Modeling age-dependent radiation-induced second cancer risks and estimation of mutation rate: an evolutionary approach

Kaveh, Kamran; Manem, Venkata S. K.; Kohandel, Mohammad; Sivaloganathan, S.

doi:10.1007/s00411-014-0576-z

Cited by 3 publications

(3 citation statements)

References 43 publications

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“…It is also important to note that due to the higher survival rate of cancer patients in recent years, the risk to develop radiation induced second tumours has now become of greater importance than ever [23]. It was recently shown that the frequency of micronuclei can be predictive of the cancer risk, which suggests that higher amounts of genetic damage after irradiation is correlated with early events in carcinogenesis [24].…”

Section: Discussionmentioning

confidence: 99%

Improved normal tissue protection by proton and X-ray microchannels compared to homogeneous field irradiation

et al. 2015

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The risk of developing normal tissue injuries often limits the radiation dose that can be applied to the tumour in radiation therapy. Microbeam Radiation Therapy (MRT), a spatially fractionated photon radiotherapy is currently tested at the European Synchrotron Radiation Facility (ESRF) to improve normal tissue protection. MRT utilizes an array of microscopically thin and nearly parallel X-ray beams that are generated by a synchrotron. At the ion microprobe SNAKE in Munich focused proton microbeams ("proton microchannels") are studied to improve normal tissue protection. Here, we comparatively investigate microbeam/microchannel irradiations with sub-millimetre X-ray versus proton beams to minimize the risk of normal tissue damage in a human skin model, in vitro. Skin tissues were irradiated with a mean dose of 2 Gy over the irradiated area either with parallel synchrotron-generated X-ray beams at the ESRF or with 20 MeV protons at SNAKE using four different irradiation modes: homogeneous field, parallel lines and microchannel applications using two different channel sizes. Normal tissue viability as determined in an MTT test was significantly higher after proton or X-ray microchannel irradiation compared to a homogeneous field irradiation. In line with these findings genetic damage, as determined by the measurement of micronuclei in keratinocytes, was significantly reduced after proton or X-ray microchannel compared to a homogeneous field irradiation. Our data show that skin irradiation using either X-ray or proton microchannels maintain a higher cell viability and DNA integrity compared to a homogeneous irradiation, and thus might improve normal tissue protection after radiation therapy.

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Section: Discussionmentioning

confidence: 99%

Improved normal tissue protection by proton and X-ray microchannels compared to homogeneous field irradiation

et al. 2015

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“…Various theoretical models for radiation-induced cancer have been developed with model parameters fitted to clinical data. [1][2][3][4][5][6][7][8][9][10][11][12] Recent studies [16][17][18][19] have applied the S-model 8,10 to estimate the outcome of different treatment modalities with regard to radiation-induced cancer. Based on assumptions on cell repopulation/repair, mutation, and sterilization, the S-model gives a dose dependent formulation for the excess absolute risk (EAR).…”

Section: Methodsmentioning

confidence: 99%

“…Phenomenological risk models are frequently applied to estimate the risk of radiation-induced cancers at radiotherapy doses. [1][2][3][4][5][6][7][8][9][10][11][12] From the analysis of the Hiroshima and Nagasaki atomicbomb (A-bomb) survivors, it is known that solid cancer risk per unit dose varies significantly with both age at exposure and attained age. 13,14 Any realistic model of radiation-induced cancer at radiotherapy doses should therefore include the age dependence of risk.…”

Section: Introductionmentioning

confidence: 99%

Age at exposure and attained age variations of cancer risk in the Japanese A‐bomb and radiotherapy cohorts

Schneider

Walsh

2015

Medical Physics

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Genetic Analysis of T Cell Lymphomas in Carbon Ion-Irradiated Mice Reveals Frequent Interstitial Chromosome Deletions: Implications for Second Cancer Induction in Normal Tissues during Carbon Ion Radiotherapy

Blyth¹,

Kakinuma²,

Sunaoshi³

et al. 2015

PLoS ONE

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Monitoring mice exposed to carbon ion radiotherapy provides an indirect method to evaluate the potential for second cancer induction in normal tissues outside the radiotherapy target volume, since such estimates are not yet possible from historical patient data. Here, male and female B6C3F1 mice were given single or fractionated whole-body exposure(s) to a monoenergetic carbon ion radiotherapy beam at the Heavy Ion Medical Accelerator in Chiba, Japan, matching the radiation quality delivered to the normal tissue ahead of the tumour volume (average linear energy transfer = 13 keV.μm-1) during patient radiotherapy protocols. The mice were monitored for the remainder of their lifespan, and a large number of T cell lymphomas that arose in these mice were analysed alongside those arising following an equivalent dose of 137Cs gamma ray-irradiation. Using genome-wide DNA copy number analysis to identify genomic loci involved in radiation-induced lymphomagenesis and subsequent detailed analysis of Notch1, Ikzf1, Pten, Trp53 and Bcl11b genes, we compared the genetic profile of the carbon ion- and gamma ray-induced tumours. The canonical set of genes previously associated with radiation-induced T cell lymphoma was identified in both radiation groups. While the pattern of disruption of the various pathways was somewhat different between the radiation types, most notably Pten mutation frequency and loss of heterozygosity flanking Bcl11b, the most striking finding was the observation of large interstitial deletions at various sites across the genome in carbon ion-induced tumours, which were only seen infrequently in the gamma ray-induced tumours analysed. If such large interstitial chromosomal deletions are a characteristic lesion of carbon ion irradiation, even when using the low linear energy transfer radiation to which normal tissues are exposed in radiotherapy patients, understanding the dose-response and tissue specificity of such DNA damage could prove key to assessing second cancer risk in carbon ion radiotherapy patients.

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Modeling age-dependent radiation-induced second cancer risks and estimation of mutation rate: an evolutionary approach

Cited by 3 publications

References 43 publications

Improved normal tissue protection by proton and X-ray microchannels compared to homogeneous field irradiation

Improved normal tissue protection by proton and X-ray microchannels compared to homogeneous field irradiation

Age at exposure and attained age variations of cancer risk in the Japanese A‐bomb and radiotherapy cohorts

Genetic Analysis of T Cell Lymphomas in Carbon Ion-Irradiated Mice Reveals Frequent Interstitial Chromosome Deletions: Implications for Second Cancer Induction in Normal Tissues during Carbon Ion Radiotherapy

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