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Article ; Online: Relative biological effectiveness in proton beam therapy - Current knowledge and future challenges.

Lühr, Armin / von Neubeck, Cläre / Krause, Mechthild / Troost, Esther G C

Clinical and translational radiation oncology

2018 Volume 9, Page(s) 35–41

Language	English
Publishing date	2018-02-01
Publishing country	Ireland
Document type	Journal Article ; Review
ISSN	2405-6308
ISSN (online)	2405-6308
DOI	10.1016/j.ctro.2018.01.006
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A joint physics and radiobiology DREAM team vision - Towards better response prediction models to advance radiotherapy.

Vens, C / van Luijk, P / Vogelius, R I / El Naqa, I / Humbert-Vidan, L / von Neubeck, C / Gomez-Roman, N / Bahn, E / Brualla, L / Böhlen, T T / Ecker, S / Koch, R / Handeland, A / Pereira, S / Possenti, L / Rancati, T / Todor, D / Vanderstraeten, B / Van Heerden, M /

Ullrich, W / Jackson, M / Alber, M / Marignol, L

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

2024 , Page(s) 110277

Abstract: Radiotherapy developed empirically through experience balancing tumour control and normal tissue toxicities. Early simple mathematical models formalized this practical knowledge and enabled effective cancer treatment to date. Remarkable advances in ... ...

Abstract	Radiotherapy developed empirically through experience balancing tumour control and normal tissue toxicities. Early simple mathematical models formalized this practical knowledge and enabled effective cancer treatment to date. Remarkable advances in technology, computing, and experimental biology now create opportunities to incorporate this knowledge into enhanced computational models. The ESTRO DREAM (Dose Response, Experiment, Analysis, Modelling) workshop brought together experts across disciplines to pursue the vision of personalized radiotherapy for optimal outcomes through advanced modelling. The ultimate vision is leveraging quantitative models dynamically during therapy to ultimately achieve truly adaptive and biologically guided radiotherapy at the population as well as individual patient-based levels. This requires the generation of models that inform response-based adaptations, individually optimized delivery and enable biological monitoring to provide decision support to clinicians. The goal is expanding to models that can drive the realization of personalized therapy for optimal outcomes. This position paper provides their propositions that describe how innovations in biology, physics, mathematics, and data science including AI could inform models and improve predictions. It consolidates the DREAM team's consensus on scientific priorities and organizational requirements. Scientifically, it stresses the need for rigorous, multifaceted model development, comprehensive validation and clinical applicability and significance. Organizationally, it reinforces the prerequisites of interdisciplinary research and collaboration between physicians, medical physicists, radiobiologists, and computational scientists throughout model development. Solely by a shared understanding of clinical needs, biological mechanisms, and computational methods, more informed models can be created. Future research environment and support must facilitate this integrative method of operation across multiple disciplines.
Language	English
Publishing date	2024-04-24
Publishing country	Ireland
Document type	Journal Article ; Review
ZDB-ID	605646-5
ISSN	1879-0887 ; 0167-8140
ISSN (online)	1879-0887
ISSN	0167-8140
DOI	10.1016/j.radonc.2024.110277
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Zs.A 1926: Show issues

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Article ; Online: Advancing rare cancer research by MALDI mass spectrometry imaging: Applications, challenges, and future perspectives in sarcoma.

Stillger, Maren Nicole / Li, Mujia Jenny / Hönscheid, Pia / von Neubeck, Cläre / Föll, Melanie Christine

Proteomics

2024 , Page(s) e2300001

Abstract: MALDI mass spectrometry imaging (MALDI imaging) uniquely advances cancer research, by measuring spatial distribution of endogenous and exogenous molecules directly from tissue sections. These molecular maps provide valuable insights into basic and ... ...

Abstract	MALDI mass spectrometry imaging (MALDI imaging) uniquely advances cancer research, by measuring spatial distribution of endogenous and exogenous molecules directly from tissue sections. These molecular maps provide valuable insights into basic and translational cancer research, including tumor biology, tumor microenvironment, biomarker identification, drug treatment, and patient stratification. Despite its advantages, MALDI imaging is underutilized in studying rare cancers. Sarcomas, a group of malignant mesenchymal tumors, pose unique challenges in medical research due to their complex heterogeneity and low incidence, resulting in understudied subtypes with suboptimal management and outcomes. In this review, we explore the applicability of MALDI imaging in sarcoma research, showcasing its value in understanding this highly heterogeneous and challenging rare cancer. We summarize all MALDI imaging studies in sarcoma to date, highlight their impact on key research fields, including molecular signatures, cancer heterogeneity, and drug studies. We address specific challenges encountered when employing MALDI imaging for sarcomas, and propose solutions, such as using formalin-fixed paraffin-embedded tissues, and multiplexed experiments, and considerations for multi-site studies and digital data sharing practices. Through this review, we aim to spark collaboration between MALDI imaging researchers and clinical colleagues, to deploy the unique capabilities of MALDI imaging in the context of sarcoma.
Language	English
Publishing date	2024-02-25
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	2032093-0
ISSN	1615-9861 ; 1615-9853
ISSN (online)	1615-9861
ISSN	1615-9853
DOI	10.1002/pmic.202300001
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Zs.A 5386: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.A 1868: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)

