**3.2. Image-guided radiation therapy**

portal-imaging device (EPID) or a cone beam CT (CBCT). CBCT generates an image of the tumor and all surrounding normal structures using the same linear accelerator with which the patient is being treated. Linear accelerators produce the images of CBCT through either the same treating megavoltage beams (MV-CBCT) or built-in kilovoltage device (KV-CBCT). Appropriate adjustments of the exact treatment position can then be made daily to ensure that the tumor is receiving the prescribed dose of radiation, and normal tissues are receiving doses within their tolerance range. Recently, there are different devices for setup accuracy using either ultrasonography, infrared, radiofrequency for verification or setup positioning and to

The major hypothesized benefits of IMRT are a reduction in the dose to normal structures, as well as the potential for dose escalation. In IMRT, radiation beam is subdivided into a very large number of optimized small beamlets each with a unique intensity of radiation, influ‐ enced by the patient's anatomy in the path of the beamlet allowing tailored radiation dose distributions, to both the tumor and normal tissues. Three-dimensionally concave or convex shape configuration is one of the important characteristics of IMRT, resulting in a dramatic reduction of high doses of radiation to normal structures near the target. Moreover, it allows for differential doses to be delivered within the same target, giving the component at higher risk of recurrence higher dose while the rest of the target is being treated to a conventional dose. This technique is called simultaneous integrated boost (SIB). This is attractive in certain situations, in that it allows a higher dose per fraction to the target, while giving a lower dose per fraction to normal structures. Biologically effective dose (BED), which is calculated based on the linear-quadratic (LQ) model, is commonly used on trial to relate the unconventional

The main disadvantage of IMRT, in some instances, is the increase in low doses to normal tissues leading to increase in the body integral dose (i.e., higher total dose of a large volume). Other challenges of IMRT are the rapid fall-off of dose; therefore, patient immobilization and daily setup verification become critical. Slight motion or setup error may result in a geograph‐ ic miss; the high dose is deposited in the critical structure designated for avoidance. Therefore, it is always stated that daily setup verification better precedes IMRT especially if proximity of a nearby critical structure is a concern. Fortunately, the brain moves minimally, and stand‐ ard immobilization devices yield relatively high daily setup accuracy. Because IMRT dose distributions are highly complex, it is not unusual to see unanticipated toxicities in low-dose areas, such as alopecia or mucositis, in the exit-beam regions [7]. Increased incidence of second malignancy was postulated as a serious late side effect. However, it remains unclear wheth‐ er second malignancies are a real or a hypothetical risk [40]. Intensity-modulated radiothera‐ py has several potential benefits in specific CNS tumors. Medulloblastoma represents a good example that is treated after surgery with radiotherapy and cisplatin-based chemotherapy, and radiation. Both platinum and radiotherapy significantly contribute to the occurrence of ototoxicity. However, the use of IMRT can spare the auditory apparatus (cochlea) while still maintaining full dose to the target. Reduction in cochlear dose from 54.2 to 36.7 Gy leads to reduction of grade 3 or 4 hearing loss from 64 to 13% with the use of IMRT, compared with

deal with intra-fractional movements.

460 Neurooncology - Newer Developments

dose to that for the well-known conventional fractionation.

Image-guided radiation therapy (IGRT) is the technique of using imaging technology at the time of each treatment to verify accurate positioning.

There are several types of IGRT including CBCT, MV CT (helical tomotherapy), CT-on-rails, the use of electronic portal imaging devices (EPIDs), ultrasound guidance radiofrequency, and fiducial monitoring. Advances in IGRT have allowed selective boost of dose to some targets while at the same time selectively sparing normal structures more aggressively.

#### **3.3. Stereotactic radiosurgery and stereotactic fractionated radiotherapy**

The term *radiosurgery* was selected because of its similarity to stereotactic neurosurgery. Radiosurgery technology has become increasingly more available, and its application has widened. Its current indications include arteriovenous malformations, benign brain tumors, malignant brain tumors, and functional disorders. Delivery of radiosurgery is complex and coordination of care by the neurosurgeon, radiation oncologist, and medical physicist is essential. Appropriate coordination leads to improved quality of care, reduction in practice variation, and improved patient satisfaction [42].

Radiosurgery entails a single treatment, whereas conventional RT used multiple treatments. Further, in conventional fractionation regimens, normal brain tissue adjacent to the target receives a considerable dose of radiation. Taking into consideration late toxicity, radiosur‐ gery is able to treat with considerably high-dose gradients adjacent to a nonmobile target that makes its use in the brain ideal. The use of a very large number of beams (significantly modulated beams) ensures that the geometry provides ideal physical dose distribution for targets less than 4 cm in greatest dimension with maximally low dose to surrounding tissues. Beyond this limit, it is difficult to achieve a rapid fall-off in these normal tissues. Radiosur‐ gery can be performed using various devices, including the gamma knife, particle beam devices, or modified linear accelerators (X-knife, cyberknife). With the great technologic advances in software and hardware, there is no clear advantage of one technology over the other [43]. The linear accelerator-based units can serve to treat non-radiosurgery patients.

Radiosurgery and neurosurgical approaches are often complementary, with the advantage that radiosurgery does not require a craniotomy, nor general anesthesia and patients are usually discharged the same day.

#### **3.4. Charged particles**

Proton beam therapy gained great interest in the radiation oncology community especially the pediatric one. This is related mainly to the dosimetric advantages of protons. Proton beam deposits its energy rapidly in what is known as the Bragg peak, a narrow range energy deposition where at the end of its path length the particle slows and. delivers radiation with

a rapid fall-off. This confines the radiation to a smaller volume (clinical tumor volume) and extremely reduces the exit dose. The beam stops at a given depth that depends on their initial energy. Therefore, the possibility of wide low doses of radiation to normal tissues is mini‐ mal; different from IMRT. The dose fall-off beyond the Bragg peak is very rapid, reaching zero within a few millimeters beyond the maximum [44–46]. Despite the lack of Level 1 evidence, retrospective studies do exist to support its use in pediatric intracranial lesions. Traditional proton therapy and intensity-modulated proton therapy (IMPT) resulted in more efficient sparing of normal tissue compared to photon-based IMRT [47]. A model was designed to predict neurocognitive dysfunction after RT. The reduction in lower-dose volumes and mean dose afforded by proton therapy might reduce the incidence of late-term sequelae in chil‐ dren with medulloblastomas, craniopharyngiomas, and optic-pathway gliomas [48].
