Cell survival and radiosensitisation: modulation of the linear and quadratic parameters of the LQ model (Review)

Nicolaas A P Franken, Arlene L Oei, H Petra Kok, Hans M Rodermond, Peter Sminia, Johannes Crezee, Lukas J A Stalpers, Gerrit W Barendsen

Research output: Contribution to journalReview articleAcademicpeer-review

Abstract

The linear-quadratic model (LQ model) provides a biologically plausible and experimentally established method to quantitatively describe the dose-response to irradiation in terms of clonogenic survival. In the basic LQ formula, the clonogenic surviving fraction Sd/S₀ following a radiation dose d (Gy) is described by an inverse exponential approximation: Sd/S₀ = e-(αd+βd²), wherein α and β are experimentally derived parameters for the linear and quadratic terms, respectively. Radiation is often combined with other agents to achieve radiosensitisation. In this study, we reviewed radiation enhancement ratios of hyperthermia (HT), halogenated pyrimidines (HPs), various cytostatic drugs and poly(ADP-ribose) polymerase‑1 (PARP1) inhibitors expressed in the parameters α and β derived from cell survival curves of various mammalian cell cultures. A significant change in the α/β ratio is of direct clinical interest for the selection of optimal fractionation schedules in radiation oncology, influencing the dose per fraction, dose fractionation and dose rate in combined treatments. The α/β ratio may increase by a mutually independent increase of α or decrease of β. The results demonstrated that the different agents increased the values of both α and β. However, depending on culture conditions, both parameters can also be separately influenced. Moreover, it appeared that radiosensitisation was more effective in radioresistant cell lines than in radiosensitive cell lines. Furthermore, radiosensitisation is also dependent on the cell cycle stage, such as the plateau or exponentially growing phase, as well as on post-treatment plating conditions. The LQ model provides a useful tool in the quantification of the effects of radiosensitising agents. These insights will help optimize fractionation schedules in multimodality treatments.

Original languageEnglish
Pages (from-to)1501-1515
Number of pages15
JournalInternational Journal of Oncology
Volume42
Issue number5
DOIs
Publication statusPublished - May 2013

Cite this

Franken, Nicolaas A P ; Oei, Arlene L ; Kok, H Petra ; Rodermond, Hans M ; Sminia, Peter ; Crezee, Johannes ; Stalpers, Lukas J A ; Barendsen, Gerrit W. / Cell survival and radiosensitisation : modulation of the linear and quadratic parameters of the LQ model (Review). In: International Journal of Oncology. 2013 ; Vol. 42, No. 5. pp. 1501-1515.
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abstract = "The linear-quadratic model (LQ model) provides a biologically plausible and experimentally established method to quantitatively describe the dose-response to irradiation in terms of clonogenic survival. In the basic LQ formula, the clonogenic surviving fraction Sd/S₀ following a radiation dose d (Gy) is described by an inverse exponential approximation: Sd/S₀ = e-(αd+βd²), wherein α and β are experimentally derived parameters for the linear and quadratic terms, respectively. Radiation is often combined with other agents to achieve radiosensitisation. In this study, we reviewed radiation enhancement ratios of hyperthermia (HT), halogenated pyrimidines (HPs), various cytostatic drugs and poly(ADP-ribose) polymerase‑1 (PARP1) inhibitors expressed in the parameters α and β derived from cell survival curves of various mammalian cell cultures. A significant change in the α/β ratio is of direct clinical interest for the selection of optimal fractionation schedules in radiation oncology, influencing the dose per fraction, dose fractionation and dose rate in combined treatments. The α/β ratio may increase by a mutually independent increase of α or decrease of β. The results demonstrated that the different agents increased the values of both α and β. However, depending on culture conditions, both parameters can also be separately influenced. Moreover, it appeared that radiosensitisation was more effective in radioresistant cell lines than in radiosensitive cell lines. Furthermore, radiosensitisation is also dependent on the cell cycle stage, such as the plateau or exponentially growing phase, as well as on post-treatment plating conditions. The LQ model provides a useful tool in the quantification of the effects of radiosensitising agents. These insights will help optimize fractionation schedules in multimodality treatments.",
keywords = "Cell Survival, Combined Modality Therapy, Humans, Linear Models, Models, Theoretical, Neoplasms/radiotherapy, Poly(ADP-ribose) Polymerases/therapeutic use, Radiation Dosage, Radiation Tolerance, Radiation-Sensitizing Agents/therapeutic use",
author = "Franken, {Nicolaas A P} and Oei, {Arlene L} and Kok, {H Petra} and Rodermond, {Hans M} and Peter Sminia and Johannes Crezee and Stalpers, {Lukas J A} and Barendsen, {Gerrit W}",
year = "2013",
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Franken, NAP, Oei, AL, Kok, HP, Rodermond, HM, Sminia, P, Crezee, J, Stalpers, LJA & Barendsen, GW 2013, 'Cell survival and radiosensitisation: modulation of the linear and quadratic parameters of the LQ model (Review)' International Journal of Oncology, vol. 42, no. 5, pp. 1501-1515. https://doi.org/10.3892/ijo.2013.1857

Cell survival and radiosensitisation : modulation of the linear and quadratic parameters of the LQ model (Review). / Franken, Nicolaas A P; Oei, Arlene L; Kok, H Petra; Rodermond, Hans M; Sminia, Peter; Crezee, Johannes; Stalpers, Lukas J A; Barendsen, Gerrit W.