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Article: Similar additive effects of doxorubicin in combination with photon or proton irradiation in soft tissue sarcoma models.

Bernardo, Teresa / Behrends, Carina / Klein, Diana / Kuntze, Anna / Timmermann, Beate / von Neubeck, Cläre

Frontiers in oncology

2023 Volume 13, Page(s) 1211984

Abstract: High-precision radiotherapy with proton beams is frequently used in the management of aggressive soft tissue sarcoma (STS) and is often combined with doxorubicin (Dox), the first-line chemotherapy for STS. However, current treatment approaches continue ... ...

Abstract	High-precision radiotherapy with proton beams is frequently used in the management of aggressive soft tissue sarcoma (STS) and is often combined with doxorubicin (Dox), the first-line chemotherapy for STS. However, current treatment approaches continue to result in high local recurrence rates often occurring within the treatment field. This strongly indicates the need of optimized treatment protocols taking the vast heterogeneity of STS into account, thereby fostering personalized treatment approaches. Here, we used preclinical STS models to investigate the radiation response following photon (X) or proton (H) irradiation alone and in combination with different treatment schedules of Dox. As preclinical models, fibrosarcoma (HT-1080), undifferentiated pleiomorphic sarcoma (GCT), and embryonal rhabdomyosarcoma (RD) cell lines were used; the latter two are mutated for TP53. The cellular response regarding clonogenic survival, apoptosis, cell-cycle distribution, proliferation, viability, morphology, and motility was investigated. The different STS cell types revealed a dose-dependent radiation response with reduced survival, proliferation, viability, and motility whereas G2/M phase arrest as well as apoptosis were induced. RD cells showed the most radiosensitive phenotype; the linear quadratic model fit could not be applied. In combined treatment schedules, Dox showed the highest efficiency when applied after or before and after radiation; Dox treatment only before radiation was less efficient. GCT cells were the most chemoresistant cell line in this study most probably due to their TP53 mutation status. Interestingly, similar additive effects could be observed for X or H irradiation in combination with Dox treatment. However, the additive effects were determined more frequently for X than for H irradiation. Thus, further investigations are needed to specify alternative drug therapies that display superior efficacy when combined with H therapy.
Language	English
Publishing date	2023-07-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2023.1211984
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Article ; Online: Relative biological effectiveness in proton beam therapy – Current knowledge and future challenges

Armin Lühr / Cläre von Neubeck / Mechthild Krause / Esther G.C. Troost

Clinical and Translational Radiation Oncology, Vol 9, Iss C, Pp 35-

2018 Volume 41

Keywords	RBE ; Relative biological effectiveness ; Clinical side-effects ; In vitro and in vivo models ; MRI ; Dose recalculation ; Medical physics. Medical radiology. Nuclear medicine ; R895-920 ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
Language	English
Publishing date	2018-02-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Endothelial Cell Response to Combined Photon or Proton Irradiation with Doxorubicin.

Bernardo, Teresa / Kuntze, Anna / Klein, Diana / Heinzelmann, Feline / Timmermann, Beate / von Neubeck, Cläre

International journal of molecular sciences

2023 Volume 24, Issue 16

Abstract: Surgery, radiotherapy, and chemotherapy are essential treatment modalities to target cancer cells, but they frequently cause damage to the normal tissue, potentially leading to side effects. As proton beam radiotherapy (PBT) can precisely spare normal ... ...

