Purpose: This study investigates a new concept for radiotherapy treatment of metastatic sites using a systemic anti-tumor immune response known as the abscopal effect. We hypothesize that irradiating only a sub-volume of the gross tumor volume from the primary tumor while administering an immunoadjuvant is needed for priming a robust immune response to kill cancer cells in distant un-irradiated sites.
Methods: Immunocompetent male C57BL/6 mice were inoculated with the lewis lung carcinoma cells LLC1, growing two subcutaneous tumors. One tumor acting as primary tumor was treated with the immunoadjuvant Anti-CD40, delivered either as intratumoral injection or as sustained delivery from a loaded biomaterial. Irradiation of the primary tumor was given either as entire tumor radiation or sub-tumor irradiation while delivering the same radiation dose. Statistical significance of survival data was analyzed using Log-rank test.
Results: Tumor growth in the secondary, non-treated tumor representing a metastasis was lowest when radiation was delivered to only a tumor sub-volume when the immunoadjuvant was released over time and was stable with direct injection of Anti-CD40. In the treated primary tumor sub-volume and full-volume irradiation had a similar outcome in tumor volume. Overall survival for mice treated with immunoadjuvants released over time increased significantly for full (p<0.01) and sub-volume (p<0.0001) irradiation, respectively.
Conclusion: These results confirm the hypothesis that treating metastases by priming the abscopal effect can be achieved by irradiating only a tumor sub-volume of the primary tumor while having no notable drawback for the primary tumor. This finding provides impetus for future studies optimizing the dose for maximal outcome towards potential clinical translation of an approach, where clinical or planning target volumes may not be needed in using radiotherapy to treat patients with metastatic disease, including patients with recurrence who are close to normal tissue toxicity limits.