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Minibeam Radiation Is Superior to Uniform Radiation for Abscopal Effect When Combined with PD-L1 Checkpoint Inhibitor Immunotherapy

S Chang1,2*, J Rivera2, K Laemont3, S Stryler3, A Tovmasyan3, G Palmer3, (1) Department of Radiation Oncology, University of North Carolina, Chapel Hill, NC, (2) Department of Biomedical Engineering, A Joint Program of the University of North Carolina and North Carolina State University, Chapel Hill, NC, (3) Duke University School of medicine, Durham, NC

Presentations

(Sunday, 7/12/2020)   [Eastern Time (GMT-4)]

Room: AAPM ePoster Library

Purpose:
To investigate whether spatially-fractionated radiation therapy is superior to uniform radiation in eliciting abscopal effect in an untreated tumor when combined with immune checkpoint inhibitor therapy.

Methods:
An immune competent dual-tumor model of six-week old female C57BL/6 mice injected on both flanks with murine mammary adenocarcinoma (EQ771) cells. The right tumor is the primary tumor and targeted for radiation while the left tumors is untreated. 10Gy-UniformRT +/- anti-PD-L1, 50Gy-MinibeamRT +/- anti-PD-L1, and a control group were used. Four dose of 200µg anti-PD-L1 was given on day 0,3,6,9 after a single radiation. The 10 or 50Gy are the surface maximum dose. The minibeam width is 0.31mm and c-t-c distance is 1.21mm. Spleen and both the treated and untreated tumors are harvested (~5 animals per group) 14 days post-radiation for flow-cytometry immunophenotypic analysis (Cd45+, CD3+, CD4+, CD8+ cells and additionally B cells and NK cells for the spleen tissues). Tumor growth of both tumors was monitored by tumor volume change measured by digital caliper.

Results:
For the treated tumor, 10Gy-UniformRT appears to have superior tumor growth control compared to the 50Gy-MinibeamRT, with or without anti-PD-L1 drug. For the untreated tumor, in the absence of anti-PD-L1 drug both the 10Gy-UniformRT and 50Gy-MinibeamRT showed no difference in tumor growth compared to the control group. When combined with anti-PD-L1 drug only the 50Gy-MinibeamRT showed the abscopal effect, a statistically significant reduction of tumor size for the untreated tumor. When combined with anti-PD-L1 therapy the 50Gy-MinibeamRT group showed elevated CD8+ cell population compared to the 10Gy-UniformRT group, which is consistent with the observed abscopal effect from the 50GyMinibeamRT group.

Conclusion:
Our study shows that when combined with anti-PD-L1 therapy spatially-fractionated radiation therapy is superior to uniform radiation in eliciting abscopal effect. However, uniform radiation is superior to minibeam radiation for treated tumor growth control.

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Keywords

Not Applicable / None Entered.

Taxonomy

TH- Small Animal RT: Response assessment

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