Low dose hyper-radiosensitivity in metastatic tumors

Harney, J.; Short, Susan; Shah, Nihal; Joiner, Michael C.; Saunders, Michele I.

doi:10.1016/j.ijrobp.2003.12.029

Cited by 60 publications

(51 citation statements)

References 37 publications

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“…However, a series of experiments initiated in the mid-1980s [28,29] have shown that the LQ model fails to predict the cell response to very small doses of radiation (below 0.5Á1 Gy). This hypersensitivity to low doses has been shown to exist in vivo both in normal tissues [28Á31] and in tumours [32,33] as well as in a wide range of cell lines studied in vitro [34Á42]. Experiments are still performed in order to establish the mechanism of the hypersensitivity at low doses, but it seems that it has a molecular origin, being an adaptive response to radiation damage, similar to other stress responses [43Á45].…”

Section: Mathematical Models To Describe Tissue Response To Radiationmentioning

confidence: 99%

Treatment modelling: The influence of micro-environmental conditions

Daşu¹,

Toma-Daşu

2008

Acta Oncologica

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The interest in theoretical modelling of radiation response has grown steadily from a fast method to estimate the gain of new treatment strategies to an individualisation tool that may be used as part of the treatment planning algorithms. While the advantages of biological optimisation of plans are obvious, accurate theoretical models and realistic information about the micro-environmental conditions in tissues are needed.This paper aimed to investigate the clinical implications of taking into consideration the details of the tumour microenvironmental conditions. The focus was on the availability of oxygen and other nutrients to tumour cells and the relationship between cellular energy reserves and DNA repair ability as this is thought to influence the response of the various hypoxic cells. The choice of the theoretical models for predicting the response (the linear quadratic model or the inducible repair model) was also addressed.The modelling performed in this project has shown that the postulated radiobiological differences between acute and chronic hypoxia have some important clinical implications which may help to understand the mechanism behind the current success rates of radiotherapy. The results also suggested that it is important to distinguish between the two types of hypoxia in predictive assays and other treatment simulations.

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Section: Mathematical Models To Describe Tissue Response To Radiationmentioning

confidence: 99%

Treatment modelling: The influence of micro-environmental conditions

Daşu¹,

Toma-Daşu

2008

Acta Oncologica

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mentioning

confidence: 99%

“…Since then, it has emerged in many cell lines of both tumour and normal tissues [4], as well as in human metastatic tumours [5]. Its possible application to irradiate radioresistant tumours using ultrafractionated schemes has been investigated [5][6][7]. The LDHRS influence on the normal tissue response in fractionated regimes [8] and in low-dose fractionated radiotherapy concurrent with chemotherapy [9] has also been investigated.…”

mentioning

confidence: 99%

Low-dose radiation hyper-radiosensitivity in multicellular tumour spheroids

Guirado¹,

Aranda²,

Ortiz³

et al. 2012

BJR

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Objective: We propose and study a new model aimed at describing the low-dose hyperradiosensitivity phenomenon appearing in the survival curves of different cell lines. Methods: The model uses the induced repair assumption, considering that the critical dose at which this mechanism begins to act varies from cell to cell in a given population. The model proposed is compared with the linear-quadratic model and the modified linear-quadratic model, which is commonly used in literature and in which the induced repair is taken into account in a heuristic way. The survival curve for the MCF-7 line of human breast cancer is measured at low absorbed doses and the uncertainties in these doses are estimated using thermoluminiscent dosemeters. Results: It is shown that these multicellular spheroids present low-dose hyperradiosensitivity. The new model permits an accurate description of the data of two human cell lines (previously published) and of the multicellular spheroids of the MCF-7 line here measured. Conclusion: The model shows enough flexibility to account for data with very different characteristics and considers in a faithful way the hypothesis of the repair induction.

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“…The improvement in radiobiological understanding has for a long time lagged behind this technological development, but it is expected to play a more significant role in the further advancement of radiotherapy for both curative and palliative care. The favorable outcomes of some pilot studies on radioresistant malignant tumors (8 patients), recurrent breast carcinoma (17 patients), and glioblastoma multiforme (103 patients) 2,3,14 not only demonstrated the clinical effectiveness of the PRDR technique for these body sites but also provided convincing evidence to support future large scale and=or randomized clinical trials to determine the efficacy of the PRDR technique for other recurrent and potentially radioresistant cancers.…”

Section: Opening Statementmentioning

confidence: 91%

“…The rich in-vitro and in-vivo experimental results have laid a strong radiobiological foundation for the PRDR technique and these have been used to guide pilot studies to find optimal doses, dose rates, and fractionation schemes for particular body sites. 2,3,8,14,15 A clear advantage of the PRDR technique over conventional radiotherapy is the reduced normal tissue damage at lower dose rates, which has offered hope for some recurrent patients with severe and=or life threatening symptoms, who have been otherwise considered unsuitable for re-irradiation with conventional radiotherapy. The fact that many radioresistant tumor cells exhibit higher RHS=IRR ratios at lower doses and dose rates 6 also suggests that the PRDR technique may be a better choice than conventional radiotherapy for some recurrent cancers because of the possible existence of such radioresistant tumor cells.…”

Section: Opening Statementmentioning

confidence: 99%