Lei Dong

University of Pennsylvania | UP · Department of Radiation Oncology

Recent studies suggest that ultrahigh-dose-rate, “FLASH,” radiation therapy (RT) decreases normal tissue damage while maintaining tumor response compared with conventional dose rate RT. Our group has designed and tested the first system to accurately deliver dosimetrically identical FLASH Proton RT (F-PRT; 60-110 Gy/sec) or Standard Proton RT (S-PR...

Purpose: To investigate the transcriptomic changes induced by FLASH proton radiotherapy (F-PRT) that could be responsible for the protection of normal epithelial tissues by radiation-induced toxicities as have been previously shown by us and others. Methods: C57BL/6J mice received 30 Gy of F-PRT or S-PRT to the hind leg at respective dose rates of...

The major aim of radiation therapy is to provide curative or palliative treatment to cancerous malignancies while minimizing damage to healthy tissues. Charged particle radiotherapy utilizing carbon ions or protons is uniquely suited for this task due to its ability to achieve highly conformal dose distributions around the tumor volume. For these t...

Dose uncertainty induced by respiratory motion remains a major concern for treating thoracic and abdominal lesions using particle beams. This Task Group report reviews the impact of tumor motion and dosimetric considerations in particle radiotherapy, current motion‐management techniques, and limitations for different particle‐beam delivery modes (i...

Objective: We conducted a Monte Carlo study to comprehensively investigate the fetal dose resulting from proton pencil beam scanning (PBS) craniospinal irradiation (CSI) during pregnancy. Approach: The gestational-age dependent pregnant phantom series developed at the University of Florida (UF) were converted into DICOM-RT format (CT images and...

Deep learning, a new branch of machine learning algorithm, has emerged as a fast growing trend in medical imaging and become the state-of-the-art method in various clinical applications such as Radiology, Histo-pathology and Radiation Oncology. Specifically in radiation oncology, deep learning has shown its power in performing automatic segmentatio...

Purpose/Objective(s) During lung cancer radiotherapy, tumor motion magnitude may change, resulting in either inadequate margins or non-ideal dose conformality (margins are unnecessarily too big). To predict large motion change using only patient-specific clinical information and the simulation 4DCT images, we proposed an ensemble learning model (EL...

Purpose/Objective(s) A novel O-ring Linac (ORL) offers a fully enclosed gantry with a single energy (6 MV) flattening filter-free photon beam, improved kV CBCT, a maximum treatment length of 36 cm (dual-isocenter setup), and a translation-only 3DOF couch for IGRT. The purpose of this study was to evaluate the viability of this ORL for use in a sing...

Compared with photon stereotactic body radiotherapy (SBRT) plans that may have to use many more penetrating x-ray beams for each isocenter, proton SBRT with ultrahypofractionated doses use fewer beam angles and offer significantly reduced low-dose radiation bath to normal liver tissue. We demonstrate techniques to deliver safe and effective proton...

Ultra-high dose rate FLASH proton radiotherapy (F-PRT) has been shown to reduce normal tissue toxicity compared to standard dose rate proton radiotherapy (S-PRT) in experiments using the entrance portion of the proton depth dose profile, while proton therapy uses a spread-out Bragg peak (SOBP) with unknown effects on FLASH toxicity sparing. To inve...

In studies of electron and proton radiotherapy, ultrahigh dose rates of FLASH radiation therapy appear to produce fewer toxicities than standard dose rates while maintaining local tumor control. FLASH-proton radiotherapy (F-PRT) brings the spatial advantages of PRT to FLASH dose rates (>40 Gy/sec), making it important to understand if and how F-PRT...

Research efforts in FLASH radiotherapy have increased at an accelerated pace recently. FLASH radiotherapy involves ultra-high dose rates and has shown to reduce toxicity to normal tissue while maintaining tumor response in pre-clinical studies when compared to conventional dose rate radiotherapy. The goal of this review is to summarize the studies...

