Organs at\ua0Risk (OAR) Tolerance in Hypofractionated Radiosurgery

For CyberKnife radiosurgery, the precise interpretation of the normal probability of tissue complications (NTCP) is extremely important due to the reverse planning algorithm and the non-isocentric irradiation geometry adopted by the system, which requires the setting of dose constraints for any organ at risk (OAR). Despite eight decades of practice in radiation therapy, the current understanding of radiobiology remains fairly imprecise, especially the tolerance limits of OAR at hypofractioned schedules. Here, we provide an overview of the radiation tolerance limits of the optic pathway, spinal cord, brain and other central nervous system OARs. Above all, we summarize the basic principles of radiobiology and describe how these can be used to aid decision making for hypofractionated treatments. Basically, we provide radiobiological bases to build models that can be used to safely and effectively extrapolate the doses to be delivered in hypofractioned schedules starting from single fraction clinical data and conventionally fractionated radiotherapy. Although this approach has several limitations, it can provide some practical suggestions and help users to increase confidence with hypofractionated approache

Large Vestibular Schwannomas

Single-fraction radiosurgery has demonstrated its efficacy in large and very large series of patients with vestibular schwannomas. However, single-fraction radiosurgery is reserved to small- to medium-sized lesions. The current standard therapeutic dose (12\u201314 Gy) may actually be too high to be tolerated by healthy surrounding nerve structures, such as the brainstem, which are in direct contact with large schwannomas. Furthermore, there is a direct correlation between tumor size and facial nerve damage. Hypofractionated treatments can be adopted in larger lesions when the patient is not a candidate for surgical resection. The lower dose per fraction used in hypofractionated schedules is, in theory, less harmful for the surrounding healthy structures allowing for higher rates of hearing, facial, and trigeminal nerve preservation, especially in such large lesions. Despite the limited experience in the treatment of Koos grade IV vestibular schwannomas, the results appear interesting, with local tumor control at midterm that are not very different from those obtained in smaller tumors. The major complication is represented by a form of subacute hydrocephalus that affects 10\u201315% of patients that become symptomatic in weeks and can be treated without the necessity of tumor resection. Although controversial, a similar approach represents a valid and effective treatment modality at least for elderly patients or for those with severe medical comorbidities, for whom radiosurgery can be a treatment option. Here, we review the role of hypofraction for the treatment of large and very large vestibular schwannomas and provide practical suggestions for its application