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BEST IN PHYSICS (THERAPY): Influence of Treatment Parameters on Enhancement of Abscopal Effect: A Pancreatic Cancer Model

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S Yasmin-Karim

S Yasmin-Karim1*, M Moreau2 , W Ngwa3 , (1) Brigham and Women's Hospital, Boston, Massachusetts, (2) University of Massachusetts Lowell, Lowell, MA, (3) Harvard Medical School, Boston, MA

Presentations

MO-DE-605-6 (Monday, July 31, 2017) 1:45 PM - 3:45 PM Room: 605


Purpose: Mole described the abscopal effect whereby radiotherapy at one site may lead to regression of metastatic cancer at other sites, which were not irradiated. In nature, this phenomenon is not very predictable. Immunoadjuvants has been shown as an enhancer of this phenomenon. The purpose of this study is to optimize the time and dose of radiation and immunotherapy to achieve the highest enhancement of abscopal effect with lower adverse reaction.

Methods: A syngeneic murine model of pancreatic cancer was generated in the C57/BL6 mice in both flanks with mouse Panc-02 cell line. Anti-CD40 antibody was used in-situ for immunoadjuvant. For analyzing radiation dose, tumors of left flanks were treated as different randomized cohorts with X -ray radiation of total 30 Gy using fractionate doses (5Gy x 6 fraction or and 10 Gy x 3 fractions) for consecutive days. Anti-CD40 (20 µg/tumor) was given in two consecutive days right after radiation. A Small Animal Radiation and Research platform (SARRP) was used for image-guided radiation therapy at 220 kVp and 13 mA. Tumor growth was measured on both sides. For treatment onset analysis, tumor size of 1-3 mm diameter was chosen for early onset and 4 - 6 mm for late onset treatment group. Left sided tumors were treated with 5 Gy of single dose followed by single injection of 20 µg of anti-CD40 per/tumor.

Results: Multiple outcomes were developed from this study. It was shown that use of anti CD40 as immunoadjuvant enhances the direct and abscopal effects. Also shows 30 Gy of radiation with 5 Gy fractional is better for abscopal effect and early starting of treatment gives longer survival.

Conclusion: Overall, the results look promising. Preliminary results support lower radiation along with anti-CD40 is very promising. High radiation may reduce the functional capacity to some of immunoadjuvants locally.


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