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Investigation Into the Effects of Radiation Spatial-Fractionation Pattern On Treatment Response in a Rat Tumor Model

JN Rivera1,2*, SK Kasoji1,2 , TM Kierski1,2 , PA Dayton1,2 , SX Chang1,3 , (1) (2) University of North Carolina, Chapel Hill, NC, (2) NC State University, Raleigh, NC (3) UNC School of Medicine, Chapel Hill, NC

Presentations

(Tuesday, 7/31/2018) 9:30 AM - 10:00 AM

Room: Exhibit Hall | Forum 4

Purpose: Decades of preclinical research has shown that spatially-fractionated radiation therapy (SFRT), such as microbeam radiation therapy (MRT), can eradicate tumors while sparing normal tissue functions exposed to the same radiation. However, the underlying working mechanism of all forms of SFRT remains poorly understood. We hypothesize that (1) tumors respond differently to SFRT compared to conventional broad-beam radiation of the same integral dose, (2) tumor microvasculature responds differently to different spatial fractionation patterns, and (3) SFRT parameters may be optimized to maximize therapeutic ratio.

Methods: We study longitudinal changes in tumor volume and tumor microvasculature post a single-dose of radiation from various SFRT patterns and conventional radiation using a rat fibrosarcoma tumor model. We modify a research irradiator to produce four different SFRT patterns and one broad-beam radiation (BRT) pattern using custom-built collimators. Thirty-six female Fisher 344 rats are implanted with tumor tissue in the right flank. Six treatment groups (n=6 animals per group) include four SFRT-pattern groups, one conventional BRT group, and one control group. All groups were treated with 20Gy integral dose to tumor, except for untreated (control) and MRT-HD (high 50Gy integral dose) groups. Tumor volume and vascular density were imaged using traditional B-mode and contrast-enhanced high-resolution ultrasound, acoustic angiography, at pre-treatment baseline and every 3 days.

Results: Our data shows that among same-integral-dose groups the conventional radiation group has the best tumor control; however, tumor microvasculature density changes seen in the SFRT groups are very different than that of the conventional BRT group. Further, toxicity (body weight loss) is highest in the conventional BRT group.

Conclusion: Our data indicate that radiation spatial fractionation leads to very different changes in tumor volume and microvasculature compared to conventional radiation. Further studies are needed to reveal the true clinical potential of SFRT as a high therapeutic ratio cancer treatment.

Keywords

Radiobiology, Radiation Therapy

Taxonomy

TH- Radiobiology(RBio)/Biology(Bio): Bio- tissue and microenvironment

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