title: Biological measures to minimize the risk of radiotherapy-associated second cancer: A research perspective.
abstract: Purpose Second cancers are among the most serious sequelae for cancer survivors who receive radiotherapy. This article aims to review current knowledge regarding how the risk of radiotherapy-associated second cancer can be minimized by biological measures and to discuss relevant research needs. Results The risk of second cancer can be reduced not only by physical measures to decrease the radiation dose to normal tissues but also by biological means that interfere with the critical determinants of radiation-induced carcinogenesis. Requirements for such biological means include the targeting of tumor types relevant to radiotherapy-associated risk, concrete safety and efficacy evidence and feasibility and minimal invasiveness. Mechanistic insights into the process of radiation carcinogenesis provide rational approaches to minimize the risk. Five mechanism-based strategies are proposed herein based on the current state of knowledge. Epidemiological studies on the joint effects of radiation and lifestyle or other factors can provide evidence for factors that modify radiation-associated risks if deliberately controlled. Conclusions Mechanistic and epidemiological evidence indicates that it is possible to develop interventional measures to minimize the second cancer risk associated with radiotherapy. Research is needed regarding the critical determinants of radiation-induced carcinogenesis available for intervention and joint effects of radiation and controllable factors.
authors.affiliation: a National Institute of Radiological Sciences, Radiobiology for Children's Health Program, Research Center for Radiation Protection , Chiba , Japan ;|d Radiation Effect Accumulation and Prevention Project, Fukushima Projects Headquarters , Chiba , Japan ;
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Imaoka
authors.affiliation: b Waste Management Research Team, Research Center for Radiation Protection , Chiba , Japan ;
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Ishii
authors.affiliation: c Regulatory Sciences Research Program, Research Center for Radiation Protection , National Institute of Radiological Sciences , Chiba , Japan ;
authors.forename: Isao
authors.initials: I
authors.lastname: Kawaguchi
authors.affiliation: a National Institute of Radiological Sciences, Radiobiology for Children's Health Program, Research Center for Radiation Protection , Chiba , Japan ;|d Radiation Effect Accumulation and Prevention Project, Fukushima Projects Headquarters , Chiba , Japan ;
authors.forename: Shino
authors.initials: S
authors.lastname: Homma-Takeda
authors.affiliation: c Regulatory Sciences Research Program, Research Center for Radiation Protection , National Institute of Radiological Sciences , Chiba , Japan ;|e Project for Human Health, Fukushima Projects Headquarters , National Institute of Radiological Sciences , Chiba , Japan ;
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Doi
authors.affiliation: a National Institute of Radiological Sciences, Radiobiology for Children's Health Program, Research Center for Radiation Protection , Chiba , Japan ;|d Radiation Effect Accumulation and Prevention Project, Fukushima Projects Headquarters , Chiba , Japan ;
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Daino
authors.affiliation: f Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy , National Institute of Radiological Sciences , Chiba , Japan ;
authors.forename: Ikuo
authors.initials: I
authors.lastname: Nakanishi
authors.affiliation: b Waste Management Research Team, Research Center for Radiation Protection , Chiba , Japan ;
authors.forename: Keiko
authors.initials: K
authors.lastname: Tagami
authors.affiliation: g Department of Technical Support and Development, Research Development and Support Center , National Institute of Radiological Sciences , Chiba , Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kokubo
authors.affiliation: a National Institute of Radiological Sciences, Radiobiology for Children's Health Program, Research Center for Radiation Protection , Chiba , Japan ;|d Radiation Effect Accumulation and Prevention Project, Fukushima Projects Headquarters , Chiba , Japan ;
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Morioka
authors.affiliation: d Radiation Effect Accumulation and Prevention Project, Fukushima Projects Headquarters , Chiba , Japan ;
authors.forename: Ayaka
authors.initials: A
authors.lastname: Hosoki
authors.affiliation: a National Institute of Radiological Sciences, Radiobiology for Children's Health Program, Research Center for Radiation Protection , Chiba , Japan ;
authors.forename: Masaru
authors.initials: M
authors.lastname: Takabatake
authors.affiliation: c Regulatory Sciences Research Program, Research Center for Radiation Protection , National Institute of Radiological Sciences , Chiba , Japan ;|e Project for Human Health, Fukushima Projects Headquarters , National Institute of Radiological Sciences , Chiba , Japan ;
authors.forename: Shinji
authors.initials: S
authors.lastname: Yoshinaga
mesh_terms: D000818:Animals; D035843:Biomedical Research / Q000639:trends; D004307:Dose-Response Relationship, Radiation; D019317:Evidence-Based Medicine; D006801:Humans; D015994:Incidence; D009381:Neoplasms, Radiation-Induced / Q000401:mortality* / Q000517:prevention & control*; D058958:Organs at Risk / Q000528:radiation effects*; D011835:Radiation Protection / Q000379:methods*; D011878:Radiotherapy / Q000379:methods* / Q000401:mortality*; D011879:Radiotherapy Dosage; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome
keywords: Cancer prevention; radiation carcinogenesis; radiotherapy; second malignant neoplasm