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Radiation Planning and the Dosimetric Impact On An Orthotopic and Syngeneic Murine Model of Breast Cancer

S Rusu1*, B Janic2, S Brown3, G Valadie4, J Ewing5, I Chetty6, N Wen7, (1) Henry Ford Hospital, Detroit, MI, (2) Henry Ford Hospital System, Grosse Point Woods, MI, (3) Henry Ford Hospital, Detroit, MI, (4) Wayne State University, Detroit, MI, (5) Henry Ford Hospital System, Detroit, MI, (6) Henry Ford Health System, Canton, MI, (7) Henry Ford Health System, Detroit, MI


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

Room: AAPM ePoster Library

Purpose: To present the impact of 3D dose distributions on radiation response and overall animal survival on an orthotopic syngeneic murine breast cancer model (4T1Luc tumor) using a Small-Animal Radiation Research Platform(SARRP). This animal model and evaluation of the dose conformality’s effect on overall survival are useful tools needed to evaluate novel therapies.

Methods: Balb/c mice (n=10) were orthotopically implanted into the mammary fat pad with 2x106 of 4T1Luc cells that are used as a model for aggressive triple negative breast cancer(TNBC). The orthotopic implantation of 4T1 cells gives rise to primary tumors and subsequent metastases resembling multiple stages of malignant breast cancer. Approximately 2 weeks after implantation, mice were imaged using a high resolution cone beam-CT (CBCT), integral to the SARRP, and planned using the Muriplan 2.2.2 Software (Xstrahl Inc.,Suwanee,GA). Treatment plans were evaluated using dose volume histogram and isodose contours and were assessed as useful if measurable tumor responses without toxicity (monitored for about two months) were produced. Survival time was defined as the duration from tumor implantation to euthanasia, dictated by a decrease in animal health (loss of 20% body weight or characteristic behavior identified by animal care personnel or Staff Veterinarian).

Results: Mice received 20Gy in four equal daily fractions as either 4 non-coplanar arcs (n=3) or two tangential fields (n=7) to the 90% isodose line. Using 4 non-coplanar arcs, mice died within 7 days of radiotherapy implicating a lethal dose to the adjacent intestines. Using two tangential fields, measurable tumor response without toxicity was achieved, specifically, minimal weight loss and no deaths occurred.

Conclusion: the SARRP, image guidance, and the planning software to perform real time planning allowed for the evaluation of the effect of 3D dose distribution on overall survival in a practical model of human TNBC. Two tangent plans achieved measureable tumor response.

Funding Support, Disclosures, and Conflict of Interest: The work was supported by a Research Scholar Grant, RSG-15-137-01-CCE from the American Cancer Society. The studies presented with partially supported by NIH CA218596 (co-PIs: Ewing, Brown).


Cone-beam CT, Dosimetry, Dose Volume Histograms


TH- Small Animal RT: Response assessment

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