forest (RSF) model for predicting biochemical failure, comparing it with a Cox model, and assessing predictive accuracy over time. Multinational cohort data will validate the model's performance, aiming to improve clinical management of recurrent prostate cancer. METHODS This multicenter retrospective study collected data from 13 medical facilities across 5 countries: Germany, Cyprus, Australia, Italy, and Switzerland. A total of 1029 patients who underwent sRT following PSMA-PET-based assessment for PSA persistence or recurrence were included. Patients were treated between July 2013 and June 2020, with clinical decisions guided by PSMA-PET results and contemporary standards. The primary end point was freedom from biochemical failure, defined as 2 consecutive PSA rises >0.2 ng/mL after treatment. Data were divided into training (708 patients), testing (271 patients), and external validation (50 patients) sets for machine learning algorithm development and validation. RSF models were used, with 1000 trees per model, optimizing predictive performance using the Harrell concordance index and Brier score. Statistical analysis used R Statistical Software (R Foundation for Statistical Computing), and ethical approval was obtained from participating institutions. RESULTS Baseline characteristics of 1029 patients undergoing sRT PSMA-PET-based assessment were analyzed. The median age at sRT was 70 (IQR 64-74) years. PSMA-PET scans revealed local recurrences in 43.9% (430/979) and noda

BACKGROUND Surgical resection is the standard of care for patients with large or symptomatic brain metastases (BMs). Despite improved local control after adjuvant stereotactic radiotherapy, the risk of local failure (LF) persists. Therefore, we aimed to develop and externally validate a pre-therapeutic radiomics-based prediction tool to identify patients at high LF risk. METHODS Data were collected from A Multicenter Analysis of Stereotactic Radiotherapy to the Resection Cavity of Brain Metastases (AURORA) retrospective study (training cohort: 253 patients from two centers; external test cohort: 99 patients from five centers). Radiomic features were extracted from the contrast-enhancing BM (T1-CE MRI sequence) and the surrounding edema (FLAIR sequence). Different combinations of radiomic and clinical features were compared. The final models were trained on the entire training cohort with the best parameter set previously determined by internal 5-fold cross-validation and tested on the external test set. RESULTS The best performance in the external test was achieved by an elastic net regression model trained with a combination of radiomic and clinical features with a concordance index (CI) of 0.77, outperforming any clinical model (best CI: 0.70). The model effectively stratified patients by LF risk in a Kaplan-Meier analysis (p < 0.001) and demonstrated an incremental net clinical benefit. At 24 months, we found LF in 9% and 74% of the low and high-risk groups, respectively. CONCLUSIONS A combination of clinical and radiomic features predicted freedom from LF better than any clinical feature set alone. Patients at high risk for LF may benefit from stricter follow-up routines or intensified therapy.

Background: Novel radiotherapeutic modalities using carbon ions provide an increased relative biological effectiveness (RBE) compared to photons, delivering a higher biological dose while reducing radiation exposure for adjacent organs. This prospective phase 2 trial investigated bimodal radiotherapy using photons with carbon-ion (C12)-boost in patients with WHO grade 2 meningiomas following subtotal resection (Simpson grade 4 or 5).Methods:A total of 33 patients were enrolled from July 2012 until July 2020. The study treatment comprised a C12-boost (18 Gy [RBE] in 6 fractions) applied to the macroscopic tumor in combination with photon radiotherapy (50 Gy in 25 fractions). The primary endpoint was the 3-year progression-free survival (PFS), and the secondary endpoints included overall survival, safety and treatment toxicities. Results:With a median follow-up of 42 months, the 3-year estimates of PFS, local PFS and overall survival were 80.3%, 86.7%, and 89.8%, respectively. Radiation-induced contrast enhancement (RICE) was encountered in 45%, particularly in patients with periventricularly located meningiomas. Patients exhibiting RICE were mostly either asymptomatic (40%) or presented immediate neurological and radiological improvement (47%) after the administration of corticosteroids or bevacizumab in case of radiation necrosis (3/33). Treatment-associated complications occurred in 1 patient with radiation necrosis who died due to postoperative complications after resection of radiation necrosis. The study was prematurely terminated after recruiting 33 of the planned 40 patients. Conclusions:Our study demonstrates a bimodal approach utilizing photons with C12-boost may achieve a superior local PFS to conventional photon RT, but must be balanced against the potential risks of toxicities.

Background: The aim of this study was to investigate the role of clinical, dosimetric and pretherapeutic magnetic resonance imaging (MRI) features for lesion-specific outcome prediction of stereotactic radiotherapy (SRT) in patients with brain metastases from malignant melanoma (MBM). Methods: In this multicenter, retrospective analysis, we reviewed 517 MBM from 130 patients treated with SRT (single fraction or hypofractionated). For each gross tumor volume (GTV) 1576 radiomic features (RF) were calculated (788 each for the GTV and for a 3 mm margin around the GTV). Clinical parameters, radiation dose and RF from pretherapeutic contrast-enhanced T1-weighted MRI from different institutions were evaluated with a feature processing and elimination pipeline in a nested cross-validation scheme. Results: Seventy-two (72) of 517 lesions (13.9%) showed a local failure (LF) after SRT. The processing pipeline showed clinical, dosimetric and radiomic features providing information for LF prediction. The most prominent ones were the correlation of the gray level co-occurrence matrix of the margin (hazard ratio (HR): 0.37, confidence interval (CI): 0.23-0.58) and systemic therapy before SRT (HR: 0.55, CI: 0.42-0.70). The majority of RF associated with LF was calculated in the margin around the GTV. Conclusions: Pretherapeutic MRI based RF connected with lesion-specific outcome after SRT could be identified, despite multicentric data and minor differences in imaging protocols. Image data analysis of the surrounding metastatic environment may provide therapy-relevant information with the potential to further individualize radiotherapy strategies.

