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Title: TU-EF-304-09: Quantifying the Biological Effects of Therapeutic Protons by LET Spectrum Analysis

Journal Article · · Medical Physics
DOI:https://doi.org/10.1118/1.4925664· OSTI ID:22565369

Purpose: To correlate in vitro cell kill with linear energy transfer (LET) spectra using Monte Carlo simulations and knowledge obtained from previous high-throughput in vitro proton relative biological effectiveness (RBE) measurements. Methods: The Monte Carlo simulation toolkit Geant4 was used to design the experimental setups and perform the dose, dose-averaged LET, and LET spectra calculations. The clonogenic assay was performed using the H460 lung cancer cell line in standard 6-well plates. Using two different experimental setups, the same dose and dose-averaged LET (12.6 keV/µm) was delivered to the cell layer; however, each respective energy or LET spectrum was different. We quantified the dose contributions from high-LET (≥10 keV/µm, threshold determined by previous RBE measurements) events in the LET spectra separately for these two setups as 39% and 53%. 8 dose levels with 1 Gy increments were delivered. The photon reference irradiation was performed using 6 MV x-rays from a LINAC. Results: The survival curves showed that both proton irradiations demonstrated an increased RBE compared to the reference photon irradiation. Within the proton-irradiated cells, the setup with 53% dose contribution from high-LET events exhibited the higher biological effectiveness. Conclusion: The experimental results indicate that the dose-averaged LET may not be an appropriate indicator to quantify the biological effects of protons when the LET spectrum is broad enough to contain both low- and high-LET events. Incorporating the LET spectrum distribution into robust intensity-modulated proton therapy optimization planning may provide more accurate biological dose distribution than using the dose-averaged LET. NIH Program Project Grant 2U19CA021239-35.

OSTI ID:
22565369
Journal Information:
Medical Physics, Vol. 42, Issue 6; Other Information: (c) 2015 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA); ISSN 0094-2405
Country of Publication:
United States
Language:
English