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The place of personalized treatments is highly increasing in medical and radiation oncology. During the last decades, a huge number of assays have been developed to predict responses of normal tissues and tumours. These tests have not yet been included into daily clinical practice but the recent developments of radiation oncology are paving the way of personalized strategies including the risk of tumour recurrence and normal tissue reactions. Concerning tumor radiosensitivity prediction, no test are currently used, even if the radiosensitivity index and the genome-based model for adjusting radiotherapy dose assays seem the most promising with level II of evidence. Commercial developments are under progress. Concerning normal tissue radiosensitivity prediction, single nucleotide polymorphims of prostate cancer patients and radiation-induced CD8 T-lymphocyte apoptosis breast and prostate assays are of level I of evidence. They can be proposed before the beginning of radiotherapy in order to propose personalized treatments according to both risks of tumour and normal tissue radiosensitivity. Commercial developments are also under way. [ABSTRACT FROM AUTHOR]

Abstract: Individual response to ionizing radiation is an important information required to apply an efficient radiotherapy treatment against tumour and to avoid any adverse effects in normal tissues. In 1981, Fertil and Malaise have demonstrated that the post-irradiation local tumor control determined in vivo is correlated with clonogenic cell survival assessed in vitro. Furthermore, these authors have reminded the relevance of the concept of intrinsic radiosensitivity that is specific to each individual organ (Fertil and Malaise, 1981) . To date, since clonogenicity assays are too time-consuming and do not provide any other molecular information, a plethora of research groups have attempted to determine the molecular bases of intrinsic radiosensitivity in order to propose reliable and faster predictive assays. To this aim, several approaches have been developed. Notably, the recent revolution in genomic and proteomic technologies is providing a considerable number of data but their link with radiosensitivity still remains to be elucidated. On another hand, the systematic screening of some candidate genes potentially involved in the radiation response is highlighting the complexity of the molecular and cellular mechanisms of DNA damage sensoring and signalling and shows that an abnormal radiation response is not necessarily due to the impairment of one single protein. Finally, more modest approaches consisting in focusing some specific functions of DNA repair seem to provide more reliable clues to predict over-acute reactions caused by radiotherapy. In this review, we endeavoured to analyse the contributions of these major approaches to predict human radiosensitivity. [Copyright &y& Elsevier]

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Abstract: The impact of curative radiotherapy depends mainly on the total dose delivered homogenously in the targeted volume. Nevertheless, the dose delivered to the surrounding healthy tissues may reduce the therapeutic ratio of many radiation treatments. Two different side effects (acute and late) can occur during and after radiotherapy. Of particular interest are the radiation-induced sequelae due to their irreversibility and the potential impact on daily quality of life. In a same population treated in one centre with the same technique, it appears that individual radiosensitivity clearly exists. In the hypothesis that genetic is involved in this area of research, lymphocytes seem to be the tissue of choice due to easy accessibility. Recently, low percentage of CD4 and CD8 lymphocyte apoptosis were shown to be correlated with high grade of sequelae. In addition, recent data suggest that patients with severe radiation-induced late side effects possess four or more single nucleotide polymorphisms (SNP) in candidate genes (ATM, SOD2, TGFB1, XRCC1, and XRCC3) and low radiation-induced CD8 lymphocyte apoptosis in vitro. On-going studies are being analyzing the entire genome using a Genome-wide association study (GWAS) analysis. [ABSTRACT FROM AUTHOR]

Abstract: The impact of curative radiotherapy depends mainly on the total dose delivered homogenously in the targeted volume. Nevertheless, the dose delivery is limited by the tolerated dose of the surrounding healthy tissues. Two different side effects (acute and late) can occur during and after radiotherapy. Of particular interest are the radiation-induced sequelae due to their irreversibility and the potential impact on daily quality of life. In a population treated in one center with the same technique, it appears that individual radiosensitivity clearly exists. In the hypothesis that genetic is involved in this area of research, lymphocytes seem to be the tissue of choice due to easy accessibility. Recently, low percentage of CD4 and CD8 lymphocyte apoptosis were shown to be correlated with high grade of sequelae. In addition, recent data suggest that patients with severe radiation-induced late side effects possess four or more SNP in candidate genes (ATM, SOD2, TGFB1, XRCC1 et XRCC3) and low radiation-induced CD8 lymphocyte apoptosis in vitro. [Copyright &y& Elsevier]

Abstract: Among the large spectrum of DNA damage induced by radiation, DNA double-strand breaks (DSBs) are considered, to date, as the key-lesions responsible for the cell killing. However, although it was always intuitive to radiobiologists, such a conclusion has only been reached after technical developments and conceptual advances and remains consensual rather than demonstrated formally. In this article, we have reviewed the results that have lead to the conclusion that the assessment of successful DSB repair can be the basis of reliable assays predictive of the clinical response to radiotherapy and some chemotherapeutic treatments. We have discussed a number of technical artifacts, the biases due to the extrapolation of data obtained in yeast and rodent model systems to the human situation and the variety of phenotypes observed in human cells and in particular: 1) the most recent techniques developed, based on immunofluorescence, which have revolutionized our understanding of the molecular events occurring early after irradiation but have also raised the crucial questions about the choice of techniques to assess DSB repair and their specificity for different steps of the repair process; 2) While the homologous recombination repair pathway is predominant in yeasts, its importance in human cells appears less obvious, and raises the problem that the existence of randomized repair events may produce many more errors in human cells than in small genome organisms; 3) the impairment of DSB repair is observed in a plethora of genetic diseases, leading to radiosensitivity, immunodeficiency and sometimes cancer-proneness, but the low frequency and the pleiotropism of such diseases makes difficult the development of a single predictive assay. Therefore, although complete DSB repair appears to be crucial for cell survival, further research is still needed to provide innovative techniques fro measuring repair which can be successfully transferred to the clinic and used to ensure the avoidance of deleterious side-effects to cancer therapies. [Copyright &y& Elsevier]

Si la loi du 4 mars 2002 contient des avancées importantes pour les droits des patients, elle a également le mérite de reprendre, en les regroupant, des dispositions déjà contenues dans divers textes législatifs ou réglementaires, et de transposer les devoirs imposés par la déontologie des professionnels de santé, en droits pour les patients. Les informations génétiques ont largement bénéficié des apports de cette loi. Réalisée dans le cadre d''un partenariat de recherche Franco-québécois, cette analyse a pour objet de présenter les particularités de la protection des données génétiques en France avec quelques comparaisons avec le droit Québécois. Nous exposons le cadre légal préexistant, et sa modification par la loi du 4 mars. [Copyright 2004 Elsevier]