Purpose To describe an implementation of dual-energy computed tomography (DECT) for calculation of proton stopping-power ratios (SPRs) in a commercial treatment-planning system. The process for validation and the workflow for safe deployment of DECT is described, using single-energy computed tomography (SECT) as a safety check for DECT dose calcula...

Ultrahigh dose rate (FLASH) proton therapy is of great interest due to potential reduced normal tissue toxicities without compromising tumor killing effect compared to current clinical proton practices. However, the ionization chamber response to proton beams under ultra-high dose rates (>40Gy/s) has not been thoroughly investigated. In this study,...

Introduction: Ultra-high dose rate (FLASH) radiotherapy has become a popular research topic with the potential to reduce normal tissue toxicities without losing the benefit of tumor control. The development of FLASH proton pencil beam scanning (PBS) delivery requires accurate dosimetry despite high beam currents with correspondingly high ionizatio...

Total Skin Electron Therapy (TSET) utilizes high-energy electrons to treat cancers on the entire body surface. The otherwise invisible radiation beam can be observed via the optical Cherenkov photons emitted from interaction between the high-energy electron beam and tissue. Cherenkov emission can be used to evaluate the dose uniformity on the surfa...

Purpose Proton Pencil Beam Scanning (PBS) is an attractive solution to realize the advantageous normal tissue sparing elucidated from FLASH high dose rates. The mechanics of PBS spot delivery will impose limitations on the effective field dose rate for PBS. Methods This study incorporates measurements from clinical and FLASH research beams on unif...

Introduction: The intracranial skull-base meningioma is in proximity to multiple critical organs and heterogeneous tissues. Steep dose gradients often result from avoiding critical organs in proton treatment plans. Dose uncertainties arising from setup errors under image-guided radiation therapy are worthy of evaluation. Patients and Methods: Fourt...

Intensity-based deformable registration with spatial-invariant regularization generally fails when distinct motion exists across different types of tissues. The purpose of this work was to develop and validate a new regularization approach for deformable image registration that is tissue-specific and able to handle motion discontinuities. Our appro...

The treatment of cancer with proton radiation therapy was first suggested in 1946 followed by the first treatments in the 1950s. As of 2020, almost 200,000 patients have been treated with proton beams worldwide and the number of operating proton therapy facilities will soon reach one hundred. Proton therapy has long moved from research institutions...

Background This study investigates daily breast geometry and delivered dose to prone-positioned patients undergoing tangential whole breast radiation therapy (WBRT) on an O-ring linear accelerator with 6X flattening filter free mode (6X-FFF), planned with electronic compensation (ECOMP) method. Most practices rely on skin marks or daily planar imag...

Background and purpose Scatter correction of cone-beam computed tomography (CBCT) projections may enable accurate online dose-delivery estimations in photon and proton-based radiotherapy. This study aimed to evaluate the impact of scatter correction in CBCT-based proton range/dose calculations, in scans acquired in both proton and photon gantries....

Introduction Modern technologies, like intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT), have improved the therapeutic ratio of thoracic radiotherapy (TRT) for lung cancer (LC). Halcyon™ (Varian Medical Systems, Palo Alto, CA, USA), a novel 6MV-flattening-filter-free O-ring linear accelerator (6X-FFF ORL), was des...

Purpose: To investigate the potential normal tissue sparing effects of proton FLASH radiation on skin injury, leg contraction, and soft tissue inflammation while maintaining tumor cell killing efficacy for orthotopic murine fibrosarcoma tumor. Materials and Methods: C3H/HeJ and C57BL/6J mice (n= 6) received 45 Gy of proton FLASH (>85Gy/sec) or conv...

Introduction A novel on-line adaptive radiotherapy (ART) system based on O-ring linear accelerator (LINAC) and cone-beam CT (CBCT) was evaluated for treatment and management of head & neck (H&N) cancer in an emulated environment accessed via remote desktop connection. In this on-line ART system, organs-at-risk (OARs) and target contours and radioth...

