Dose rate
Effect of high dose per pulse flattening filter-free beams on cancer cell survival

https://doi.org/10.1016/j.radonc.2011.05.072Get rights and content

Abstract

Purpose

To investigate if there is a statistically significant difference in cancer cell survival using a high dose per pulse flattening filter-free (FFF) beam compared to a standard flattened beam.

Material and methods

To validate the radiobiological effect of the flattened and FFF beam, two glioblastoma cell lines were treated with either 5 or 10 Gy using different dose rates. Dose verification was performed and colony formation assays were carried out. To compare the predictability of our data, radiobiological models were included.

Results

The results presented here demonstrate that irradiation of glioblastoma cell lines using the FFF beam is more efficient in reducing clonogenic cell survival than the standard flattened beam, an effect which becomes more significant the higher the single dose. Interestingly, in our experimental setting, the radiobiological effect of the FFF beam is dependent on dose per pulse rather than on delivery time. The used radiobiological models are able to describe the observed dose rate dependency between 6 and 24 Gy/min.

Conclusion

The results presented here show that dose per pulse might become a crucial factor which influences cancer cell survival. Using high dose rates, currently used radiobiological models as well as molecular mechanisms involved urgently need to be re-examined.

Section snippets

Cell culture

The human glioblastoma cell lines T98G, expressing mutated p53, and U87-MG, expressing functional p53, were purchased from the American Type Culture Collection (ATCC). The cells were maintained in monolayer culture in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% FBS, 1% l-Glutamine and 1% Penicillin/Streptomycin. All cells were grown in a humidified atmosphere of 5% CO2 at 37 °C.

Irradiation

Using the TrueBeam STx linear accelerator (Varian Medical Systems, Palo Alto, CA, USA) a pulsed

Increased treatment time increases tumour cell survival

For our study we used flattened as well as FFF beams generated by the TrueBeam STx linear accelerator. Since these two beams differ in their beam profile, we first performed experiments to verify the accuracy of dose application to our in vitro model system as well as the standard deviations within treatments. Two established glioblastoma cell lines, T98G and U87-MG, were irradiated with either 5 or 10 Gy at 10 MV using different dose rates: 20, 400, or 2400 cGy/min. Due to technical limitations

Discussion

The results presented here show that clonogenic survival is statistically reduced if the total dose is delivered with a higher dose per pulse. Indeed, cells irradiated using either the X10 or X10FFF beam show a difference in clonogenic survival which can be explained by the higher dose per pulse delivered by the X10FFF.

Radiation-induced double-strand breaks (DSB) are the most harmful lesions that arise after irradiation because of their impact on genome stability and cell survival [17]. The

Conflict of interest statement

The authors indicated no potential conflicts of interest.

Acknowledgements

We thank Jack Fowler for helpful suggestions and insightful comments, and Michelle Brown for scientific editing. This work was supported by the Department of Radiation Oncology, University Hospital of Zurich, by a research grant from Varian Medical Systems, Inc. (Palo Alto, California), and the foundation Hartmann Mueller (K.Z.).

References (26)

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