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The management of patients with cancer and Li-Fraumeni or heritable TP53-related cancer syndromes is complex because of their increased risk of developing second malignant neoplasms after genotoxic stresses such as systemic treatments or radiotherapy (radiosusceptibility). Clinical decision making also integrates the risks of normal tissue toxicity and sequelae (radiosensitivity) and tumour response to radiotherapy (radioresistance and radiocurability). Radiotherapy should be avoided in patients with cancer and Li-Fraumeni or heritable TP53 cancer-related syndromes, but overall prognosis might be poor without radiotherapy: radioresistance in these patients seems similar to or worse than that of the general population. Radiosensitivity in germline TP53 variant carriers seems similar to that in the general population. The risk of second malignant neoplasms according to germline TP53 variant and the patient's overall oncological prognosis should be assessed during specialised multidisciplinary staff meetings. Radiotherapy should be avoided whenever other similarly curative treatment options are available. In other cases, it should be adapted to minimise the risk of second malignant neoplasms in patients who still require radiotherapy despite its genotoxicity, in view of its potential benefit. Adaptations might be achieved through the reduction of irradiated volumes using proton therapy, non-ionising diagnostic procedures, image guidance, and minimal stray radiation. Non-ionising imaging should become more systematic. Radiotherapy approaches that might result in a lower probability of misrepaired DNA damage (eg, particle therapy biology and tumour targeting) are an area of investigation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: The ability to identify, before treatment, those patients who will overreact to radiation therapy would have sound positive clinical implications. By focusing on DNA double-strand breaks recognition and repair proteins after irradiation, we recently demonstrated that the maximal number of phosphorylated ATM (pATM) nuclear foci in the first hour (pATMmax) after ex vivo irradiation correlated with postradiation therapy toxicity severity. We performed additional analyses of our whole collection of fibroblast lines to refine the predictive performance of our assay., Methods and Materials: Immunofluorescence experiments were performed on 117 primary skin fibroblast lines irradiated at 2 Gy. The toxicity response was split into 2 binary classes: 0 if the toxicity grade was <2 and 1 otherwise. To assess the relationship between the quantity of pATMmax foci and toxicity grade, we applied a correlation and then a supervised classification analysis. Training data sets from 13 radiosensitive patients randomly drawn using a random undersampling technique were constituted. Receiver operating characteristic analyses were performed using a Monte-Carlo method to estimate the optimal threshold and discriminate the responses for each data set. The discrimination cutoff was estimated as the maximum value of the 10 4 thresholds computed from each training subset., Results: As expected, we confirmed a quasi-linear dependence between toxicity and pATMmax (Pearson correlation coefficient -0.85; P < 2.2e -16 ). When taken as a binary predictive assay with the optimal cutoff value of 34.5 pATM foci/cell, our assay showed outstanding predictive performance (sensitivity, specificity, negative predictive value, positive predictive value, and area under the curve: 100%, 92%, 100%, 99%, and 0.987, respectively)., Conclusions: The results of these experiments allowed us to identify pATMmax as a high-performance predictive parameter of patients with postradiation therapy overreactions. Additional studies are in progress to confirm that this radiosensitivity assay reaches the same performance level in any condition to adapt clinical practice., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Fabien Arcelin, physician working in Lyon, pioneer of radiology and radiotherapy, was both mentored by Destot (one of the fathers of the French radiology for his thesis of medicine) and by his own father Adrien Arcelin (one of the two codiscoverers of the prehistorical site of the Roche-de-Solutré in Burgundy) for archeological works. Hence, radiologist in Lyon during the week and archeologist during the weekend, Fabien Arcelin made significant advances in both radiation research and archeology. He was notably the discoverer of the first tombs of Aurignacian men. In radiology, he examined about 2000 radiographic heart views with the Destot's orthodiagraph to assess the cardiothoracic ratio and wrote a reference book about the use of X-rays to detect kidney stones. He made the first survey about the secondary effects of radiotherapy, important database for pointing out individual radiosensitivity. In parallel to the radiotherapy trials of Regaud at Curie institute (Paris), he performed the first series of anticancer treatments in Lyon., (Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

