Radiation repair models for clinical application

Dale, Roger G.

doi:10.1259/bjr.20180070

Cited by 14 publications

(12 citation statements)

References 44 publications

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“…Furthermore, the protraction of dose delivery for 90 Y SIRT adds another level of complexity. This effect is encapsulated by the Lea–Catcheside model of sublethal-damage repair (Dale 2018) and has previously been used to describe the in vitro cellular response to protracted photon exposure (Solanki et al 2017). However, studies using 90 Y are needed to answer fundamental questions regarding differences in the radiobiological response to 90 Y β − -particles and photons of clinically relevant energy.…”

Section: Introductionmentioning

confidence: 99%

Radiosensitivity of colorectal cancer to ⁹⁰Y and the radiobiological implications for radioembolisation therapy

Lee

Abbott²,

Able³

et al. 2019

Phys. Med. Biol.

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Approximately 50% of all colorectal cancer (CRC) patients will develop metastasis to the liver. 90 Y selective internal radiation therapy (SIRT) is an established treatment for metastatic CRC. There is still a fundamental lack of understanding regarding the radiobiology underlying the dose response. This study was designed to determine the radiosensitivity of two CRC cell lines (DLD-1 and HT-29) to 90 Y β − radiation exposure, and thus the relative effectiveness of 90 Y SIRT in relation to external beam radiotherapy (EBRT). A 90 Y-source dish was sandwiched between culture dishes to irradiate DLD-1 or HT-29 cells for a period of 6 d. Cell survival was determined by clonogenic assay. Dose absorbed per 90 Y disintegration was calculated using the PENELOPE Monte Carlo code. PENELOPE simulations were benchmarked against relative dose measurements using EBT3 GAFchromic ™ film. Statistical regression based on the linear-quadratic model was used to determine the radiosensitivity parameters and using R . These results were compared to radiosensitivity parameters determined for 6 MV clinical x-rays and 137 Cs γ -ray exposure. Equivalent dose of EBRT in 2 Gy ( ) and 10 Gy ( ) fractions were derived for 90 Y dose. HT-29 cells were more radioresistant than DLD-1 for all treatment modalities. Radiosensitivity parameters determined for 6 MV x-rays and 137 Cs γ -ray were equivalent for both cell lines. The ratio for 90 Y β − -particle exposure was over an order of magnitude higher than the other two modalities due to protraction of dose delivery. Consequently, an 90 Y SIRT absorbed dose of 60 Gy equates to an of 28.7 and 54.5 Gy and an of 17.6 and 19.3 Gy for DLD-1 and HT-29 cell lines, respectively. We derived radiosensitivity parameters for two CRC cell lines exposed to 90 Y β − -particles, 6 MV x-rays, and 137 Cs γ -ray irradiation. These radiobiological parameters are critical to understanding the dose response of CRC lesions and ultimately informs the efficacy of 90 Y SIRT relative to other radiation therapy modalities.

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Section: Introductionmentioning

confidence: 99%

Radiosensitivity of colorectal cancer to ⁹⁰Y and the radiobiological implications for radioembolisation therapy

Lee

Abbott²,

Able³

et al. 2019

Phys. Med. Biol.

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“…Repair of sub-lethally damaged cells is exponential, but other functional forms can be easily included in the model, like e.g. Michaelis-Menten repair kinetics (Murray 2003), or bi-exponential kinetics (Dale 2018).…”

