Novel Proton Beam Arrangements for Prostate Cancer Using In Vivo Range Verification May Significantly Reduce the Risk of High Grade Rectal Toxicities

77 Background: Prostate cancer is a leading cause of cancer related death in men worldwide, with recurrence being a major clinical problem after radiotherapy. There is an unmet need to better characterize radioresistant tumors and identify biomarkers to improve patient outcomes. Methods: We identified that miR-106a was overexpressed in radiation resistant cell lines compared to parental cells. We analyzed The Cancer Genome Atlas dataset to assess miR-106a expression in normal prostate, and low- to high-grade prostate tumors. To assess the functional role of miR-106a, we performed in vitro and in vivo assays for radiation response, including clonogenic survival, proliferation, senescence, and tumor xenograft growth after radiation. We performed gene array and pathway analyses to identify downstream effectors of miR-106a. Results: MiR-106a expression was significantly higher in prostate tumors with Gleason score > 7 compared to Gleason ≤ 7, suggesting miR-106a is involved in high grade disease. MiR-106a overexpression confers radioresistance in vitro and in vivo, by targeting LITAF. We now extend miR-106a’s effects to upregulation of ATM at the promoter level, thereby increasing ATM transcript and protein in the cell. Unexpectedly, we found that miR-106a’s mechanism of radioresistance through ATM upregulation does not alter DNA damage repair. ATM upregulation affects clonogenic survival through reduced senescence. KU-55933, a specific ATM kinase inhibitor, resensitizes miR-106a overexpressing cells to radiation by inducing senescence, a predominant mode of cell death in prostate cancer. Conclusions: Our research challenges the current paradigm of ATM and DNA damage repair by outlining another mechanism of radioresistance through alteration of senescence. Our findings suggest that miR-106a may be a promising biomarker for high-grade disease and radioresistant prostate cancer. In addition, we have identified a therapeutic intervention for miR-106a induced radioresistance. Improvements in bioavailability of KU-55933 may lead to its clinical use in combination with radiation therapy to radiosensitize miR-106a induced radioresistant prostate cancer.

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Detectors for in vivo range and dose verification in proton therapy

International Journal of Modern Physics Conference Series ◽

10.1142/s2010194516602179 ◽

2016 ◽

Vol 44 ◽

pp. 1660217 ◽

Cited By ~ 1

Author(s):

R. Alarcon ◽

D. Blyth ◽

E. Galyaev ◽

J. Holmes ◽

L. Ice ◽

...

Keyword(s):

Proton Beam ◽

Proton Therapy ◽

Bragg Peak ◽

Dose Verification ◽

Particle Detection ◽

Under Construction ◽

Proton Dose ◽

Better Than ◽

Range Verification

Particle detection instrumentation to address the in vivo verifications of proton dose and range is under development as part of a proton therapy research program focused on patient quality assurance. For in vivo proton range verification, a collimated gamma detector array is under construction to indirectly measure the position of the Bragg peak for each proton beam spot to within 1–2 mm precision. For dose flux verification, a proton fluence detector based on the technology of the Micromegas is under construction. This detector has an active area of about 100 cm2, coordinate resolution of better than 1 mm, and handling of incident proton beam fluxes of 109–1013 particles/s.

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SU-GG-J-149: Feasibility of In-Room PET Imaging for in Vivo Proton Beam Range Verification

Medical Physics ◽

10.1118/1.3468372 ◽

2010 ◽

Vol 37 (6Part11) ◽

pp. 3180-3180 ◽

Cited By ~ 3

Author(s):

S España ◽

X Zhu ◽

J Daartz ◽

N Liebsch ◽

G El Fakhri ◽

...

Keyword(s):

Proton Beam ◽

Pet Imaging ◽

Beam Range ◽

Range Verification

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A Study of The Clinical Viability of A Prototype Compton Camera for Prompt Gamma Imaging Based Proton Beam Range Verification

10.21203/rs.3.rs-639221/v1 ◽

2021 ◽

Author(s):

Jerimy Polf ◽

Carlos A. Barajas ◽

Gerson C. Kroiz ◽

Stephen W. Peterson ◽

Paul Maggi ◽

...

Keyword(s):

Proton Beam ◽

Prompt Gamma ◽

Reconstruction Algorithms ◽

Compton Camera ◽

Detection Rates ◽

Proton Beams ◽

Proton Beam Radiotherapy ◽

Beam Range ◽

Range Verification

Abstract We present Compton camera (CC) based PG imaging for proton range verification at clinical dose rates. PG emission from a tissue-equivalent phantom during irradiation with clinical proton beams was measured with a prototype CC. Images were reconstructed of the raw measured data and of data processed with a neural network (NN) trained to identify “true” and “false” PG events. From these images, we determine if PG images produced by the prototype CC could provide clinically useful information about the in vivo range of the proton beams delivered during proton beam radiotherapy. NN processing of the data was found necessary to allow identification of the proton beam path from the PG images. Furthermore, to allow the localization of the end of the proton beam range with a precision of ≤ 3mm with the prototype CC, ~1 x 109 protons would need to be delivered, which is on the order of magnitude delivered for a standard proton radiotherapy treatment field. To obtain higher precision in beam range determination and to allow imaging a single proton pencil beam delivered within the full treatment field, further improvements in PG detection rates by the CC, NN data processing, and image reconstruction algorithms are needed.

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