321 results on '"Lohaus F"'
Search Results
2. Stereotactic radiosurgery and radiotherapy for resected brain metastases: current pattern of care in the Radiosurgery and Stereotactic Radiotherapy Working Group of the German Association for Radiation Oncology (DEGRO)
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Rogers, S., Baumert, B., Blanck, O., Böhmer, D., Boström, J., Engenhart-Cabillic, R., Ermis, E., Exner, S., Guckenberger, M., Habermehl, D., Hemmatazad, H., Henke, G., Lohaus, F., Lux, S., Mai, S., Minasch, D., Rezazadeh, A., Steffal, C., Temming, S., Wittig, A., Zweifel, C., Riesterer, O., and Combs, S. E.
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- 2022
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3. Correction to: Stereotactic radiosurgery and radiotherapy for resected brain metastases: current pattern of care in the Radiosurgery and Stereotactic Radiotherapy Working Group of the German Association for Radiation Oncology (DEGRO)
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Rogers, S., Baumert, B., Blanck, O., Böhmer, D., Boström, J., Engenhart-Cabillic, R., Ermis, E., Exner, S., Guckenberger, M., Habermehl, D., Hemmatazad, H., Henke, G., Lohaus, F., Lux, S., Mai, S., Minasch, D., Rezazadeh, A., Steffal, C., Temming, S., Wittig, A., Zweifel, C., Riesterer, O., and Combs, S. E.
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- 2023
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4. Stereotactic body radiotherapy (SBRT) for multiple pulmonary oligometastases: Analysis of number and timing of repeat SBRT as impact factors on treatment safety and efficacy
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Klement, R.J., Hoerner-Rieber, J., Adebahr, S., Andratschke, N., Blanck, O., Boda-Heggemann, J., Duma, M., Eble, M.J., Eich, H.C., Flentje, M., Gerum, S., Hass, P., Henkenberens, C., Hildebrandt, G., Imhoff, D., Kahl, K.H., Klass, N.D., Krempien, R., Lohaus, F., Petersen, C., Schrade, E., Wendt, T.G., Wittig, A., and Guckenberger, M.
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- 2018
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5. PD-0064 Metastases-directed SRT combined with systemic therapy: 2y results of the TOaSTT real-world database
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Kroeze, S., primary, Schaule, J., additional, Spaas, M., additional, Kahl, K.H., additional, Verhoeff, J.J., additional, Schneiders, F.L., additional, Blanck, O., additional, Lohaus, F., additional, Rogers, S., additional, Kaul, D., additional, Benavente, S., additional, Combs, S.E., additional, Skazikis, G., additional, Baumann, K., additional, Popp, I., additional, Koppe, F., additional, Geinitz, H., additional, de Jaeger, K.E., additional, Siva, S., additional, Stera, S., additional, Wittig-Sauerwein, A., additional, Lewitzki, V., additional, Eckert, F., additional, Schymalla, M.M., additional, and Guckenberger, M., additional
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- 2023
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6. Nomogram based overall survival prediction in stereotactic body radiotherapy for oligo-metastatic lung disease
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Tanadini-Lang, S., Rieber, J., Filippi, A.R., Fode, M.M., Streblow, J., Adebahr, S., Andratschke, N., Blanck, O., Boda-Heggemann, J., Duma, M., Eble, M.J., Ernst, I., Flentje, M., Gerum, S., Hass, P., Henkenberens, C., Hildebrandt, G., Imhoff, D., Kahl, H., Klass, N.D., Krempien, R., Lohaus, F., Petersen, C., Schrade, E., Wendt, T.G., Wittig, A., Høyer, M., Ricardi, U., Sterzing, F., and Guckenberger, M.
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- 2017
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7. Dynamics of CXCR4 positive circulating tumor cells in prostate cancer patients during radiotherapy
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Klusa, D., Lohaus, F., Franken, A., Baumbach, M., Cojoc, M., Dowling, P., Linge, A., Offermann, A., Löck, S., Husman, D., Rivandi, M., Polzer, B., Freytag, V., Lange, T., Neubauer, H., Kücken, M., Perner, S., Hölscher, T., (0000-0002-3375-1500) Dubrovska, A., (0000-0003-1776-9556) Krause, M., Kurth, I., Baumann, M., Peitzsch, C., Klusa, D., Lohaus, F., Franken, A., Baumbach, M., Cojoc, M., Dowling, P., Linge, A., Offermann, A., Löck, S., Husman, D., Rivandi, M., Polzer, B., Freytag, V., Lange, T., Neubauer, H., Kücken, M., Perner, S., Hölscher, T., (0000-0002-3375-1500) Dubrovska, A., (0000-0003-1776-9556) Krause, M., Kurth, I., Baumann, M., and Peitzsch, C.
- Abstract
Ablative radiotherapy is a highly efficient treatment modality for patients with metastatic prostate cancer (PCa). However, a subset of patients does not respond. Currently, this subgroup with bad prognosis cannot be identified before disease progression. We hypothesize that markers indicative of radioresistance, stemness and/or bone tropism may have a prognostic potential to identify patients profiting from metastases-directed radiotherapy. Therefore, circulating tumor cells (CTCs) were analyzed in patients with metastatic PCa (n = 24) during radiotherapy with Cell-Search, multicolor flow cytometry and imaging cytometry. Analysis of copy-number alteration indicates a polyclonal CTC population that changes after radiotherapy. CTCs were found in 8 out of 24 patients (33.3%) and were associated with a shorter time to biochemical progression after radiotherapy. Whereas the total CTC count dropped after radiotherapy, a chemokine receptor CXCR4-expressing subpopulation representing 28.6% of the total CTC population remained stable up to 3 months. At once, we observed higher chemokine CCL2 plasma concentrations and proinflammatory monocytes. Additional functional analyses demonstrated key roles of CXCR4 and CCL2 for cellular radiosensitivity, tumorigenicity and stem-like potential in vitro and in vivo. Moreover, a high CXCR4 and CCL2 expression was found in bone metastasis biopsies of PCa patients. In summary, panCK+CXCR4+ CTCs may have a prognostic potential in patients with metastatic PCa treated with metastasis-directed radiotherapy.
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- 2023
8. DNA-Methylome–Based Tumor Hypoxia Classifier Identifies HPV-Negative Head and Neck Cancer Patients at Risk for Locoregional Recurrence after Primary Radiochemotherapy
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Tawk, B., Rein, K., Schwager, C., Knoll, M., Wirkner, U., Hörner-Rieber, J., Liermann, J., Kurth, I., Balermpas, P., Rödel, C., Linge, A., Löck, S., Lohaus, F., Tinhofer, I., (0000-0003-1776-9556) Krause, M., Stuschke, M., Ligia Grosu, A., Zips, D., Combs, S. E., Belka, C., Stenzinger, A., Herold-Mende, C., Baumann, M., Schirmacher, P., Debus, J., Abdollahi, A., Tawk, B., Rein, K., Schwager, C., Knoll, M., Wirkner, U., Hörner-Rieber, J., Liermann, J., Kurth, I., Balermpas, P., Rödel, C., Linge, A., Löck, S., Lohaus, F., Tinhofer, I., (0000-0003-1776-9556) Krause, M., Stuschke, M., Ligia Grosu, A., Zips, D., Combs, S. E., Belka, C., Stenzinger, A., Herold-Mende, C., Baumann, M., Schirmacher, P., Debus, J., and Abdollahi, A.
- Abstract
Purpose: 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. Experimental Design: A DNA-methylome–based tumor hypoxia classifier (Hypoxia-M) was trained in the TCGA (The Cancer Genome Atlas)-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 papillomavirus (HPV)–negative patients with HNSCC treated with primary radiochemotherapy (RCHT). Results: Although hypoxia-GES failed to stratify patients in the DKTK-ROG, Hypoxia-M was independently prognostic for local recurrence (HR, 4.3; P ¼0.001) and overall survival (HR, 2.34; P ¼ 0.03) but not distant metastasis after RCHT in both cohorts. Hypoxia-M status was inversely associated with CD8 T-cell infiltration in both cohorts. Hypoxia-M was further prognostic in the TCGA-PanCancer cohort (HR, 1.83; P ¼0.04), 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.
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- 2023
9. Multitask Learning with Convolutional Neural Networks and Vision Transformers Can Improve Outcome Prediction for Head and Neck Cancer Patients
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(0000-0001-5007-1868) Starke, S., Zwanenburg, A., Leger, K., Lohaus, F., Linge, A., Schreiber, A., Kalinauskaite, G., Tinhofer, I., Guberina, N., Guberina, M., Balermpas, P., Grün, J., Ganswindt, U., Belka, C., Peeken, J. C., Combs, S. E., Böke, S., Zips, D., (0000-0003-4261-4214) Richter, C., (0000-0001-9550-9050) Troost, E. G. C., (0000-0003-1776-9556) Krause, M., Baumann, M., (0000-0002-7017-3738) Löck, S., (0000-0001-5007-1868) Starke, S., Zwanenburg, A., Leger, K., Lohaus, F., Linge, A., Schreiber, A., Kalinauskaite, G., Tinhofer, I., Guberina, N., Guberina, M., Balermpas, P., Grün, J., Ganswindt, U., Belka, C., Peeken, J. C., Combs, S. E., Böke, S., Zips, D., (0000-0003-4261-4214) Richter, C., (0000-0001-9550-9050) Troost, E. G. C., (0000-0003-1776-9556) Krause, M., Baumann, M., and (0000-0002-7017-3738) Löck, S.