Section: Discussionmentioning

confidence: 99%

A kinetic model of continuous radiation damage to populations of cells: comparison to the LQ model and application to molecular radiotherapy

et al. 2020

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The linear-quadratic (LQ) model to describe the survival of irradiated cells may be the most frequently used biomathematical model in radiotherapy. There has been an intense debate on the mechanistic origin of the LQ model. An interesting approach is that of obtaining LQ-like behavior from kinetic models, systems of differential equations that model the induction and repair of damage. Development of such kinetic models is particularly interesting for application to continuous dose rate therapies, such as molecular radiotherapy or brachytherapy. In this work, we present a simple kinetic model that describes the kinetics of populations of tumor cells, rather than lethal/sub-lethal lesions, which may be especially useful for application to continuous dose rate therapies, as in molecular radiotherapy. The multi-compartment model consists of a set of three differential equations. The model incorporates in an easy way different cross-interacting compartments of cells forming a tumor, and may be of especial interest for studying dynamics of treated tumors. In the fast dose delivery limit, the model can be analytically solved, obtaining a simple closed-form expression. Fitting of several surviving curves with both this solution and the LQ model shows that they produce similar fits, despite being functionally different. We have also investigated the operation of the model in the continuous dose rate scenario, firstly by fitting preclinical data of tumor response to 131 I-CLR1404 therapy, and secondly by showing how damage repair and proliferation rates can cause a treatment to achieve control or not. Kinetic models like the one presented in this work may be of special interest when modeling response to molecular radiotherapy.

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“…For continuous therapy with a dose rate exponentially decreasing with time, the surviving fraction SF is given by 43 , 44 where μ is the sublethal damage recovery constant 45 , β is the potential sparing capacity for a specific tissue or effect and α is the intrinsic radio-sensitivity.…”

Section: Methodsmentioning

confidence: 99%

Modelling a new approach for radio-ablation after resection of breast ductal carcinoma in-situ based on the BAT-90 medical device

Sarnelli

Negrini

Mezzenga

et al. 2022

Sci Rep

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The majority of local recurrences, after conservative surgery of breast cancer, occurs in the same anatomical area where the tumour was originally located. For the treatment of ductal carcinoma in situ (DCIS), a new medical device, named BAT-90, (BetaGlue Technologies SpA) has been proposed. BAT-90 is based on the administration of 90Y β-emitting microspheres, embedded in a bio-compatible matrix. In this work, the Geant4 simulation toolkit is used to simulate BAT-90 as a homogenous cylindrical 90Y layer placed in the middle of a bulk material. The activity needed to deliver a 20 Gy isodose at a given distance z from the BAT-90 layer is calculated for different device thicknesses, tumour bed sizes and for water and adipose bulk materials. A radiobiological analysis has been performed using both the Poisson and logistic Tumour Control Probability (TCP) models. A range of radiobiological parameters (α and β), target sizes, and densities of tumour cells were considered. Increasing α values, TCP increases too, while, for a fixed α value, TCP decreases as a function of clonogenic cell density. The models predict very solid results in case of limited tumour burden while the activity/dose ratio could be further optimized in case of larger tumour beds.

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Radiation repair models for clinical application

Cited by 14 publications

References 44 publications

Radiosensitivity of colorectal cancer to ⁹⁰Y and the radiobiological implications for radioembolisation therapy

Radiosensitivity of colorectal cancer to ⁹⁰Y and the radiobiological implications for radioembolisation therapy

A kinetic model of continuous radiation damage to populations of cells: comparison to the LQ model and application to molecular radiotherapy

Modelling a new approach for radio-ablation after resection of breast ductal carcinoma in-situ based on the BAT-90 medical device

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Radiation repair models for clinical application

Cited by 14 publications

References 44 publications

Radiosensitivity of colorectal cancer to 90Y and the radiobiological implications for radioembolisation therapy

Radiosensitivity of colorectal cancer to 90Y and the radiobiological implications for radioembolisation therapy

A kinetic model of continuous radiation damage to populations of cells: comparison to the LQ model and application to molecular radiotherapy

Modelling a new approach for radio-ablation after resection of breast ductal carcinoma in-situ based on the BAT-90 medical device

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Radiosensitivity of colorectal cancer to ⁹⁰Y and the radiobiological implications for radioembolisation therapy

Radiosensitivity of colorectal cancer to ⁹⁰Y and the radiobiological implications for radioembolisation therapy