On the 4th July, 1896, in his medical office of Les Échelles (Savoie, France), Victor Despeignes performed the very first radiotherapy against cancer, documented by indisputable proofs. However, the intellectual and practical approach that leads to this first radiotherapy may appear unexpected to date. Indeed, it is likely that the treatment that Despeignes applied to his neighbour, who did not suffer from stomach cancer, was born with the indirect support of the Lumière brothers, on the basis of a biological theory (the parasitory theory of cancer) that is irrelevant today, with an experimental protocol based on experiments performed on tuberculosis et in a bifractionated model linked by the constraints of a district medical doctor., (Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: After radiation therapy (RT), various radiation-induced toxicities can develop in about one-fourth of patients. An international interest in using morbidity and mortality rates to monitor the quality of care and integrate morbidity and mortality review (MMR) meetings into organizations' governance processes has arisen. We report the first results of patients included in our MMR procedure that included biological assays for individual intrinsic radiosensitivity (IIRS)., Methods and Materials: Twenty-three patients were prospectively included in the MMR database. Twenty-two were evaluable for IIRS. Prostate (n=10) and breast (n=8) cancers were the most frequent disease types. The total dose delivered, determined according to the type of disease, ranged from 30 to 74 Gy. Our MMR procedure requires strict criteria: patients with unresolved toxicity of grade 3 or higher with availability of clinical (photographic) data, IIRS results obtained from skin biopsy assays, treatment modalities, and follow-up data. The RT technique and dosimetry were reviewed., Results: Our prospective registration of toxicities showed mainly rectitis, occurring in 7 cases, and skin toxicities, occurring in 9. Of the 7 patients with rectitis, 5 received 66 Gy of post-prostatectomy RT with V50 (rectum volume receiving 50 Gy) ranging from 45% to 75% and a mean maximal dose of 66.5 Gy. For dermatitis and cystitis, the mean maximal doses were in the range of classical constraints without any overdosage or dose heterogeneity. No errors were found in the review of treatment planning and positioning. Conversely, all the patients were considered biologically as radiosensitive with genomic instability and ATM (ataxia telangiectasia mutated)-dependent DNA double-strand break repair impairments., Conclusions: The MMR review of files allowed clear answers for patients on the relationship between clinical events and their IIRS. Our procedure has allowed education of all our staff to monitor, identify, and document clinical, physical, and biological aspects of radiation-induced toxicities. Thus we recommend the introduction of the MMR procedure in RT departments., (Copyright © 2016 Elsevier Inc. All rights reserved.)

This exploratory study was designed to investigate the representations of radiotherapists in relation to personalized medicine. On the basis of current?>' available radiotherapy predictive tests, we tried to understand how these tests could be used in routine radiotherapy practice and in what way this possible change of practices could affect the role of radiotherapists in treatment protocols. In the absence of any available data allowing the construction of a quantitative tool, qualitative data were recorded by individual interviews with radiotherapists. Based on textual data analysis, a second national quantitative phase was conducted using a self-administered questionnaire. Crossover analysis of the two datasets highlighted the interest of radiotherapists in personalized medicine and the use of predictive tests, while indicating certain limitations and concerns in relation to ethical issues related to personalized medicine in oncology and the physician's position.

At the beginning of the 21st century, radiation biology is at a major turning point in its history. It must meet the expectations of the radiation oncologists, radiologists and the general public, but its purpose remains the same: to understand the molecular, cellular and tissue levels of lethal and carcinogenic effects of ionizing radiation in order to better protect healthy tissues and to develop treatments more effective against tumours. Four major aspects of radiobiology that marked this decade will be discussed: technological developments, the importance of signalling and repair of radiation-induced deoxyribonucleic acid (DNA) damage, the impact of individual factor in the response to radiation and the contribution of radiobiology to better choose innovative therapies such as protontherapy or stereotactic body radiation therapy (SBRT). A translational radiobiology should emerge with the help of radiotherapists and radiation physicists and by facilitating access to the new radio and/or chemotherapy modalities., (Copyright © 2011. Published by Elsevier SAS.)

Purpose Anti-glioma strategies are generally based on trials involving rodent models whose choice remains based on proliferative capacity and availability. Recently, our group obtained the most protracted survival of rats bearing F98 gliomas by combining synchrotron X-rays and intracerebral cisplatin injection (Biston et al., Cancer Res, 64:2317-2323, 2004). The response to such treatment was suggested to be dependent on BRCA1, a tumour suppressor known to be involved in the response to radiation and cisplatin. In order to verify the impact of BRCA1 functionality upon success of anti-glioma trials, radiobiological features and BRCA1-dependent stress signalling were investigated in the most extensively used rodent glioma models. Methods Cell death pathways, cell cycle arrests, DNA repair and stress signalling were evaluated in response to radiation and cisplatin in C6, 9L and F98 models. Results Rodent glioma models showed a large spectrum of cellular radiation response. Surprisingly, BRCA1 was found to be functionally impaired in C6 and F98 favouring genomic instability, tumour heterogeneity and tolerance of unrepaired DNA damage. Significance Our findings strengthened the importance of the choice of the glioma model on genetic and radiobiological bases, inasmuch as all these rat glioma models are induced by nitrosourea-mediated mutagenesis that may favour specific gene mutations. Particularly, BRCA1 status may condition the response to anti-glioma treatments. Furthermore, since BRCA1 acts as a tumour suppressor in a number of malignancies, our findings raise also the question of the implication of BRCA1 in brain tumours formation.

