Clonogenic survival and relative biological effectiveness of pancreatic ductal adenocarcinoma under pristine and spread-out Bragg peak irradiation with protons and carbon ions.

Denbeigh, J. M.; Kneringer, A.; Radstake, W. E.; Parisi, A.; Barna, S.; Hartzell, S.; Kerschbaum-Gruber, S.; Dias, A. B.; Fischer, P.; Fuchs, H.; Slade, D. M.; Georg, D.; Beltran, C. J.

doi:10.64898/2026.09.30.754978

bioRxiv · 10.64898/2026.09.30.754978

Clonogenic survival and relative biological effectiveness of pancreatic ductal adenocarcinoma under pristine and spread-out Bragg peak irradiation with protons and carbon ions.

Denbeigh, J. M.·Kneringer, A.·Radstake, W. E.·Parisi, A.·Barna, S.·Hartzell, S.·Kerschbaum-Gruber, S.·Dias, A. B.·Fischer, P.·Fuchs, H.·Slade, D. M.·Georg, D.·Beltran, C. J.

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Abstract

Biological effectiveness in ion therapy varies with radiation quality and biological context, yet cancer cell response data acquired under well-characterized physical conditions remain limited. We investigated clonogenic survival and relative biological effectiveness (RBE) in PANC-1 and BxPC-3 pancreatic ductal adenocarcinoma (PDAC) cells irradiated at four positions along pristine 180.1 MeV proton and 352.4 MeV/u carbon ion Bragg curves, with 4 cm spread-out Bragg peak (SOBP) irradiation included as a clinically relevant comparison. Cell plane positioning and dose were verified in a water-tank system using an Advanced Markus ionization chamber, and Monte Carlo simulations using TOPAS provided dose-averaged linear energy transfer (LETD) and microdosimetric quantities. RBE was calculated relative to 200 kVp X-rays using the linear-quadratic survival model. Across the sampled pristine beam positions, spanning LETD values of approximately 1-9 keV/m for protons and 12-163 keV/m for carbon ions, RBE increased with LETD. Proton RBE10 exceeded the conventional clinical value of 1.1 at distal positions, whereas carbon ion RBE10 increased from 2.3 to 5.2 in PANC-1 and from 1.3 to 3.7 in BxPC-3, with larger differences between cell lines observed near the Bragg peak. SOBP measurements showed different biological responses across field conditions despite comparable LETD. These physically characterized survival data provide PDAC-relevant benchmarks for evaluating whether RBE models reproduce biological responses across pristine and SOBP irradiation conditions, supporting the future integration of radiation-quality-dependent effects into ion planning.

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Denbeigh, J. M., Kneringer, A., Radstake, W. E., Parisi, A., Barna, S., Hartzell, S., Kerschbaum-Gruber, S., Dias, A. B., Fischer, P., Fuchs, H., Slade, D. M., Georg, D., Beltran, C. J.. 2026-10-01. Clonogenic survival and relative biological effectiveness of pancreatic ductal adenocarcinoma under pristine and spread-out Bragg peak irradiation with protons and carbon ions.. https://doi.org/10.64898/2026.09.30.754978

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