Abstract	Surgery, radiotherapy, and chemotherapy are essential treatment modalities to target cancer cells, but they frequently cause damage to the normal tissue, potentially leading to side effects. As proton beam radiotherapy (PBT) can precisely spare normal tissue, this therapeutic option is of increasing importance regarding (neo-)adjuvant and definitive anti-cancer therapies. Akin to photon-based radiotherapy, PBT is often combined with systemic treatment, such as doxorubicin (Dox). This study compares the cellular response of human microvascular endothelial cells (HMEC-1) following irradiation with photons (X) or protons (H) alone and also in combination with different sequences of Dox. The cellular survival, cell cycle, apoptosis, proliferation, viability, morphology, and migration were all investigated. Dox monotreatment had minor effects on all endpoints. Both radiation qualities alone and in combination with longer Dox schedules significantly reduced clonogenic survival and proliferation, increased the apoptotic cell fraction, induced a longer G2/M cell cycle arrest, and altered the cell morphology towards endothelial-to-mesenchymal-transition (EndoMT) processes. Radiation quality effects were seen for metabolic viability, proliferation, and motility of HMEC-1 cells. Additive effects were found for longer Dox schedules. Overall, similar effects were found for H/H-Dox and X/X-Dox. Significant alterations between the radiation qualities indicate different but not worse endothelial cell damage by H/H-Dox.
MeSH term(s)	Humans ; Endothelial Cells ; Protons ; Photons ; Doxorubicin/pharmacology ; G2 Phase Cell Cycle Checkpoints
Chemical Substances	Protons ; Doxorubicin (80168379AG)
Language	English
Publishing date	2023-08-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241612833
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Article ; Online: Glioblastoma multiforme: emerging treatments and stratification markers beyond new drugs.

von Neubeck, C / Seidlitz, A / Kitzler, H H / Beuthien-Baumann, B / Krause, M

The British journal of radiology

2015 Volume 88, Issue 1053, Page(s) 20150354

Abstract: Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults. The standard therapy for GBM is maximal surgical resection followed by radiotherapy with concurrent and adjuvant temozolomide (TMZ). In spite of the extensive treatment, the ...

Abstract	Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults. The standard therapy for GBM is maximal surgical resection followed by radiotherapy with concurrent and adjuvant temozolomide (TMZ). In spite of the extensive treatment, the disease is associated with poor clinical outcome. Further intensification of the standard treatment is limited by the infiltrating growth of the GBM in normal brain areas, the expected neurological toxicities with radiation doses >60 Gy and the dose-limiting toxicities induced by systemic therapy. To improve the outcome of patients with GBM, alternative treatment modalities which add low or no additional toxicities to the standard treatment are needed. Many Phase II trials on new chemotherapeutics or targeted drugs have indicated potential efficacy but failed to improve the overall or progression-free survival in Phase III clinical trials. In this review, we will discuss contemporary issues related to recent technical developments and new metabolic strategies for patients with GBM including MR (spectroscopy) imaging, (amino acid) positron emission tomography (PET), amino acid PET, surgery, radiogenomics, particle therapy, radioimmunotherapy and diets.
MeSH term(s)	Adult ; Age Factors ; Brain Neoplasms/diagnosis ; Brain Neoplasms/therapy ; Clinical Trials as Topic ; Combined Modality Therapy/methods ; Diagnostic Imaging/methods ; Disease-Free Survival ; Glioblastoma/diagnosis ; Glioblastoma/therapy ; Humans ; Risk Factors ; Treatment Outcome
Language	English
Publishing date	2015-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2982-8
ISSN	1748-880X ; 0007-1285
ISSN (online)	1748-880X
ISSN	0007-1285
DOI	10.1259/bjr.20150354
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Article ; Online: Corrigendum to "Residual gammaH2AX foci in head and neck squamous cell carcinomas as predictors for tumour radiosensitivity: Evaluation in pre-clinical xenograft models and clinical specimens" [Radiother. Oncol. 137 (2019) 24-31].

Meneceur, Sarah / Löck, Steffen / Gudziol, Volker / Hering, Sandra / Bütof, Rebecca / Rehm, Maximilian / Baumann, Michael / Krause, Mechthild / von Neubeck, Cläre

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

2023 Volume 183, Page(s) 109619

Language	English
Publishing date	2023-03-29
Publishing country	Ireland
Document type	Published Erratum
ZDB-ID	605646-5
ISSN	1879-0887 ; 0167-8140
ISSN (online)	1879-0887
ISSN	0167-8140
DOI	10.1016/j.radonc.2023.109619
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Zs.A 1926: Show issues

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Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: "Radiobiology of Proton Therapy": Results of an international expert workshop.

