title: Potential strategies to ameliorate risk of radiotherapy-induced second malignant neoplasms.
abstract: This review is aimed at the issue of radiation-induced second malignant neoplasms (SMN), which has become an important problem with the increasing success of modern cancer radiotherapy (RT). It is imperative to avoid compromising the therapeutic ratio while addressing the challenge of SMN. The dilemma is illustrated by the role of reactive oxygen species in both the mechanisms of tumor cell kill and of radiation-induced carcinogenesis. We explore the literature focusing on three potential routes of amelioration to address this challenge. An obvious approach to avoiding compromise of the tumor response is the use of radioprotectors or mitigators that are selective for normal tissues. We also explore the opportunities to avoid protection of the tumor by topical/regional radioprotection of normal tissues, although this strategy limits the scope of protection. Finally, we explore the role of the bystander/abscopal phenomenon in radiation carcinogenesis, in association with the inflammatory response. Targeted and non-targeted effects of radiation are both linked to SMN through induction of DNA damage, genome instability and mutagenesis, but differences in the mechanisms and kinetics between targeted and non-targeted effects may provide opportunities to lessen SMN. The agents that could be employed to pursue each of these strategies are briefly reviewed. In many cases, the same agent has potential utility for more than one strategy. Although the parallel problem of chemotherapy-induced SMN shares common features, this review focuses on RT associated SMN. Also, we avoid the burgeoning literature on the endeavor to suppress cancer incidence by use of antioxidants and vitamins either as dietary strategies or supplementation.
authors.affiliation: Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne, VIC 3002, Australia; Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne, VIC 3002, Australia; The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: olga.martin@petermac.org.
authors.forename: Olga A
authors.initials: OA
authors.lastname: Martin
authors.affiliation: Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne, VIC 3002, Australia; Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne, VIC 3002, Australia. Electronic address: sherry.yin@petermac.org.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Yin
authors.affiliation: Centre for Innate Immunity and Infectious Disease, Hudson Institute of Medical Research, Clayton, VIC, Australia; Department of Molecular and Translational Sciences, Monash University, Clayton, VIC, Australia. Electronic address: helen.forrester@hudson.org.au.
authors.forename: Helen B
authors.initials: HB
authors.lastname: Forrester
authors.affiliation: Centre for Innate Immunity and Infectious Disease, Hudson Institute of Medical Research, Clayton, VIC, Australia; Department of Molecular and Translational Sciences, Monash University, Clayton, VIC, Australia. Electronic address: carl.sprung@hudson.org.au.
authors.forename: Carl N
authors.initials: CN
authors.lastname: Sprung
authors.affiliation: Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne, VIC 3002, Australia; The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: roger.martin@petermac.org.
authors.forename: Roger F
authors.initials: RF
authors.lastname: Martin
mesh_terms: D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004249:DNA Damage / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D009381:Neoplasms, Radiation-Induced / Q000188:drug therapy* / Q000517:prevention & control*; D016609:Neoplasms, Second Primary / Q000188:drug therapy / Q000209:etiology; D011837:Radiation-Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011878:Radiotherapy / Q000009:adverse effects*
chemical_list: D000975:Antioxidants; D011837:Radiation-Protective Agents
keywords: Antioxidants; Inflammation; Radiation-induced bystander effect; Radioprotectors; Radiotherapy; Second malignant neoplasms