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Radiotherapy with No Margins

S Yasmin-Karim1,2 , M Moreau3 , W Ngwa1,2,3*, (1) Harvard Medical School, Boston, MA, (2) Brigham and Womens Hospital, Dana-Farber Cancer Institute and Harvard Me, Boston, Massachusetts, (3) ,


(Thursday, 8/2/2018) 7:30 AM - 9:30 AM

Room: Karl Dean Ballroom A1

Purpose: This study investigates the feasibility of radiotherapy without adding clinical target volume margins. We hypothesis that only a sub-volume of the gross tumor volume (GTV) is needed for priming a robust immune respone, to kill cancer cells in the rest of the tumor, as well as cancer cells in distant un-irradiated sites.

Methods: To test our hypothesis, we administered smart radiotherapy biomaterials (SRBs) incorporating nanoparticles with the immunoadjuvant anti-CD40 into a tumor sub-volume in mice cohorts with lung and pancreatic tumors. The tumor sub-volume was then irradiated using a small animal radiation research platform (SARRP). Tumor volume measurements of the treated tumors and distant untreated tumors on the same mice were assessed, as well as survival and metastatic progression.

Results: For mice with both treated and untreated lung tumors on each flank of the mice, results showed a remarkable 60% of mice administered with SRBs with complete tumor regression by 25 weeks, while no mice treated with only radiotherapy at the same dose survived. Similar robust immune response was observed for mice with pancreatic cancer. Further analysis of immune-cell populations showed significant presence of killer T-cells in the untreated tumors of mice administered with SRBs compared to mice only treated with radiotherapy. Pathological examination of excised lungs from sacrificed mice also showed no metastasis after 60 days in 90% of mice with pancreatic tumors. Meanwhile mice treated with only radiotherapy all had lung cancer metastasis.

Conclusion: Our results confirm the hypothesis that treating only a tumor sub-volume with SRBs could result in complete tumor regression and major increase in survival, and inhibition of metastastic progression. These results provide major impetus for more studies where successful development of such an approach could usher in an era of radiotherapy without need for margins like the clinical target volume.


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