Impact of enhancements in the local effect model (LEM) on the predicted RBE-weighted target dose distribution in carbon ion therapy

Grün, Rebecca; Friedrich, Thomas; Elsässer, Thilo; Krämer, M.; Zink, Klemens; Karger, Christian P.; Durante, Marco; Engenhart‐Cabillic, Rita; Scholz, M.

doi:10.1088/0031-9155/57/22/7261

Cited by 93 publications

(64 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, clustered RIF tend to be more persistent than isolated RIF (Figure 3), suggesting that DSBs associated with RIF clusters are more difficult to repair. In agreement, recent modeling work suggested that DSBs in close proximity have a higher probability of inducing cell death than isolated DSBs [94, 95]. In this model, experimental radiation survival curves can be fitted accurately if one assumes that two DSBs located in the same large chromatin region (a unit of chromatin that spans several megabases, called a ‘Giant Loop’, [96, 97]) have a higher probability of inducing cell death than two DSBs on distinct Giant Loops [98].…”

Section: Use Of Rif Spatio-temporal Properties As Biomarkers For Repasupporting

confidence: 80%

Nuclear dynamics of radiation-induced foci in euchromatin and heterochromatin

Chiolo

Tang

Georgescu

et al. 2013

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

105

View full text Add to dashboard Cite

Repair of double strand breaks (DSBs) is essential for cell survival and genome integrity. While much is known about the molecular mechanisms involved in DSB repair and checkpoint activation, the roles of nuclear dynamics of radiation-induced foci (RIF) in DNA repair are just beginning to emerge. Here, we summarize results from recent studies that point to distinct features of these dynamics in two different chromatin environments: heterochromatin and euchromatin. We also discuss how nuclear architecture and chromatin components might control these dynamics, and the need of novel quantification methods for a better description and interpretation of these phenomena. These studies are expected to provide new biomarkers for radiation risk and new strategies for cancer detection and treatment.

show abstract

Section: Use Of Rif Spatio-temporal Properties As Biomarkers For Repasupporting

confidence: 80%

Nuclear dynamics of radiation-induced foci in euchromatin and heterochromatin

Chiolo

Tang

Georgescu

et al. 2013

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

105

View full text Add to dashboard Cite

show abstract

“…The value of this RBE is between 3 and 5 depending on different factors. 9 In a recent study on the use of carbon ions for the treatment of patients with chondrosarcoma of the skull base, excellent tumor control rates of 96.2% at 3 years were proven. 10 The purpose of the current study was to evaluate the long-term results in all patients with skull base chondrosarcoma who were treated at the GSI Helmholtz Centre for Heavy Ion Research in Darmstadt using carbon ions.…”

Section: Introductionmentioning

confidence: 99%

High control rate in patients with chondrosarcoma of the skull base after carbon ion therapy: First report of long‐term results

Uhl

Mattke

Welzel

et al. 2014

Cancer

View full text Add to dashboard Cite

BACKGROUND:The current study was performed to evaluate the safety and effectiveness of irradiation with carbon ions using raster scanning as well as prognostic factors in patients with skull base chondrosarcomas. METHODS: Between 1998 and 2008, 79 patients with chondrosarcoma of the skull base were treated using carbon ions in raster scanning. The applied median total dose was 60 gray equivalent (GyE) at 3 GyE per fraction. Local control and overall survival (OS) were evaluated using the Kaplan-Meier method. Longterm toxicity was quantitatively assessed using questionnaires. RESULTS: The median follow-up after irradiation was 91 months (range, 3 months-175 months). Within the follow-up, 10 patients developed local disease recurrence. The 3-year, 5-year, and 10-year local control rates were 95.9%, 88%, and 88%, respectively; the corresponding OS rates were 96.1%, 96.1%, and 78.9%, respectively. With a median follow-up of 110 months after first diagnosis, the corresponding 3-year, 5-year, and 10-year OS rates were 97.5%, 97.5%, and 91.5%, respectively. Age 45 years and boost volume 55 mL were associated with significantly better local control rates. We observed a clinically relevant improvement in cranial nerve deficits 7 to 10 years after treatment (range, 45.5%-53.3%) compared with the baseline (73.4%). During follow-up, none of the patients in the current study developed a secondary malignancy. CONCLUSIONS: Carbon ion therapy is a safe and effective treatment in patients with chondrosarcoma of the skull base. For further evaluation, a prospective randomized phase 3 trial comparing protons versus carbon ions has been recruiting patients with low-grade and intermediate-grade chondrosarcoma of the skull base since 2009. Cancer 2014;120:1579-85.

show abstract

“…The same concept of DSB classification into iDSB and cDSB is also implemented in the Local Effect Model (LEM IV [26,27]) that allows predicting the effects of high-LET radiation based on the known response of a cell or tissue to low-LET radiation. This model is used in the framework of treatment planning for ion beam therapy [28,29]. …”

Section: Introductionmentioning

confidence: 99%

Induction and Processing of the Radiation-Induced Gamma-H2AX Signal and Its Link to the Underlying Pattern of DSB: A Combined Experimental and Modelling Study

et al. 2015

View full text Add to dashboard Cite

We present here an analysis of DSB induction and processing after irradiation with X-rays in an extended dose range based on the use of the γH2AX assay. The study was performed by quantitative flow cytometry measurements, since the use of foci counting would result in reasonable accuracy only in a limited dose range of a few Gy. The experimental data are complemented by a theoretical analysis based on the GLOBLE model. In fact, original aim of the study was to test GLOBLE predictions against new experimental data, in order to contribute to the validation of the model. Specifically, the γH2AX signal kinetics has been investigated up to 24 h after exposure to increasing photon doses between 2 and 500 Gy. The prolonged persistence of the signal at high doses strongly suggests dose dependence in DSB processing after low LET irradiation. Importantly, in the framework of our modelling analysis, this is related to a gradually increased fraction of DSB clustering at the micrometre scale. The parallel study of γH2AX dose response curves shows the onset of a pronounced saturation in two cell lines at a dose of about 20 Gy. This dose is much lower than expected according to model predictions based on the values usually adopted for the DSB induction yield (≈ 30 DSB/Gy) and for the γH2AX foci extension of approximately 2 Mbp around the DSB. We show and discuss how theoretical predictions and experimental findings can be in principle reconciled by combining an increased DSB induction yield with the assumption of a larger genomic extension for the single phosphorylated regions. As an alternative approach, we also considered in our model the possibility of a 3D spreading-mechanism of the H2AX phosphorylation around the induced DSB, and applied it to the analysis of both the aspects considered. Our results are found to be supportive for the basic assumptions on which GLOBLE is built. Apart from giving new insights into the H2AX phosphorylation process, experiments performed at high doses are of relevance in the context of radiation therapy, where hypo-fractionated schemes become increasingly popular.

show abstract

Impact of enhancements in the local effect model (LEM) on the predicted RBE-weighted target dose distribution in carbon ion therapy

Cited by 93 publications

References 27 publications

Nuclear dynamics of radiation-induced foci in euchromatin and heterochromatin

Nuclear dynamics of radiation-induced foci in euchromatin and heterochromatin

High control rate in patients with chondrosarcoma of the skull base after carbon ion therapy: First report of long‐term results

Induction and Processing of the Radiation-Induced Gamma-H2AX Signal and Its Link to the Underlying Pattern of DSB: A Combined Experimental and Modelling Study

Contact Info

Product

Resources

About