title: On differences in radiosensitivity estimation: TCP experiments versus survival curves. A theoretical study.
abstract: We have compared two methods of estimating the cellular radiosensitivity of a heterogeneous tumour, namely, via cell-survival and via tumour control probability (TCP) pseudo-experiments. It is assumed that there exists intra-tumour variability in radiosensitivity and that the tumour consists predominantly of radiosensitive cells and a small number of radio-resistant cells.Using a multi-component, linear-quadratic (LQ) model of cell kill, a pseudo-experimental cell-survival versus dose curve is derived. This curve is then fitted with a mono-component LQ model describing the response of a homogeneous cell population. For the assumed variation in radiosensitivity it is shown that the composite pseudo-experimental survival curve is well approximated by the survival curve of cells with uniform radiosensitivity.For the same initial cell radiosensitivity distribution several pseudo-experimental TCP curves are simulated corresponding to different fractionation regimes. The TCP model used accounts for clonogen proliferation during a fractionated treatment. The set of simulated TCP curves is then fitted with a mono-component TCP model. As in the cell survival experiment the fit with a mono-component model assuming uniform radiosensitivity is shown to be highly acceptable.However, the best-fit values of cellular radiosensitivity produced via the two methods are very different. The cell-survival pseudo-experiment yields a high radiosensitivity value, while the TCP pseudo-experiment shows that the dose-response is dominated by the most resistant sub-population in the tumour, even when this is just a small fraction of the total.
authors.affiliation: Radiation Oncology, Ospedale 'Sacro Cuore-don Calabria', Negrar (VR), Italy.
authors.forename: Pavel
authors.initials: P
authors.lastname: Stavrev
authors.forename: Nadejda
authors.initials: N
authors.lastname: Stavreva
authors.forename: Ruggero
authors.initials: R
authors.lastname: Ruggieri
authors.forename: Alan
authors.initials: A
authors.lastname: Nahum
mesh_terms: D002470:Cell Survival / Q000528:radiation effects; D019583:Dose Fractionation, Radiation; D006801:Humans; D016014:Linear Models; D008954:Models, Biological; D008962:Models, Theoretical; D009369:Neoplasms / Q000473:pathology* / Q000532:radiotherapy*; D011836:Radiation Tolerance