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Résumé: Entre le 4 et le 23 juillet 1896, Victor Despeignes a effectué la première radiothérapie anticancéreuse validée par des publications et des faits pratiques incontestables. Toutefois, les événements et l’approche intellectuelle qui l’amena à réaliser ce traitement unique sont méconnues. Cette biographie inédite s’efforce de mieux connaître l’œuvre de Victor Despeignes, qui fut tout d’abord un médecin hygiéniste. La conjonction des idées pasteuriennes, de la découverte des rayons X et de l’aide technique probable des frères Lumière l’amena logiquement à irradier une tumeur cancéreuse. La vie de Victor Despeignes peut se découper en trois grandes parties : la période lyonnaise de 1866 à 1894 pendant laquelle il devint médecin et chercheur en parasitologie en travaillant sur la qualité des eaux de ville et la tuberculose ; la période passée à Buis-les-Baronnies (Drôme) puis aux Échelles (Savoie) de 1894 à 1907 pendant laquelle il fut simple médecin de canton et appliqua la première radiothérapie ; enfin la période chambérienne de 1907 à 1937, pendant laquelle il dirigea le bureau d’Hygiène de la ville de Chambéry en menant une action majeure en santé publique. [ABSTRACT FROM AUTHOR]

Abstract: Born in 1870, Claudius Regaud was a pioneer of radiobiology and radiotherapy. As histologist, he developed a new staining technique that allowed him to describe in detail all the reproduction system of a number of animal models. As radiobiologist, he contradicted the interpretations of Tribondeau and Bergonié about relationships between cell proliferation and radiosensitivity. In 1908, he suggested that chromatin was the main target of radiation. As physician, he defined the first bases of anti-cancer radiation treatments and treated patients suffering from incurable cancer from 1911. As military doctor, he organized war hospitals by creating multidisciplinary teams for the surgery of hurts. Organizer, he was one of the founders of the League against Cancer. As radiotherapist and brachytherapist, he contributed to make Institut Curie an international reference center for research and teaching, with nearly a thousand treated patients. As globe-trotter, he was at the origin of the creation of numerous worldwide radiotherapy and radiobiology centers. He died in December 1940 and let an impressive but still misknown scientific heritage. A re-reading of the familial archives and the Regaud Fund of Institut Curie is the occasion to remind the contribution of Regaud. [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]

Abstract: Radiobiologists have pointed out a novel radiobiological phenomenon observed in many tumor and normal cell lines: hyper-radiosensitivity to very low-dose (HRS) followed by induced radioresistance (IRR) after a threshold dose of 0.1–0.3 Gy that depends on the cell line. Radioresistance at high dose (i.e. higher than 0.5 Gy) and metastatic potential of tumor cells are likely major factors of failure in radiotherapy. A careful review of literature suggests that: 1) radiotherapy does not increase the metastatic potential of tumor cells; 2) radioresistance at high dose and metastatic potential are not related. However, inside a given tumor cell line, highly metastatic clones may elicit more cells showing HRS or are more radiosensitive at high dose than poorly metastatic ones. Recent data obtained from molecular techniques (comet and immunofluorescence assays) applied to single cells irradiated at very low radiation doses (1–100 mGy) suggest that DNA single-strand breaks (SSB) and double-strand breaks (DSB) may be the key-lesions responsible for the HRS phenomenon. These data suggest that the HRS phenomenon may find application in radiotherapy for micrometastasis. These early disseminated and probably unvascularised cells may escape the influence of high-dose chemotherapy after excision of the primary tumor. Considering the link between metastatic potential and HRS, we have previously proposed to apply very low-dose total body irradiation (TBI) at M0 stage that may prevent the development of micrometastases. Literature data suggest that the smallest radiation dose that can produce HRS without increasing the risk of cancer may be in the milliGrays range. [Copyright &y& Elsevier]