Im Rahmen dieser Arbeit wird ein Kollektiv von 124 Patienten mit verschiedenen Grunderkrankungen und Behandlungsindikationen, welches an der Forschungsneutronenquelle Heinz Maier-Leibnitz in Garching zwischen 2007 und 2013 in insgesamt 136 Zyklen mit Neutronen bestrahlt wurde, retrospektiv untersucht. Dabei liegt der Schwerpunkt auf lokalem PFS, OS sowie akuten und chronischen Nebenwirkungen. Die Ergebnisse werden kritisch beleuchtet und in den Kontext der aktuellen Literatur gebracht., This dissertation examines retrospectively a collective of 124 patients with various underlying diseases and treatment indications, which was irradiated with neutrons in a total of 136 cycles at the Heinz Maier-Leibnitz research neutron source in Garching between 2007 and 2013. The focus is on local PFS, OS and acute and chronic side effects. The results are critically examined and placed in the context of current literature.

Die palliative Strahlentherapie von schmerzhaften Wirbelsäulenmetastasen führt nur bei zwei Drittel der Patienten zu einem Schmerzansprechen. Ein zuverlässiges Vorhersagemodell des Schmerzansprechens und der Überlebenszeit könnte helfen, eine individuelle Entscheidung bezüglich der Strahlentherapie zu treffen. In dieser retrospektiven Studie untersuchen wir den Zusammenhang zwischen prätherapeutischen Daten und dem Schmerzansprechen bzw. der Überlebenszeit von betroffenen Patienten., Palliative radiation therapy of painful spinal bone metastases (SBM) triggers a pain response in only two-thirds of treated patients. A reliable prediction model of pain and overall survival may help to personalize the decision for radiation therapy. In this retrospective study, we investigated the relationship between several pretherapeutic data, pain response and overall survival in SBM patients.

Bei 180 Patienten mit Vestibularis-Schwannom, die mittels Fraktionierter Stereotaktischer Radiotherapie oder Stereotaktischen Radiochirurgie behandelt wurden, wurde nachträglich die Cochlea in die CT-Schnittbilder konturiert und so eine volumetrische Analyse durchgeführt. Es wurde der Zusammenhang zum Hörvermögen nach der Behandlung untersucht. Unterschiede zwischen den Bestrahlungsgruppen waren hinsichtlich des Volumens der Cochlea und der Veränderung des Hörvermögens nicht signifikant., For 180 patients with vestibular schwannoma who were either treated with fractionated stereotactic radiotherapy or radiosurgery, the cochlea was contoured into their CT-scans and a volumetric analysis was performed. A connection in terms of the hearing ability after the therapy was examined. Differences between the two groups of radiotherapy regarding the volume of the cochlea and the change in hearing ability was not significant.

In dieser Arbeit werden die Ergebnisse der primär radiotherapeutischen Behandlung von Patienten mit einem Analkarzinom von 2004-2018 der Klinik für RadioOnkologie und Strahlentherapie bezüglich relevanter klinischer Endpunkte, wie dem Gesamt-, dem krankheitsfreien- und dem Kolostomie-freien Überleben analysiert und mit veröffentlichter Literatur verglichen. Ergänzend erfolgt eine Analyse der Lebensqualität mehrere Jahre nach Therapieabschluss auf Grundlage von validierten Fragebögen der EORTC., In this work, the results of a primary radiotherapeutic treatment of patients with anal cancer from 2004-2018 at the Clinic for RadioOncology and Radiotherapy are analyzed with respect to relevant clinical endpoints such as overall, disease-free and colostomy-free survival and compared with already published literature. In addition, an analysis of the quality of life is carried out several years after the end of therapy on the basis of validated questionnaires from the EORTC.

Bedingt durch die gute Blutversorgung sind sowohl die Leber als auch die Nebenniere häufig von einer Fernmetastasierung betroffen. Anhand dieser Patientenkohorte wurden insbesondere die lokale Kontrolle, das progressionsfreie Überleben, das Gesamtüberleben und die Toxizitätsraten nach einer Hochpräzisionsradiotherapie bewertet. Ziel war es, mit Hilfe der gewonnenen Erkenntnisse zu prüfen, ob die stereotaktische Bestrahlung eine valide Therapiealternative für betroffene Patienten, die für invasive Maßnahmen nicht in Frage kommen, darstellt und eine klinisch relevante Behandlungsempfehlung abgeben zu können., Due to the rich blood supply, the liver and the adrenal gland are often affected by distant metastases. In this study, we focused on local control, progression-free survival, overall survival, and toxicity rates after high-precision radiotherapy. This work aimed to review whether stereotactic radiotherapy is a valid therapy option for patients with liver- and adrenal metastases, who are not suitable for more invasive treatments due to comorbidities and to form a clinically relevant treatment recommendation.

Das Pankreaskarzinom ist eine der tödlichsten Tumorerkrankungen weltweit. Curcumin werden unter anderem anti-inflammatorische, -oxidative und -karzinogene Wirkungen zugeschrieben. Es wurde das Einwirken von Curcumin auf Überleben, Wachstum, Zellzyklus, DNA-Schäden und Apoptose in Kombination mit Bestrahlung in Pankreaskarzinomzellen in vitro untersucht. Es zeigten sich additive Effekte in beiden untersuchten Zelllinien, während sich in Panc-1 Zellen eine Strahlen-Sensibilisierung darstellte. Als Ursache wurde ein curcumin-induzierter G2-Arrest festgestellt., Pancreatic cancer is one of the most lethal cancers worldwide. Curcumin as potential phytotherapeutic agent in cancer therapy should be investigated in a combinated treatment with radiation in pancreatic cancer cell model. Curcumins influences on survival, proliferation, cell cycle, DNA damage and apoptosis were investigated. Both treated cell lines show additive impact of Curcumin to radiation treatment, but curcumin sensitizes cancer cells for radiation therapy in an overadditive way through inducing g2-cell-cycle arrest in Panc-1 cells, but not in MiaPaCa-2 cell line.

