Browsing by Author "Meng, Boyu"
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Item Open Access Clinical CBCT-Based Dose Simulation for 80 kVp X-PACT Treatment Using FLUKA Monte Carlo Package(2017) Meng, BoyuX-PACT as a novel cancer therapy utilizes kilovoltage x-ray beam, phosphor and psoralen to treat solid tumors. Since x-ray beam is not commonly used for radiation therapy treatment purposes, a lack of treatment planning tool and plan based dose calculation is hindering the development of X-PACT. In this study, we try to approach the challenge by creating a Monte Carlo model that is an accurate representation of the actual treatment. The Monte Carlo model will be validated with commissioning measurements and is applicable to clinical data.
FLUKA is used as the Monte Carlo package for our simulations. The Monte Carlo model is created based on the Variantm OBI system. The geometry is created and optimized in Flair. To improve simulation efficiency, we collected the filtered simulated 80 kVp x-ray spectrum and used that as the source file for photon simulation. This way, the x-ray tube is bypassed, and 80 kVp photon can be simulated directly.
The validation process consists of two qualities: the back-scatter factor and the percentage depth dose. The commissioning was done separately from this study [1], and the commissioning data was used to compare with simulation results. The Model shows good overall matching to the commissioning PDD data. At small or large field size, a discrepancy between the simulation PDD data and commissioning PDD data can be observed at the surface, the differences are with 3-4%.
The final step is to apply the model to the Phase I canine trial. The clinical trial includes six dog study cases. In this thesis, Monte Carlo dose calculation based on the CBCT images of each dog study was performed for all six dog studies. The result is a 3D dose matrix for the CBCT images. According to the prescription dose for each dog study, the simulated dose was normalized, and the dose distribution for each dog was generated..
Item Open Access Enhancing Radiation Therapy Through Cherenkov Light-Activated Phototherapy.(International journal of radiation oncology, biology, physics, 2018-03) Yoon, Suk W; Tsvankin, Vadim; Shrock, Zachary; Meng, Boyu; Zhang, Xiaofeng; Dewhirst, Mark; Fecci, Peter; Adamson, Justus; Oldham, MarkThis work investigates a new approach to enhance radiotherapy through a photo therapeutic agent activated by Cherenkov light produced from the megavoltage photon beam. The process is termed Radiotherapy Enhanced with Cherenkov photo-Activation (RECA). RECA is compatible with various photo-therapeutics, but here we focus on use with psoralen, an ultraviolet activated therapeutic with extensive history of application in superficial and extracorporeal settings. RECA has potential to extend the scope of psoralen treatments beyond superficial to deep seated lesions.In vitro studies in B16 melanoma and 4T1 murine breast cancer cells were performed to investigate the potential of RT plus RECA versus RT alone for increasing cytotoxicity (local control) and increasing surface expression of major histocompatibility complex I (MHC I). The latter represents potential for immune response amplification (increased antigen presentation), which has been observed in other psoralen therapies. Cytotoxicity assays included luminescence and clonogenics. The MHC I assays were performed using flow cytometry. In addition, Cherenkov light intensity measurements were performed to investigate the possibility of increasing the Cherenkov light intensity per unit dose from clinical megavoltage beams, to maximize psoralen activation.Luminescence assays showed that RECA treatment (2 Gy at 6 MV) increased cytotoxicity by up to 20% and 9.5% for 4T1 and B16 cells, respectively, compared with radiation and psoralen alone (ie, Cherenkov light was blocked). Similarly, flow cytometry revealed median MHC I expression was significantly higher in RECA-treated cells, compared with those receiving radiation and psoralen alone (approximately 450% and 250% at 3 Gy and 6 Gy, respectively, P << .0001). Clonogenic assays of B16 cells at doses of 6 Gy and 12 Gy showed decreases in tumor cell viability of 7% (P = .017) and 36% (P = .006), respectively, when Cherenkov was present.This work demonstrates for the first time the potential for photo-activation of psoralen directly in situ, from Cherenkov light generated by a clinical megavoltage treatment beam.Item Open Access X-Ray Psoralen Activated Cancer Therapy (X-PACT).(PLoS One, 2016) Oldham, Mark; Yoon, Paul; Fathi, Zak; Beyer, Wayne F; Adamson, Justus; Liu, Leihua; Alcorta, David; Xia, Wenle; Osada, Takuya; Liu, Congxiao; Yang, Xiao Y; Dodd, Rebecca D; Herndon, James E; Meng, Boyu; Kirsch, David G; Lyerly, H Kim; Dewhirst, Mark W; Fecci, Peter; Walder, Harold; Spector, Neil LThis work investigates X-PACT (X-ray Psoralen Activated Cancer Therapy): a new approach for the treatment of solid cancer. X-PACT utilizes psoralen, a potent anti-cancer therapeutic with current application to proliferative disease and extracorporeal photopheresis (ECP) of cutaneous T Cell Lymphoma. An immunogenic role for light-activated psoralen has been reported, contributing to long-term clinical responses. Psoralen therapies have to-date been limited to superficial or extracorporeal scenarios due to the requirement for psoralen activation by UVA light, which has limited penetration in tissue. X-PACT solves this challenge by activating psoralen with UV light emitted from novel non-tethered phosphors (co-incubated with psoralen) that absorb x-rays and re-radiate (phosphoresce) at UV wavelengths. The efficacy of X-PACT was evaluated in both in-vitro and in-vivo settings. In-vitro studies utilized breast (4T1), glioma (CT2A) and sarcoma (KP-B) cell lines. Cells were exposed to X-PACT treatments where the concentrations of drug (psoralen and phosphor) and radiation parameters (energy, dose, and dose rate) were varied. Efficacy was evaluated primarily using flow cell cytometry in combination with complimentary assays, and the in-vivo mouse study. In an in-vitro study, we show that X-PACT induces significant tumor cell apoptosis and cytotoxicity, unlike psoralen or phosphor alone (p<0.0001). We also show that apoptosis increases as doses of phosphor, psoralen, or radiation increase. Finally, in an in-vivo pilot study of BALBc mice with syngeneic 4T1 tumors, we show that the rate of tumor growth is slower with X-PACT than with saline or AMT + X-ray (p<0.0001). Overall these studies demonstrate a potential therapeutic effect for X-PACT, and provide a foundation and rationale for future studies. In summary, X-PACT represents a novel treatment approach in which well-tolerated low doses of x-ray radiation are delivered to a specific tumor site to generate UVA light which in-turn unleashes both short- and potentially long-term antitumor activity of photo-active therapeutics like psoralen.