The sensitivity of radiobiological models in carbon ion radiotherapy (CIRT) and its consequences on the clinical treatment plan: Differences between LEM and MKM models.

Carbon ion radiotherapy (CIRT) relies on relative biological effectiveness (RBE)-weighted dose calculations. Japanese clinics predominantly use the microdosimetric kinetic model (MKM), while European centers utilize the local effect model (LEM). Despite both models estimating RBE-distributions in tissue, their physical and mathematical assumptions differ, leading to significant disparities in RBE-weighted doses. Several European clinics adopted Japanese treatment schedules, necessitating adjustments in dose prescriptions and organ at risk (OAR) constraints. In the context of these two clinically used standards for RBE-weighted dose estimation, the objective of this study was to highlight specific scenarios for which the translations between models diverge, as shortcomings between them can influence clinical decisions. Our aim was to discuss planning strategies minimizing those discrepancies, ultimately striving for more accurate and robust treatments. Evaluations were conducted in a virtual water phantom and patient CT-geometry, optimizing LEM RBE-weighted dose first and recomputing MKM thereafter. Dose-averaged linear energy transfer (LETd) distributions were also assessed. Results demonstrate how various parameters influence LEM/MKM translation. Similar LEM-dose distributions lead to markedly different MKM-dose distributions and variations in LETd. Generally, a homogeneous LEM RBE-weighted dose aligns with lower MKM values in most of the target volume. Nevertheless, paradoxical MKM hotspots may emerge (at the end of the range), potentially influencing clinical outcomes. Therefore, translation between models requires great caution. Understanding the relationship between these two clinical standards enables combining European and Japanese based experiences. The implementation of optimal planning strategies ensures the safety and acceptability of the clinical plan for both models and therefore enhances plan robustness from the RBE-weighted dose and LETd distribution point of view. This study emphasizes the importance of optimal planning strategies and the need for comprehensive CIRT plan quality assessment tools. In situations where simultaneous LEM and MKM computation capabilities are lacking, it can provide guidance in plan design, ultimately contributing to enhanced CIRT outcomes.

Góra J ，Grosshagauer S ，Fossati P ，Mumot M ，Stock M ，Schafasand M ，Carlino A ... -  《Journal of Applied Clinical Medical Physics》

Organs at risk dose constraints in carbon ion radiotherapy at MedAustron: Translations between LEM and MKM RBE models and preliminary clinical results.

Carbon ion radiotherapy (CIRT) treatment planning is based on relative biological effectiveness (RBE) weighted dose calculations. A large amount of clinical evidence for CIRT was collected in Japan with RBE estimated by the modified microdosimetric kinetic model (MKM) while all European centres apply the first version of the local effect model (LEM). Japanese schedules have been used in Europe with adapted prescription dose and organs at risk (OAR) dose constraints. Recently, less conservative adapted LEM constraints have been implemented in clinical practice. The aim of this study was to analyse the new set of LEM dose constraints for brain parenchyma, brainstem and optic system considering both RBE models and evaluating early clinical data. 31 patients receiving CIRT at MedAustron were analysed using the RayStation v9A planning system by recalculating clinical LEM-based plans in MKM. Dose statistics (D1cm3, D5cm3, D0.1cm3, D0.7cm3, D10%, D20%) were extracted for relevant critical OARs. Curve fitting for those values was performed, resulting in linear quadratic translation models. Clinical and radiological toxicity was evaluated. Based on derived fits, currently applied LEM constraints matched recommended MKM constraints with deviations between -8% and +3.9%. For particular cases, data did not follow the expected LEM vs MKM trends resulting in outliers. Radiological (asymptomatic) toxicity was detected in two outlier cases. Respecting LEM constraints does not automatically ensure that MKM constraints are met. Constraints for both RBE models need to be fulfilled for future CIRT patients at MedAustron. Careful selection of planning strategies is essential.

Grosshagauer S ，Fossati P ，Schafasand M ，Carlino A ，Poljanc K ，Radakovits T ，Stock M ，Hug E ，Georg P ，Pelak M ，Góra J ... -  《-》

RBE-weighted dose conversions for patients with recurrent nasopharyngeal carcinoma receiving carbon-ion radiotherapy from the local effect model to the microdosimetric kinetic model.

Zhang L ，Wang W ，Hu J ，Lu J ，Kong L ... -  《Radiation Oncology》

Conversion and validation of rectal constraints for prostate carcinoma receiving hypofractionated carbon-ion radiotherapy with a local effect model.

Wang W ，Li P ，Sheng Y ，Huang Z ，Zhao J ，Hong Z ，Shahnazi K ，Jiang GL ，Zhang Q ... -  《Radiation Oncology》

RBE-weighted dose conversions for carbon ionradiotherapy between microdosimetric kinetic model and local effect model for the targets and organs at risk in prostate carcinoma.

The aim of this study was to establish curves for the conversion of RBE-weighted doses for targets and organs at risk (OARs) from the microdosimetric kinetic model (MKM) calculation to that of the local effect model I (LEM) for carbon ion radiotherapy (CIRT) for prostate carcinoma (PCA). This study was performed in the experimental treatment planning system (eTPS, V8A, Raystation, Sweden), which incorporates both MKM and LEM. CIRT plans from 10 PCA patients were collected. There were 5 steps to establish the curves: (1) design MKM plans in eTPS; (2) recalculate the physical doses from MKM to LEM and create a LEM plan in eTPS; (3) plot the RBE-weighted MKM to LEM conversion curves; (4) convert the MKM rectum constraint dose volume histogram (DVH) from NIRS to a LEM DVH; and (5) compare patients' rectum DVHs and follow-up with the converted constraint DVH. The conversion factors for MKM doses of 0.18 Gy (RBE) to 4.55 Gy (RBE) per fraction to LEM doses were 2.72-1.06. For fraction sizes of >1 Gy (RBE), the conversion factors matched Fossati's curve and for fraction sizes of <1.00 Gy (RBE) the values were on the extrapolated Fossati's curve. A LEM rectum constraint DVH was established. Ten patients' rectum DVHs were all lower than LEM constraint DVHs. No complications were reported clinically. For PCA receiving CIRT, the RBE-weighted doses using MKM for targets and OARs could be converted to LEM doses using conversion curves.

Wang W ，Huang Z ，Sheng Y ，Zhao J ，Shahnazi K ，Zhang Q ，Jiang G ... -  《-》