Toward tailoring radiation protection strategies at an individual level

s, slides and videos are downloadable from the ICRP website (ICRP 2017a): ICRP is also going to publish the proceedings in the Annals of the ICRP. Among them, in the ICRP/MELODI session on ‘Effects, risks, and detriment at low dose and low dose rates’ (co-chaired by Simon Bouffler and Thomas Jung), Andrzej Wojcik as a member of C1 WP delivered a talk ‘Human radiosensitivity and prospects for prediction’ (Wojcik 2017). Wojcik pointed out that the use of a common term ‘individual radiosensitivity’ to describe the proneness to stochastic effects and tissue reactions is confusing (Foray et al. 2016). Wojcik also highlighted that testing of individual IR responses of low-dose occupationally exposed CONTACT Nobuyuki Hamada hamada-n@criepi.denken. or.jp Radiation Safety Research Center, Nuclear Technology Research Laboratory, Central Research Institute of Electric Power Industry (CRIEPI), 2-11-1 Iwado-kita, Komae, Tokyo 201-8511, Japan 2018 Taylor & Francis Group, LLC INTERNATIONAL JOURNAL OF RADIATION BIOLOGY 2018, VOL. 94, NO. 11, 951–954 https://doi.org/10.1080/09553002.2018. 1513178 individuals is questionable from radiation protection viewpoints, owing to the limited contribution of genetic background. C1 WP is reviewing papers on individual IR responses that have come out since the 2013 AGIR report (HPA 2013) and is preparing a report that aims to address whether predictive assays/markers are available and to identify open questions (ICRP 2017b). Two papers related to C1 WP have thus far been published (Rajaraman et al. 2018; Wojcik et al. 2018). Out of 14 symposium sessions at ERPW 2017, two sessions were dedicated to individual IR responses. Session 8 ‘Biomarkers and cohorts suitable for exploring low-dose/lowdose-rate exposure effects and individual susceptibility (humans, animals and plants)’ (co-chaired by Almudena Real and Michaela Kreuzer) had two pertinent talks: one was ‘Cohorts for radiation research with focus on low-dose/lowdose-rate exposure effects and individual susceptibility’ by Olivier Laurent from the viewpoint of epidemiology, the other being ‘Biomarkers for radiation research with a focus on human susceptibility’ by Catharine West from the viewpoint of the REQUITE project (REQUITE 2018). West pointed out the need of a roadmap for the validation of biomarkers in prospective cohorts. Perhaps surprisingly, many of the common genetic variants in terms of single nucleotide polymorphisms (SNPs) observed in the genome wide association studies (GWAS) on late radiation toxicity include not only genes involved in DNA damage response pathways but also those in various functions of the tissues, such as muscle cell regeneration (Fachal et al. 2014), regulation of angiogenesis (Kerns et al. 2013) and smooth muscle contraction (Barnett et al. 2014). In the radiation protection context, a roadmap was provided for the development of biomarkers from discovery to implementation and used to summarize the current status of proposed biomarkers for epidemiological studies, but most potential biomarkers still remain in the discovery stage (Hall et al. 2017). All of four talks in Session 14 ‘Individualized approaches for radiation protection’ (cochaired by Hildegarde Vandenhove and Elisabeth Ainsbury) were relevant: ‘Challenges of individualized radiation protection: identification of individual radiation sensitivity’ by Ulrike Kulka who raised the need of more scientific knowledge and ethical considerations, ‘Individual radiation protection approaches in medical applications’ by Wolfgang D€ orr from the medical viewpoint, ‘Individual approaches in emergency scenarios’ by Andrzej Wojcik from the viewpoint of the Realizing the European Network of Biodosimetry (RENEB) project (RENEB 2018), and ‘Individual sensitivity; neither the issue or its solution should be thought of as radiation specific’ by Christopher Kalman from the viewpoint of occupational protection. Individual variability in radiation sensitivity is of major concern in radiation protection. Established and novel biomarkers will allow for a more sensitive and fast identification. This applies for emergency and accident exposures. For all medical radiation applications, the ‘justifying indication’ guarantees individualization. Moreover, radiotherapy in itself is a highly individualized procedure. It needs to be emphasized that the ethical, scientific and practical difficulties of standards based on individual sensitivity are huge; the ethical impact must not be underestimated. MELODI–CONCERT workshop 2018 MELODI, at its management board meeting held on 9 October 2017, decided to hold the workshop on individual IR responses in Malta in March 2018, and actually held the MELODI–CONCERT workshop on individual radiosensitivity and radiosusceptibility on 12–14 March 2018 (MELODI 2018). Clinical and epidemiological observations, mechanisms involved in radiation sensitivity, and identification of sensitive subpopulations were particularly discussed in the workshop. About five percent of patients develop severe adverse effects and many more show moderate toxicity after radiotherapy. It would be useful to have a registry of overresponding patients; however, there are no standard criteria to identify them. There is a need for validated prediction tools to identify radiosensitive and radiosusceptible patients. If radiosensitive patient is identified, guidelines are then needed for alternative treatment. As for the reported outcomes, it was concluded that outcomes reported objectively by a physician and subjectively by a patient are both important. A long term follow-up of patients would be needed for effects such as heart/lung complications or second cancer. Recommendations on the collection of data and samples and on the follow-up were discussed and will be further developed. Cohorts of radiotherapy patients available for retrospective or prospective studies were reviewed, and alternative strategies by using nonradiotherapy cohorts with biosamples (such as national biobanks) were also considered. Even though there are rare genetic syndromes (e.g. ataxia telangiectasia) that come with very high sensitivity to radiation, the majority of overresponding patients do not carry mutations in the known DNA damage and damage response genes. It is not clear why they overrespond to radiotherapy and whether the underlying cause is genetic or environmental. Functional tests that would have the potential to identify overresponding patients were discussed. Among the most promising ones are levels of 8-oxo-dG in the serum or urine (Pour Khavari et al. 2018), the nuclear shuttling of ataxia telangiectasia-mutated (ATM) proteins (Pereira et al. 2018), and the apoptosis of lymphocytes (Azria et al. 2015). MELODI is preparing a position paper predicated on discussions made in the workshop, and will have a continued discussion on individual IR responses at the third ERPW meeting in October 2018.