Abstract
Purpose: To determine a self-consistent set of radiobiological parameters in prostate cancer. Methods and Materials: A method to estimate intrinsic radiosensitivity (α), fractionation sensitivity (α/β), repopulation doubling time, number of clonogens, and kick-off time for accelerated repopulation of prostate cancer has been developed. Based on the generalized linear-quadratic model and without assuming the isoeffective hypothesis, the potential applications of the method were investigated using the clinical outcome of biochemical relapse-free survival recently reviewed in the literature. The strengths and limitations of the method, regarding the fitted parameters and 95% confidence intervals (CIs), are also discussed. Results: Our best estimate of α/β is 2.96 Gy (95% CI 2.41-3.53 Gy). The corresponding α value is 0.16 Gy-1 (95% CI 0.14-0.18 Gy -1), which is compatible with a realistic number of clonogens: 6.5 × 106 (95% CI 1.5 × 106-2.1 × 10 7). The estimated cell doubling time is 5.1 days (95% CI 4.2-7.2 days), very low if compared with that reported in the literature. This corresponds to the dose required to offset the repopulation occurring in 1 day of 0.52 Gy/d (95% CI 0.32-0.68 Gy/d). However, a long kick-off time of 31 days (95% CI 22-41 days) from the start of radiation therapy was found. Conclusion: The proposed analytic/graphic method has allowed the fitting of clinical data, providing a self-consistent set of radiobiological parameters for prostate cancer. With our analysis we confirm a low value for α/β with a correspondingly high value of intrinsic radiosensitivity, a realistic average number of clonogens, a long kick-off time for accelerated repopulation, and a surprisingly fast repopulation that suggests the involvement of subpopulations of specifically tumorigenic stem cells during continuing radiation therapy.
| Original language | English |
|---|---|
| Journal | International Journal of Radiation Oncology Biology Physics |
| Volume | 85 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Apr 1 2013 |
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ASJC Scopus subject areas
- Oncology
- Radiology Nuclear Medicine and imaging
- Radiation
- Cancer Research
Cite this
Estimation of a self-consistent set of radiobiological parameters from hypofractionated versus standard radiation therapy of prostate cancer. / Pedicini, Piernicola; Strigari, Lidia; Benassi, Marcello.
In: International Journal of Radiation Oncology Biology Physics, Vol. 85, No. 5, 01.04.2013.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Estimation of a self-consistent set of radiobiological parameters from hypofractionated versus standard radiation therapy of prostate cancer
AU - Pedicini, Piernicola
AU - Strigari, Lidia
AU - Benassi, Marcello
PY - 2013/4/1
Y1 - 2013/4/1
N2 - Purpose: To determine a self-consistent set of radiobiological parameters in prostate cancer. Methods and Materials: A method to estimate intrinsic radiosensitivity (α), fractionation sensitivity (α/β), repopulation doubling time, number of clonogens, and kick-off time for accelerated repopulation of prostate cancer has been developed. Based on the generalized linear-quadratic model and without assuming the isoeffective hypothesis, the potential applications of the method were investigated using the clinical outcome of biochemical relapse-free survival recently reviewed in the literature. The strengths and limitations of the method, regarding the fitted parameters and 95% confidence intervals (CIs), are also discussed. Results: Our best estimate of α/β is 2.96 Gy (95% CI 2.41-3.53 Gy). The corresponding α value is 0.16 Gy-1 (95% CI 0.14-0.18 Gy -1), which is compatible with a realistic number of clonogens: 6.5 × 106 (95% CI 1.5 × 106-2.1 × 10 7). The estimated cell doubling time is 5.1 days (95% CI 4.2-7.2 days), very low if compared with that reported in the literature. This corresponds to the dose required to offset the repopulation occurring in 1 day of 0.52 Gy/d (95% CI 0.32-0.68 Gy/d). However, a long kick-off time of 31 days (95% CI 22-41 days) from the start of radiation therapy was found. Conclusion: The proposed analytic/graphic method has allowed the fitting of clinical data, providing a self-consistent set of radiobiological parameters for prostate cancer. With our analysis we confirm a low value for α/β with a correspondingly high value of intrinsic radiosensitivity, a realistic average number of clonogens, a long kick-off time for accelerated repopulation, and a surprisingly fast repopulation that suggests the involvement of subpopulations of specifically tumorigenic stem cells during continuing radiation therapy.
AB - Purpose: To determine a self-consistent set of radiobiological parameters in prostate cancer. Methods and Materials: A method to estimate intrinsic radiosensitivity (α), fractionation sensitivity (α/β), repopulation doubling time, number of clonogens, and kick-off time for accelerated repopulation of prostate cancer has been developed. Based on the generalized linear-quadratic model and without assuming the isoeffective hypothesis, the potential applications of the method were investigated using the clinical outcome of biochemical relapse-free survival recently reviewed in the literature. The strengths and limitations of the method, regarding the fitted parameters and 95% confidence intervals (CIs), are also discussed. Results: Our best estimate of α/β is 2.96 Gy (95% CI 2.41-3.53 Gy). The corresponding α value is 0.16 Gy-1 (95% CI 0.14-0.18 Gy -1), which is compatible with a realistic number of clonogens: 6.5 × 106 (95% CI 1.5 × 106-2.1 × 10 7). The estimated cell doubling time is 5.1 days (95% CI 4.2-7.2 days), very low if compared with that reported in the literature. This corresponds to the dose required to offset the repopulation occurring in 1 day of 0.52 Gy/d (95% CI 0.32-0.68 Gy/d). However, a long kick-off time of 31 days (95% CI 22-41 days) from the start of radiation therapy was found. Conclusion: The proposed analytic/graphic method has allowed the fitting of clinical data, providing a self-consistent set of radiobiological parameters for prostate cancer. With our analysis we confirm a low value for α/β with a correspondingly high value of intrinsic radiosensitivity, a realistic average number of clonogens, a long kick-off time for accelerated repopulation, and a surprisingly fast repopulation that suggests the involvement of subpopulations of specifically tumorigenic stem cells during continuing radiation therapy.
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U2 - 10.1016/j.ijrobp.2012.11.033
DO - 10.1016/j.ijrobp.2012.11.033
M3 - Article
VL - 85
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
SN - 0360-3016
IS - 5
ER -