Background: Radiation therapy (RT) can provide effective symptomatic palliation in patients with malignant pleural mesothelioma (MPM). Advances in RT technology, including intensity-modulated RT (IMRT) and volumetric-modulated arc therapy (VMAT), have improved treatment conformality, potentially improving the therapeutic ratio of RT. A novel 6-MV...

Background This study investigates daily breast geometry and delivered dose to prone-positioned patients undergoing tangential whole breast radiation therapy (WBRT) on an O-ring linear accelerator with 6X flattening filter free mode (6X-FFF), planned with electronic compensation (ECOMP) method. Most practices rely on skin marks or daily planar imag...

Background: This study investigates daily breast geometry and delivered dose to prone-positioned patients undergoing tangential whole breast radiation therapy (WBRT) on an O-ring linear accelerator with 6X flattening filter free mode (6X-FFF), planned with electronic compensation (ECOMP) method. Most practices rely on skin marks or daily planar ima...

Purpose: In IMPT, unaccounted-for variation in biological effectiveness contributes to the discrepancy between the constant relative biological effectiveness (RBE) model prediction and experimental observation. It is desirable to incorporate biological doses in treatment planning to improve modeling accuracy and consequently achieve a higher thera...

Purpose: To achieve a superior balance between dosimetry and the delivery efficiency of intensity modulated proton therapy (IMPT) using as few beams as possible in a single fraction, we optimally vary beams in different fractions. Methods: In the optimization, 400~800 feasible non-coplanar beams were included in the candidate pool. For each beam...

Purpose The dosimetric parameters used clinically to reduce the likelihood of radiation pneumonitis (RP) for lung cancer radiotherapy have traditionally been V20Gy≤30-35% and mean lung dose ≤20-23Gy; however, these parameters are derived based on studies from photon therapy. The purpose of this study is to evaluate if such dosimetric predictors for...

Purpose Radiation therapy (RT) is commonly used in the treatment of gynecologic cancers. Intensity-modulated RT (IMRT) has been shown to reduce gastrointestinal toxicity compared with 2-dimensional and 3-dimensional RT modalities. We report the initial clinical experience using IMRT for gynecologic cancers with a novel 6MV flattening filter free O-...

Purpose: Spot-scanning proton arc therapy (SPAT) is an emerging modality to improve plan conformality and delivery efficiency. A greedy and heuristic method is proposed in the existing SPAT algorithm to select energy layers and sequence energy switching with gantry rotation, which does not promise optimality in either dosimetry or efficiency. We a...

Purpose: We hypothesize that the radiation dose in high-ventilation portions of the lung better predicts radiation pneumonitis (RP) outcome for patients treated with proton (PR) and photon (PH) radiotherapy. Methods and materials: 74 patients (38 protons, 36 photons) with locally advanced non-small cell lung (NSCLC) cancer treated with concurren...

Background: While the review of radiotherapy treatment plans and charts by a medical physicist is a key component of safe, high-quality care, very few specific recommendations currently exist for this task. Aims: The goal of TG-275 is to provide practical, evidence-based recommendations on physics plan and chart review for radiation therapy. Whi...

Purpose: Recent studies suggest that ultrahigh-dose-rate, "FLASH," electron radiation therapy (RT) decreases normal tissue damage while maintaining tumor response compared with conventional dose rate RT. Here, we describe a novel RT apparatus that delivers FLASH proton RT (PRT) using double scattered protons with computed tomography guidance and p...

We develop a fully automated QA process to compare the image quality of all kV CBCT protocols on a Halcyon linac with ring gantry design, and evaluate image quality stability over a 10-month period. A total of 19 imaging scan and reconstruction protocols were characterized with measurement on a newly released QUART phantom. A set of image analysis...

Objectives To evaluate dosimetric consequences of inter fraction set up variation and anatomical changes in patients receiving multi field optimised (MFO) intensity modulated proton therapy for post-operative oropharyngeal (OPC) and oral cavity (OCC) cancers. Methods Six patients receiving MFO for postoperative OPC and OCC were evaluated. Plans we...