Die TomoTherapie (RT) ist eine lokale Behandlungsmöglichkeit für anatomisch komplexe Tumore. Fokus dieser Dissertation liegt auf multi-target RT (mtRT) von kindlichen Sarkomen. Von 2008-2017 wurden insgesamt 43 Kinder behandelt. Angesichts der oftmals fortgeschrittenen Erkrankung sind die Raten akuter und später Toxizität akzeptabel. Das 5-Jahres-Überleben von 55,6%±18,7% war für Kinder mit multifokalen Ewing Sarkom bemerkenswert. Unter Berücksichtigung der geringen Patientenanzahl, bietet mtRT somit einen vielversprechenden und innovativen Behandlungsansatz., TomoTherapy (RT) is a local treatment option for anatomically complex tumors. This dissertation focuses on multi-target RT (mtRT) of pediatric sarcomas. A total of 43 children were treated from 2008-2017. Given the often advanced disease, the rates of acute and late toxicity are acceptable. The 5-year survival of 55.6%±18.7% was remarkable for children with multifocal Ewing sarcoma. Considering the small number of patients, mtRT thus offers a promising and innovative treatment approach.

2002 bis 2016 wurden am Klinikum rechts der Isar in München 2075 Patienten mittels stereotaktischer Bestrahlungen intrakraniell, an der Schädelbasis und der Halsregion behandelt. Zentrale Fragen dieser Arbeit sind, welche Tumorentitäten im untersuchten Zeitraum bestrahlt, welche Therapiekonzepte durchgeführt wurden, und wie sich das Gesamtüberleben der Patienten gestaltete. Besonderes Augenmerk wurde auf Hirnmetastasen, Meningeome, Vestibularisschwannome und Hypophysenadenome gelegt., Between 2002 and 2016 2075 patients were treated with stereotactic radiotherapy of the head and neck region at the Klinikum rechts der Isar in Munich. The present paper analyses the types of tumors treated during this period, the treatment plans used and the overall survival rate and time of the patients. In this context, a particular focus is placed on brain metastases, meningiomas, vestibular schwannoma and pituitary adenoma.

Das Ziel ist es, die Präzision der Lagerung von Patienten zur intrakraniellen Bestrahlung mithilfe von ExacTrac und CBCT in einem großen Patientenkollektiv zu untersuchen. Zudem sollen Abweichungen der abgegebenen Strahlendosis bei intrakranieller Radiotherapie im Zielvolumen und den angrenzenden Risikoorganen untersucht werden, die durch unzureichende Korrektur von Rotationsfehlern verursacht werden. Hierfür wurden Rotationsfehler auf CT-Datensätze übertragen und Dosisänderungen berechnet., The aim is to investigate the precision of patient positioning for intracranial radiotherapy using ExacTrac and CBCT in a large patient collective. In addition, alteration of delivered radiation doses during intracranial radiotherapy in the target volume and adjacent organs at risk caused by insufficient correction of rotational errors will be investigated. For this purpose, rotational errors were transferred to CT data sets and dose changes were calculated.

Es wurden radiogen induzierte Veränderungen der SWOARs (swallowing organs at risk) anhand von MRT-Bildgebungen analysiert und die Zusammenhänge von Nebenwirkungen wie Dysphagie und Dysphonie mit der applizierten Dosis im SWOAR untersucht., The study analysed side effects of radiotherapy in SWOARs (swallowing organs at risk) by using MRI conturing. In addition the connection between chronic side effects like dysphagia and dysphonia and the applied dose (to the SWOARs) was examinated.

Ziel dieser Arbeit ist die Analyse von prätherapeutischen 18F-FDG-PET/CT basierten Bildparametern hinsichtlich ihrer Eignung als Prädiktoren für das Gesamtüberleben und das histopathologische Ansprechen auf eine neoadjuvante Radiochemotherapie bei Patienten mit ösophagealen Plattenepithelkarzinomen. Es handelt sich um eine retrospektive Studie mit insgesamt 38 Patienten. Die Auswertung der Daten zeigt, dass Heterogenitätsparameter statistisch signifikant das Gesamtüberleben vorhersagen können., The aim of this thesis is to analyse clinical factors and image parameters derived from pre-therapeutic 18F-FDG-PET/CT imaging as predictors of overall survival and histopathologic response to neoadjuvant chemoradiation in patients with esophageal squamous cell carcinoma. It is a retrospective study with a total of 38 cases. In summary, image parameters based on tumor heterogeneity are independent predictors of overall survival.

INTRODUCTION: Historical reservations regarding stereotactic radiosurgery (SRS) for small-cell lung cancer (SCLC) brain metastases include concerns for short-interval and diffuse central nervous system (CNS) progression, poor prognoses, and increased neurological mortality specific to SCLC histology. We compared SRS outcomes for SCLC and non-small cell lung cancer (NSCLC) where SRS is well established. METHODS: Multicenter first-line SRS outcomes for SCLC and NSCLC from 2000 to 2022 were retrospectively collected (n = 892 SCLC, n = 4785 NSCLC). Data from the prospective Japanese Leksell Gamma Knife Society (JLGK0901) clinical trial of first-line SRS were analyzed as a comparison cohort (n = 98 SCLC, n = 814 NSCLC). Overall survival (OS) and CNS progression were analyzed using Cox proportional hazard and Fine-Gray models, respectively, with multivariable adjustment for cofactors including age, sex, performance status, year, extracranial disease status, and brain metastasis number and volume. Mutation-stratified analyses were performed in propensity score-matched retrospective cohorts of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) positive NSCLC, mutation-negative NSCLC, and SCLC. RESULTS: OS was superior for patients with NSCLC compared to SCLC in the retrospective dataset (median OS = 10.5 vs 8.6 months; P < .001) and in the JLGK0901 dataset. Hazard estimates for first CNS progression favoring NSCLC were similar in both datasets but reached statistical significance in the retrospective dataset only (multivariable hazard ratio = 0.82, 95% confidence interval = 0.73 to 0.92, P = .001). In the propensity score-matched cohorts, there were continued OS advantages for NSCLC patients (median OS = 23.7 [EGFR and ALK positive NSCLC] vs 13.6 [mutation-negative NSCLC] vs 10.4 months [SCLC], pairwise P values < 0.001), but no statistically significant differences in CNS progression were observed in the matched cohorts. Neurological mortali

