What Happens during radiosurgery?

key aspects of stereotactic radiosurgery:

Accuracy of treatment delivery
A single, large fraction
High central dose escalation
Sharp peripheral dose-fall.

Tumours are mitotic pathologies and grow due to uncontrolled cell growth. A single, high dose of radiation makes an impact on the DNA of the tumour cell, which is a key element for the tumour's growth. It is common to all cells exposed to radiation. However, when a single large dose is delivered, breaks are created in the strands of helical DNA molecules. In other techniques, where the dose is delivered in pieces, the effects are much lesser because radiosurgery causes much more DNA double-strand breaks, as compared to treatment through multiple small doses. It makes the repair of these breaks difficult, hence a more pronounced effect.

Cell Cycle and DNA damage

Cell cycles of benign tumours like acoustic schwannoma and meningioma are very slow as compared to malignant tumours, which are usually treated by fractionated radiation. Low-dose treatment can damage malignant tumours like gliomas, where most cells are under the G2 and M phase of the cell cycle, as compared to benign tumours where most cells are under the G0 and S phase. The cells in G0 and S phase are resistant to low doses and respond to a single high dose of radiosurgery.

If the interval between doses is about 6 hrs, these resistant cells move to the sensitive G2/M phase. In Benign or slow growing tumours, reassortment is not true. So, Single large fraction Radiosurgery is more effective than fractionation in these tumours.

(Elkind MM et al Radiat Res 1965)

However, these defects become pronounced when the resting phase cells enter the G2 and M phase. Immunological effects of high-dose radiation make it difficult for tumour cells to survive.

Direct Effect of Radiation

During radiation, photons directly interact with the tumour DNA, causing direct damage. At the same time, secondary electrons from photons interact with other molecules like water to produce free radicals like OH-radical and produce more widespread damage.

In the case of Arteriovenous Malformation, since there is no abnormal mitotic growth, the proliferation is in response to abnormal shunt of arterial blood to the venous side. When a Radiosurgical dose is delivered, there is widespread endothelial damage leading to fibrous proliferation, foam cell accumulation, and hyalinization. This leads to narrowing of arterial lumen leading to obliteration of vascular lumen, and ultimately there is a blockage of abnormal shunt curing arteriovenous malformation.

All these biological processes take place a long time after radiosurgery. That is why the tumour, or AVM does not disappear immediately after radiosurgery but takes a few months to years to stop growing and reduce in size. In the case of malignant tumors, the reduction is faster as compared to benign tumors.

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