title: Risk of second cancers in the era of modern radiation therapy: does the risk/benefit analysis overcome theoretical models?
abstract: In the era of modern radiation therapy, the compromise between the reductions in deterministic radiation-induced toxicities through highly conformal devices may be impacting the stochastic risk of second malignancies. We reviewed the clinical literature and evolving theoretical models evaluating the impact of intensity-modulated radiation therapy (IMRT) on the risk of second cancers, as a consequence of the increase in volumes of normal tissues receiving low doses. The risk increase (if any) is not as high as theoretical models have predicted in adults. Moreover, the increase in out-of-field radiation doses with IMRT could be counterbalanced by the decrease in volumes receiving high doses. Clinical studies with short follow-up have not corroborated the hypothesis that IMRT would drastically increase the incidence of second cancers. In children, the risk of radiation-induced carcinogenesis increases from low doses and consequently the relative risk of second cancers after IMRT could be higher than in adults, justifying current developments of proton therapy with priority given to this population. Although only longer follow-up will allow a true assessment of the real impact of these modern techniques on radiation-induced carcinogenesis, a comprehensive risk-adapted strategy will help minimize the probability of second cancers.
authors.affiliation: Radiotherapy Department, Hôpital d'Instruction des Armées du Val-de-Grâce, Paris, France.|INSERM 1030, Molecular Radiotherapy, Gustave Roussy campus Cancer, Grand Paris, France.
authors.forename: Cyrus
authors.initials: C
authors.lastname: Chargari
authors.affiliation: Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Karyn A
authors.initials: KA
authors.lastname: Goodman
authors.affiliation: U1018 Institut National de la Santé et de la Recherche Médicale, Villejuif, France.
authors.forename: Ibrahima
authors.initials: I
authors.lastname: Diallo
authors.affiliation: Cellular and Molecular Radiotherapy Laboratory, EMR3738, 69921, Oullins, France.|Department of Radiotherapy, Lucien Neuwirth Cancer Institute, Saint Priest en Jarez, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Guy
authors.affiliation: Department of Radiotherapy, Lucien Neuwirth Cancer Institute, Saint Priest en Jarez, France.
authors.forename: Chloe
authors.initials: C
authors.lastname: Rancoule
authors.affiliation: Oncology/Radiotherapy Department, Institut Curie, 75005, Paris, France.|Charlebourg-La Défense Radiotherapy Center, Amethyst Group, La Garenne-Colombes, 92250, Paris, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Cosset
authors.affiliation: INSERM 1030, Molecular Radiotherapy, Gustave Roussy campus Cancer, Grand Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Deutsch
authors.affiliation: Cellular and Molecular Radiotherapy Laboratory, EMR3738, 69921, Oullins, France. nicolas.magne@icloire.fr.|Department of Radiotherapy, Lucien Neuwirth Cancer Institute, Saint Priest en Jarez, France. nicolas.magne@icloire.fr.|Chef du Département de Radiothérapie, Directeur de la Recherche et de l'Innovation, Institut de Cancérologie Lucien Neuwirth, 108 bis, avenue Albert Raimond, BP 60008, 42270, Saint-Priest en Jarez cedex, France. nicolas.magne@icloire.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Magne
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008962:Models, Theoretical; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000209:etiology*; D011829:Radiation Dosage; D061089:Radiotherapy, Image-Guided / Q000009:adverse effects / Q000379:methods; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects* / Q000379:methods; D012306:Risk
keywords: Intensity-modulated radiation therapy; Linear no-threshold model; Low doses; Proton therapy; Radiation therapy; Second malignancies