title: 3D calculation of radiation-induced second cancer risk including dose and tissue response heterogeneities.
abstract: OBJECTIVE
  Tools for comparing relative induced second cancer risk, to inform choice of radiotherapy treatment plan, are becoming increasingly necessary as the availability of new treatment modalities expands. Uncertainties, in both radiobiological models and model parameters, limit the confidence of such calculations. The aim of this study was to develop and demonstrate a software tool to produce a malignant induction probability (MIP) calculation which incorporates patient-specific dose and allows for the varying responses of different tissue types to radiation.
  
  
  METHODS
  The tool has been used to calculate relative MIPs for four different treatment plans targeting a subtotally resected meningioma: 3D conformal radiotherapy (3DCFRT), volumetric modulated arc therapy (VMAT), intensity-modulated x-ray therapy (IMRT), and scanned protons.
  
  
  RESULTS
  Two plausible MIP models, with considerably different dose-response relationships, were considered. A fractionated linear-quadratic induction and cell-kill model gave a mean relative cancer risk (normalized to 3DCFRT) of 113% for VMAT, 16% for protons, and 52% for IMRT. For a linear no-threshold model, these figures were 105%, 42%, and 78%, respectively. The relative MIP between plans was shown to be significantly more robust to radiobiological parameter uncertainties compared to absolute MIP. Both models resulted in the same ranking of modalities, in terms of MIP, for this clinical case.
  
  
  CONCLUSIONS
  The results demonstrate that relative MIP is a useful metric with which treatment plans can be ranked, regardless of parameter- and model-based uncertainties. With further validation, this metric could be used to discriminate between plans that are equivalent with respect to other planning priorities.
authors: Particle Therapy Cancer Research Institute, University of Oxford, Oxfordshire OX1 3RH, United Kingdom and Department of Physics, University of Oxford, Oxfordshire OX1 3RH, United Kingdom.
authors: C
authors: C
authors: Timlin
authors: Particle Therapy Cancer Research Institute, University of Oxford, Oxfordshire OX1 3RH, United Kingdom and Department of Physics, University of Oxford, Oxfordshire OX1 3RH, United Kingdom.
authors: D R
authors: DR
authors: Warren
authors: Particle Therapy Cancer Research Institute, University of Oxford, Oxfordshire OX1 3RH, United Kingdom and Department of Physics, University of Oxford, Oxfordshire OX1 3RH, United Kingdom.
authors: B
authors: B
authors: Rowland
authors: Particle Therapy Cancer Research Institute, University of Oxford, Oxfordshire OX1 3RH, United Kingdom and Department of Physics, University of Oxford, Oxfordshire OX1 3RH, United Kingdom.
authors: A
authors: A
authors: Madkhali
authors: Particle Therapy Cancer Research Institute, University of Oxford, Oxfordshire OX1 3RH, United Kingdom and Department of Physics, University of Oxford, Oxfordshire OX1 3RH, United Kingdom.
authors: J
authors: J
authors: Loken
authors: CRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford OX3 7DQ, United Kingdom.
authors: M
authors: M
authors: Partridge
authors: CRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford OX3 7DQ, United Kingdom.
authors: B
authors: B
authors: Jones
authors: Mayo Clinic, Rochester, Minnesota 55905.
authors: J
authors: J
authors: Kruse
authors: Mayo Clinic, Rochester, Minnesota 55905.
authors: R
authors: R
authors: Miller
mesh_terms: D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008579:Meningioma / Q000532:radiotherapy / Q000601:surgery; D008954:Models, Biological; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D016609:Neoplasms, Second Primary / Q000209:etiology*; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D011881:Radiotherapy, Computer-Assisted / Q000009:adverse effects; D018570:Risk Assessment / Q000379:methods*; D012984:Software; D035501:Uncertainty