title: Impact of dose and sensitivity heterogeneity on TCP.
abstract: This present paper presents an analytical description and numerical simulations of the influence of macroscopic intercell dose variations and intercell sensitivity variations on the probability of controlling the tumour. Computer simulations of tumour control probability accounting for heterogeneity in dose and radiation sensitivity were performed. An analytical expression for tumor control probability accounting for heterogeneity in sensitivity was also proposed and validated against simulations. The results show good agreement between numerical simulations and the calculated TCP using the proposed analytical expression for the case of a heterogeneous dose and sensitivity distributions. When the intratumour variations of dose and sensitivity are taken into account, the total dose required for achieving the same level of control as for the case of homogeneous distribution is only slightly higher, the influence of the variations in the two factors taken into account being additive. The results of this study show that the interplay between cell or tumour variation in the sensitivity to radiation and the inherent heterogeneity in dose distribution is highly complex and therefore should be taken into account when predicting the outcome of a given treatment in terms of tumor control probability.
authors.affiliation: Medical Radiation Physics, Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Kristin
authors.initials: K
authors.lastname: Wiklund
authors.affiliation: Medical Radiation Physics, Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Iuliana
authors.initials: I
authors.lastname: Toma-Dasu
authors.affiliation: Department of Oncology and Pathology, Karolinska Institutet, P.O. Box 260, 171 76 Stockholm, Sweden.
authors.forename: Bengt K
authors.initials: BK
authors.lastname: Lind
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008962:Models, Theoretical; D009369:Neoplasms / Q000473:pathology* / Q000532:radiotherapy*; D016012:Poisson Distribution; D011336:Probability; D011836:Radiation Tolerance; D011878:Radiotherapy / Q000379:methods; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D015203:Reproducibility of Results