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Boosting the Abscopal Effect with a Boost Dose of Radiotherapy and Immunoadjuvants in the Treatment of Aggressive Metastatic Pancreatic Cancer: A Preclinical Study

V Ainsworth1,2*, S Yasmin-Karim1,3,7, K DeCosmo1,5, R Mueller1,4,7, J Wood1,6, W Ngwa1,2,3,7 (1) Dana Farber Cancer Institute, Boston, MA, (2) University of Massachusetts Lowell, Lowell, MA, (3)Harvard Medical School, Boston, MA, (4)Heidelberg University, 69117 Heidelberg, Germany,(5)Northeastern University, Boston, MA,(6)University of Veterinary Medicine and Pharmacy in Kosice, Kosice, Slovakia, (7) Brigham and Womens Hospital, Boston, MA

Presentations

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

Room: AAPM ePoster Library

Purpose:
Pancreatic adenocarcinoma is among the most aggressive cancers. By the time of diagnosis, many people have already developed metastasis. The purpose of this study was to investigate the hypothesis that a combination of radiotherapy (RT) and immunoadjuvant to the primary tumor followed by a RT boost to a secondary tumor will lead to a robust abscopal effect, preventing progression of both treated and untreated tumors.

Methods:
Murine pancreatic cancer cell line Panc02 was used to implant a subcutaneous tumor on each flank of animals and a dorsal tumor, with one tumor representing the primary tumor, and the other tumors representing multiple metastasis. Once tumors reached treatable size, animals were randomized into different cohorts. The largest tumor was chosen as the primary tumor, receiving 6 Gy of image-guided RT using the Small Animal Radiation Research Platform plus immunoadjuvant anti-CD40. The contralateral tumor received a boost dose of RT 7 days after the first treatment. The size of both treated and untreated tumors were monitored to assess response. The study was then repeated incorporating immunoadjuvant anti-PDL1 with anti-CD40.

Results:
The results for both studies showed inhibition in tumor growth for the treated groups compared to the control group where all tumors grew progressively. For example, by day 15 after treatment, the primary tumor in control group was up to 9.5 times larger than those in treated groups, and abscopal effect was observed where progression of untreated tumors was also inhibited. The boost dose did not show any significant additional benefit.

Conclusion:
Using RT and immunoadjuvants can lead to enhanced therapy outcomes in aggressive/metastatic models of pancreatic cancer. Results for use of single fraction of RT were similar to those when using a boost dose of RT to secondary tumors.

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Keywords

Radiation Therapy, Image-guided Therapy

Taxonomy

TH- Small Animal RT: General (most aspects)

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