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Advancing RBE Models for High LET Particles Beyond the Linear-Quadratic Model

O Vassiliev*, C Peterson, D Grosshans, R Mohan, UT MD Anderson Cancer Center, Houston, TX


(Sunday, 7/12/2020)   [Eastern Time (GMT-4)]

Room: AAPM ePoster Library


Experimental data show that cell survival curves attain a constant slope as the dose increases. Several models of this property have been proposed. None offers an insight into the mechanism. Instead, a constant slope is set rather artificially. The Non-Poisson Multi-Hit model (NPMH) is an exception. It predicts a constant slope and attributes it to the statistics of energy depositions in a subcellular target volume. We tested a simple version of the model for consistency with experimental data for high LET ions.


We used published experimental cell survival data to test a version of the NPMH model, in which the microdosimetric quantity yF is replaced with LET. The data was for ions: ²H, ³He, 4He, ¹²C, ¹6O, ¹?F; the LET range was 40 to 600 keV/µm. We fitted the model to nine cell survival curves simultaneously. We used an innovative optimization technique, in which the hard constraint S(0)=1 was removed to account for uncertainties in the plating efficiency. The correct normalization was restored after an optimal solution was found.


The model agreed with experimental data. The formula for cell survival in this version of the model was as follows: S(D)=[1+ab×exp(-b)]×exp[-a+a×exp(-b)], where a=DA/LET, b=LET/L0. It has two parameters, A and L0. The best fit values were A=575 keV/µm/Gy, L0=148 keV/µm. Although very simple, the formula predicted correctly how the shape of a survival curve changes with increasing LET: the shoulder gradually disappears, and at very high LETs the slope starts to decrease. The RBE versus LET curve had the well known shape that for low doses has a maximum around 200 keV/µm.


With only two parameters, the NPMH model achieved agreement with experimental data for several ions, over a broad LET range. It predicted correctly the shape of cell survival curves and how it changes with LET.

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Funding Support, Disclosures, and Conflict of Interest: The study was supported by NIH/NCI grant R01 CA225961


Heavy Ions, Radiobiology


TH- Radiobiology(RBio)/Biology(Bio): RBio- Particle therapy- other

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