Table 1.

Proposed fundamental and supporting requirements to facilitate augmented abscopal effect.

Requirements and Strategies	Effects
1. Fundamental prerequisite: minimal disruption of tumor and normal tissue vasculature	Enhances oxygenation, fixes potentially lethal damage, and maintains sensitivity to further doses of SBRT; enhances tumor hostile TME, e.g., normal physio-biochemical response and immune metabolism; permits continued delivery of subsequent doses of drugs; encourages cancer cell–TILs and NK cell interaction; carries tumor neoantigens and primes cancer killer cells for abscopal action, reduces side effects
2. Harmonization of a combination of therapies with SBRT/radiosensitization of cancer cells	Additive/synergistic (rarely antagonistic) effects; augments immune stimulation, handles heterogeneous cancer cell population
3. Enhancing tumor vasculature (under cover of anticancer treatment) or increasing resistance of endothelial cells or both	Converts hypoxic and anoxic cells to oxic cells to sensitize them for subsequent doses of SBRT, clears degraded and dead necrotic cell products, continues to present neoantigens, avoids endothelial senescence and long-term toxicities
4. Immunoadjuvants and abscopal effect enhancers	Has multiplier effects of abscopal reaction, facilitates in-vivo/in-situ therapeutic vaccine induction
5. Immunological RT planning: appropriate dose per fraction, dose painting, and concomitant SBRT boost	Optimizes SBRT for abscopal effect, improves cancer stem cell kill, improves immunological milieu, maintains supple ECM, and simultaneously reduces the side effects
6. SBRT as delayed boost	Targeting residual resistant population and stem cells to prevent recurrence and reseeding; reduced side effects