The Radiobiology of Radiosurgery
Validity of the linear quadratic model (LQM) is generally supported in the dose ranges of 1 to 5Gy. This makes LQM applicable to most standard fractionation and hypofractionation therapies. Beyond this range, however, debate exists as to the validity of the model.
Non-LQM Radiobiological Mechanisms
The abscopal effect is a phenomenon in which local radiotherapy is associated with the regression of metastatic cancer in unirradiated locations. Abscopal effect is more common in radiosurgery treatments than in conventional fractionation, possibly because of improved immune mediated response and proximal vascular damage.
Treatments over 10Gy/fraction result in significant vascular damage. According to the LQ model, this should induce radio-resistance via hypoxia and acidification. However, the larger fraction dose fractions used in radiatiosurgery have been shown to continue cell killing for as long as 3 days after irradiation due to vascular damage.
In contrast to standard fractionation, which induces an immunosuppressive effect, radiosurgery appears to induce local release of tumor specific antigens. These antigens, combined with a pro-inflamitory and pro-axidant cytokines, improve priming of tumor specific T cells. The net effect is increase immune response to combat the cancer.
Physical Parameters Impacting Biological Response
Geometric Window of Opportunity
Geometric Window of Opportunity simply refers to the ability of highly conformal dose distributions achieved in SRS and SAbR/SBRT to avoid critical structure all together. This capacity allows for significant dose escalation improving tumor control probability. Thanks to improvements in real time localization techniques, the geometric window of opportunity is expanding.
Sublethal repair begins, to some extent, immediately and the repair times for tumors are generally shorter than those for normal tissue. Therefore, reducing treatment duration in the SRS/SBRT regime is desirable from a tumor killing prospective.
Treatment duration may be subdivided into two categories:
Intra-fraction time is the time it takes for a given delivery. Increased delivery time increases the likelihood of patient/organ motion which can reduce the geometric window of opportunity. Additionally, treatment times exceeding 30 minutes may lead to significant reduction of tumor cell sterilization.
Inter-fraction time is the time between treatments in a given treatment regimen. Increased inter-fraction time allows for proliferation and repopulation of tumor cells, reducing TCP. However, allowing 24 hours or more inter-fraction time allows for re-oxygenation of the tumor which increases its radio-sensitivity and increasing TCP.
SRS/SBRT plans typically have significant dose heterogeneity in order to optimize dose fall-off outside the target. This is typically acceptable and may even be desirable as, up to a point, increased dose increases TCP.
Dose heterogeneity also increases the consequences of geometric misalignment which can result in severe overdose of adjacent normal structures or under dose to the target.
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