Es wurden die Expressionsmuster nach Bestrahlung von WNT3, POU2AF1, FDXR und DDB2 in B- und T-Lymphozyten sowie in NK-Zellen und Granulozyten untersucht. Dabei waren die T-Lymphozyten nach Bestrahlung überwiegend für die Hochregulation von FDXR/DDB2 und die B-Lymphozyten überwiegend für die Herunterregulation von POU2AF1/WNT3 hauptverantwortlich., We looked at radiation-induced gene expression of WNT3, POU2AF1, FDXR and DDB2 in B- and T-lymphocytes as well as in NK-cells and granulocytes. T-lymphocytes contributed mostly to the radiation-induced up-regulation of FDXR/DDB2 and B-lymphocytes to the down-regulation of POU2AF1/WNT3.

BACKGROUND Tumor hypoxia is a paradigmatic negative prognosticator of treatment resistance in Head and Neck Squamous Cell Carcinoma (HNSCC). The lack of robust and reliable hypoxia classifiers limits the adaptation of stratified therapies. We hypothesized that the tumor DNA methylation landscape might indicate epigenetic reprogramming induced by chronic intratumoral hypoxia. METHODS A DNA methylome-based tumor hypoxia classifier (Hypoxia-M) was trained in the TCGA-HNSCC cohort based on matched assignments using gene expression-based signatures of hypoxia (Hypoxia-GES). Hypoxia-M was validated in a multicenter DKTK-ROG trial consisting of Human Papilloma Virus (HPV)-negative HNSCC patients treated with primary radiochemotherapy (RCHT). RESULTS While hypoxia-GSEs failed to stratify patients in the DKTK-ROG, Hypoxia-M was independently prognostic for local recurrence (LR, HR=4.3, p=0.001) and overall survival (OS, HR=2.34, p=0.03) but not distant metastasis (DM) after RCHT in the both cohorts. Hypoxia-M status was inversely associated with CD8 T-cells infiltration in both cohorts. Hypoxia-M was further prognostic in the TCGA-PanCancer cohort (HR=1.83, p=0.04), underscoring the breadth of this classifier for predicting tumor hypoxia status. CONCLUSIONS Our findings highlight an unexplored avenue for DNA Methylation-based classifiers as biomarkers of tumoral hypoxia for identifying high-risk features in patients with HNSCC tumors. TRIAL REGISTRATION Retrospective observational study from the German Cancer Consortium (DKTK-ROG), not interventional.

BACKGROUND Many automatic approaches to brain tumor segmentation employ multiple magnetic resonance imaging (MRI) sequences. The goal of this project was to compare different combinations of input sequences to determine which MRI sequences are needed for effective automated brain metastasis (BM) segmentation. METHODS We analyzed preoperative imaging (T1-weighted sequence ± contrast-enhancement (T1/T1-CE), T2-weighted sequence (T2), and T2 fluid-attenuated inversion recovery (T2-FLAIR) sequence) from 339 patients with BMs from seven centers. A baseline 3D U-Net with all four sequences and six U-Nets with plausible sequence combinations (T1-CE, T1, T2-FLAIR, T1-CE + T2-FLAIR, T1-CE + T1 + T2-FLAIR, T1-CE + T1) were trained on 239 patients from two centers and subsequently tested on an external cohort of 100 patients from five centers. RESULTS The model based on T1-CE alone achieved the best segmentation performance for BM segmentation with a median Dice similarity coefficient (DSC) of 0.96. Models trained without T1-CE performed worse (T1-only: DSC = 0.70 and T2-FLAIR-only: DSC = 0.73). For edema segmentation, models that included both T1-CE and T2-FLAIR performed best (DSC = 0.93), while the remaining four models without simultaneous inclusion of these both sequences reached a median DSC of 0.81-0.89. CONCLUSIONS A T1-CE-only protocol suffices for the segmentation of BMs. The combination of T1-CE and T2-FLAIR is important for edema segmentation. Missing either T1-CE or T2-FLAIR decreases performance. These findings may improve imaging routines by omitting unnecessary sequences, thus allowing for faster procedures in daily clinical practice while enabling optimal neural network-based target definitions.

IMPORTANCE Prostate-specific antigen membrane positron-emission tomography (PSMA-PET) is increasingly used to guide salvage radiotherapy (sRT) after radical prostatectomy for patients with recurrent or persistent prostate cancer. OBJECTIVE To develop and validate a nomogram for prediction of freedom from biochemical failure (FFBF) after PSMA-PET-based sRT. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study included 1029 patients with prostate cancer treated between July 1, 2013, and June 30, 2020, at 11 centers from 5 countries. The initial database consisted of 1221 patients. All patients had a PSMA-PET scan prior to sRT. Data were analyzed in November 2022. EXPOSURES Patients with a detectable post-radical prostatectomy prostate-specific antigen (PSA) level treated with sRT to the prostatic fossa with or without additional sRT to pelvic lymphatics or concurrent androgen deprivation therapy (ADT) were eligible. MAIN OUTCOMES AND MEASURES The FFBF rate was estimated, and a predictive nomogram was generated and validated. Biochemical relapse was defined as a PSA nadir of 0.2 ng/mL after sRT. RESULTS In the nomogram creation and validation process, 1029 patients (median age at sRT, 70 years [IQR, 64-74 years]) were included and further divided into a training set (n = 708), internal validation set (n = 271), and external outlier validation set (n = 50). The median follow-up was 32 months (IQR, 21-45 months). Based on the PSMA-PET scan prior to sRT, 437 patients (42.5%) had local recurrences and 313 patients (30.4%) had nodal recurrences. Pelvic lymphatics were electively irradiated for 395 patients (38.4%). All patients received sRT to the prostatic fossa: 103 (10.0%) received a dose of less than 66 Gy, 551 (53.5%) received a dose of 66 to 70 Gy, and 375 (36.5%) received a dose of more than 70 Gy. Androgen deprivation therapy was given to 325 (31.6%) patients. On multivariable Cox proportional hazards regression analysis, pre-sRT PSA level (hazard ratio