- Abstract
Neural-network-based outcome predictions may enable further treatment personalization of patients with head and neck cancer. The development of neural networks can prove challenging when a limited number of cases is available. Therefore, we investigated whether multitask learning strategies, implemented through the simultaneous optimization of two distinct outcome objectives (multi-outcome) and combined with a tumor segmentation task, can lead to improved performance of convolutional neural networks (CNN) and vision transformers (ViT). Model training was conducted on two distinct multicenter datasets for the endpoints loco-regional control (LRC) and progression-free survival (PFS), respectively. The first dataset consisted of pre-treatment computed tomography (CT) imaging for 290 patients and the second dataset contained combined positron emission tomography (PET)/CT for 224 patients. Discriminative performance was assessed by the concordance index (C-index). Risk stratification was evaluated using log-rank tests. Across both datasets, CNN and ViT model ensembles achieved similar results. Multitask approaches showed favorable performance in most investigations. Multi-outcome CNN models trained with segmentation loss were identified as the optimal strategy across cohorts. On the PET/CT dataset, an ensemble of multi-outcome CNNs trained with segmentation loss achieved the best discrimination (C-index: 0.29, 95% confidence interval (CI): 0.22-0.36) and successfully stratified patients into groups with low and high risk of disease progression (p=0.003). On the CT dataset, ensembles of multi-outcome CNNs and of single-outcome ViTs trained with segmentation loss performed best (C-index: 0.26 and 0.26, CI: 0.18-0.34 and 0.18-0.35, respectively), both with significant risk stratification for LRC in independent validation (p=0.002 and p=0.011). Further validation of the developed multitask-learning models is planned based on a prospective validation study, which is currently
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- 2023
10. Reduction of intrafraction pancreas motion using an abdominal corset compatible with proton therapy and MRI
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(0000-0002-5771-5213) Schneider, S., (0000-0002-8107-1649) Stefanowicz, S., Jentsch, C., (0000-0003-4043-7066) Lohaus, F., Thiele, J., Haak, D., (0000-0001-6814-1131) Valentini, C., (0000-0002-5933-8108) Platzek, I., (0000-0001-9550-9050) Troost, E. G. C., (0000-0002-5821-3135) Hoffmann, A. L., (0000-0002-5771-5213) Schneider, S., (0000-0002-8107-1649) Stefanowicz, S., Jentsch, C., (0000-0003-4043-7066) Lohaus, F., Thiele, J., Haak, D., (0000-0001-6814-1131) Valentini, C., (0000-0002-5933-8108) Platzek, I., (0000-0001-9550-9050) Troost, E. G. C., and (0000-0002-5821-3135) Hoffmann, A. L.
- Abstract
Background and Purpose: Motion mitigation is of crucial importance in particle therapy (PT) of patients with abdominal tumors to ensure high-precision irradiation. Magnetic resonance imaging (MRI) is an excellent modality for target volume delineation and motion estimation of mobile soft-tissue tumors. Thus, the aims of this study were to develop an MRI- and PT-compatible abdominal compression device, to investigate its effect on pancreas motion reduction, and to evaluate patient tolerability and acceptance. Materials and Methods: In a prospective clinical study, 16 patients with abdominal tumors received an individualized polyethylene-based abdominal corset. Pancreas motion was analyzed using time- and phase resolved MRI scans (orthogonal 2D-cine and 4D MRI) with and without compression by the corset. The pancreas was manually segmented in each MRI data set and the population-averaged center-of-mass motion in inferior-superior (IS), anterior-posterior (AP) and left-right (LR) directions was determined. A questionnaire was developed to investigate the level of patient acceptance of the corset, which the patients completed after acquisition of the planning computed tomography (CT) and MRI scans. Results: The corset was found to reduce pancreas motion predominantly in IS direction by on average 47 % - 51 % as found in the 2D-cine and 4D MRI data, respectively, while motion in the AP and LR direction was not significantly reduced. Most patients reported no discomfort when wearing the corset. Conclusion: An MRI- and PT-compatible individualized abdominal corset was presented, which substantially reduced breathing-induced pancreas motion and can be safely applied with no additional discomfort for the patients. The corset has been successfully integrated into our in-house clinical workflow for PT of tumors of the upper abdomen.
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- 2023
11. Data publication: Multitask learning with convolutional neural networks and vision transformers can improve outcome prediction for head and neck cancer patients
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(0000-0001-5007-1868) Starke, S., Zwanenburg, A., Leger, K., Lohaus, F., Linge, A., Schreiber, A., Kalinauskaite, G., Tinhofer, I., Guberina, N., Guberina, M., Balermpas, P., Grün, J., Ganswindt, U., Belka, C., Peeken, J. C., Combs, S. E., Böke, S., Zips, D., (0000-0003-4261-4214) Richter, C., (0000-0001-9550-9050) Troost, E. G. C., (0000-0003-1776-9556) Krause, M., Baumann, M., (0000-0002-7017-3738) Löck, S., (0000-0001-5007-1868) Starke, S., Zwanenburg, A., Leger, K., Lohaus, F., Linge, A., Schreiber, A., Kalinauskaite, G., Tinhofer, I., Guberina, N., Guberina, M., Balermpas, P., Grün, J., Ganswindt, U., Belka, C., Peeken, J. C., Combs, S. E., Böke, S., Zips, D., (0000-0003-4261-4214) Richter, C., (0000-0001-9550-9050) Troost, E. G. C., (0000-0003-1776-9556) Krause, M., Baumann, M., and (0000-0002-7017-3738) Löck, S.
- Abstract
This dataset contains the model checkpoints, predictions and performance metrics for the multitask neural networks presented in the corresponding manuscript.
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- 2023
12. Stereotactic radiosurgery and radiotherapy for resected brain metastases: current pattern of care in the Radiosurgery and Stereotactic Radiotherapy Working Group of the German Association for Radiation Oncology (DEGRO) (vol 198, pg 919, 2022)
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Rogers, S., Baumert, B., Blanck, O., Boehmer, D., Bostroem, J., Engenhart-Cabillic, R., Ermis, E., Exner, S., Guckenberger, M., Habermehl, D., Hemmatazad, H., Henke, G., Lohaus, F., Lux, S., Mai, S., Minasch, D., Rezazadeh, A., Steffal, C., Temming, S., Wittig, A., Zweifel, C., Riesterer, O., Combs, S. E., Rogers, S., Baumert, B., Blanck, O., Boehmer, D., Bostroem, J., Engenhart-Cabillic, R., Ermis, E., Exner, S., Guckenberger, M., Habermehl, D., Hemmatazad, H., Henke, G., Lohaus, F., Lux, S., Mai, S., Minasch, D., Rezazadeh, A., Steffal, C., Temming, S., Wittig, A., Zweifel, C., Riesterer, O., and Combs, S. E.
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- 2023
13. Interobserver agreement on definition of the target volume in stereotactic radiotherapy for pancreatic adenocarcinoma using different imaging modalities
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Gkika, E; https://orcid.org/0000-0001-5455-252X, Kostyszyn, D, Fechter, T, Moustakis, C, Ernst, F, Boda-Heggemann, J, Sarria, G, Dieckmann, K, Dobiasch, S, Duma, M N, Eberle, F, Kroeger, K, Häussler, B, Izaguirre, V, Jazmati, D, Lautenschläger, S, Lohaus, F, Mantel, F, Menzel, J, Pachmann, S, Pavic, M, Radlanski, K, Riesterer, O, Gerum, S, Röder, F, Willner, J, Barczyk, S, Imhoff, D, Blanck, O, Wittig, A, et al, Guckenberger, M, Gkika, E; https://orcid.org/0000-0001-5455-252X, Kostyszyn, D, Fechter, T, Moustakis, C, Ernst, F, Boda-Heggemann, J, Sarria, G, Dieckmann, K, Dobiasch, S, Duma, M N, Eberle, F, Kroeger, K, Häussler, B, Izaguirre, V, Jazmati, D, Lautenschläger, S, Lohaus, F, Mantel, F, Menzel, J, Pachmann, S, Pavic, M, Radlanski, K, Riesterer, O, Gerum, S, Röder, F, Willner, J, Barczyk, S, Imhoff, D, Blanck, O, Wittig, A, et al, and Guckenberger, M
- Abstract
PURPOSE The aim of this study was to evaluate interobserver agreement (IOA) on target volume definition for pancreatic cancer (PACA) within the Radiosurgery and Stereotactic Radiotherapy Working Group of the German Society of Radiation Oncology (DEGRO) and to identify the influence of imaging modalities on the definition of the target volumes. METHODS Two cases of locally advanced PACA and one local recurrence were selected from a large SBRT database. Delineation was based on either a planning 4D CT with or without (w/wo) IV contrast, w/wo PET/CT, and w/wo diagnostic MRI. Novel compared to other studies, a combination of four metrics was used to integrate several aspects of target volume segmentation: the Dice coefficient (DSC), the Hausdorff distance (HD), the probabilistic distance (PBD), and the volumetric similarity (VS). RESULTS For all three GTVs, the median DSC was 0.75 (range 0.17-0.95), the median HD 15 (range 3.22-67.11) mm, the median PBD 0.33 (range 0.06-4.86), and the median VS was 0.88 (range 0.31-1). For ITVs and PTVs the results were similar. When comparing the imaging modalities for delineation, the best agreement for the GTV was achieved using PET/CT, and for the ITV and PTV using 4D PET/CT, in treatment position with abdominal compression. CONCLUSION Overall, there was good GTV agreement (DSC). Combined metrics appeared to allow a more valid detection of interobserver variation. For SBRT, either 4D PET/CT or 3D PET/CT in treatment position with abdominal compression leads to better agreement and should be considered as a very useful imaging modality for the definition of treatment volumes in pancreatic SBRT. Contouring does not appear to be the weakest link in the treatment planning chain of SBRT for PACA.
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- 2023
14. The impact of local control on overall survival after stereotactic body radiotherapy for liver and lung metastases from colorectal cancer: a combined analysis of 388 patients with 500 metastases
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Klement, Rainer J., Abbasi-Senger, N., Adebahr, S., Alheid, H., Allgaeuer, M., Becker, G., Blanck, O., Boda-Heggemann, J., Brunner, T., Duma, M., Eble, M. J., Ernst, I., Gerum, S., Habermehl, D., Hass, P., Henkenberens, C., Hildebrandt, G., Imhoff, D., Kahl, H., Klass, N. D., Krempien, R., Lewitzki, V., Lohaus, F., Ostheimer, C., Papachristofilou, A., Petersen, C., Rieber, J., Schneider, T., Schrade, E., Semrau, R., Wachter, S., Wittig, A., Guckenberger, M., and Andratschke, N.
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- 2019
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15. Correction to: Stereotactic radiosurgery and radiotherapy for resected brain metastases: current pattern of care in the Radiosurgery and Stereotactic Radiotherapy Working Group of the German Association for Radiation Oncology (DEGRO)
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Rogers, S., primary, Baumert, B., additional, Blanck, O., additional, Böhmer, D., additional, Boström, J., additional, Engenhart-Cabillic, R., additional, Ermis, E., additional, Exner, S., additional, Guckenberger, M., additional, Habermehl, D., additional, Hemmatazad, H., additional, Henke, G., additional, Lohaus, F., additional, Lux, S., additional, Mai, S., additional, Minasch, D., additional, Rezazadeh, A., additional, Steffal, C., additional, Temming, S., additional, Wittig, A., additional, Zweifel, C., additional, Riesterer, O., additional, and Combs, S. E., additional
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- 2022
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16. Interobserver agreement on definition of the target volume in stereotactic radiotherapy for pancreatic adenocarcinoma using different imaging modalities
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Gkika, E, Kostyszyn, D, Fechter, T, Moustakis, C, Ernst, F, Boda-Heggemann, J, Sarria, G, Dieckmann, K, Dobiasch, S, Duma, M N, Eberle, F, Kroeger, K, Häussler, B, Izaguirre, V, Jazmati, D, Lautenschläger, S, Lohaus, F, Mantel, F, Menzel, J, Pachmann, S, Pavic, M, Radlanski, K, Riesterer, O, Gerum, S, Röder, F, Willner, J, Barczyk, S, Imhoff, D, Blanck, O, Wittig, A, et al, and Guckenberger, M
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- 2023
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17. Interobserver variability in target volume delineation of hepatocellular carcinoma: An analysis of the working group “Stereotactic Radiotherapy” of the German Society for Radiation Oncology (DEGRO)
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Gkika, E., Tanadini-Lang, S., Kirste, S., Holzner, P. A., Neeff, H. P., Rischke, H. C., Reese, T., Lohaus, F., Duma, M. N., Dieckmann, K., Semrau, R., Stockinger, M., Imhoff, D., Kremers, N., Häfner, M. F., Andratschke, N., Nestle, U., Grosu, A. L., Guckenberger, M., and Brunner, T. B.
