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Ultrahigh Dose Rate FLASH Radiation Does Not Spare the Immune System in Cardiac and Splenic Models of Lymphopenia

B Venkatesulu*, A Sharma , J Pollard-Larkin , R Sadagopan , R Tailor , G Aleman , S Neri , J Symons , M Gillin , P Balter , S Lin , S Krishnan , UT MD Anderson Cancer Center, Houston, TX


(Tuesday, 7/16/2019) 1:15 PM - 1:45 PM

Room: Exhibit Hall | Forum 4

Purpose: Recent reports have shown that very high dose rate radiation referred as FLASH tend to spare the normal tissues while retaining the therapeutic effect on tumor. We investigated if 35Gy/sec can spare the immune system in models of radiation induced lymphopenia.

Methods: We modified a decommissioned Linear accelerator in which very dose rates of 20Mev electrons could be given in very short pulses. We compared 35Gy/sec and conventional dose rate 0.1Gy/min radiation in a classic clonogenic assay in murine KPC, Panco2 pancreatic cancer cell lines. We also assessed if there is a differential lymphocyte sparing property in cardiac and splenic models of murine lymphopenia. We compared single fraction hypofractioanted dose vs multiple fractionated dose to assess the impact of dose and fraction interaction with dose-rate and lymphopenia outcomes.

Results: We did a classic clonogenic assay with 0,2,4,6 and 8 Gy of radiation with KPC and Panc02 cells at conventional and ultra-high dose rates. The ultra-high dose rate was more potent in killing KPC and Panco2 tumor cells compared to conventional dose rate with a radiation dose enhancement factor (DEF10) of 1.310 and 1.365 respectively. We found that both ultra-high dose rate and conventional dose rate tends to kill tumor cells predominantly through apoptosis. We found that ultra-high dose rate caused depletion of circulating CD3, CD4, CD8, and CD19 cells similar to conventional dose rate in cardiac model of lymphopenia at a dose of 2Gy per day for 5 days.

Conclusion: Our study shows that at dose rates of 35Gy/sec there is no immune compartment sparing in cardiac and splenic models of lymphopenia. The optimal dose rate for sparing the lymphocytes needs to defined. Future experiments should be tuned to define the optimal dose, dose rate and fraction size for reducing the normal tissue complication probability.

Funding Support, Disclosures, and Conflict of Interest: This study was supported in part by the MD Anderson Cancer Center support grant P30 CA16672, a seed grant and the John E. and Dorothy J. Harris Endowed Professorship(S.K) and U01CA216468 (S.H.L and S.K.). The flow cytometry experiments were supported by NCI P30CA016672 grant.


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