In: International Journal of Oncology, Vol. 42, No. 5, 05.2013, p. 1501-1515.

Research output: Contribution to journalReview articleAcademicpeer-review

TY - JOUR

T1 - Cell survival and radiosensitisation

T2 - modulation of the linear and quadratic parameters of the LQ model (Review)

AU - Franken, Nicolaas A P

AU - Oei, Arlene L

AU - Kok, H Petra

AU - Rodermond, Hans M

AU - Sminia, Peter

AU - Crezee, Johannes

AU - Stalpers, Lukas J A

AU - Barendsen, Gerrit W

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N2 - The linear-quadratic model (LQ model) provides a biologically plausible and experimentally established method to quantitatively describe the dose-response to irradiation in terms of clonogenic survival. In the basic LQ formula, the clonogenic surviving fraction Sd/S₀ following a radiation dose d (Gy) is described by an inverse exponential approximation: Sd/S₀ = e-(αd+βd²), wherein α and β are experimentally derived parameters for the linear and quadratic terms, respectively. Radiation is often combined with other agents to achieve radiosensitisation. In this study, we reviewed radiation enhancement ratios of hyperthermia (HT), halogenated pyrimidines (HPs), various cytostatic drugs and poly(ADP-ribose) polymerase‑1 (PARP1) inhibitors expressed in the parameters α and β derived from cell survival curves of various mammalian cell cultures. A significant change in the α/β ratio is of direct clinical interest for the selection of optimal fractionation schedules in radiation oncology, influencing the dose per fraction, dose fractionation and dose rate in combined treatments. The α/β ratio may increase by a mutually independent increase of α or decrease of β. The results demonstrated that the different agents increased the values of both α and β. However, depending on culture conditions, both parameters can also be separately influenced. Moreover, it appeared that radiosensitisation was more effective in radioresistant cell lines than in radiosensitive cell lines. Furthermore, radiosensitisation is also dependent on the cell cycle stage, such as the plateau or exponentially growing phase, as well as on post-treatment plating conditions. The LQ model provides a useful tool in the quantification of the effects of radiosensitising agents. These insights will help optimize fractionation schedules in multimodality treatments.

AB - The linear-quadratic model (LQ model) provides a biologically plausible and experimentally established method to quantitatively describe the dose-response to irradiation in terms of clonogenic survival. In the basic LQ formula, the clonogenic surviving fraction Sd/S₀ following a radiation dose d (Gy) is described by an inverse exponential approximation: Sd/S₀ = e-(αd+βd²), wherein α and β are experimentally derived parameters for the linear and quadratic terms, respectively. Radiation is often combined with other agents to achieve radiosensitisation. In this study, we reviewed radiation enhancement ratios of hyperthermia (HT), halogenated pyrimidines (HPs), various cytostatic drugs and poly(ADP-ribose) polymerase‑1 (PARP1) inhibitors expressed in the parameters α and β derived from cell survival curves of various mammalian cell cultures. A significant change in the α/β ratio is of direct clinical interest for the selection of optimal fractionation schedules in radiation oncology, influencing the dose per fraction, dose fractionation and dose rate in combined treatments. The α/β ratio may increase by a mutually independent increase of α or decrease of β. The results demonstrated that the different agents increased the values of both α and β. However, depending on culture conditions, both parameters can also be separately influenced. Moreover, it appeared that radiosensitisation was more effective in radioresistant cell lines than in radiosensitive cell lines. Furthermore, radiosensitisation is also dependent on the cell cycle stage, such as the plateau or exponentially growing phase, as well as on post-treatment plating conditions. The LQ model provides a useful tool in the quantification of the effects of radiosensitising agents. These insights will help optimize fractionation schedules in multimodality treatments.

KW - Cell Survival

KW - Combined Modality Therapy

KW - Humans

KW - Linear Models

KW - Models, Theoretical

KW - Neoplasms/radiotherapy

KW - Poly(ADP-ribose) Polymerases/therapeutic use

KW - Radiation Dosage

KW - Radiation Tolerance

KW - Radiation-Sensitizing Agents/therapeutic use

U2 - 10.3892/ijo.2013.1857

DO - 10.3892/ijo.2013.1857

M3 - Review article

VL - 42

SP - 1501

EP - 1515

JO - International Journal of Oncology

JF - International Journal of Oncology

SN - 1019-6439

IS - 5

ER -