Lühr, Armin / von Neubeck, Cläre / Pawelke, Jörg / Seidlitz, Annekatrin / Peitzsch, Claudia / Bentzen, Søren M / Bortfeld, Thomas / Debus, Jürgen / Deutsch, Eric / Langendijk, Johannes A / Loeffler, Jay S / Mohan, Radhe / Scholz, Michael / Sørensen, Brita S / Weber, Damien C / Baumann, Michael / Krause, Mechthild

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

2018 Volume 128, Issue 1, Page(s) 56–67

Abstract: The physical properties of proton beams offer the potential to reduce toxicity in tumor-adjacent normal tissues. Toward this end, the number of proton radiotherapy facilities has steeply increased over the last 10-15 years to currently around 70 ... ...

Abstract	The physical properties of proton beams offer the potential to reduce toxicity in tumor-adjacent normal tissues. Toward this end, the number of proton radiotherapy facilities has steeply increased over the last 10-15 years to currently around 70 operational centers worldwide. However, taking full advantage of the opportunities offered by proton radiation for clinical radiotherapy requires a better understanding of the radiobiological effects of protons alone or combined with drugs or immunotherapy on normal tissues and tumors. This report summarizes the main results of the international expert workshop "Radiobiology of Proton Therapy" that was held in November 2016 in Dresden. It addresses the major topics (1) relative biological effectiveness (RBE) in proton beam therapy, (2) interaction of proton radiobiology with radiation physics in current treatment planning, (3) biological effects in proton therapy combined with systemic treatments, and (4) testing biological effects of protons in clinical trials. Finally, important research avenues for improvement of proton radiotherapy based on radiobiological knowledge are identified. The clinical distribution of radiobiological effectiveness of protons alone or in combination with systemic chemo- or immunotherapies as well as patient stratification based on biomarker expressions are key to reach the full potential of proton beam therapy. Dedicated preclinical experiments, innovative clinical trial designs, and large high-quality data repositories will be most important to achieve this goal.
MeSH term(s)	Humans ; Neoplasms/radiotherapy ; Proton Therapy ; Radiobiology ; Relative Biological Effectiveness
Language	English
Publishing date	2018-06-01
Publishing country	Ireland
Document type	Journal Article ; Review
ZDB-ID	605646-5
ISSN	1879-0887 ; 0167-8140
ISSN (online)	1879-0887
ISSN	0167-8140
DOI	10.1016/j.radonc.2018.05.018
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Zs.A 1926: Show issues

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Article ; Online: Influence of acute hypoxia and radiation quality on cell survival.

Tinganelli, Walter / Ma, Ning-Yi / Von Neubeck, Cläre / Maier, Andreas / Schicker, Corinna / Kraft-Weyrather, Wilma / Durante, Marco

Journal of radiation research

2013 Volume 54 Suppl 1, Page(s) i23–30

Abstract: ... were exposed to X-rays and to C-, N- or O-ions with linear energy transfer (LET) values ranging ...

Abstract	To measure the effect of acute oxygen depletion on cell survival for different types of radiation, experiments have been performed using Chinese hamster ovary (CHO) cells and RAT-1 rat prostate cancer cells. A special chamber has been developed to perform irradiations under different levels of oxygenation. The oxygen concentrations used were normoxia (air), hypoxia (94.5% N2, 5% CO2, 0.5% O2) and anoxia (95% N2, 5% CO2). Cells were exposed to X-rays and to C-, N- or O-ions with linear energy transfer (LET) values ranging from 100-160 keV/µm. The oxygen enhancement ratio (OER) and relative biological effectiveness (RBE) values have been calculated from the measured clonogenic survival curves. For both cell lines, the X-ray OER depended on the survival level. For particle irradiation, OER was not dependent on the survival level but decreased with increasing LET. The RBE of CHO cells under oxic conditions reached a plateau for LET values above 100 keV/µm, while it was still increasing under anoxia. In conclusion, the results demonstrated that our chamber could be used to measure radiosensitivity under intermediate hypoxia. Measurements suggest that ions heavier than carbon could be of additional advantage in the irradiation, especially of radioresistant hypoxic tumor regions.
MeSH term(s)	Animals ; CHO Cells ; Cell Hypoxia/radiation effects ; Cell Line, Tumor ; Cell Survival/radiation effects ; Cricetinae ; Cricetulus ; Dose-Response Relationship, Radiation ; Fibroblasts/drug effects ; Humans ; Ions/therapeutic use ; Linear Energy Transfer ; Male ; Oxygen/metabolism ; Prostatic Neoplasms/pathology ; Radiotherapy ; Rats ; X-Rays
Chemical Substances	Ions ; Oxygen (S88TT14065)
Language	English
Publishing date	2013-07-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603983-2
ISSN	1349-9157 ; 0449-3060
ISSN (online)	1349-9157
ISSN	0449-3060
DOI	10.1093/jrr/rrt065
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