Back to Search
Start Over
Optimizing Sequence of PD-L1 Immune-Checkpoint Inhibitors and Radiation Therapy in Bladder Cancer
- Source :
- Bladder Cancer. 6:295-302
- Publication Year :
- 2020
- Publisher :
- IOS Press, 2020.
-
Abstract
- BACKGROUND: New bladder preserving strategies are needed for muscle invasive bladder cancer (MIBC). Combined therapy of immune-checkpoint inhibitors and radiation was shown to have synergistic antitumoral effects in preclinical studies. OBJECTIVES: We aim to evaluate whether the sequence of administration of this combined therapy impacts antitumoral response. METHODS: We developed an in-vivo syngeneic MIBC mouse model where murine bladder cancer cells (MB49) were injected subcutaneously in the right flank of C57BL/6 mice. Mice were then randomized to the following treatments: control, anti-programmed cell death ligand 1 (PD-L1) alone, radiation alone (XRT) consisting of 6.25 Gy x2 fractions, concurrent anti-PD-L1 with XRT, neoadjuvant anti-PD-L1 followed by XRT, or XRT followed by adjuvant anti-PD-L1 therapy. Tumor growth, survival, and rate of response were analyzed. RESULTS: Total of 60 mice were randomized. One-way analysis of variance showed statistically significant difference in tumor growth rate across the treatment arms (p = 0.029). Importantly, timing of immunotherapy (neoadjuvant, concurrent, or adjuvant) did not alter either tumor growth or survival (p > 0.05). The rate of response was also similar in each combination arm (p > 0.05). CONCLUSION: Combining anti-PD-L1 immunotherapy and radiation therapy offers optimal antitumoral responses. Timing of immunotherapy (neoadjuvant, concurrent, or adjuvant) does not appear to affect outcomes. Whether the toxicity profile differs across various sequential deliveries of combination therapy requires further evaluation.
- Subjects :
- 0301 basic medicine
Bladder cancer
biology
business.industry
Urology
Immune checkpoint inhibitors
medicine.medical_treatment
medicine.disease
Radiation therapy
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
Oncology
030220 oncology & carcinogenesis
PD-L1
medicine
biology.protein
Cancer research
business
Sequence (medicine)
Subjects
Details
- ISSN :
- 23523735 and 23523727
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Bladder Cancer
- Accession number :
- edsair.doi...........b47202b4e21d650c7b69803bba4d524d
- Full Text :
- https://doi.org/10.3233/blc-200315