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- 2017
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18. MO-0139 PORT-C improves LRC in a subset of patients with intermediate-risk HNSCC: A matched pair analysis
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Patil, S., primary, Linge, A., additional, Hiepe, H., additional, Grosser, M., additional, Lohaus, F., additional, Gudziol, V., additional, Nowak, A., additional, Tinhofer, I., additional, Budach, V., additional, Guberina, M., additional, Stuschke, M., additional, Balermpas, P., additional, Rödel, C., additional, Schäfer, H., additional, Grosu, A., additional, Abdollahi, A., additional, Debus, J., additional, Belka, C., additional, Pigorsch, S., additional, Combs, S.E., additional, Boeke, S., additional, Zips, D., additional, Baumann, M., additional, Krause, M., additional, and Löck, S., additional
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- 2022
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19. PO-1304 Impact of blood parameters and normal tissue dose on overall survival in esophageal cancer patients
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Troost, E., primary, Häberlein, L., additional, Bütof, R., additional, Jentsch, C., additional, Lohaus, F., additional, Makocki, S., additional, Valentini, C., additional, and Löck, S., additional
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- 2022
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20. OC-0256 Biomarker development from joint analyses of HNSCC xenografts and patients treated by PORT-C
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Linge, A., primary, Patil, S., additional, Gurtner, K., additional, Grosser, M., additional, Lohaus, F., additional, Gudziol, V., additional, Nowak, A., additional, Tinhofer, I., additional, Budach, V., additional, Guberina, M., additional, Stuschke, M., additional, Balermpas, P., additional, Rödel, C., additional, Schäfer, H., additional, Grosu, A., additional, Abdollahi, A., additional, Debus, J., additional, Belka, C., additional, Pigorsch, S., additional, Combs, S.E., additional, Boeke, S., additional, Zips, D., additional, Baumann, M., additional, Löck, S., additional, and Krause, M., additional
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- 2022
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21. Impact of blood parameters and normal tissue dose on treatment outcome in esophageal cancer patients undergoing neoadjuvant radiochemotherapy
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Bütof, R., Häberlein, L., Jentsch, C., Kotzerke, J., Lohaus, F., Makocki, S., Valentini, C., Weitz, J., Löck, S., (0000-0001-9550-9050) Troost, E. G. C., Bütof, R., Häberlein, L., Jentsch, C., Kotzerke, J., Lohaus, F., Makocki, S., Valentini, C., Weitz, J., Löck, S., and (0000-0001-9550-9050) Troost, E. G. C.
- Abstract
Despite technological advances, normal tissue sparing in photon beam irradiation is still challenging. Since in esophageal cancer this may inflict damage on the lungs, heart and bone marrow, possibly impacting on outcome, the aim of this study was to investigate the association of normal tissue dose and blood parameters on the survival of patients having undergone neoadjuvant radiochemotherapy (RCTx) followed by surgery. This retrospective study included 125 patients irradiated to 40–41.4 Gy with photons or protons combined with concurrent chemotherapy. On initial and restaging 18F-FDG-PET/CT, the lungs and heart were contoured as organs at risk for which standardized uptake values (SUV) were evaluated. The mean radiation dose (Dmean) to the lungs and heart, the volume of the lungs receiving at least 20 Gy (V20Gy_lung) and various pre- and per-treatment blood parameters were included in the Cox regression analyses. Results: The median follow-up time was 19.8 months and median overall survival 37 months (95% confidence interval: 16–58.9 months). In multivariate analysis, higher radiation doses to the lungs and heart were statistically significantly associated with decreased overall survival (Dmean_lung: p < 0.001; V20Gy_lung: p < 0.002; Dmean_heart: p = 0.005). Neither the 18F-FDG-PET nor blood parameters were predictive for overall survival. In patients with locally advanced esophageal cancer treated with RCTx, the radiation dose to the heart and lungs was significantly associated with overall survival.
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- 2022
22. Integrated radiogenomics analyses allow for subtype classification and improved outcome prognosis of patients with locally advanced HNSCC
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(0000-0002-1508-9410) Rabasco Meneghetti, A., (0000-0002-0342-9545) Zwanenburg, A., (0000-0001-9636-1721) Linge, A., (0000-0003-4043-7066) Lohaus, F., (0000-0001-9865-208X) Grosser, M., (0000-0002-4051-6306) Baretton, G., (0000-0003-3798-1546) Kalinauskaite, G., (0000-0002-0512-549X) Tinhofer, I., (0000-0002-1205-559X) Guberina, N., (0000-0001-6836-0940) Stuschke, M., (0000-0001-5261-6446) Balermpas, P., (0000-0002-9371-7814) Grün, J., (0000-0003-4492-614X) Ganswindt, U., (0000-0002-1287-7825) Belka, C., (0000-0003-2679-9853) Peeken, J. C., (0000-0002-5233-1536) Combs, S. E., (0000-0002-3210-3368) Böke, S., (0000-0001-5779-9675) Zips, D., (0000-0001-9550-9050) Troost, E. G. C., (0000-0003-1776-9556) Krause, M., Baumann, M., (0000-0002-7017-3738) Löck, S., (0000-0002-1508-9410) Rabasco Meneghetti, A., (0000-0002-0342-9545) Zwanenburg, A., (0000-0001-9636-1721) Linge, A., (0000-0003-4043-7066) Lohaus, F., (0000-0001-9865-208X) Grosser, M., (0000-0002-4051-6306) Baretton, G., (0000-0003-3798-1546) Kalinauskaite, G., (0000-0002-0512-549X) Tinhofer, I., (0000-0002-1205-559X) Guberina, N., (0000-0001-6836-0940) Stuschke, M., (0000-0001-5261-6446) Balermpas, P., (0000-0002-9371-7814) Grün, J., (0000-0003-4492-614X) Ganswindt, U., (0000-0002-1287-7825) Belka, C., (0000-0003-2679-9853) Peeken, J. C., (0000-0002-5233-1536) Combs, S. E., (0000-0002-3210-3368) Böke, S., (0000-0001-5779-9675) Zips, D., (0000-0001-9550-9050) Troost, E. G. C., (0000-0003-1776-9556) Krause, M., Baumann, M., and (0000-0002-7017-3738) Löck, S.
- Abstract
Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) may benefit from personalised treatment, requiring biomarkers that characterize the tumour and predict treatment response. We integrate pre-treatment CT radiomics and whole-transcriptome data from a multicentre retrospective cohort of 206 patients with locally advanced HNSCC treated with primary radiochemotherapy to classify tumour molecular subtypes based on radiomics, develop surrogate radiomics signatures for gene-based signatures related to different biological tumour characteristics and evaluate the potential of combining radiomics features with full-transcriptome data for the prediction of loco-regional control (LRC). Using end-to-end machine-learning, we developed and validated a model to classify tumours of the atypical subtype (AUC [95% confidence interval]: 0.69 [0.53-0.83]) based on CT imaging, observed that CT-based radiomics models have limited value as surrogates for six selected gene signatures (AUC<0.60), and showed that combining a radiomics signature with a transcriptomics signature consisting of two metagenes representing the hedgehog pathway and E2F transcriptional targets improves the prognostic value for LRC compared to both individual sources (validation C-index [95% confidence interval], combined: 0.63 [0.55-0.73] vs radiomics: 0.60 [0.50-0.71] and transcriptomics: 0.59 [0.49-0.69]). These results underline the potential of multi-omics analyses to generate reliable biomarkers for future application in personalized oncology.
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- 2022
23. A Novel 2-Metagene Signature to Identify High-Risk HNSCC Patients amongst Those Who Are Clinically at Intermediate Risk and Are Treated with PORT
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Patil, S. G., Linge, A., Hiepe, H., Grosser, M., Lohaus, F., Gudziol, V., Kemper, M., Nowak, A., Haim, D., Tinhofer, I., Budach, V., Guberina, M., Stuschke, M., Balermpas, P., Grün, J. V. D., Schäfer, H., Grosu, A.-L., Abdollahi, A., Debus, J., Ganswindt, U., Belka, C., Pigorsch, S., Combs, S. E., Boeke, S., Zips, D., Jöhrens, K., Baretton, G. B., Baumann, M., (0000-0003-1776-9556) Krause, M., (0000-0002-7017-3738) Löck, S., Patil, S. G., Linge, A., Hiepe, H., Grosser, M., Lohaus, F., Gudziol, V., Kemper, M., Nowak, A., Haim, D., Tinhofer, I., Budach, V., Guberina, M., Stuschke, M., Balermpas, P., Grün, J. V. D., Schäfer, H., Grosu, A.-L., Abdollahi, A., Debus, J., Ganswindt, U., Belka, C., Pigorsch, S., Combs, S. E., Boeke, S., Zips, D., Jöhrens, K., Baretton, G. B., Baumann, M., (0000-0003-1776-9556) Krause, M., and (0000-0002-7017-3738) Löck, S.
- Abstract
(1) Background: Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who are at biologically high risk for the development of loco-regional recurrences af-ter 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 multicentre retrospective cohort of 221 patients that were treated with postoper-ative radiochemotherapy (PORT-C) and 283 patients that were treated with PORT alone. Propen-sity score analysis was used to identify matched patient pairs from both cohorts. From differen-tial gene expression analysis and Cox regression, a predictive gene signature was identified. (3) Results: 108 patient 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 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 identi-fied 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.
