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Experimental Validation of the Enhancement of Biological Effects Using Enhanced-LET Proton Therapy

D Ma*, M Kerr , L Bronk , X Wang , N Sahoo , D Grosshans , R Mohan , F Guan , UT MD Anderson Cancer Center, Houston, TX


(Tuesday, 7/16/2019) 1:15 PM - 1:45 PM

Room: Exhibit Hall | Forum 4

Purpose: To experimentally validate the hypothesis that increasing the intensity of low-energy protons with high linear energy transfer (LET) in target tumors can enhance the biological effects therein.

Methods: The depth dose and dose-averaged LET (LETd) in a water phantom for scanned proton beams have been pre-calculated using Geant4. An in-house Python code was used to perform physical dose optimizations to generate desired dose profiles and resultant LETd. A flat and a downslope spread-out Bragg peak (SOBP) dose distributions within a 4-cm wide target (5.8–9.8 cm) were generated separately. Two opposed flat or downslope fields were then used to generate a uniform target dose distribution. Using downslope fields can enhance the target LETd values due to the increased intensity of low-energy protons. The high-throughput method was adopted to spatially map the biological effects by employing a custom multi-step irradiation jig and 96-well plates. The middle eight columns of a 96-well plate were placed within the uniform dose region. The clonogenic survival was selected as the biological endpoint. The lung cancer H460 cells were irradiated. The Cs-137 photon source was used as the reference radiation.

Results: For proton irradiations, the cell surviving fractions for the middle six columns of the 96-well plates were averaged. At 2 Gy, the mean surviving fraction is 0.61±0.01, 0.50±0.02 and 0.45±0.02 using photons, opposed flat proton fields (LETd = 3.0 keV/μm), and opposed downslope proton fields (LETd = 4.6 keV/μm). At 4 Gy, the mean cell surviving fraction is 0.16±0.01, 0.14±0.01, and 0.08±0.01, respectively.

Conclusion: Two opposed downslope dose fields are more biologically effective in the target tumor in spite of the increased out-of-target dose. This beam delivery strategy has the potential for LET escalation in clinical practice, e.g., treatment for prostate cancer patients where parallel opposed fields are typically used.


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