RBE-weighted dose in carbon ion therapy for ACC patients: Impact of the RBE model translation on treatment outcomes.

The purpose of this study is to assess the impact of the conversion scheme for relative biological effectiveness (RBE)-weighted dose (DRBE), implemented at our center, on treatment outcomes of adenoid cystic carcinoma (ACC) patients. Treatment plans of 78 ACC patients, optimized with the Local Effect Model (LEM), were recalculated with the modified Microdosimetric Kinetic Model (mMKM). DRBE to 95%, 50% and 2% (DV%) of the clinical target volume (CTV), were selected as relevant parameters to compare LEM and mMKM DRBE. The pattern of failure of ACC treatments was analyzed in relation to uncertainties involved in the DRBE translation methodology. mMKM recalculations of LEM plans, optimized to a prescription dose of 68.8 Gy(RBE), showed a D50% 8% higher, on average, than the expected value (60.8 Gy(RBE)), closer to the most frequently used mMKM prescription DRBE (64 Gy(RBE)). D95% and D2% deviations, with respect to the optimization goals in the two RBE systems, increased of 0.5% and 14.2%, respectively, due to the steeper mMKM RBE variation along the beam path. Local recurrences were mainly (63%) reported in areas where CTV coverage was not satisfactory in the original LEM plan and the mMKM analysis showed that OARs constraints were too conservative. No case of local recurrence could be explained by inadequate mMKM target coverage that was not already present in the LEM plan. New constraints have been defined for optic pathways and brainstem to improve target coverage with no expected increase in tissue complications.

Molinelli S ，Bonora M ，Magro G ，Casale S ，Dale JE ，Fossati P ，Hasegawa A ，Mirandola A ，Ronchi S ，Russo S ，Preda L ，Valvo F ，Orecchia R ，Ciocca M ，Vischioni B ... -  《-》

Dose prescription in carbon ion radiotherapy: How to compare two different RBE-weighted dose calculation systems.

In carbon ion radiotherapy (CIRT), the use of different relative biological effectiveness (RBE) models in the RBE-weighted dose (DRBE) calculation can lead to deviations in the physical dose (Dphy) delivered to the patient. Our aim is to reduce target Dphy deviations by converting prescription dose values. Planning data of patients treated at the National Institute of Radiological Sciences (NIRS) were collected, with prescribed doses per fraction ranging from 3.6Gy (RBE) to 4.6Gy (RBE), according to the Japanese semi-empirical model. The Dphy was Monte Carlo (MC) re-calculated simulating the NIRS beamline. The local effect model (LEM)_I was then applied to estimate DRBE. Target median DRBE ratios between MC+LEM_I and NIRS plans determined correction factors for the conversion of prescription doses. Plans were re-optimized in a LEM_I-based commercial system, prescribing the NIRS uncorrected and corrected DRBE. The MC+LEM_I target median DRBE was respectively 15% and 5% higher than the NIRS reference, for the lowest and highest dose levels. Uncorrected DRBE prescription resulted in significantly lower target Dphy in re-optimized plans, with respect to NIRS plans. Prescription dose conversion factors could minimize target physical dose variations due to the use of different radiobiological models in the calculation of CIRT RBE-weighted dose.

Molinelli S ，Magro G ，Mairani A ，Matsufuji N ，Kanematsu N ，Inaniwa T ，Mirandola A ，Russo S ，Mastella E ，Hasegawa A ，Tsuji H ，Yamada S ，Vischioni B ，Vitolo V ，Ferrari A ，Ciocca M ，Kamada T ，Tsujii H ，Orecchia R ，Fossati P ... -  《-》

Rapid effective dose calculation for raster-scanning (4)He ion therapy with the modified microdosimetric kinetic model (mMKM).

To develop and verify effective dose (DRBE) calculation in 4He ion beam therapy based on the modified microdosimetric kinetic model (mMKM) and evaluate the bio-sensitivity of mMKM-based plans to clinical parameters using a fast analytical dose engine. Mixed radiation field particle spectra (MRFS) databases have been generated with Monte-Carlo (MC) simulations for 4He-ion beams. Relative biological effectiveness (RBE) and DRBE calculation using MRFS were established within a fast analytical engine. Spread-out Bragg-Peaks (SOBPs) in water were optimized for two dose levels and two tissue types with photon linear-quadratic model parameters αph, βph, and (α/β)ph to verify MRFS-derived database implementation against computations with MC-generated mixed-field α and β databases. Bio-sensitivity of the SOBPs was investigated by varying absolute values of βph, while keeping (α/β)ph constant. Additionally, dose, dose-averaged linear energy transfer, and bio-sensitivity were investigated for two patient cases. Using MRFS-derived databases, dose differences ≲2% in the plateau and SOBP are observed compared to computations with MC-generated databases. Bio-sensitivity studies show larger deviations when altering the absolute βph value, with maximum D50% changes of ~5%, with similar results for patient cases. Bio-sensitivity analysis indicates a greater impact on DRBE varying (α/β)ph than βph in mMKM. The MRSF approach yielded negligible differences in the target and small differences in the plateau compared to MC-generated databases. The presented analyses provide guidance for proper implementation of RBE-weighted 4He ion dose prescription and planning with mMKM. The MRFS-DRBE calculation approach using mMKM will be implemented in a clinical treatment planning system.

Kopp B ，Mein S ，Tessonnier T ，Besuglow J ，Harrabi S ，Heim E ，Abdollahi A ，Haberer T ，Debus J ，Mairani A ... -  《-》

How LEM-based RBE and dose-averaged LET affected clinical outcomes of sacral chordoma patients treated with carbon ion radiotherapy.

To understand the role of relative biological effectiveness (RBE) and dose-averaged linear energy transfer (LETd) distributions in the treatment of sacral chordoma (SC) patients with carbon ion radiotherapy (CIRT). Clinical plans of 50 SC patients consecutively treated before August 2018 with a local effect model-based optimization were recalculated with the modified microdosimetric kinetic RBE model (mMKM). Twenty-six patients were classified as progressive disease and the relapse volume was contoured on the corresponding follow-up diagnostic sequence. The remaining 24 patients populated the control group. Target prescription dose (DRBE|50%), near-to-minimum- (DRBE|95%) and near-to-maximum- (DRBE|2%) doses were compared between the two cohorts in both RBE systems. LETd distribution was evaluated for in-field relapsed cases with respect to the control group. Target DMKM|50% and DMKM|95% were respectively 10% and 18% lower than what we aimed at. Dosimetric evaluators showed no significant difference, in neither of the RBE frameworks, between relapsed and control sets. Half of the relapse volumes were located in a well-covered high dose region. On average, over these cases, median target LETd was significantly lower than the control cohort mean value (27 vs 30 keV/μm). Most notably, the volume receiving dose from high-LET particles (>50 keV/μm) lay substantially below recently reported data in the literature. A combined multi model RBE- and LET-based optimization could play a key role in the enhancement of the therapeutic ratio of CIRT for large radioresistant tumors such as sacral chordomas.

Molinelli S ，Magro G ，Mairani A ，Allajbej A ，Mirandola A ，Chalaszczyk A ，Imparato S ，Ciocca M ，Fiore MR ，Orlandi E ... -  《-》

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》