Purpose: Metastatic castration-resistant prostate cancer (MCRPC) is the most lethal form of prostate cancer and new treatment options are urgently needed. The purpose of this study is to investigate a new marginless radiotherapy (MRT) treatment strategy, targeting only sub-gross tumor volume (GTV) to generate an abscopal effect that will cause inhibition or regression of metastatic cancer.
Methods: Syngeneic murine model of MCRPC was generated in C57BL/6 mice using TRAMP-C1 cell line. Two tumors were created in each mouse, one subcutaneous (SQ) for direct treatment and another distant SQ/orthotopic tumor to observe abscopal effect. One SQ tumor was treated with a single dose of RT and FDA approved biodegradable polymer (SRB) loaded with 20 Âµg anti-CD40 antibody. Image-guided 5 Gy RT was given in a single dose. In treatment cohorts, either the PTV (planning target volume) with 10x10 collimator or GTV sub-volume (with 1x1, 3x3, and 5x5mm collimators) were irradiated. Intra-tumoral infiltration of dendritic (CD11b+) and Macrophage (F4/80+) along with helper (CD4+) and cytotoxic (CD8+) T lymphocytes were investigated in both treated and untreated tumors. Statistical analyses were achieved using Anova, Student t test, and Log-rank test.
Results: Significant tumor volume reduction to complete regression of tumors were observed in both treated and untreated tumors when a sub-volume of the GTV was treated with RT. (p<0.001). These results included orthotopic tumors, where both SQ and orthotopic models demonstrate increase survival duration (p<0.001) and (p<0.001) respectively. High infiltration of dendritic cells and T lymphocytes were observed in both treated and untreated tumors of the same mice, corroborating an immune-mediated abscopal response.
Conclusion: This study proffers a new MRT strategy for treating metastatic prostate cancer, leveraging the abscopal effect more efficaciously by treating only a GTV sub-volume. This strategy may spare peripheral dendritic cells, which are crucial in driving the immune-mediated abscopal effect.