Treatment Planning System for Electron FLASH Radiotherapy: Open-source for Clinical Implementation
Mahbubur Rahman, M. Ramish Ashraf, David J. Gladstone, Petr Bruza, Lesley A. Jarvis, Philip E. Schaner, Xu Cao, Brian W. Pogue, P. Jack Hoopes, Rongxiao Zhang
Purpose: A Monte Carlo (MC) beam model and its implementation in a clinical treatment planning system (TPS, Varian Eclipse) are presented for a modified ultra-high dose-rate electron FLASH radiotherapy (eFLASH-RT) LINAC.
Methods: The gantry head without scattering foils or targets, representative of the LINAC modifications, was modelled in Geant4. The energy spectrum (σE) and beam source emittance cone angle (θcone) were varied to match the calculated and Gafchromic film measured central-axis percent depth dose (PDD) and lateral profiles. Its Eclipse configuration was validated with measured profiles of the open field and nominal fields for clinical applicators. eFLASH-RT plans were MC forward calculated in Geant4 for a mouse brain treatment and compared to a conventional (Conv-RT) plan in Eclipse for a human patient with metastatic renal cell carcinoma.
Results: The beam model and its Eclipse configuration agreed best with measurements at σE=0.5 MeV and θcone=3.9+/-0.2 degrees to clinically acceptable accuracy (the absolute average error was within 1.5% for in-water lateral, 3% for in-air lateral, and 2% for PDD). The forward dose calculation showed dose was delivered to the entire mouse brain with adequate conformality. The human patient case demonstrated the planning capability with routine accessories in relatively complex geometry to achieve an acceptable plan (90% of the tumor volume receiving 95% and 90% of the prescribed dose for eFLASH and Conv-RT, respectively).
Conclusion: To the best of our knowledge, this is the first functional beam model commissioned in a clinical TPS for eFLASH-RT, enabling planning and evaluation with minimal deviation from Conv-RT workflow. It facilitates the clinical translation as eFLASH-RT and Conv-RT plan quality were comparable for a human patient. The methods can be expanded to model other eFLASH irradiators.
Current Views on Mechanisms of the FLASH Effect in Cancer Radiotherapy
Peking University（北京大学）；the Second Affiliated Hospital of Wenzhou Medical University（温州医科大学附属第二医院）；College of Chemistry and Molecular Engineering, Peking University（北京大学化学与分子工程学院）；Sun Yat-sen University（中山大学）；KIRI Precision Particle Therapy Flash Technologies Research Center（基锐精准粒子治疗闪速技术研究中心）；The University of Hong Kong-Shenzhen Hospital（香港大学深圳医院）
It has been postulated that the delivery of radiotherapy at ultra-high dose rates ("FLASH") reduces normal tissue toxicities by depleting them of oxygen. The fraction of normal tissue and cancer cells surviving radiotherapy depends on dose and oxygen levels in an exponential manner and even a very small fraction of tissue at low oxygen levels can determine radiotherapy response. The effect of FLASH on radiation-induced normal and tumour tissue cell killing was studied by simulating oxygen diffusion, metabolism, and radiolytic oxygen depletion over domains with simulated capillary architectures…
An in-silico study of conventional and FLASH radiotherapy iso-effectiveness: Radiolytic oxygen depletion and its potential impact on tumor control probability
FLASH is a new treatment modality that requires optimization of dose, dose rate, and LET. Here we validate these three quantities under FLASH conditions, which includes the quantum uncertainty in the time-dependent instantaneous dose rate (IDR) curves and LET spectra that underlie the newly proposed integrated optimization framework. Measurements of dose, IDR, and LET were performed at the Emory Proton Therapy Center using a FLASH proton beam with a nominal energy of 250 MeV and a 3D printed ridge filter. Because 3D printing resin is made from a proprietary chemical formula, we developed a met…
While spatial dose conformity delivered to a target volume has been pushed to its practical limits with advanced treatment planning and delivery, investigations in novel temporal dose delivery are unfolding new mechanisms. Recent advances in ultra-high dose radiotherapy, abbreviated as FLASH, indicate the potential for reduction in healthy tissue damage while preserving tumor control. FLASH therapy relies on very high dose rate of > 40Gy/sec with sub-second temporal beam modulation, taking a seemingly opposite direction from the conventional paradigm of fractionated therapy. FLASH brings uniqu…
Beam monitoring for radiotherapy from conventional to FLASH dose rates using Low Gain Avalanche Silicon detectors
Universidad de Sonora（索诺拉大学）；University of Kansas（堪萨斯大学）；Washington University School of Medicine（华盛顿大学医学院）；Rice University（莱斯大学）；University of Kansas Cancer Center（堪萨斯大学癌症中心）；The University of Texas MD Anderson Cancer Center（德克萨斯大学安德森癌症中心）
