title: Estimated risk of radiation-induced cancer following paediatric cranio-spinal irradiation with electron, photon and proton therapy.
abstract: BACKGROUND
  Improvement in radiotherapy during the past decades has made the risk of developing a radiation-induced secondary cancer as a result of dose to normal tissue a highly relevant survivorship issue. Important factors expected to influence secondary cancer risk include dose level and dose heterogeneity, as well as gender and type of tissue irradiated. The elevated radio-sensitivity in children calls for models particularly tailored to paediatric cancer patients.
  
  
  METHODS
  Treatment plans of six paediatric medulloblastoma patients were analysed with respect to secondary cancer risk following cranio-spinal irradiation (CSI), using either: 1) electrons and photons combined; 2) conformal photons; 3) double-scattering (DS) protons; or 4) intensity-modulated proton therapy (IMPT). The relative organ equivalent dose (OED) concept was applied in three dose-risk scenarios: a linear response model, a plateau response and an organ specific linear-exponential response. Life attributable risk (LAR) was calculated based on the BEIR VII committee's preferred models for estimating age- and site-specific solid cancer incidence. Uncertainties in the model input parameters were evaluated by error propagation using a Monte Carlo sampling procedure.
  
  
  RESULTS
  Both DS protons and IMPT achieved a significantly better dose conformity compared to the photon and electron irradiation techniques resulting in a six times lower overall risk of radiation-induced cancer. Secondary cancer risk in the thyroid and lungs contributed most to the overall risk in all compared modalities, while no significant difference was observed for the bones. Variations between DS protons and IMPT were small, as were differences between electrons and photons.
  
  
  CONCLUSIONS
  Regardless of technique, using protons decreases the estimated risk of secondary cancer following paediatric CSI compared to conventional photon and electron techniques. Substantial uncertainties in the LAR estimates support relative risk comparisons by OED.
authors.affiliation: Department of Physics and Oncology, Haukeland University Hospital , Bergen , Norway.
authors.forename: Camilla H
authors.initials: CH
authors.lastname: Stokkevåg
authors.forename: Grete-May
authors.initials: GM
authors.lastname: Engeseth
authors.forename: Kristian S
authors.initials: KS
authors.lastname: Ytre-Hauge
authors.forename: Dieter
authors.initials: D
authors.lastname: Röhrich
authors.forename: Odd Harald
authors.initials: OH
authors.lastname: Odland
authors.forename: Ludvig P
authors.initials: LP
authors.lastname: Muren
authors.forename: Marianne
authors.initials: M
authors.lastname: Brydøy
authors.forename: Liv B
authors.initials: LB
authors.lastname: Hysing
authors.forename: Artur
authors.initials: A
authors.lastname: Szostak
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Palmer
authors.forename: Jørgen B B
authors.initials: JB
authors.lastname: Petersen
mesh_terms: D001859:Bone Neoplasms / Q000209:etiology; D002528:Cerebellar Neoplasms / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D003110:Colonic Neoplasms / Q000209:etiology; D061888:Craniospinal Irradiation / Q000009:adverse effects*; D004307:Dose-Response Relationship, Radiation; D004583:Electrons / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology; D008297:Male; D008527:Medulloblastoma / Q000532:radiotherapy*; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D016609:Neoplasms, Second Primary / Q000209:etiology*; D058958:Organs at Risk / Q000528:radiation effects; D017785:Photons / Q000009:adverse effects*; D061766:Proton Therapy / Q000009:adverse effects*; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods; D018570:Risk Assessment; D012737:Sex Factors; D013964:Thyroid Neoplasms / Q000209:etiology