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- 2022
24. Analyses of molecular subtypes and their association to mechanisms of radioresistance in patients with HPV-negative HNSCC treated by postoperative radiochemotherapy
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Patil, S., Tawk, B., Grosser, M., Lohaus, F., Gudziol, V., Kemper, M., Nowak, A., Haim, D., Tinhofer, I., Budach, V., Guberina, M., Stuschke, M., Balermpas, P., Rödel, C., Schäfer, H., Grosu, A.-L., Abdollahi, A., Debus, J., Ganswindt, U., Belka, C., Pigorsch, S., Combs, S. E., Boeke, S., Zips, D., Baretton, G. B., Baumann, M., (0000-0003-1776-9556) Krause, M., (0000-0002-7017-3738) Löck, S., Linge, A., Patil, S., Tawk, B., Grosser, M., Lohaus, F., Gudziol, V., Kemper, M., Nowak, A., Haim, D., Tinhofer, I., Budach, V., Guberina, M., Stuschke, M., Balermpas, P., Rödel, C., Schäfer, H., Grosu, A.-L., Abdollahi, A., Debus, J., Ganswindt, U., Belka, C., Pigorsch, S., Combs, S. E., Boeke, S., Zips, D., Baretton, G. B., Baumann, M., (0000-0003-1776-9556) Krause, M., (0000-0002-7017-3738) Löck, S., and Linge, A.
- Abstract
Purpose To assess the relation of the previously reported classification of molecular subtypes to the outcome of patients with HNSCC treated with postoperative radio(chemo)therapy (PORT-C), and to assess the association of these subtypes with gene expressions reflecting known mechanisms of radioresistance. Material and methods Gene expression analyses were performed using the GeneChip Human Transcriptome Array 2.0 on a multicentre retrospective patient cohort (N = 128) of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG) with locally advanced HNSCC treated with PORT-C. Tumours were assigned to four molecular subtypes, and correlation analyses between subtypes and clinical risk factors were performed. In addition, the classifications of eight genes or gene signatures related to mechanisms of radioresistance, which have previously shown an association with outcome of patients with HNSCC, were compared between the molecular subtypes. The endpoints loco-regional control (LRC) and overall survival (OS) were evaluated by log-rank tests and Cox regression. Results Tumours were classified into the four subtypes basal (19.5%), mesenchymal (18.8%), atypical (15.6%) and classical (14.1%). The remaining tumours could not be classified (32.0%). Tumours of the mesenchymal subtype showed a lower LRC compared to the other subtypes (p = 0.012). These tumours were associated with increased epithelial-mesenchymal transition (EMT) and overexpression of a gene signature enriched in DNA repair genes. The majority of the eight considered gene classifiers were significantly associated to LRC or OS in the whole cohort. Conclusion Molecular subtypes, previously identified on HNSCC patients treated with primary radio(chemo)therapy or surgery, were related to LRC for patients treated with PORT-C, where mesenchymal tumours presented with worse prognosis. After prospective validation, subtype-based patient stratification, potentially in combination with other molecular classifiers
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- 2022
25. Biomarker signatures for primary radiochemotherapy of locally advanced HNSCC – Hypothesis generation on a multicentre cohort of the DKTK-ROG
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Löck, S., Linge, A., Lohaus, F., Ebert, N., Gudziol, V., Nowak, A., Tinhofer, I., Kalinauskaite, G., Guberina, M., Stuschke, M., Balermpas, P., Grün, J., Grosu, A.-L., Debus, J., Ganswindt, U., Belka, C., Peeken, J. C., Combs, S. E., De-Colle, C., Zips, D., Baretton, G. B., (0000-0003-1776-9556) Krause, M., Baumann, M., Löck, S., Linge, A., Lohaus, F., Ebert, N., Gudziol, V., Nowak, A., Tinhofer, I., Kalinauskaite, G., Guberina, M., Stuschke, M., Balermpas, P., Grün, J., Grosu, A.-L., Debus, J., Ganswindt, U., Belka, C., Peeken, J. C., Combs, S. E., De-Colle, C., Zips, D., Baretton, G. B., (0000-0003-1776-9556) Krause, M., and Baumann, M.
- Abstract
Purpose: To develop prognostic biomarker signatures for patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated by primary radiochemotherapy (RCTx) based on previously published molecular analyses of the retrospective biomarker study of the German Cancer Consortium – Radiation Oncology Group (DKTK-ROG).
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- 2022
26. Development and validation of a 6-gene signature for the prognosis of loco-regional control in patients with HPV-negative locally advanced HNSCC treated by postoperative radio(chemo)therapy
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Patil, S., Linge, A., Grosser, M., Lohaus, F., Gudziol, V., Kemper, M., Nowak, A., Haim, D., Tinhofer, I., Budach, V., Guberina, M., Stuschke, M., Balermpas, P., Rödel, C., Schäfer, H., Grosu, A.-L., Abdollahi, A., Debus, J., Ganswindt, U., Belka, C., Pigorsch, S., Combs, S. E., Boeke, S., Zips, D., Baretton, G. B., Baumann, M., (0000-0003-1776-9556) Krause, M., Löck, S., Patil, S., Linge, A., Grosser, M., Lohaus, F., Gudziol, V., Kemper, M., Nowak, A., Haim, D., Tinhofer, I., Budach, V., Guberina, M., Stuschke, M., Balermpas, P., Rödel, C., Schäfer, H., Grosu, A.-L., Abdollahi, A., Debus, J., Ganswindt, U., Belka, C., Pigorsch, S., Combs, S. E., Boeke, S., Zips, D., Baretton, G. B., Baumann, M., (0000-0003-1776-9556) Krause, M., and Löck, S.
- Abstract
Purpose: The aim of this study was to develop and validate a novel gene signature from full-transcriptome data using machine-learning approaches to predict loco-regional control (LRC) of patients with human papilloma virus (HPV)-negative locally advanced head and neck squamous cell carcinoma (HNSCC), who received postoperative radio(chemo)therapy (PORT-C). Materials and methods: Gene expression analysis was performed using Affymetrix GeneChip Human Transcriptome Array 2.0 on a multicentre retrospective training cohort of 128 patients and an independent validation cohort of 114 patients from the German Cancer Consortium - Radiation Oncology Group (DKTK-ROG). Genes were filtered based on differential gene expression analyses and Cox regression. The identified gene signature was combined with clinical parameters and with previously identified genes related to stem cells and hypoxia. Technical validation was performed using nanoString technology. Results: We identified a 6-gene signature consisting of four individual genes CAV1, GPX8, IGLV3-25, TGFBI, and one metagene combining the highly correlated genes INHBA and SERPINE1. This signature was prognostic for LRC on the training data (ci = 0.84) and in validation (ci = 0.63) with a significant patient stratification into two risk groups (p = 0.005). Combining the 6-gene signature with the clinical parameters T stage and tumour localisation as well as the cancer stem cell marker CD44 and the 15-gene hypoxia-associated signature improved the validation performance (ci = 0.69, p = 0.001). Conclusion: We have developed and validated a novel prognostic 6-gene signature for LRC of HNSCC patients with HPV-negative tumours treated by PORT-C. After successful prospective validation the signature can be part of clinical trials on the individualization of radiotherapy.
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- 2022
27. Toxicity and Efficacy of Local Ablative, Image-guided Radiotherapy in Gallium-68 Prostate-specific Membrane Antigen Targeted Positron Emission Tomography-staged, Castration-sensitive Oligometastatic Prostate Cancer: The OLI-P Phase 2 Clinical Trial
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Hölscher, T., Baumann, M., Kotzerke, J., Zöphel, K., Paulsen, F., Müller, A.-C., Zips, D., Koi, L., Thomas, C., Löck, S., Krause, M., Wirth, M., Lohaus, F., Hölscher, T., Baumann, M., Kotzerke, J., Zöphel, K., Paulsen, F., Müller, A.-C., Zips, D., Koi, L., Thomas, C., Löck, S., Krause, M., Wirth, M., and Lohaus, F.
- Abstract
Background: Local ablative radiotherapy (aRT) of oligometastatic prostate cancer (PCa) is very promising and has become a focus of current clinical research. Objective: We hypothesize that aRT is safe and effective in gallium-68 prostate-specific membrane antigen targeted positron emission tomography (PSMA-PET)-staged oligometastatic PCa patients. Design, setting, and participants: A nonrandomized, prospective, investigator-initiated phase 2 trial recruited patients with oligometastatic PCa (five or fewer lymph node or osseous metastases) after local curative therapy, without significant comorbidity and androgen deprivation therapy (ADT), at two German centers from 2014 to 2018. Intervention: All PSMA-PET-positive metastases were treated with aRT. No systemic therapy was initiated. Outcome measurements and statistical analysis: The primary endpoint was treatment-related toxicity (grade ≥2) 24 mo after aRT. A one-sided single-sample test of proportions was planned to test whether the endpoint occurs in <15% of the patients. Key secondary endpoints were time to progression of prostate-specific antigen (PSA) and time to ADT, which were associated with potential prognostic factors by Cox regression. Results and limitations: Of 72 patients, 63 received aRT (13% dropout rate). The median follow-up was 37.2 mo. No treatment-related grade ≥2 toxicity was observed 2 yr after treatment. The median time to PSA progression and time to ADT were 13.2 and 20.6 mo, respectively. Of the patients, 21.4% were free of PSA progression after 3 yr. Conclusions: It was observed that aRT is safe, and midterm PSA progression and ADT-free time were achieved in one of five patients. Randomized clinical trials are indicated to further evaluate the option of delaying ADT in selected patients. Patient summary: In this clinical trial, 63 patients with up to five metastases of prostate cancer without androgen deprivation therapy were included. We showed that local ablative radiotherapy is safe and
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- 2022
28. Local control after locally ablative, image-guided radiotherapy of oligometastases identified by Gallium-68-PSMA-Positron Emission Tomography in castration-sensitive prostate cancer patients (OLI-P)
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Hölscher, T., Baumann, M., Kotzerke, J., Zöphel, K., Paulsen, F., Müller, A., Zips, D., Thomas, C., Wirth, M., (0000-0001-9550-9050) Troost, E. G. C., (0000-0003-1776-9556) Krause, M., Löck, S., Lohaus, F., Hölscher, T., Baumann, M., Kotzerke, J., Zöphel, K., Paulsen, F., Müller, A., Zips, D., Thomas, C., Wirth, M., (0000-0001-9550-9050) Troost, E. G. C., (0000-0003-1776-9556) Krause, M., Löck, S., and Lohaus, F.