Brain metastases (BMs) are the most frequently occurring brain tumors. The treatment of patients having multiple BMs with stereo tactic radiosurgery necessitates accurate localization of the metastases. Neural networks can assist in this time-consuming and costly task that is typically performed by human experts. Particularly challenging is the detection of small lesions since they are often underrepresented in exist ing approaches. Yet, lesion detection is equally important for all sizes. In this work, we develop an ensemble of neural networks explicitly fo cused on detecting and segmenting small BMs. To accomplish this task, we trained several neural networks focusing on individual aspects of the BM segmentation problem: We use blob loss that specifically addresses the imbalance of lesion instances in terms of size and texture and is, therefore, not biased towards larger lesions. In addition, a model using a subtraction sequence between the T1 and T1 contrast-enhanced sequence focuses on low-contrast lesions. Furthermore, we train additional models only on small lesions. Our experiments demonstrate the utility of the ad ditional blob loss and the subtraction sequence. However, including the specialized small lesion models in the ensemble deteriorates segmentation results. We also find domain-knowledge-inspired postprocessing steps to drastically increase our performance in most experiments. Our approach enables us to submit a competitive challenge entry to the ASNR-MICCAI BraTS Brain Metastasis Challenge 2023.

In der Klinik und Poliklinik für RadioOnkologie und Strahlentherapie des Klinikums rechts der Isar werden seit 2002 extrakranielle Läsionen stereotaktisch bestrahlt. Die einzelnen Behandlungsdiagnosen wurden gruppiert und Überlebensanalysen durchgeführt. Am Kollektiv der Patienten mit Lungenmetastasen wurden die Nebenwirkungen der Therapie und ein Patient-reported Outcome erhoben. Es zeigte sich eine gute Verträglichkeit bei sehr guter lokalen Kontrolle. Außerdem konnten mehrere prognostisch relevante Parameter ermittelt werden., Since 2002 stereotactic body radiation therapy is conducted at Klinik und Poliklinik für RadioOnkologie und Strahlentherapie des Klinikums rechts der Isar. Different treatment diagnoses were split into groups to analyse survival. The patients with pulmonary metastases were examined further to estimate the treatment’s side effects. We also asked the patients alive to participate in our patient-reported outcome. There was good tolerability and excellent local control. Furthermore we detected several prognostic factors.

Die vorliegende Arbeit untersucht den Nutzen der Atem-Gating Technik bei der Stereotaktischen Bestrahlung von Lungentumoren hinsichtlich der Dosisreduktion von gesundem Gewebe und Risikoorganen in der Nähe des Tumors und versucht Faktoren zu identifizieren, die diesen Nutzen verstärken., The present work examines the benefit of respiratory gating in stereotactic radiation of lung tumors with regard to the dose reduction of healthy tissue and organs at risk in the vicinity of the tumor and tries to identify factors that increase this benefit.

Radioresistance in pancreatic cancer patients remains a critical obstacle to overcome. Understanding the molecular mechanisms underlying radioresistance and targeting the respective signaling pathways may lead to a better response to radiotherapy and thus to a better treatment outcome. In this thesis, two radioresistant pancreatic cancer cell lines were generated by fractionated radiation, and the cell lines were investigated in vitro and in vivo. This study provides new insights into the radioresistance of pancreatic cancer and identifies potential biomarkers and treatment targets for personalized therapy., Die Strahlenresistenz des Pankreaskarzinoms stellt eine große Herausforderung dar. Das Verständnis der molekularen Mechanismen, die der Strahlenresistenz zugrunde liegen könnte zu einem besseren Ansprechen auf die Strahlentherapie führen. Im Rahmen dieser Dissertation wurden zwei strahlenresistente Pankreaskarzinomzelllinien durch fraktionierte Bestrahlung generiert und anschließend in vitro und in vivo untersucht. Diese Arbeit liefert neue Erkenntnisse über die Strahlenresistenz von Pankreaskarzinomen und identifiziert potentielle Biomarker und Zielstrukturen für eine personalisierte Therapie.

Radiomics analyses commonly apply imaging features of different complexity for the prediction of the endpoint of interest. However, the prognostic value of each feature class is generally unclear. Furthermore, many radiomics models lack independent external validation that is decisive for their clinical application. Therefore, in this manuscript we present two complementary studies. In our modelling study, we developed and validated different radiomics signatures for outcome prediction after neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) based on computed tomography (CT) and T2-weighted (T2w) magnetic resonance (MR) imaging datasets of 4 independent institutions (training: 122, validation 68 patients). We compared different feature classes extracted from the gross tumour volume for the prognosis of tumour response and freedom from distant metastases (FFDM): morphological and first order (MFO) features, second order texture (SOT) features, and Laplacian of Gaussian (LoG) transformed intensity features. Analyses were performed for CT and MRI separately and combined. Model performance was assessed by the area under the curve (AUC) and the concordance index (CI) for tumour response and FFDM, respectively. Overall, intensity features of LoG transformed CT and MR imaging combined with clinical T stage (cT) showed the best performance for tumour response prediction, while SOT features showed good performance for FFDM in independent validation (AUC = 0.70, CI = 0.69). In our external validation study, we aimed to validate previously published radiomics signatures on our multicentre cohort. We identified relevant publications on comparable patient datasets through a literature search and applied the reported radiomics models to our dataset. Only one of the identified studies could be validated, indicating an overall lack of reproducibility and the need of further standardization of radiomics before clinical application.

