Rectum Dose Constraints for Carbon Ion Therapy: Relative Biological Effectiveness Model Dependence in Relation to Clinical Outcomes.

The clinical application of different relative biological effectiveness (RBE) models for carbon ion RBE-weighted dose calculation hinders a global consensus in defining normal tissue constraints. This work aims to update the local effect model (LEM)-based constraints for the rectum using microdosimetric kinetic model (mMKM)-defined values, relying on RBE translation and the analysis of long-term clinical outcomes. LEM-optimized plans of treated patients, having suffered from prostate adenocarcinoma (n = 22) and sacral chordoma (n = 41), were recalculated with the mMKM using an in-house developed tool. The relation between rectum dose-volume points in the two RBE systems (DLEM|v and DMKM|v) was fitted to translate new LEM-based constraints. Normal tissue complication probability (NTCP) values, predicting late rectal toxicity, were obtained by applying published parameters. No late rectal toxicity events were reported within the patient cohort. The rectal toxicity outcome was confirmed using dosimetric analysis: DMKMVHs lay largely below original constraints; the translated DLEM|v values were 4.5%, 8.3%, 18.5%, and 35.4% higher than the nominal DMKM|v of the rectum volume, v-1%, 5%, 10% and 20%. The average NTCP value ranged from 5% for the prostate adenocarcinoma, to 0% for the sacral chordoma group. The redefined constraints, to be confirmed prospectively with clinical data, are DLEM|5cc ≤ 61 Gy(RBE) and DLEM|1cc ≤ 66 Gy(RBE).

Dosimetric validation of Monte Carlo and analytical dose engines with raster-scanning 1H, 4He, 12C, and 16O ion-beams using an anthropomorphic phantom.

With high-precision radiotherapy on the rise towards mainstream healthcare, comprehensive validation procedures are essential, especially as more sophisticated technologies emerge. In preparation for the upcoming translation of novel ions, case-/disease-specific ion-beam selection and advanced multi-particle treatment modalities at the Heidelberg Ion-beam Therapy Center (HIT), we quantify the accuracy limits in particle therapy treatment planning under complex heterogeneous conditions for the four ions (1H, 4He, 12C, 16O) using a Monte Carlo Treatment Planning platform (MCTP), an independent GPU-accelerated analytical dose engine developed in-house (FRoG) and the clinical treatment planning system (Syngo RT Planning). Attaching an anthropomorphic half-head Alderson RANDO phantom to entrance window of a dosimetric verification water tank, a cubic target spread-out Bragg peak (SOBP) was optimized using the MCTP to best resolve effects of anatomic heterogeneities on dose homogeneity. Subsequent forward calculations were executed in FRoG and Syngo. Absolute and relative dosimetry was performed in the experimental beam room using 1D and 2D array ionization chamber detectors. Mean absolute percent deviation in dose (|%Δ|) between predictions and PinPoint ionization chamber measurements were within ∼2% for all investigated ions for both MCTP and FRoG. For protons and carbon ions, |%Δ| values were ∼4% for Syngo. For the four ions, 3D-γ analysis (3%/3mm criteria) of FLUKA and FRoG presented mean passing rates of 97.0(±2.4)% and 93.6(±4.2)%. FRoG demonstrated satisfactory agreement with gold standard Monte Carlo simulation and measurement, superior to the commercial system. Our pre-clinical trial landmarks the first measurements taken in anthropomorphic settings for helium, carbon and oxygen ion-beam therapy.

FRoG-A New Calculation Engine for Clinical Investigations with Proton and Carbon Ion Beams at CNAO.

A fast and accurate dose calculation engine for hadrontherapy is critical for both routine clinical and advanced research applications. FRoG is a graphics processing unit (GPU)-based forward calculation tool developed at CNAO (Centro Nazionale di Adroterapia Oncologica) and at HIT (Heidelberg Ion Beam Therapy Center) for fast and accurate calculation of both physical and biological dose. FRoG calculation engine adopts a triple Gaussian parameterization for the description of the lateral dose distribution. FRoG provides dose, dose-averaged linear energy transfer, and biological dose-maps, -profiles, and -volume-histograms. For the benchmark of the FRoG calculation engine, using the clinical settings available at CNAO, spread-out Bragg peaks (SOBPs) and patient cases for both proton and carbon ion beams have been calculated and compared against FLUKA Monte Carlo (MC) predictions. In addition, FRoG patient-specific quality assurance (QA) has been performed for twenty-five proton and carbon ion fields. As a result, for protons, biological dose values, using a relative biological effectiveness (RBE) of 1.1, agree on average with MC within ~1% for both SOBPs and patient plans. For carbon ions, RBE-weighted dose (DRBE) agreement against FLUKA is within ~2.5% for the studied SOBPs and patient plans. Both MKM (Microdosimetric Kinetic Model) and LEM (Local Effect Model) DRBE are implemented and tested in FRoG to support the NIRS (National Institute of Radiological Sciences)-based to LEM-based biological dose conversion. FRoG matched the measured QA dosimetric data within ~2.0% for both particle species. The typical calculation times for patients ranged from roughly 1 to 4 min for proton beams and 3 to 6 min for carbon ions on a NVIDIA® GeForce® GTX 1080 Ti. This works demonstrates FRoG's potential to bolster clinical activity with proton and carbon ion beams at CNAO.

Fast robust dose calculation on GPU for high-precision 1H, 4He, 12C and 16O ion therapy: the FRoG platform.

Radiotherapy with protons and heavier ions landmarks a novel era in the field of high-precision cancer therapy. To identify patients most benefiting from this technologically demanding therapy, fast assessment of comparative treatment plans utilizing different ion species is urgently needed. Moreover, to overcome uncertainties of actual in-vivo physical dose distribution and biological effects elicited by different radiation qualities, development of a reliable high-throughput algorithm is required. To this end, we engineered a unique graphics processing unit (GPU) based software architecture allowing rapid and robust dose calculation. FRoG, Fast Recalculation on GPU, currently operates with four particle beams available at Heidelberg Ion Beam Therapy center, i.e., raster-scanning proton (1H), helium (4He), carbon (12C) and oxygen ions (16O). FRoG enables comparative analysis of different models for estimation of physical and biological effective dose in 3D within minutes and in excellent agreement with the gold standard Monte Carlo (MC) simulation. This is a crucial step towards development of next-generation patient specific radiotherapy.