- Abstract
Progression of prostate-specific antigen (PSA) values after curative treatment of prostate cancer patients is common. Prostate-specific membrane antigen (PSMA-) PET imaging can identify patients with metachronous oligometastatic disease even at low PSA levels. Metastases-directed local ablative radiotherapy (aRT) has been shown to be a safe treatment option. In this prospective clinical trial, we evaluated local control and the pattern of tumor progression. Between 2014 and 2018, 63 patients received aRT of 89 metastases (MET) (68 lymph node (LN-)MET and 21 bony (OSS-)MET) with one of two radiation treatment schedules: 50 Gy in 2 Gy fractions in 34 MET or 30 Gy in 10 Gy fractions in 55 MET. The mean gross tumor volume and planning target volume were 2.2 and 14.9 mL, respectively. The median follow-up time was 40.7 months. Local progression occurred in seven MET, resulting in a local control rate of 93.5% after three years. Neither treatment schedule, target volume, nor type of lesion was associated with local progression. Regional progression in the proximity to the LN-MET was observed in 19 of 47 patients with at least one LN-MET (actuarial 59.3% free of regional progression after 3 years). In 33 patients (52%), a distant progression was reported. The median time to first tumor-related clinical event was 16.6 months, and 22.2% of patients had no tumor-related clinical event after three years. A total of 14 patients (22%) had another aRT. In conclusion, local ablative radiotherapy in patients with PSMA-PET staged oligometastatic prostate cancer may achieve local control, but regional or distant progression is common. Further studies are warranted, e.g., to define the optimal target volume coverage in LN-MET and OSS-MET.
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- 2022
29. Tumor DNA-methylome derived epigenetic fingerprint identifies HPV-negative head and neck patients at risk for locoregional recurrence after postoperative radiochemotherapy
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Tawk, B., Wirkner, U., Schwager, C., Rein, K., Zaoui, K., Federspil, P. A., Adeberg, S., Linge, A., Ganswindt, U., Hess, J., Unger, K., Tinhofer, I., Budach, V., Lohaus, F., (0000-0003-1776-9556) Krause, M., Guberina, M., Stuschke, M., Balermpas, P., Rödel, C., Grosu, A. L., Schäfer, H., Zips, D., Combs, S. E., Pigorsch, S., Zitzelsberger, H., Baumeister, P., Kirchner, T., Bewerunge-Hudler, M., Weichert, W., Herpel, E., Belka, C., Baumann, M., Debus, J., Abdollahi, A., DKTK-ROG, Tawk, B., Wirkner, U., Schwager, C., Rein, K., Zaoui, K., Federspil, P. A., Adeberg, S., Linge, A., Ganswindt, U., Hess, J., Unger, K., Tinhofer, I., Budach, V., Lohaus, F., (0000-0003-1776-9556) Krause, M., Guberina, M., Stuschke, M., Balermpas, P., Rödel, C., Grosu, A. L., Schäfer, H., Zips, D., Combs, S. E., Pigorsch, S., Zitzelsberger, H., Baumeister, P., Kirchner, T., Bewerunge-Hudler, M., Weichert, W., Herpel, E., Belka, C., Baumann, M., Debus, J., Abdollahi, A., and DKTK-ROG
- Abstract
Biomarkers with relevance for loco-regional therapy are needed in human papillomavirus negative aka HPV(-) head and neck squamous cell carcinoma (HNSCC). Based on the premise that DNA methylation pattern is highly conserved, we sought to develop a reliable and robust methylome-based classifier identifying HPV(-) HNSCC patients at risk for loco-regional recurrence (LR) and all-event progression after postoperative radiochemotherapy (PORT-C). The training cohort consisted of HPV-DNA negative HNSCC patients (n = 128) homogeneously treated with PORT-C in frame of the German Cancer Consortium-Radiation Oncology Group (DKTK-ROG) multicenter biomarker trial. DNA Methylation analysis was performed using Illumina 450 K and 850 K-EPIC microarray technology. The performance of the classifier was integrated with a series of biomarkers studied in the training set namely hypoxia-, 5-microRNA (5-miR), stem-cell gene-expression signatures and immunohistochemistry (IHC)-based immunological characterization of tumors (CD3/CD8/PD-L1/PD1). Validation occurred in an independent cohort of HPV(-) HNSCC patients, pooled from two German centers (n = 125). We identified a 38-methylation probe-based HPV(-) Independent Classifier of disease Recurrence (HICR) with high prognostic value for LR, distant metastasis and overall survival (P < 10-9 ). HICR remained significant after multivariate analysis adjusting for anatomical site, lymph node extracapsular extension (ECE) and size (T-stage). HICR high-risk tumors were enriched for younger patients with hypoxic tumors (15-gene signature) and elevated 5-miR score. After adjustment for hypoxia and 5-miR covariates, HICR maintained predicting all endpoints. HICR provides a novel mean for assessing the risk of LR in HPV(-) HNSCC patients treated with PORT-C and opens a new opportunity for biomarker-assisted stratification and therapy adaptation in these patients.
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- 2022
30. Data publication: Integrated radiogenomics analyses allow for subtype classification and improved outcome prognosis of patients with locally advanced HNSCC
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(0000-0002-1508-9410) Rabasco Meneghetti, A., (0000-0002-0342-9545) Zwanenburg, A., (0000-0001-9636-1721) Linge, A., (0000-0003-4043-7066) Lohaus, F., (0000-0001-9865-208X) Grosser, M., (0000-0002-4051-6306) Baretton, G., (0000-0003-3798-1546) Kalinauskaite, G., (0000-0002-0512-549X) Tinhofer, I., (0000-0002-1205-559X) Guberina, N., (0000-0001-6836-0940) Stuschke, M., (0000-0001-5261-6446) Balermpas, P., (0000-0002-9371-7814) Grün, J., (0000-0003-4492-614X) Ganswindt, U., (0000-0002-1287-7825) Belka, C., (0000-0003-2679-9853) Peeken, J. C., (0000-0002-5233-1536) Combs, S. E., (0000-0002-3210-3368) Böke, S., (0000-0001-5779-9675) Zips, D., (0000-0001-9550-9050) Troost, E. G. C., (0000-0003-1776-9556) Krause, M., Baumann, M., (0000-0002-7017-3738) Löck, S., (0000-0002-1508-9410) Rabasco Meneghetti, A., (0000-0002-0342-9545) Zwanenburg, A., (0000-0001-9636-1721) Linge, A., (0000-0003-4043-7066) Lohaus, F., (0000-0001-9865-208X) Grosser, M., (0000-0002-4051-6306) Baretton, G., (0000-0003-3798-1546) Kalinauskaite, G., (0000-0002-0512-549X) Tinhofer, I., (0000-0002-1205-559X) Guberina, N., (0000-0001-6836-0940) Stuschke, M., (0000-0001-5261-6446) Balermpas, P., (0000-0002-9371-7814) Grün, J., (0000-0003-4492-614X) Ganswindt, U., (0000-0002-1287-7825) Belka, C., (0000-0003-2679-9853) Peeken, J. C., (0000-0002-5233-1536) Combs, S. E., (0000-0002-3210-3368) Böke, S., (0000-0001-5779-9675) Zips, D., (0000-0001-9550-9050) Troost, E. G. C., (0000-0003-1776-9556) Krause, M., Baumann, M., and (0000-0002-7017-3738) Löck, S.
- Abstract
RDS data of models developed and reported for the article entitled "Integrated radiogenomics analyses allow for subtype classification and improved outcome prognosis of patients with locally advanced HNSCC". Software package version is also available in repository
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- 2022
31. Data publication: Integrated radiogenomics analyses allow for subtype classification and improved outcome prognosis of patients with locally advanced HNSCC
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Rabasco Meneghetti, A., Zwanenburg, A., Linge, A., Lohaus, F., Grosser, M., Baretton, G., Kalinauskaite, G., Tinhofer, I., Guberina, N., Stuschke, M., Balermpas, P., Grün, J., Ganswindt, U., Belka, C., Peeken, J. C., Combs, S. E., Böke, S., Zips, D., Troost, E. G. C., Krause, M., Baumann, M., and Löck, S.
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Machine Learning ,Prognostic markers ,Radiomics ,Radiogenomics ,Transcriptomics ,HNSCC - Abstract
RDS data of models developed and reported for the article entitled "Integrated radiogenomics analyses allow for subtype classification and improved outcome prognosis of patients with locally advanced HNSCC". Software package version is also available in repository
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- 2022
32. Toxicity of SRT combined with targeted agents: prospective analysis of the TOaSTT database
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Kroeze, S., Schaule, J., Spaas, M., Kahl, K. H., Verhoeff, J. J., Schneiders, F. L., Blanck, O., Lohaus, F., Rogers, S., Kaul, D., Benavente, S., Combs, S. E., Skazikis, G., Baumann, K., Popp, I., Koppe, F., Geinitz, H., de Jaeger, K. E., Siva, S., Stera, S., Wittig-Sauerwein, A., Lewitzki, V., Eckert, F., Schymalla, M. M., Guckenberger, M., Molecular cell biology and Immunology, and Radiation Oncology
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- 2021
33. Toxicity of stereotactic Radiotherapy in Combination with targeted System Therapies: prospective Analysis of the TOaSTT Database
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Kroeze, S., Fritz, C., Schaule, J., Spaas, M., Kahl, K., Verhoeff, J., Schneiders, F., Blanck, O., Lohaus, F., Rogers, S., Kaul, D., Benavente, S., Combs, S., Skazikis, G., Baumann, K., Popp, I., Koppe, F., Geinitz, H., de Jaeger, K., Siva, S., Stera, S., Wittig-Sauerwein, A., Lewitzki, V., Eckert, F., Schymalla, M., Guckenberger, M., Molecular cell biology and Immunology, and Radiation Oncology
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- 2021
34. OC-0638 Integrated radiogenomics analyses for outcome prognosis in patients with locally advanced HNSCC
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Rabasco, A., primary, Zwanenburg, A., additional, Linge, A., additional, Lohaus, F., additional, Grosser, M., additional, Baretton, G., additional, Kalinauskaite, G., additional, Tinhofer, I., additional, Guberina, N., additional, Guberina, M., additional, Balermpas, P., additional, von der Grün, J., additional, Ganswindt, U., additional, Belka, C., additional, Peecken, J.C., additional, Combs, S.E., additional, Böcke, S., additional, Zips, D., additional, Baumann, M., additional, Troost, E.G., additional, Krause, M., additional, and Löck, S., additional
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- 2021
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35. PD-0835 Bone-tropic circulating tumor cell population in mCRPC patients under ablative radiotherapy
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Klusa, D., primary, Lohaus, F., additional, Neubauer, H., additional, Franken, A., additional, Rivandi, M., additional, Polzer, B., additional, Husman, D., additional, Kücken, M., additional, Hölscher, T., additional, Kurth, I., additional, Krause, M., additional, Dubrovska, A., additional, Baumann, M., additional, and Peitzsch, C., additional
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- 2021
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36. OC-0626 Toxicity of SRT combined with targeted agents: prospective analysis of the TOaSTT database
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Kroeze, S., primary, Schaule, J., additional, Spaas, M., additional, Kahl, K.H., additional, Verhoeff, J.J., additional, Schneiders, F.L., additional, Blanck, O., additional, Lohaus, F., additional, Rogers, S., additional, Kaul, D., additional, Benavente, S., additional, Combs, S.E., additional, Skazikis, G., additional, Baumann, K., additional, Popp, I., additional, Koppe, F., additional, Geinitz, H., additional, de Jaeger, K.E., additional, Siva, S., additional, Stera, S., additional, Wittig-Sauerwein, A., additional, Lewitzki, V., additional, Eckert, F., additional, Schymalla, M.M., additional, and Guckenberger, M., additional
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- 2021
- Full Text
- View/download PDF
37. PO-1332 OLI-P trial: pattern of progression after radiotherapy in PSMA-PET positive METs of prostate cancer
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Hölscher, T., primary, Baumann, M., additional, Kotzerke, J., additional, Wirth, M., additional, Thomas, C., additional, Zips, D., additional, Löck, S., additional, Krause, M., additional, and Lohaus, F., additional
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- 2021
- Full Text
- View/download PDF
38. Reduction of respiratory pancreas motion using an MRI and proton therapy compatible abdominal corset
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Schneider, S., Stefanowicz, S., Jentsch, C., Lohaus, F., Valentini, C., Platzek, I., Troost, E. G. C., and Hoffmann, A. L.