We present a microscopic mechanism that accounts for the outward burst of "cold" ion species (IS) in a high-energy particle track due to coupling with ''hot" non-ion species (NIS). IS refers to radiolysis products of ionized molecules, whereas NIS refers to non-ionized excitations of molecules in a medium. The interaction is mediated by a quantized field of acoustic phonons, a channel that allows conversion of thermal energy of NIS to kinetic energy of IS, a flow of heat from the outer to the inner core of the track structure. We demonstrate the coexistence of "hot" NIS with "cold" IS in the r…
Radiotherapy, due to its technology-intensive nature and reliance on digital data and human-machine interactions, is particularly suited to benefit from artificial intelligence (AI) to improve the accuracy and efficiency of its clinical workflow. Recently, various artificial intelligence (AI) methods have been successfully developed to exploit the benefit of the inherent physical properties of particle therapy. Many reviews about AI applications in radiotherapy have already been published, but none were specifically dedicated to particle therapy. In this article, we present a comprehensive rev…
Review of oxygen measurement and relevance to the mechanisms of FLASH radiotherapy
Thayer School of Engineering at Dartmouth（达特茅斯学院泰耶尔工程学院）；Giesel School of Medicine at Dartmouth（达特茅斯学院吉塞尔医学院）；University of Wisconsin School of Medicine and Public Health（威斯康星大学医学院和公共卫生学院）
Modern external beam cancer radiotherapy applies prescribed radiation doses to tumor targets while minimally affecting nearby vulnerable organs-at-risk (OARs). Creating a treatment plan is difficult and time-consuming with no guarantee of optimality. Knowledge-based planning (KBP) mitigates this uncertainty by guiding planning with probabilistic models based on populations of prior clinical-quality plans. We have developed a KBP-inspired planning model that predicts plans as realizations of the treatment machine parameters. These are tuples of linear accelerator (Linac) gantry angles, multi-le…
Divergent Clinical Equivalence Findings from DVH and NTCP Metrics for Alternative OAR Delineations with Increasing Setup Variability in Head-and-Neck Radiotherapy
Diffuse low grade gliomas are slowly growing tumors that always recur after treatment. In this paper, we revisit the modeling of the tumor radius evolution before and after the radiotherapy process and propose a novel model that is simple, yet biologically motivated, and that remedies some shortcomings of previously proposed ones. We confront it with clinical data consisting in time-series of tumor radius for 43 patient records, using a stochastic optimization technique and obtain very good fits in all the cases. Since our model describes the evolution of the tumor from the very first glioma c…
We present a first-principles molecular dynamics (MD) simulation and expound upon a mechanism of oxygen depletion hypothesis to explain the mitigation of normal tissue injury observed in ultra-high-dose-rate (UHDR) FLASH radiotherapy. We simulated damage to a segment of DNA (also representing other bio-molecules such as RNA and proteins) in a simulation box filled with H$_2$O and O$_2$ molecules. Attoseconds physical interactions (ionizations, electronic and vibrational excitations) were simulated by using the Monte Carlo track structure code Geant4-DNA. Immediately after ionization, {\it ab i…
Purpose: To evaluate the clinical need for automated decision-support platforms for Adaptive Radiotherapy Therapy (ART) of Head & Neck cancer (HNC) patients. Methods: We tested RTapp (SegAna), a new decision-support software for ART, to investigate 22 HNC patients data retrospectively. For each fraction, RTapp estimated the daily and cumulative doses received by targets and OARs from daily 3D imaging in real-time. RTapp also included a prediction algorithm that analyzed dosimetric parameters (DP) trends against dosimetric endpoints (DE) to trigger adaptation up to 4 fractions ahead. Warning (V…
Ultra high dose rate electron beams also known as FLASH radiotherapy is becoming of importance in several preclinial cancer treatment studies. However, due to the dose rate used during the irradiation sessions, no real time dose monitoring device exists to date. In this work, we present the development of a beam current transformer (BCT), from the choice of the ferromagnetic component and the realisation of the shielding to the design of a front-end electronics based on a trans-impedance circuit in order to perform a low noise optimization of the detector. The BCT prototype is able to monitor …
An MRI-only adaptive radiotherapy (ART) workflow is desirable for managing interfractional changes in anatomy, but producing synthetic CT (sCT) data through paired data-driven deep learning (DL) for abdominal dose calculations remains a challenge due to the highly variable presence of intestinal gas. We present the preliminary dosimetric evaluation of our novel approach to sCT reconstruction that is well suited to handling intestinal gas in abdominal MRI-only ART. We utilize a paired data DL approach enabled by the intensity projection prior, in which well-matching training pairs are created b…
