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Quantifying the Biological Effects of Therapeutic Protons by LET Spectrum Analysis

F Guan

F Guan*, L Bronk , M Kerr , U Titt , X Wang , R Taleei , C Peeler , D Patel , D Mirkovic , D Grosshans , R Mohan , UT MD Anderson Cancer Center, Houston, TX


TU-EF-304-9 (Tuesday, July 14, 2015) 1:45 PM - 3:45 PM Room: 304

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.

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.

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.

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.

Funding Support, Disclosures, and Conflict of Interest: NIH Program Project Grant 2U19CA021239-35

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