Purpose: To characterize the dosimetric features and limitations of the dynamic beam flattening (DBF) on the Halcyon 2.0 linear accelerator (Varian Medical Systems). Methods: A pre-defined multi-leaf collimator (MLC) sequence was introduced and used to flatten the 6MV flattening filter free (FFF) beam on the Halcyon 2.0. Dosimetric characterizat...

Background: Total Skin Electron Therapy (TSET) utilizes high-energy electrons to treat malignancies on the entire body surface. The otherwise invisible radiation beam can be observed via the optical Cherenkov photons emitted from interactions between the high-energy electron beam and tissue. Methods & materials: With a time-gated intensified cam...

In cancer radiation therapy, large tumor motion due to respiration can lead to uncertainties in tumor target delineation and treatment delivery, thus making active motion management an essential step in thoracic and abdominal tumor treatment. In current practice, patients with tumor motion may be required to receive two sets of CT scans – the initi...

Purpose: Superficial dose is an important parameter in breast cancer radiation therapy. When treated with conventional linacs, bolus is commonly applied to improve target coverage near the surface while also managing the risk of severe skin reactions and negative cosmesis. With the introduction of modern linacs with 6X flattening filter free (FFF)...

Purpose: This manuscript describes the experience of two institutions in commissioning the new HalcyonTM platform. Its purpose is to: 1) validate the pre-defined beam data, 2) compare relevant commissioning data acquired independently by two separate institutions, and 3) report on any significant differences in commissioning between the Halcyon li...

The purpose of this study is to investigate the dosimetric impact of multi‐leaf collimator (MLC) positioning errors on a Varian Halcyon for both random and systematic errors, and to evaluate the effectiveness of portal dosimetry quality assurance in catching clinically significant changes caused by these errors. Both random and systematic errors we...

Purpose: The Varian Halcyon includes an ultrafast 6 MV flattening filter free (FFF) cone-beam computed tomography (MV-CBCT). Although a kV-CBCT add-on is available, in the basic configuration MV is used for image guided radiotherapy (IGRT). We characterized the MV-CBCT imager in terms of reproducibility, linearity, field of view (FOV) dependence, d...

Purpose: Three-dimensional (3D) conformal radiation therapy is the standard technique used for adjuvant breast radiation. We report the clinical use of a novel 6-MV flattening-filter-free O-ring linear accelerator (6X-FFF ORL) for breast cancer that may improve upon 3D conformal radiation therapy with its higher dose rate and faster rotation and l...

Purpose/Objectives: There are several popular treatment options currently available for stereotactic radiosurgery (SRS) of multiple brain metastases: 60Co sources and cone collimators around a spherical geometry (GammaKnife), multi-aperture dynamic conformal arcs on a linac (BrainLab Elements™ v1.5), and volumetric arc therapy on a linac (VMAT) cal...

Purpose: Dose conformality and robustness are equally important in Intensity Modulated Proton Therapy (IMPT). Despite the obvious implication of beam orientation on both dosimetry and robustness, an automated, robust beam orientation optimization algorithm has not been incorporated due to the problem complexity and paramount computational challeng...

Purpose: Small animal x-ray irradiation platforms are expanding the capabilities and future pathways for radiobiology research. Meanwhile, proton radiotherapy is transitioning to a standard treatment modality in the clinician's precision radiotherapy toolbox, highlighting a gap between state-of-the-art clinical radiotherapy and small animal radiob...

The purpose of this study is to evaluate the effect of an intravenous (IV) contrast agent on proton therapy dose calculation using dual-energy computed tomography (DECT). Two DECT methods are considered. The first one, ρe-Zmed, attempts to accurately predict the proton stopping powers relative to water (SPR) of contrast enhanced (CE) DECT images, w...

Purpose: Spine SBRT requires treatment plans with steep dose gradients and tight limits to the cord maximal dose. A new dual-layer staggered 1-cm MLC in Halcyon™ treatment platform has improved leakage, speed, and DLG compared to 120-Millennium (0.5-cm) and High-Definition (0.25-cm) MLCs in the TrueBeam platform. Halcyon™ 2.0 with SX2 MLC modulates...