T Dos Santos*, D Cvetkovic, D Yang, L Chen, C Ma, Fox Chase Cancer Center, Philadelphia, PA

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  T Dos Santos

PO-GePV-T-444 (Sunday, 7/10/2022)   [Eastern Time (GMT-4)]

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Purpose: To clinically leverage the healthy tissue sparing effects of pulsed low-dose-rate radiotherapy (PLDR) and its comparable tumoricidal effects when compared to conventional radiotherapy (CRT), a quantification of the biologically equivalent dose BED of healthy tissues between the two treatment modalities is needed. This work investigates the radiation response of healthy tissues in vivo to CRT and PLDR in murine models.

Methods: A total-body dose-gradation single-fraction study was conducted on 49 adolescent female C3H mice organized into three groups: Control [9 mice receiving 0 Gy], PLDR and CRT [each with two sub-groups with 3&5-day post-irradiation end points, with duplicates of mice receiving 4, 6, 8, 10, 12 Gy integral doses]. Radiation delivery was performed on a Varian iX with SSD setup placing the central portion of the mice at the Dmax for 6MV photons with appropriate buildup. Effective PLDR dose rate was 10 cGy/min, and was achieved by delivering a train of 33 MU pulses at 3 minute intervals. CRT utilized a clinically relevant dose rate of 500 MU/min. Appropriate mice, 3 and 5 days after radiation delivery were euthanized, and the following were harvested for histological analysis: whole blood (count and proportion of components), spleen, lymph nodes, stomach, small intestine, large intestine, bone marrow, brain, pancreas, lungs and heart. Immunohistochemistry staining for radiation inducing inflammatory marker, TGF-b, were applied to harvested organs.

Results: Presented in Figure 1, is a subset of the results. H&E staining of small intestine cross-section; increase of atrophy and adenomatous hyperplasia observed for both CRT and PLDR in a dose dependent manner, when compared to control, where there are marked increases in tissue damage in CRT treated mice when compared to PLDR treated mice for each integral dose.

Conclusion: A sparing effect was observed for PLDR treated tissue lining the small intestine.

Keywords

Radiation Effects, TBI, Tissue Equivalency

Taxonomy

TH- Small Animal RT: Response assessment

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