Die Bedeutung der Allgemeinmedizin wurde in Deutschland in den letzten Jahren gestärkt. Trotz dieser Bemühungen bleiben das Medizinstudium und die klinische Weiterbildung von der spezialisierten Versorgung in Krankenhäusern dominiert. In Studien konnte gezeigt werden, dass viele deutsche Allgemeinmediziner komplementärmedizinische Verfahren anwenden. In der vorliegenden Studie wurde die Rolle komplementärmedizinischer Verfahren beim Übergang von der Klinik in die hausärztliche Praxis bei jungen Allgemeinärzten untersucht., Although the role of general practice has been strengthened in recent years, undergraduate teaching at medical schools and the clinical phase of specialist training remain dominated by specialized care in hospitals. In surveys was shown that general practitioners often use complementary treatments. In the present survey, the role of complementary treatments as part of the transition from clinical education to the work as a general practitioner, was examined.

Glioblastoma, the most common primary malignant brain tumor, still carries a bleak prognosis. To guide more efficient treatment options, a lot of scientific effort is put into investigating the peritumoral edema for microscopic tumor infiltration. Here, Diffusion Tensor Imaging (DTI) has emerged as a promising imaging tool. However, its application is impeded by the diffusion effects of free-water. In this thesis, a novel Deep Learning-based approach for correcting the free-water contamination of DTI data is evaluated for its utility in recurrence prediction of glioblastoma., Die Prognose von Glioblastom-Patienten ist bis heute infaust. Ein wichtiger Forschungsschwerpunkt ist deshalb die Weiterentwicklung bildgebender Methoden zur Evaluation der Tumorausbreitung im Gewebe. Insbesondere die Diffusions-Tensor-Bildgebung hat sich dabei als vielversprechend erwiesen. Allerdings ist ihre Anwendbarkeit im Perifokalödem des Tumors durch die Wasserkomponente beeinträchtigt. Diese Arbeit stellt einen neuen, auf maschinellem Lernen basierenden Ansatz vor, mit dem diese Wasserkontamination eliminiert werden kann und demonstriert ihren Nutzen für die Rezidivprädiktion von Glioblastomen.

Ziel dieser Arbeit ist die Analyse von prätherapeutischen 18F-FDG-PET/CT basierten Bildparametern hinsichtlich ihrer Eignung als Prädiktoren für das Gesamtüberleben und das histopathologische Ansprechen auf eine neoadjuvante Radiochemotherapie bei Patienten mit ösophagealen Plattenepithelkarzinomen. Es handelt sich um eine retrospektive Studie mit insgesamt 38 Patienten. Die Auswertung der Daten zeigt, dass Heterogenitätsparameter statistisch signifikant das Gesamtüberleben vorhersagen können., The aim of this thesis is to analyse clinical factors and image parameters derived from pre-therapeutic 18F-FDG-PET/CT imaging as predictors of overall survival and histopathologic response to neoadjuvant chemoradiation in patients with esophageal squamous cell carcinoma. It is a retrospective study with a total of 38 cases. In summary, image parameters based on tumor heterogeneity are independent predictors of overall survival.

Es wurden radiogen induzierte Veränderungen der SWOARs (swallowing organs at risk) anhand von MRT-Bildgebungen analysiert und die Zusammenhänge von Nebenwirkungen wie Dysphagie und Dysphonie mit der applizierten Dosis im SWOAR untersucht., The study analysed side effects of radiotherapy in SWOARs (swallowing organs at risk) by using MRI conturing. In addition the connection between chronic side effects like dysphagia and dysphonia and the applied dose (to the SWOARs) was examinated.

2002 bis 2016 wurden am Klinikum rechts der Isar in München 2075 Patienten mittels stereotaktischer Bestrahlungen intrakraniell, an der Schädelbasis und der Halsregion behandelt. Zentrale Fragen dieser Arbeit sind, welche Tumorentitäten im untersuchten Zeitraum bestrahlt, welche Therapiekonzepte durchgeführt wurden, und wie sich das Gesamtüberleben der Patienten gestaltete. Besonderes Augenmerk wurde auf Hirnmetastasen, Meningeome, Vestibularisschwannome und Hypophysenadenome gelegt., Between 2002 and 2016 2075 patients were treated with stereotactic radiotherapy of the head and neck region at the Klinikum rechts der Isar in Munich. The present paper analyses the types of tumors treated during this period, the treatment plans used and the overall survival rate and time of the patients. In this context, a particular focus is placed on brain metastases, meningiomas, vestibular schwannoma and pituitary adenoma.

(1) Background: Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who are biologically at high risk for the development of loco–regional recurrences after postoperative radiotherapy (PORT) but at intermediate risk according to clinical risk factors may benefit from additional concurrent chemotherapy. In this matched-pair study, we aimed to identify a corresponding predictive gene signature. (2) Methods: Gene expression analysis was performed on a multicenter retrospective cohort of 221 patients that were treated with postoperative radiochemotherapy (PORT-C) and 283 patients who were treated with PORT alone. Propensity score analysis was used to identify matched patient pairs from both cohorts. From differential gene expression analysis and Cox regression, a predictive gene signature was identified. (3) Results: 108 matched patient pairs were selected. We identified a 2-metagene signature that stratified patients into risk groups in both cohorts. The comparison of the high-risk patients between the two types of treatment showed higher loco–regional control (LRC) after treatment with PORT-C (p < 0.001), which was confirmed by a significant interaction term in Cox regression (p = 0.027), i.e., the 2-metagene signature was indicative for the type of treatment. (4) Conclusion: We have identified a novel gene signature that may be helpful to identify patients with high-risk HNSCC amongst those at intermediate clinical risk treated with PORT, who may benefit from additional concurrent chemotherapy.

Automatic localization and segmentation of organs-at-risk (OAR) in CT are essential pre-processing steps in medical image analysis tasks, such as radiation therapy planning. For instance, the segmentation of OAR surrounding tumors enables the maximization of radiation to the tumor area without compromising the healthy tissues. However, the current medical workflow requires manual delineation of OAR, which is prone to errors and is annotator-dependent. In this work, we aim to introduce a unified 3D pipeline for OAR localization-segmentation rather than novel localization or segmentation architectures. To the best of our knowledge, our proposed framework fully enables the exploitation of 3D context information inherent in medical imaging. In the first step, a 3D multi-variate regression network predicts organs' centroids and bounding boxes. Secondly, 3D organ-specific segmentation networks are leveraged to generate a multi-organ segmentation map. Our method achieved an overall Dice score of $0.9260\pm 0.18 \%$ on the VISCERAL dataset containing CT scans with varying fields of view and multiple organs.