The aim of this work is to describe the technical characteristics of an AI-powered radiotherapy workflow that enables full-process automation (All-in-One), evaluate its performance implemented for on-couch initial treatment of rectal cancer, and provide insight into the behavior of full-workflow automation in the specialty of radiotherapy. The All-in-One workflow was developed based on a CT-integrated linear accelerator. It incorporates routine radiotherapy procedures from simulation, autosegmentation, autoplanning, image guidance, beam delivery, and in vivo quality assurance (QA) into one sch…
Purpose: Various dose calculation algorithms are available for radiation therapy for cancer patients. However, these algorithms are faced with the tradeoff between efficiency and accuracy. The fast algorithms are generally less accurate, while the accurate dose engines are often time consuming. In this work, we try to resolve this dilemma by exploring deep learning (DL) for dose calculation. Methods: We developed a new radiotherapy dose calculation engine based on a modified Hierarchically Densely Connected U-net (HD U-net) model and tested its feasibility with prostate intensity-modulated rad…
Background and Purpose: Stereotactic body radiotherapy (SBRT) for lung cancer accompanies a non-negligible risk of radiation pneumonitis (RP). This study presents a Bayesian network (BN) model that connects biological, dosimetric, and clinical RP risk factors. Material and Methods: 43 non-small-cell lung cancer patients treated with SBRT with 5 fractions or less were studied. Candidate RP risk factors included dose-volume parameters, previously reported clinical RP factors, 6 protein biomarkers at baseline and 6 weeks post-treatment. A BN ensemble model was built from a subset of the variables…
\item[Purpose] A recent study revealed that polyethylene (PE) would cause extra carbon-ion attenuation per range shift by 0.45\%/cm due to compositional differences in nuclear interactions. The present study aims to assess the influence of PE range compensators on tumor dose in carbon-ion radiotherapy. \item[Methods] Carbon-ion radiation was modeled to be composed of primary carbon ions and secondary particles, for each of which the dose and the relative biological effectiveness (RBE) were estimated at a tumor depth in the middle of spread-out Bragg peak. Assuming exponential behavior for atte…
Dose distribution (depthwise and laterally) to organs outside the radiotherapy treatment field can be significant and therefore is of clinical interest from the radiation protection point of view. In the present work, measurements were performed in a locally fabricated polystyrene phantom using TLD chips (LiF-100) for different teletherapy units (Cobalt-60 gamma ray, 120 kVp X-ray and 250 kVp X-ray) to estimate the dose distribution at distances up to 40 cm from the field edge along the central axes of the field size. Finally, the dose distribution for Cobalt-60 beam energy is parameterized as…
University of Texas Southwestern Medical Center（德克萨斯大学西南医学中心）
In post-operative radiotherapy for prostate cancer, the cancerous prostate gland has been surgically removed, so the clinical target volume (CTV) to be irradiated encompasses the microscopic spread of tumor cells, which cannot be visualized in typical clinical images such as computed tomography or magnetic resonance imaging. In current clinical practice, physicians segment CTVs manually based on their relationship with nearby organs and other clinical information, per clinical guidelines. Automating post-operative prostate CTV segmentation with traditional image segmentation methods has been a…
Precise patient positioning and thus precise positioning of the planning target volume (PTV) is a prerequisite for effective treatment in percutaneous radiation therapy. Conventional imaging modalities used to ensure exact positioning for treatment typically involve additional radiation exposure of the patient. A different approach to patient alignment without additional exposure is provided by optical 3D surface scanning and registration systems. We investigated two systems Catalyst and AlignRT, which allowed us to generate and validate surface images of 50 patients undergoing irradiation on …
In a treatment plan optimization problem for radiotherapy, a clinically acceptable plan is usually generated by an optimization process with weighting factors or reference doses adjusted for organs. Recent discoveries indicate that adjusting parameters associated with each voxel may lead to better plan quality. However, it is still unclear regarding the mathematical reasons behind it. To answer questions related to this problem, we establish in this work a new mathematical framework equipped with two theorems. The new framework clarifies the different consequences of adjusting organ-dependent …
