title: Uncomplicated and Cancer-Free Control Probability (UCFCP): A new integral approach to treatment plan optimization in photon radiation therapy.
abstract: OBJECTIVE
  Biological treatment plan evaluation does not currently consider second cancer induction from peripheral doses associated to photon radiotherapy. The aim is to propose a methodology to characterize the therapeutic window by means of an integral radiobiological approach, which considers not only Tumour Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) but also Secondary Cancer Probability (SCP).
  
  
  METHODS
  Uncomplicated and Cancer-Free Control Probability (UCFCP) function has been proposed assuming a statistically uncorrelated response for tumour and normal tissues. The Poisson's and Lyman's models were chosen for TCP and NTCP calculations, respectively. SCP was modelled as the summation of risks associated to photon and neutron irradiation of radiosensitive organs. For the medium (>4Gy) and low dose regions, mechanistic and linear secondary cancer risks models were used, respectively. Two conformal and intensity-modulated prostate plans at 15MV (same prescription dose) were selected to illustrate the UCFCP features.
  
  
  RESULTS
  UCFCP exhibits a bell-shaped behaviour with its maximum inside the therapeutic window. SCP values were not different for the plans analysed (∼2.4%) and agreed with published epidemiological results. Therefore, main differences in UCFCP came from differences in rectal NTCP (18% vs 9% for 3D-CRT and IMRT, respectively). According to UCFCP values, the evaluated IMRT plan ranked first.
  
  
  CONCLUSIONS
  The level of SCP was found to be similar to that of NTCP complications which reinforces the importance of considering second cancer risks as part of the possible late sequelae due to treatment. Previous concerns about the effect of peripheral radiation, especially neutrons, in the induction of secondary cancers can be evaluated by quantifying the UCFCP.
authors.affiliation: Instituto de Física, Pontificia Universidad Católica de Chile, Av. Vicuña Mackenna 4880, Macul, Santiago, Chile. Electronic address: bsanchez@fis.puc.cl.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sánchez-Nieto
authors.affiliation: Departament de Física, Universitat Autònoma de Barcelona, Edifici C, Campus UAB E-08193, Bellaterra, Spain. Electronic address: mariateresa.romero@uab.cat.
authors.forename: Maite
authors.initials: M
authors.lastname: Romero-Expósito
authors.affiliation: Servicio de Radiofísica, Hospital Universitario Virgen Macarena, Av. Doctor Fedriani, 3, 41009 Sevilla, Spain. Electronic address: jose.terron.sspa@juntadeandalucia.es.
authors.forename: José A
authors.initials: JA
authors.lastname: Terrón
authors.affiliation: Servicio de Radiofísica, Hospital Universitario Virgen Macarena, Av. Doctor Fedriani, 3, 41009 Sevilla, Spain; Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Av. Doctor Fedriani S/N, 41009 Sevilla, Spain. Electronic address: paco@us.es.
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Doblado
mesh_terms: D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000517:prevention & control*; D016609:Neoplasms, Second Primary / Q000517:prevention & control*; D058958:Organs at Risk; D017785:Photons / Q000627:therapeutic use*; D011336:Probability; D011471:Prostatic Neoplasms / Q000532:radiotherapy; D011835:Radiation Protection / Q000379:methods*; D011874:Radiometry; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D050397:Radiotherapy, Intensity-Modulated; D012007:Rectum / Q000528:radiation effects
keywords: Radiobiological modelling; Secondary cancer probability; Treatment success