- Subjects
abdominal compression ,time resolved MRI ,MR guided radiation therapy ,4D MRI - Abstract
Objectives: An MRI- and particle therapy compatible patient-individualized abdominal corset was developed and its efficacy to reduce respiratory-induced pancreas motion was evaluated by orthogonal 2D-cine and 4D-MRI. Patients & Methods: Nine patients (6 female; average age 72.9±9.6 years) with tumors of the pancreas (7), gallbladder (1), or liver (1) provided written informed consent to be scanned on a 3T MRI scanner (Philips Healthcare) by means of orthogonal 2D-cine and 4D-MRI, without and with a patient-individualized abdominal corset, respectively. A polyethylene (PE) abdominal corset (ORD Dresden GmbH) was customized based on an optical 3D-surface scan (Artec Eva®). For MR imaging the patients were positioned supine on a flat tabletop using an anterior coil holder to avoid compression of the chest wall. For 2D-cine MRI, coronal and sagittal slices were selected to image the pancreatic head. The 4D-MRI dataset was reconstructed by retrospectively resorting a multi-slice 2D acquisition into 10 respiratory phases. Pancreas motion was determined as center-of-mass displacement in three orthogonal directions (inferior-superior (IS), anterior-posterior (AP), left-right (LR)). Results and Conclusion: MRI revealed predominant motion in IS direction, which was reduced by 42% (p
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- 2021
39. Reduzierung von respirationsbedingter Pankreasbewegung mittels eines MRT- und Partikeltherapie-kompatiblen abdominellen Korsetts
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Schneider, S., Stefanowicz, S., Jentsch, C., Lohaus, F., Valentini, C., Platzek, I., Troost, E., and Hoffmann, A.
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intrafraktionelle Bewegung ,MRT geführte Partikeltherapie ,Pankreaskarzinom - Abstract
Fragestellung: Die intrafraktionelle Bewegung von abdominellen Tumoren erfordert entsprechend große Sicherheitssäume in der Radioonkologie und führt zu einer erhöhten Strahlenbelastung des umliegenden gesunden Gewebes. Für die geplante Magnetresonanztomographie (MRT)-geführte Partikeltherapie (PT) von Pankreaskarzinomen wurde ein innovatives, patientenspezifisches abdominelles Korsett zur Reduktion der atmungsbedingten Pankreasbewegung entwickelt, welches die hohen Materialansprüche der MRT sowie der PT erfüllt. Das Maß an Bewegungsreduktion durch das Korsetts und dessen Verträglichkeit wurde in einer Patientenstudie untersucht. Methodik: Vorbereitend wurden drei abdominelle Korsetts unterschiedlicher Beschaffenheit und Patientenindividualität in ihrer Anwendbarkeit für die MRT-geführte PT bei abdominellen Tumoren untersucht. Das Modell, das die höchste Reproduzierbarkeit in der PT bei Oberbauchtumoren ermöglichte und so eine konformale Strahlentherapie ermöglichte, wurde in einer durch die lokale Ethikkommissioin gebilligte Patientenstudie getestet. Für 12 Patienten (neun weiblich, Alter 71.6±8.6 Jahre) mit Tumoren des Oberbauchs wurde ein Polyethylene-Korsett individuell hergestellt. An einem 3T MRT Scanner wurden von den Patienten sowohl mit Korsett als direkt darauffolgend auch ohne Korsett unter freier Atmung zeitauflösende Bildsequenzen (orthogonale 2D-cine MRT und retrospektiv rekonstruierte 4D-MRT) akquiriert. Das Pankreas wurde in allen Bildern manuell konturiert und die Bewegung des Massenschwerpunktes zwischen maximaler Inspiration und Exspiration in 3D analysiert. Basierend auf einem detaillierten Erhebungsbogen wurde die Verträglichkeit des Korsetts in klinischer Anwendung untersucht. Ergebnis: Durch Applikation des Korsetts wurde bei hoher Patientenverträglichkeit eine Reduktion der Pankreasbewegung vorwiegend in der Hauptrichtung der Atmung (inferior-superior) um 49% (p
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- 2021
40. Metastasis directed stereotactic radiotherapy in NSCLC patients progressing under targeted- or immunotherapy: efficacy and safety reporting from the 'TOaSTT' database
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Kroeze, SGC, Schaule, J, Fritz, C, Kaul, D, Blanck, O, Kahl, KH, Roeder, F, Siva, S, Verhoeff, JJC, Adebahr, S, Schymalla, MM, Glatzer, M, Szuecs, M, Geier, M, Skazikis, G, Sackerer, I, Lohaus, F, Eckert, F, Guckenberger, M, Kroeze, SGC, Schaule, J, Fritz, C, Kaul, D, Blanck, O, Kahl, KH, Roeder, F, Siva, S, Verhoeff, JJC, Adebahr, S, Schymalla, MM, Glatzer, M, Szuecs, M, Geier, M, Skazikis, G, Sackerer, I, Lohaus, F, Eckert, F, and Guckenberger, M
- Abstract
BACKGROUND: Metastasis directed treatment (MDT) is increasingly performed with the attempt to improve outcome in non-small cell lung cancer (NSCLC) patients receiving targeted- or immunotherapy (TT/IT). This study aimed to assess the safety and efficacy of metastasis directed stereotactic radiotherapy (SRT) concurrent to TT/IT in NSCLC patients. METHODS: A retrospective multicenter cohort of stage IV NSCLC patients treated with TT/IT and concurrent (≤ 30 days) MDT was established. 56% and 44% of patients were treated for oligoprogressive disease (OPD) or polyprogressive disease (PPD) under TT/IT, polyprogressive respectively. Survival was analyzed using Kaplan-Meier and log rank testing. Toxicity was scored using CTCAE v4.03 criteria. Predictive factors for overall survival (OS), progression free survival (PFS) and time to therapy switch (TTS) were analyzed with uni- and multivariate analysis. RESULTS: MDT of 192 lesions in 108 patients was performed between 07/2009 and 05/2018. Concurrent TT/IT consisted of EGFR/ALK-inhibitors (60%), immune checkpoint inhibitors (31%), VEGF-antibodies (8%) and PARP-inhibitors (1%). 2y-OS was 51% for OPD and 25% for PPD. After 1 year, 58% of OPD and 39% of PPD patients remained on the same TT/IT. Second progression after MDT was oligometastatic (≤ 5 lesions) in 59% of patients. Severe acute and late toxicity was observed in 5.5% and 1.9% of patients. In multivariate analysis, OS was influenced by the clinical metastatic status (p = 0.002, HR 2.03, 95% CI 1.30-3.17). PFS was better in patients receiving their first line of systemic treatment (p = 0.033, HR 1.7, 95% CI 1.05-2.77) and with only one metastases-affected organ (p = 0.023, HR 2.04, 95% CI 1.10-3.79). TTS was 6 months longer in patients with one metastases-affected organ (p = 0.031, HR 2.53, 95% CI 1.09-5.89). Death was never therapy-related. CONCLUSIONS: Metastases-directed SRT in NSCLC patients can be safely performed concurrent to TT/IT with a low risk of severe toxicity
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- 2021
41. Continued versus Interrupted Targeted Therapy during Metastasis-Directed Stereotactic Radiotherapy: A Retrospective Multi-Center Safety and Efficacy Analysis
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Kroeze, SGC, Fritz, C, Schaule, J, Blanck, O, Kahl, KH, Kaul, D, Siva, S, Gerum, S, Claes, A, Sundahl, N, Adebahr, S, Stera, S, Schymalla, MM, Abbasi-Senger, N, Buergy, D, Geier, M, Szuecs, M, Lohaus, F, Henke, G, Combs, SE, Guckenberger, M, Kroeze, SGC, Fritz, C, Schaule, J, Blanck, O, Kahl, KH, Kaul, D, Siva, S, Gerum, S, Claes, A, Sundahl, N, Adebahr, S, Stera, S, Schymalla, MM, Abbasi-Senger, N, Buergy, D, Geier, M, Szuecs, M, Lohaus, F, Henke, G, Combs, SE, and Guckenberger, M
- Abstract
The increasing use of targeted therapy (TT) has resulted in prolonged disease control and survival in many metastatic cancers. In parallel, stereotactic radiotherapy (SRT) is increasingly performed in patients receiving TT to obtain a durable control of resistant metastases, and thereby to prolong the time to disseminated disease progression and switch of systemic therapy. The aims of this study were to analyze the safety and efficacy of SRT combined with TT in metastatic cancer patients and to assess the influence of continuous vs. interrupted TT during metastasis-directed SRT. The data of 454 SRTs in 158 patients from the international multicenter database (TOaSTT) on metastatic cancer patients treated with SRT and concurrent TT (within 30 days) were analyzed using Kaplan-Meier and log rank testing. Toxicity was defined by the CTCAE v4.03 criteria. The median FU was 19.9 mo (range 1-102 mo); 1y OS, PFS and LC were 59%, 24% and 84%, respectively. Median TTS was 25.5 mo (95% CI 11-40). TT was started before SRT in 77% of patients. TT was interrupted during SRT in 44% of patients, with a median interruption of 7 (range 1-42) days. There was no significant difference in OS or PFS whether TT was temporarily interrupted during SRT or not. Any-grade acute and late SRT-related toxicity occurred in 63 (40%) and 52 (33%) patients, respectively. The highest toxicity rates were observed for the combination of SRT and EGFRi or BRAF/MEKi, and any-grade toxicity was significantly increased when EGFRi (p = 0.016) or BRAF/MEKi (p = 0.009) were continued during SRT. Severe (≥grade 3) acute and late SRT-related toxicity were observed in 5 (3%) and 7 (4%) patients, respectively, most frequently in patients treated with EGFRi or BRAF/MEKi and in the intracranial cohort. There was no significant difference in severe toxicity whether TT was interrupted before and after SRT or not. In conclusion, SRT and continuous vs. interrupted TT in metastatic cancer patients did not influence OS or
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- 2021
42. Comparison of the composition of lymphocyte subpopulations in non-relapse and relapse patients with squamous cell carcinoma of the head and neck before, during radiochemotherapy and in the follow-up period: a multicenter prospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)
- Author
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Niu, M., E. Combs, S., Linge, A., (0000-0003-1776-9556) Krause, M., Baumann, M., Lohaus, F., Ebert, N., Tinhofer, I., Budach, V., Grün, J., Rödel, F., Grosu, A.-L., Multhoff, G., Niu, M., E. Combs, S., Linge, A., (0000-0003-1776-9556) Krause, M., Baumann, M., Lohaus, F., Ebert, N., Tinhofer, I., Budach, V., Grün, J., Rödel, F., Grosu, A.-L., and Multhoff, G.
