15.1 Introduction

With over 100 years of clinical practice and scientific evaluation, much is known about the application of radiotherapy to address malignancies. Important in this perspective is the relationship of cell kill versus cell survival. Simplistically, the former relates to eradicating cancer and the latter to preservation of adjacent normal tissue. The scientific endeavor to demonstrate and explain this is radiobiology. By this means, the clinical practice of radiotherapy is explained, and methods of modifying the standard approach explored. The basic component of the science is the cell-survival curve whereby in vitro a population of cells are irradiated, and the proportion of surviving cells, after varying doses and fractions over time, is evaluated. From this, the most valid demonstration of what is achieved is modeled by the linear quadratic (LQ) equation.s. Literatur ^,​ s. Literatur There are two components to the graphical demonstration of this equation: the alpha (α) component (single-hit/linear kinetics) and the beta (β) component (double-hit/quadratic kinetics).s. Literatur ^,​ s. Literatur Both malignant lesions and normal tissue can then be qualitatively described as being of early or late responding nature.s. Literatur

There are significant challenges, however, in using this approach to describe what happens clinically when any form of radiotherapy is utilized to treat benign tumors, such as vestibular schwannomas.s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur Cell kill, while it can occur, at least with vestibular schwannoma, is much more difficult to demonstrate clinically and experimentally. Upward of 40% of treated vestibular schwannomas can demonstrate “central necrosis” radiologically in short-term follow-up, associated with a small component of volume expansion, subsequently settling down, and not regarded as true increase in size.s. Literatur On magnetic resonance (MR), this central component has the imaging characteristics of necrosis (an implosion effect), demonstrated in the few publications where resected cases post–stereotactic radiosurgery have (SRS; ≥12 Gy single session) enlargement and are pathologically evaluated.s. Literatur In a series where single-digit patient numbers were reported, ischemic infarction is evident, but with viable cells present on the periphery of the resected tumor.s. Literatur This feature was evident in all four surgically resected cases in this series.s. Literatur

The difficulty in extrapolating this circumstance is that, as stated earlier, only 40% of vestibular schwannomas treated demonstrate this central necrosis radiographically, there is still a minimum of another 50% of treated cases (given that >90% are locally controlled) that do not demonstrate this feature but are still “controlled,” with long-term follow-up. In addition, those operated upon post-SRS where enlargement is evident, that form part of the typically less than 10% of patients treated, may not be biologically the same as those who remain controlled.s. Literatur An experimental model has been developed with a subrenal capsule xenograph in mice that may provide an answer.s. Literatur Histological review indicates decreased tumor size with cytotoxic and vascular effect, at higher SRS doses than are used in the clinical situation.

Comparable control figures are reported for meningiomas, when treated by the same means, presumably with the same biological effect, but with a much lower circumstance of “central necrosis” demonstrated in follow-up. Conti et al, in describing the outcomes of CyberKnife management of perioptic meningiomas, discussed the radiobiology of hypofractionated multisession radiotherapy.s. Literatur This is in the context of the optic nerve being the dose critical structure. This study graphically demonstrates using the LQ model, and an α/β of 2 for the tumor and 0.55 for the optic nerve, a means of creating a total dose and fraction number relationship for meningiomas, a tumor comparable to vestibular schwannomas. Others have reported, however, that the LQ model does not predict for optic neuropathy.s. Literatur ^,​ s. Literatur ^,​ s. Literatur

Classical radiobiology, in demonstrating an effect, relies descriptively upon the four “Rs” (re-oxygenation, redistribution, repopulation, and repair) with intrinsic radiosensitivity added as a fifth in more recent years.s. Literatur A concern is how applicable this methodology is to single session (≥12 Gy) SRS or multisession hypofractionated radiotherapy.s. Literatur ^,​ s. Literatur ^,​ s. Literatur To date, it has not been evident whether there is a good alternative model, although the linear quadratic debate continues.s. Literatur Radiobiological effects have been reported to impact upon the outcomes of treatment. In the early 1990s, long-term cranial nerve deficit rates post-SRS were regarded as being high, even in the context of high tumor control. Since then, there was a reduction in the utilized dose, with minor perceptible change in local control, but with improvement in cranial nerve preservation rates.s. Literatur This dose change, associated with significant technological advances, accompanies many biological events.

15.2 Important Topics

Related posts:

17 Linear Accelerator Radiosurgery for Treatment of Vestibular Schwannoma (Non-CyberKnife) 21 Secondary Radiation Treatment of Vestibular Schwannoma After Prior Microsurgery or Radiosurgery 19 CyberKnife Radiotherapy for Treatment of Sporadic Vestibular Schwannoma 18 Conventional Fractionation LINAC-Based Stereotactic Radiotherapy for Treatment of Sporadic Vestibular Schwannoma 23 Complications of Radiosurgery and Fractionated Radiotherapy for Vestibular Schwannoma 25 Imaging Follow-up After Radiosurgery of Vestibular Schwannoma

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