Room: Stars at Night Ballroom 1
Immunomodulatory effects, vascular damage, stem cells, and dose escalation are among explanations for the exceptionally high tumor control rates of Stereotactic Body Radiation Therapy (SBRT). Recent evidence for these hypotheses will be explored, as well as strategies for synergistic improvement.
An expanding body of evidence supports the concept that SBRT yields immunogenic effects that may augment local and systemic anti-tumor responses. The induction of immunogenic cell death, increased presentation of antigens, and enhanced immune cell infiltration of the tumor microenvironment appear to be important mediators of the anti-tumor immune effects of SBRT. Given the potential to modulate immune responses, there have been concerted efforts to combine SBRT with various immunotherapies in order to improve treatment responses and survival.
The earliest clinical example of vascular damage, arteriovenous malformation (AVM) obliteration, is one of the original successes with radiosurgery, and indeed, capillaries and tumor vasculature are particularly susceptible to radiation doses above 10Gy per fraction. The physical radiation doses used in SBRT of human tumors (30-50Gy in 1-5 fractions) may be insufficient to kill all tumor cells through DNA double-strand breaks alone. Vascular damage and resultant secondary tumor cell death appears to play an important role in SBRT.
However, it is also possible that there is no need to invoke a “new biology� to explain the high tumor control rates of SBRT, that it can be entirely modeled by dose escalation with standard radiobiological concepts.
These three leading hypotheses, immunomodulatory effects, vascular damage, and dose escalation, will be discussed and compared in this session.
Learning Objectives:
1. Understand the hypothesis of immunomodulatory interactions with SBRT
2. Understand the hypothesis of vascular damage from SBRT
3. Understand the biologically effective dose escalation concepts in SBRT
Funding Support, Disclosures, and Conflict of Interest: Dr. Grimm reports grants from Accuray, grants from NovoCure, outside the submitted work; In addition, Dr. Grimm has a patent DVH Evaluator issued.