- Abstract
Background Radiochemotherapy (RCT) has been shown to induce changes in immune cell homeostasis which might affect antitumor immune responses. In the present study, we aimed to compare the composition and kinetics of major lymphocyte subsets in the periphery of patients with non-locoregional recurrent (n = 23) and locoregional recurrent (n = 9) squamous cell carcinoma of the head and neck (SCCHN) upon primary RCT. Methods EDTA-blood of non-locoregional recurrent SCCHN patients was collected before (t0), after application of 20–30 Gy (t1), in the follow-up period 3 (t2) and 6 months (t3) after RCT. In patients with locoregional recurrence blood samples were taken at t0, t1, t2 and at the time of recurrence (t5). EDTA-blood of age-related, healthy volunteers (n = 22) served as a control (Ctrl). Major lymphocyte subpopulations were phenotyped by multiparameter flow cytometry. Results Patients with non-recurrent SCCHN had significantly lower proportions of CD19+ B cells compared to healthy individuals before start of any therapy (t0) that dropped further until 3 months after RCT (t2), but reached initial levels 6 months after RCT (t3). The proportion of CD3+ T and CD3+/CD4+ T helper cells continuously decreased between t0 and t3, whereas that of CD8+ cytotoxic T cells and CD3+/CD56+ NK-like T cells (NKT) gradually increased in the same period of time in non-recurrent patients. The percentage of CD4+/CD25+/FoxP3+ regulatory T cells (Tregs) decreased directly after RCT, but increased above initial levels in the follow-up period 3 (t2) and 6 (t3) months after RCT. Patients with locoregional recurrence showed similar trends with respect to B, T cells and Tregs between t0 and t5. CD4+ T helper cells remained stably low between t0 and t5 in patients with locoregional recurrence compared to Ctrl. NKT/NK cell subsets (CD56+/CD69+, CD3−/CD56+, CD3−/CD94+, CD3−/NKG2D+, CD3−/NKp30+, CD3−/NKp46+) increased continuously up to 6 months after RCT (t0-t3) in patients without locoregiona
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- 2021
43. Metastatic Spread in Prostate Cancer Patients Influencing Radiotherapy Response
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Klusa, D., Lohaus, F., Furesi, G., Rauner, M., Benešová, M., Krause, M., Kurth, I., Peitzsch, C., Klusa, D., Lohaus, F., Furesi, G., Rauner, M., Benešová, M., Krause, M., Kurth, I., and Peitzsch, C.
- Abstract
Radiotherapy and surgery are curative treatment options for localized prostate cancer (PCa) with a 5-year survival rate of nearly 100%. Once PCa cells spread into distant organs, such as bone, the overall survival rate of patients drops dramatically. The metastatic cascade and organotropism of PCa cells are regulated by different cellular subtypes, organ microenvironment, and their interactions. This cross-talk leads to pre-metastatic niche formation that releases chemo-attractive factors enforcing the formation of distant metastasis. Biological characteristics of PCa metastasis impacting on metastatic sites, burden, and latency is of clinical relevance. Therefore, the implementation of modern hybrid imaging technologies into clinical routine increased the sensitivity to detect metastases at earlier stages. This enlarged the number of PCa patients diagnosed with a limited number of metastases, summarized as oligometastatic disease. These patients can be treated with androgen deprivation in combination with local-ablative radiotherapy or radiopharmaceuticals directed to metastatic sites. Unfortunately, the number of patients with disease recurrence is high due to the enormous heterogeneity within the oligometastatic patient population and the lack of available biomarkers with predictive potential for metastasis-directed radiotherapy. Another, so far unmet clinical need is the diagnosis of minimal residual disease before onset of clinical manifestation and/or early relapse after initial therapy. Here, monitoring of circulating and disseminating tumor cells in PCa patients during the course of radiotherapy may give us novel insight into how metastatic spread is influenced by radiotherapy and vice versa. In summary, this review critically compares current clinical concepts for metastatic PCa patients and discuss the implementation of recent preclinical findings improving our understanding of metastatic dissemination and radiotherapy resistance into standard of care.
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- 2021
44. Definition and validation of a radiomics signature for loco-regional tumour control in patients with locally advanced head and neck squamous cell carcinoma
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(0000-0002-1508-9410) Rabasco Meneghetti, A., (0000-0002-0342-9545) Zwanenburg, A., (0000-0002-7910-2928) Leger, S., Leger, K., (0000-0001-9550-9050) Troost, E. G. C., (0000-0001-9636-1721) Linge, A., (0000-0003-4043-7066) Lohaus, F., Schreiber, A., (0000-0003-3798-1546) Kalinauskaite, G., (0000-0002-0512-549X) Tinhofer, I., (0000-0002-1205-559X) Guberina, N., (0000-0003-3218-0539) Guberina, M., (0000-0001-5261-6446) Balermpas, P., (0000-0002-9371-7814) Grün, J., (0000-0003-4492-614X) Ganswindt, U., (0000-0002-1287-7825) Belka, C., (0000-0003-2679-9853) Peeken, J. C., (0000-0002-5233-1536) Combs, S. E., Böke, S., (0000-0001-5779-9675) Zips, D., (0000-0003-1776-9556) Krause, M., Baumann, M., (0000-0002-7017-3738) Löck, S., (0000-0002-1508-9410) Rabasco Meneghetti, A., (0000-0002-0342-9545) Zwanenburg, A., (0000-0002-7910-2928) Leger, S., Leger, K., (0000-0001-9550-9050) Troost, E. G. C., (0000-0001-9636-1721) Linge, A., (0000-0003-4043-7066) Lohaus, F., Schreiber, A., (0000-0003-3798-1546) Kalinauskaite, G., (0000-0002-0512-549X) Tinhofer, I., (0000-0002-1205-559X) Guberina, N., (0000-0003-3218-0539) Guberina, M., (0000-0001-5261-6446) Balermpas, P., (0000-0002-9371-7814) Grün, J., (0000-0003-4492-614X) Ganswindt, U., (0000-0002-1287-7825) Belka, C., (0000-0003-2679-9853) Peeken, J. C., (0000-0002-5233-1536) Combs, S. E., Böke, S., (0000-0001-5779-9675) Zips, D., (0000-0003-1776-9556) Krause, M., Baumann, M., and (0000-0002-7017-3738) Löck, S.
- Abstract
Purpose: To develop and validate a CT-based radiomics signature for the prognosis of loco-regional tumour control (LRC) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated by primary radiochemotherapy (RCTx) based on retrospective data from 6 partner sites of the German Cancer Consortium – Radiation Oncology Group (DKTK-ROG). Material and methods: Pre-treatment CT images of 318 patients with locally advanced HNSCC were collected. Four-hundred forty-six features were extracted from each primary tumour volume and then filtered through stability analysis and clustering. First, a baseline signature was developed from demographic and tumour-associated clinical parameters. This signature was then supplemented by CT imaging features. A final signature was derived using repeated 3-fold cross-validation on the discovery cohort. Performance in external validation was assessed by the concordance index (C-Index). Furthermore, calibration and patient stratification in groups with low and high risk for loco-regional recurrence were analysed. Results: For the clinical baseline signature, only the primary tumour volume was selected. The final signature combined the tumour volume with two independent radiomics features. It achieved moderately good discriminatory performance (C-Index [95% confidence interval]: 0.66 [0.55-0.75]) on the validation cohort along with significant patient stratification (p=0.005) and good calibration. Conclusion: We identified and validated a clinical-radiomics signature for LRC of locally advanced HNSCC using a multi-centric retrospective dataset. Prospective validation will be performed on the primary cohort of the HNprädBio trial of the DKTK-ROG once follow-up is completed.
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- 2021
45. ERCC2 gene single-nucleotide polymorphism as a prognostic factor for locally advanced head and neck carcinomas after definitive cisplatin-based radiochemotherapy
- Author
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Guberina, M., Sak, A., Pöttgen, C., Tinhofer-Keilholz, I., Budach, V., Balermpas, P., Grün, J., Michael Rödel, C., Gkika, E., Grosu, A.-L., Abdollahi, A., Debus, J., Belka, C., Pigorsch, S., E. Combs, S., Mönnich, D., Zips, D., De-Colle, C., Welz, S., Linge, A., Lohaus, F., Baretton, G., Gauler, T., Baumann, M., Krause, M., Schuler, M., Bankfalvi, A., Höing, B., Lang, S., Stuschke, M., Guberina, M., Sak, A., Pöttgen, C., Tinhofer-Keilholz, I., Budach, V., Balermpas, P., Grün, J., Michael Rödel, C., Gkika, E., Grosu, A.-L., Abdollahi, A., Debus, J., Belka, C., Pigorsch, S., E. Combs, S., Mönnich, D., Zips, D., De-Colle, C., Welz, S., Linge, A., Lohaus, F., Baretton, G., Gauler, T., Baumann, M., Krause, M., Schuler, M., Bankfalvi, A., Höing, B., Lang, S., and Stuschke, M.
