Develop a Treatment Plan That Would Result in Highly Localized IFNβ production in Well-Oxygenated Tumor Cells
A Almalki1*, D Miles2, R Stewart3, K Stantz4, (1) Purdue University, West Lafayette, IN, (2) Johns Hopkins University School of Medicine, Baltimore, MD, (3) University of Washington, Seattle, WA, (4) Purdue University, West Lafayette, IN
Presentations
TU-D1000-IePD-F7-2 (Tuesday, 7/12/2022) 10:00 AM - 10:30 AM [Eastern Time (GMT-4)]
Exhibit Hall | Forum 7
Purpose: Radiation-induced immunomodulatory effect is considered a promising strategy to enhance a patient’s immune response to potentially mitigate the primary tumor and metastatic disease. This out-of-field (abscopal) effect is very rarely observed during conventional radiotherapy.However, studies have shown that immunogenic cell death can be activated through dose escalation. Treatment dose and radiation-type may be optimized to initiate these anti-cancer immune responses (type-1 interferon; IFNβ). We propose to use high-LET radiation instead of low-LET (x-rays) due to its higher efficiency at inducing large numbers of DSBs and micronuclei (MN), thus greater immunogenic potential
Methods: We developed a novel treatment planning methodology based on IFN production by integrating mathematics models based on in-vitro measurements (e.g., Merkel-Cell Carcinoma) into FLUKA Monte Carlo code. Simulations modeled the distribution of dose, LETd, RBEdsb (RadioBiological Effectiveness of double-strand-breaks) and IFNβ at 0.2mm voxel resolution for various ion beams (1p, 4He, and 12C) and colbalt-60. For each particle beam, two treatment plans were simulated and compared: (i) a uniform physical dose (UPD), and (ii) an RBEdsb weighted dose
Results: UPD planning resulted in a niche of cancer cells with significantly reduced IFNβ production (~<50%) at regions proximal to the distal edge, specifically a 5mm regions for 4He which expanded to 9.5 mm when using 12C. This can be explained by the significant increase in the LETd at the distal edge leading to more DSB-induction,its accumulation into the cytosol, and upregulation of Trex1 (IFNβ suppressor). By weighting the dose by RBEdsb a uniform level of IFNβ production over the volume-of-interest can be obtained
Conclusion: Modulating high-LET particle dose and weight is possible to obtain a uniform, optimal IFNβ production within a volume of interest, which can potentially support a robust anti-cancer immune response.Ongoing work to model IFNβ stimulation within various tumor microenvironments, such as hypoxia, is in progress
Keywords
Radiation Therapy, Heavy Ions, Treatment Planning
Taxonomy
Not Applicable / None Entered.
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