Glioblastoma, the most common primary malignant brain tumor, still carries a bleak prognosis. To guide more efficient treatment options, a lot of scientific effort is put into investigating the peritumoral edema for microscopic tumor infiltration. Here, Diffusion Tensor Imaging (DTI) has emerged as a promising imaging tool. However, its application is impeded by the diffusion effects of free-water. In this thesis, a novel Deep Learning-based approach for correcting the free-water contamination of DTI data is evaluated for its utility in recurrence prediction of glioblastoma., Die Prognose von Glioblastom-Patienten ist bis heute infaust. Ein wichtiger Forschungsschwerpunkt ist deshalb die Weiterentwicklung bildgebender Methoden zur Evaluation der Tumorausbreitung im Gewebe. Insbesondere die Diffusions-Tensor-Bildgebung hat sich dabei als vielversprechend erwiesen. Allerdings ist ihre Anwendbarkeit im Perifokalödem des Tumors durch die Wasserkomponente beeinträchtigt. Diese Arbeit stellt einen neuen, auf maschinellem Lernen basierenden Ansatz vor, mit dem diese Wasserkontamination eliminiert werden kann und demonstriert ihren Nutzen für die Rezidivprädiktion von Glioblastomen.

Die Bedeutung der Allgemeinmedizin wurde in Deutschland in den letzten Jahren gestärkt. Trotz dieser Bemühungen bleiben das Medizinstudium und die klinische Weiterbildung von der spezialisierten Versorgung in Krankenhäusern dominiert. In Studien konnte gezeigt werden, dass viele deutsche Allgemeinmediziner komplementärmedizinische Verfahren anwenden. In der vorliegenden Studie wurde die Rolle komplementärmedizinischer Verfahren beim Übergang von der Klinik in die hausärztliche Praxis bei jungen Allgemeinärzten untersucht., Although the role of general practice has been strengthened in recent years, undergraduate teaching at medical schools and the clinical phase of specialist training remain dominated by specialized care in hospitals. In surveys was shown that general practitioners often use complementary treatments. In the present survey, the role of complementary treatments as part of the transition from clinical education to the work as a general practitioner, was examined.

Evidence from a few small randomized trials and retrospective cohorts mostly including various tumor entities indicates a prolongation of disease free survival (DFS) and overall survival (OS) from local ablative therapies in oligometastatic disease (OMD). However, it is still unclear which patients benefit most from this approach. We give an overview of the several aspects of stereotactic body radiotherapy (SBRT) in extracranial OMD in breast cancer from a radiation oncology perspective. A PubMed search referring to this was conducted. An attempt was made to relate the therapeutic efficacy of SBRT to various prognostic factors. Data from approximately 500 breast cancer patients treated with SBRT for OMD in mostly in small cohort studies have been published, consistently indicating high local tumor control rates and favorable progression-free (PFS) and overall survival (OS). Predictors for a good prognosis after SBRT are favorable biological subtype (hormone receptor positive, HER2 negative), solitary metastasis, bone-only metastasis, and long metastasis-free interval. However, definitive proof that SBRT in OMD breast cancer prolongs DFS or OS is lacking, since, with the exception of one small randomized trial (n = 22 in the SBRT arm), none of the cohort studies had an adequate control group. Further studies are needed to prove the benefit of SBRT in OMD breast cancer and to define adequate selection criteria. Currently, the use of local ablative SBRT should always be discussed in a multidisciplinary tumor board.

PURPOSE To quantify neuroanatomical changes using magnetic resonance imaging (MRI) in patients with cerebral metastasized breast cancer after brain radiotherapy (RT). METHODS Fifteen patients with breast cancer with brain metastases who underwent whole brain RT (WBR), radiosurgery (RS), and/or hypofractionated stereotactic treatment (STX) were examined at four time points (TPs). A total of 48 MRIs were available: prior to RT (TP1), 5-8 months after RT (TP2), 9-11 months after RT (TP3), and >20 months after RT (TP4). Using automatic segmentation, 25 subcortical structures were analyzed. Patients were split into three groups: STX (receiving STX and RS), RS (receiving RS only), and WBR (receiving WBR at least once). After testing for a normal distribution for all values using the Kolmogorov-Smirnov test, a two-sided paired t test was used to analyze volumetric changes. For those values that were not normally distributed, the nonparametric Mann-Whitney test was employed. RESULTS The left cerebellum white matter (p = 0.028), the right pallidum (p = 0.038), and the left thalamus (p = 0.039) significantly increased at TP2 compared to TP1. The third ventricle increased at all TPs (p = 0.034-0.046). The left choroid plexus increased at TP3 (p = 0.037) compared to TP1. The left lateral ventricle increased at TP3 (p = 0.012) and TP4 (p = 0.027). Total gray matter showed a trend of volume decline in STX and WBR groups. CONCLUSIONS These findings indicate that alterations in the volume of subcortical structures may act as a sensitive parameter when evaluating neuroanatomical changes and brain atrophy due to radiotherapy. Differences observed for patients who received STX and WBR, but not those treated with RS, need to be validated further.

Automatic localization and segmentation of organs-at-risk (OAR) in CT are essential pre-processing steps in medical image analysis tasks, such as radiation therapy planning. For instance, the segmentation of OAR surrounding tumors enables the maximization of radiation to the tumor area without compromising the healthy tissues. However, the current medical workflow requires manual delineation of OAR, which is prone to errors and is annotator-dependent. In this work, we aim to introduce a unified 3D pipeline for OAR localization-segmentation rather than novel localization or segmentation architectures. To the best of our knowledge, our proposed framework fully enables the exploitation of 3D context information inherent in medical imaging. In the first step, a 3D multi-variate regression network predicts organs' centroids and bounding boxes. Secondly, 3D organ-specific segmentation networks are leveraged to generate a multi-organ segmentation map. Our method achieved an overall Dice score of 0.9260±0.18% on the VISCERAL dataset containing CT scans with varying fields of view and multiple organs.

