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RBE-Weighted Dose Models for Carbon Ion Therapy: In Vitro, in Vivo and in Patient Investigations Towards Modernization of Clinical Practice

S Mein1,2*, B Kopp1,2, C Klein1,2, G Magro3, S Harrabi1, C Karger2, T Haberer1, J Debus1,2, A Abdollahi1,2, I Dokic1,2, A Mairani1,4 (1) Heidelberg Ion-beam Therapy Center (HIT), Heidelberg, DE, (2) German Cancer Research Center (DKFZ), Heidelberg, DE, (3) National Centre of Oncological Hadrontherapy (CNAO), Pavia, Italy


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

Room: AAPM ePoster Library

Purpose: Carbon ion therapy treatment planning is conducted with assumptions for a limited number of tissue types and models for effective dose. Here, we comprehensively assess relative biological effectiveness (RBE) in carbon ion therapy and associated models towards the modernization of current clinical practice in effective dose calculation.

Methods: Using two human (A549, H460) and two mouse (B16, Renca) tumor cell lines, clonogenic cell survival assay was performed for examination of changes in RBE along the full range of clinical-like spread-out Bragg peak (SOBP) fields. Prediction power of the local effect model (LEM1 and LEM4) and the modified microdosimetric kinetic model (mMKM) was assessed. Experimentation and analysis were carried out in the frame of a multi-dimensional endpoint study for clinically relevant ranges of physical dose (D), dose-averaged linear energy transfer (LETd) and base-line photon radio-sensitivity (a/ß)x. Additionally, predictions were compared against previously reported RBE measurements in vivo and surveyed in patient cases.

Results: RBE model prediction performance varied amongst the investigated perspectives, with mMKM prediction exhibiting superior agreement with measurements both in vitro and in vivo across the three investigated endpoints. LEM1 and LEM4 performed their best in the highest LET conditions but yielded over- and underestimations in low/mid-range LET conditions, respectively, as demonstrated by comparison with measurements. Additionally, the analysis of patient treatment plans revealed substantial variability across the investigated models (±20-30% uncertainty), largely dependent on the selected model, as well as absolute values for input tissue parameters ax and ßx.

Conclusion: RBE dependencies in vitro, in vivo and in silico were investigated with respect to various clinically relevant endpoints in the context of tumor-specific tissue radio-sensitivity assignment and accurate RBE modeling. Discovered model trends and performances advocate upgrading current treatment planning schemes in carbon ion therapy and call for verification via clinical outcome analysis with large patient cohorts.


Not Applicable / None Entered.


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

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