- Abstract
Identifying patients with locally advanced head and neck carcinoma on high risk of recurrence after definitive concurrent radiochemotherapy is of key importance for the selection for consolidation therapy and for individualized treatment intensification. In this multicenter study we analyzed recurrence-associated single-nucleotide polymorphisms (SNPs) in DNA repair genes in tumor DNA from 132 patients with locally advanced head and neck carcinoma (LadHnSCC). Patients were treated with definitive radiotherapy and simultaneous cisplatin-based chemotherapy at six partner sites of the German Cancer Consortium (DKTK) Radiation Oncology Group from 2005 to 2011. For validation, a group of 20 patients was available. Score selection method using proportional hazard analysis and leave-one-out cross-validation were performed to identify markers associated with outcome. The SNPs rs1799793 and rs13181 were associated with survival and the same SNPs and in addition rs17655 with freedom from loco-regional relapse (ffLRR) in the trainings datasets from all patients. The homozygote major rs1799793 genotype at the ERCC2 gene was associated with better (Hazard ratio (HR): 0.418 (0.234-0.744), p = 0.003) and the homozygote minor rs13181 genotype at ERCC2 with worse survival (HR: 2.074, 95% CI (1.177-3.658), p = 0.017) in comparison to the other genotypes. At the ffLRR endpoint, rs1799793 and rs13181 had comparable prognostic value. The rs1799793 and rs13181 genotypes passed the leave-one-out cross-validation procedure and associated with survival and ffLRR in patients with LadHnSCC treated with definitive radiochemotherapy. While findings were confirmed in a small validation dataset, further validation is underway within a prospective biomarker study of the DKTK.
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- 2021
46. Correction: ERCC2 gene single-nucleotide polymorphism as a prognostic factor for locally advanced head and neck carcinomas after definitive cisplatin-based radiochemotherapy
- Author
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Guberina, M., Sak, A., Pöttgen, C., Tinhofer-Keilholz, I., Budach, V., Balermpas, P., Grün, J., Michael Rödel, C., Gkika, E., Grosu, A.-L., Abdollahi, A., Debus, J., Belka, C., Pigorsch, S., E. Combs, S., Mönnich, D., Zips, D., De-Colle, C., Welz, S., Linge, A., Lohaus, F., Baretton, G., Gauler, T., Baumann, M., Krause, M., Schuler, M., Bankfalvi, A., Höing, B., Lang, S., Stuschke, M., Guberina, M., Sak, A., Pöttgen, C., Tinhofer-Keilholz, I., Budach, V., Balermpas, P., Grün, J., Michael Rödel, C., Gkika, E., Grosu, A.-L., Abdollahi, A., Debus, J., Belka, C., Pigorsch, S., E. Combs, S., Mönnich, D., Zips, D., De-Colle, C., Welz, S., Linge, A., Lohaus, F., Baretton, G., Gauler, T., Baumann, M., Krause, M., Schuler, M., Bankfalvi, A., Höing, B., Lang, S., and Stuschke, M.
- Abstract
The original version of this Article contained an error in the spelling of the author Eleni Gkika, which was incorrectly given as Eleni Gikka. As well as the author Stephanie E. Combs, this was incorrectly given as Stephanie Combs. Both have now been corrected in the PDF and HTML versions of the Article.
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- 2021
47. V23-6-jD: Prädiktiver Einfluss unterschiedlicher histologischer Subtypen auf die lokale Kontrolle nach stereotaktischer Bestrahlung (SBRT) von Lungenmetastasen bei Patienten mit nicht-kleinzelligem Bronchialkarzinom (NSCLC) im oligo-metastasierten Stadium [Abstract]
- Author
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Hörner-Rieber, J., Blanck, O., Boda-Heggemann, J., Duma, M., Eble, M. J., Eich, H. T., Flentje, M., Gerum, S., Hass, P., Henkenberens, C., Herold, H.-U., Hildebrandt, G., Imhoff, D., Janssen, S., Kahl, Klaus-Henning, Klass, N. D., Krempien, R., Lautenschläger, S. F., Lohaus, F., Petersen, C., Sackerer, I., Schrade, E., Uhlmann, L., Wittig, A., and Guckenberger, M.
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ddc:610 - Published
- 2020
48. Comparison of GeneChip, nCounter and real-time polymerase chain reaction based gene expressions predicting loco-regional tumour control after primary and postoperative radiochemotherapy in head and neck squamous cell carcinoma
- Author
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Schmidt, S., Linge, A., Grosser, M., Lohaus, F., Gudziol, V., Nowak, A., Tinhofer, I., Budach, V., Sak, A., Stuschke, M., Balermpas, P., Rödel, C., Schäfer, H., Grosu, A.-L., Ganswindt, U., Belka, C., Pigorsch, S., Combs, S.E., Mönnich, D., Zips, D., Baretton, G.B., Buchholz, F., and Löck, S.
- Abstract
This article compares the expression and applicability of biomarkers, from single genes and gene signatures, identified in patients with locally advanced head and neck squamous cell carcinoma using the GeneChip Human Transcriptome Array 2.0, nCounter, and real-time PCR analyses. Two multicenter, retrospective cohorts of patients with head and neck squamous cell carcinoma from the German Cancer Consortium Radiation Oncology Group who received postoperative radiochemotherapy or primary radiochemotherapy were considered. Real-time PCR was performed for a limited number of 38 genes of the cohort who received postoperative radiochemotherapy only. Correlations between the methods were evaluated by the Spearman rank correlation coefficient. Patients were stratified based on the expression of putative cancer stem cell markers, hypoxia-associated gene signatures, and a previously developed seven-gene signature. Locoregional tumor control was compared between these patient subgroups using log-rank tests. Gene expressions obtained from nCounter analyses were moderately correlated to GeneChip analyses (median rho = approximately 0.68). A higher correlation was obtained between nCounter analyses and real-time PCR (median rho = 0.84). Significant associations with locoregional tumor control were observed for most of the considered biomarkers evaluated by GeneChip and nCounter analyses. In general, all applied biomarkers (single genes and gene signatures) classified approximately 70% to 85% of the patients similarly. Overall, gene signatures seem to be more robust and had a better transferability among different measurement methods.
- Published
- 2020
49. MRI based measurement of pancreas motion reduction with an MR- and particle therapy compatible abdominal corset
- Author
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Schneider, S., Stefanowicz, S., Lohaus, F., Jentsch, C., Troost, E. G. C., and Hoffmann, A. L.
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respiratory motion ,MR guided particle therapy ,4D MRI ,Pancreatic adenocarcinoma - Abstract
Introduction: In particle beam therapy (PBT) respiratory-induced tumor motion is commonly accounted for by the definition of an internal target volume[1] to cover the tumor in all respiratory phases. Consequentially, also a relatively large volume of healthy tissue surrounding the tumor is exposed to radiation. An appropriate immobilization of the target volume can improve the sparing of healthy tissues. Immobilization of target volumes located in the upper gastro-intestinal tract has been accomplished through abdominal compression bands or pressure plates. These, however, can exacerbate the proton beam range uncertainties when these devices extend into the treatment fields, thereby compromising an accurate dose delivery[2]. For this study, an MR- and PBT-compatible patient-individualized abdominal corset was developed to test its efficacy to reduce respiratory-induced pancreas motion as measured by means of orthogonal 2D-cine and 4D-MRI. Methods: Nine patients (6 female, 3 male; average age 72.9 ± 9.6 years) with abdominal tumors of the pancreas (7 patients), gallbladder (1 patient), or liver (1 patient) provided written informed consent (study number DRKS00010966) to be scanned by means of orthogonal 2D-cine (2 min acquisition time) and 4D-MRI (9 min acquisition time) utilizing a balanced steady-state free precession sequence. For 2D-cine MRI coronal and sagittal slices were positioned to image the pancreatic head. The 4D-MRI dataset was reconstructed by retrospectively resorting a multi-slice 2D acquisition into 10 respiratory phases by amplitude based sorting[3], thereby imaging the full volume of the pancreas. Two MRI scans were acquired per patient, one without and one with a patient-individualized abdominal corset to reduce respiratory motion. The corset was manufactured from polyethylene (Orthopädie- und Rehatechnik Dresden GmbH, Dresden, Germany) based on an optical 3D-surface scan of the patient (Artec Eva®, Artec3D, Luxembourg, Luxemburg). From the nine patients, eight orthogonal 2D-cine datasets and seven 4D-MRI datasets were successfully acquired on a 3.0T MRI scanner (Ingenuity TF PET/MR scanner, Philips Healthcare, Best, The Netherlands). The patients were scanned in supine position on a flat tabletop using an anterior coil holder to avoid anatomical deformations of the chest wall due to the weight of the receiver coils. Pancreas motion was determined as center-of-mass displacement in three orthogonal directions (inferior-superior (IS), anterior-posterior (AP), left-right (LR)) for both orthogonal 2D-cine and 4D-MRI (Fig. 1). The motion amplitude extracted from the 2D-cine dataset was evaluated as the mean peak-to-peak amplitude M95, for which the lower and upper 2.5 % of the data was discarded to reduce the effect of possible outliers. Results: Orthogonal 2D-cine MRI showed that pancreas motion was dominant in IS direction (Fig. 2). For the 8 patients analyzed, the abdominal corset reduced the motion M95 in IS direction by in average 42 % (5 mm ± 3.7 mm (standard deviation) without corset, 3.8 mm ± 1.1 mm with corset; p
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- 2020
50. Quantification of plan robustness against different uncertainty sources for classical and anatomical robust optimized treatment plans in head and neck cancer proton therapy
- Author
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Cubillos-Mesías, M., Troost, E. G. C., Lohaus, F., Agolli, L., Rehm, M., Richter, C., and Stützer, K.
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robustness analysis ,proton therapy ,head and neck cancer ,Robust optimization - Abstract
Objective: Classical robust optimization (cRO) in intensity-modulated proton therapy (IMPT) considers isocenter position and particle range uncertainties; anatomical robust optimization (aRO) aims to consider additional non-rigid positioning variations. This work compares the influence of different uncertainty sources on the robustness of cRO and aRO IMPT plans for head and neck squamous cell carcinoma (HNSCC). Methods: Two IMPT plans were optimized for twenty HNSCC patients who received weekly control CTs (cCT): cRO, using solely the planning CT, and aRO, including two additional cCTs. The robustness of the plans in terms of clinical target volume (CTV) coverage and organ at risk (OAR) sparing was analyzed considering stepwise the influence of (1) non-rigid anatomical variations given by the weekly cCT, (2) with fraction-wise added rigid random setup errors and (3) additional systematic proton range uncertainties. Results: cRO plans presented significantly higher nominal CTV coverage but are outperformed by aRO plans when considering non-rigid anatomical variations only, as cRO and aRO plans presented a median target coverage (D98%) decrease for the low-risk/high-risk CTV of 1.8/1.1 percentage points (pp) and -0.2pp/-0.3pp, respectively. Setup and range uncertainties had larger influence on cRO CTV coverage, but led to similar OAR dose changes in both plans. Considering all error sources, 10/2 cRO/aRO patients missed the CTV coverage and a limited number exceeded some OAR constraints in both plans. Conclusions: Non-rigid anatomical variations are mainly responsible for critical target coverage loss of cRO plans, whereas the aRO approach was robust against such variations. Both plans provide similar robustness of OAR parameters. Advances in knowledge: The influence of different uncertainty sources was quantified for robust IMPT HNSCC plans.
- Published
- 2020
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