Radiomics analyses commonly apply imaging features of different complexity for the prediction of the endpoint of interest. However, the prognostic value of each feature class is generally unclear. Furthermore, many radiomics models lack independent external validation that is decisive for their clinical application. Therefore, in this manuscript we present two complementary studies. In our modelling study, we developed and validated different radiomics signatures for outcome prediction after neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) based on computed tomography (CT) and T2-weighted (T2w) magnetic resonance (MR) imaging datasets of 4 independent institutions (training: 122, validation 68 patients). We compared different feature classes extracted from the gross tumour volume for the prognosis of tumour response and freedom from distant metastases (FFDM): morphological and first order (MFO) features, second order texture (SOT) features, and Laplacian of Gaussian (LoG) transformed intensity features. Analyses were performed for CT and MRI separately and combined. Model performance was assessed by the area under the curve (AUC) and the concordance index (CI) for tumour response and FFDM, respectively. Overall, intensity features of LoG transformed CT and MR imaging combined with clinical T stage (cT) showed the best performance for tumour response prediction, while SOT features showed good performance for FFDM in independent validation (AUC = 0.70, CI = 0.69). In our external validation study, we aimed to validate previously published radiomics signatures on our multicentre cohort. We identified relevant publications on comparable patient datasets through a literature search and applied the reported radiomics models to our dataset. Only one of the identified studies could be validated, indicating an overall lack of reproducibility and the need of further standardization of radiomics before clinical application.

Die Übertragbarkeit von Ergebnissen aus 2D Zellkulturversuchen auf ionisierende Bestrahlung oder Chemotherapeutika steht in der Kritik. Aus diesem Grund steigt das Interesse an dreidimensionalen Zellkulturmodellen in der Tumorforschung. In dieser Arbeit wurde das Überleben bestrahlter Tumorzellen von drei verschiedenen Zelllinien in dem Goldstandard 2D Koloniebildungstest und einem 3D Mikrotissue Modell verglichen. Es zeigte sich eine starke Korrelation zwischen der 2D Überlebensfraktion und dem reduzierten Wachstum der 3D Mikrotissues bei den getesteten Dosen., 2D monolayer cell cultures are increasingly being seen as an imperfect model for studying the cellular responses to ionizing radiation or chemotherapeutic drugs. This has prompted increased interest of 3D cell culture alternatives as a more physiological predictor of tumor treatment. In this work, the survival of irradiated cells of three different cell lines using the gold-standard 2D colony formation assay and a 3D microtissue assay was compared. A strong correlation between the 2D survival fraction and the reduced growth of 3D microtissues at the tested doses was shown.

Die vorliegende Studie vergleicht die Ergebnisse der VMAT mit der 3D-konformalen Strahlentherapie bei Patienten mit Rektumkarzinom. Insgesamt konnte mittels VMAT eine bessere Schonung der Blase und Hüftköpfe erreicht werden und die Patienten litten seltener an Stuhlinkontinenz, während sich die Lebensqualität insgesamt kaum unterschied. Außerdem zeigte sich eine Verlängerung des Gesamtüberlebens der VMAT-Patienten. Im Gesamtergebnis ist festzustellen, dass die Ergebnisse der onkologischen Behandlung der VMAT bei Rektumkarzinomen mindestens gleichwertig zu dem der etablierten 3D-konformalen Radiotherapie waren., The study was designed to compare VMAT and 3D-conformal radiotherapy in patients with rectal cancer. The bladder as well as the femoral heads could be spared better with VMAT and those patients suffered less from fecal incontinence, while there were only small differences in the reported quality of life. Furthermore the Overall Survival was longer when VMAT was applied. In conclusion, oncologic results with VMAT in patients with rectal cancer are at least to be seen as equal to the established 3D-conformal radiotherapy.

Die Arbeit analysiert immunologische Phänomene im peripheren Blut von Patienten mit Plattenepithelkarzinomen im Kopf-Hals-Bereich. Prospektiv werden sowohl Einflüsse der Tumorerkrankung selbst, als auch der lokalen Strahlentherapie als häufige Therapiemodalität auf verschiedene Blut- und Immunzellen untersucht. Die Ergebnisse der Arbeit legen nahe, dass die Bestrahlung von Plattenepithelkarzinomen im Kopf-Hals-Bereich einen immunmodulatorischen Effekt haben könnte, indem die Aktivität von tumorbekämpfenden Immunzellen angeregt wird., The thesis analyzes immunological phenomena in the peripheral blood of patients with squamous cell carcinoma of the head and neck. Prospectively, both the effects of the tumor disease itself as well as local radiation therapy as a common therapy modality on various blood and immune cells are examined. The results of the work suggest that the radiation of squamous cell carcinomas of the head and neck could have an immunomodulatory effect by stimulating the activity of tumor-fighting immune cells.

In der vorliegenden Arbeit wurde das onkologische Ergebnis und die Toxizitäten einer adjuvanten versus frühe Salvage Radiotherapie bei Patienten mit Prostatakarzinom nach radikaler Prostatektomie untersucht. Es zeigte sich kein Unterschied im biochemisch-rezidivfreien Überleben. Patienten nach direkt postoperativer Radiotherapie zeigten eine erhöhte Rate an Proktitiden und Harnröhrenstrikturen., Goal of this dissertation was the evaluation of the oncological outcome and toxicity profiles for patients treated with adjuvant versus early salvage radiotherapy after radical prostatectomy. There was no difference in biochemical relapse-free survival. However, patients treated with immediate postoperative radiotherapy were at higher risk for proctitis and obstructive uropathy.