**3. Radiotherapy**

RT is an essential treatment for most of the neuro-oncology patients. It is frequently used together with either surgery or chemotherapy or both as a curative treatment. Furthermore, its use in the palliative setting is vital in many situations for symptom relieving [35]. There are two types of RT: 1. teletherapy (external beam therapy) treating patients with MV energy, such as cobalt units and linear accelerators (Linacs), and 2. brachytherapy (internal application of radioactive sources). It is worth noting that providing effective, reliable, and safe RT is a

complex, tedious, and expensive procedure. It requires specialized building structures (bankers) for radiation protection, investment in expensive machinery, dosimetric measure‐ ments, and verification devices used by trained staff capable of efficiently using and optimal‐ ly maintaining such equipment. Furthermore, it requires continuously ongoing quality assurance and training programs for allocated staff. For these reasons, RT infrastructure in general may be poor in LMICs, to the extent that only four countries in Africa treat more than 100 children per year with RT, due to lack of radiation oncology staff, infrastructure, and services [36]. All RT programs require trained medical physicists and technical engineer staff to maintain their machines and to provide quality assurance of the treatment machines and planning programs. Highly trained radiation therapy technicians (RTT) responsible for planning RT treatment and for operating the machines are extremely needed for the appro‐ priate therapy procedures. Unfortunately, skilled staff is frequently attracted away to betterresourced countries providing them with superior payment and better standard of living representing a major issue that needs serious challenge.

Accommodation for the patient and accompanying adult are frequently problematic. In some countries, accommodation and transport for these patients are frequently offered by charity organizations. The major challenge that staff face when dealing with pediatric patients in RT department is the length of time that is needed. Children (and their parents) are more likely to be cooperative when they are not being rushed, and when the team takes the time to explain all the details with patience and when accommodating their fears and anxieties.

In general, it is essential to

**2.5. Spinal cord neoplasms**

456 Neurooncology - Newer Developments

**2.6. Management of cystic tumors**

choice for intracystic chemotherapy.

**2.7. Management of tumor recurrence**

**3. Radiotherapy**

providing sufficient materials for histological diagnosis.

Intramedullary spinal cord tumors are rare in the pediatric population, representing around 4% of all CNS tumors. Complete surgical excision if feasible or debulking is the general approach for spinal cord tumors. This procedure often leads to favorable outcome besides

Many pediatric CNS tumors are composed of a cystic component or having both cystic and solid parts. The potential space of the cystic portion creates an isolated microenvironment that may hinder local treatment (radiotherapy or local chemotherapy). Simple aspiration of the fluid that composes the cyst may sometimes be a sufficient treatment. Moreover, surgical resection can be considered for most cystic tumors. Local treatment may be applied includ‐ ing the insertion of a device in which medical therapy will be administered. Specifically, the use of intracystic radioisotope (radioactive iodine-125 or phosphorus 32) and intracavitary chemotherapy may be used in selected cases [31]. The main advantage of this treatment is the low rate of long-term sequelae. Intracystic chemotherapy has been advocated to delay aggressive treatment such as radical resection or irradiation. This method allows for admin‐ istration of effective therapy (commonly bleomycin or interferon) and abolishes the systemic toxicity of the systemic chemotherapy and the morbidity of surgical resection. Ommaya reservoir and instillations of single or multiple doses of active drugs remain the method of

The decision to reoperate on a recurred tumor must be taken in the light of the patient's life expectancy and QoL, tumor histology, time length between initial resection and recurrence, the risks and benefits of a second surgery, and the potential for adjuvant therapy such as radiotherapy and chemotherapy. Each case should be individually evaluated through multidisciplinary discussion taking into consideration the patient's family opinion and preference. It is worth emphasizing that surgical treatment of recurrent tumors should be seriously considered as reoperation has improved survival for many tumors such as choroid

RT is an essential treatment for most of the neuro-oncology patients. It is frequently used together with either surgery or chemotherapy or both as a curative treatment. Furthermore, its use in the palliative setting is vital in many situations for symptom relieving [35]. There are two types of RT: 1. teletherapy (external beam therapy) treating patients with MV energy, such as cobalt units and linear accelerators (Linacs), and 2. brachytherapy (internal application of radioactive sources). It is worth noting that providing effective, reliable, and safe RT is a

plexus tumors, ependymomas, and cerebellar astrocytomas [32–34].


Anesthesia may be oral or intravenous. The American Society of Anesthesiologists has proposed a grading system for sedation use as follows: [38].

**1.** Minimal sedation/anxiolysis.


For the two-dimensional (2D) RT, the procedure is a clinical anatomical decision-making process, determining the tumor location as well as the proximity of critical normal tissues. Setting up two orthogonal radiation beam fields on an X-ray simulator with bony anatomy provides the bulk of the guidance. The target was identified on a planar X-ray, and areas not to be treated were blocked, originally with lead or cerrobend alloy, converting a square or a rectangular beam offered by the machine into an irregularly shaped beam, at least in two directions. Bony anatomy visualized on plain radiographs was the primary method of determining field placement using orthogonal, and occasionally oblique or vertex fields. The uncertainty in target determination with this rudimentary method mandated the incorpora‐ tion of error as a significant element in the radiation field design, generally resulting in large volumes being irradiated [37]. The tremendous advancement in computers and telecommu‐ nication allowed more complex treatment planning systems (TPS). Technical advances such as multileaf collimation (MLC), digitally reconstructed radiographs (DRRs), and electronic portal imaging (EPI) greatly contributed to the integration of three-dimensional conformal radiation therapy (3DCRT) effective delivery. The planning process for 3DCRT is significant‐ ly more complex than for conventional RT. Therefore, multiple well-coordinated steps are taken by the different categories of radiation oncology team; radiation technologist, dosimet‐ rist, physicist, and radiation oncologist. With the advancement in CT technology, it became possible to incorporate 3D data for both normal organ at risk and tumor into treatment planning systems. This results not only to delineate targets accurately but also to calculate radiation doses efficiently from multiple beams through multiple directions, and to block out (and save) normal tissue more effectively, thus yielding a more conformal 3D radiation plan.

#### **3.1. Immobilization and imaging**

The initial step of the planning process is to place the patient in a reproducible position that optimizes treatment of the entire tumor volume while sparing surrounding critical struc‐ tures. Variable customizable immobilization devices may be used, including thermoplastic facemasks, alpha cradles, and vacuum mattresses. It is important to ensure that these devices are comfortable, reproducible, and sustainable along the whole radiotherapy treatment. Upon the optimal position of the patient, localization (determining points of origin through a laser device) is determined and marks are placed. With the patient in the treatment position, CT images of the area of interest are obtained and the data are transferred to the planning system. At this stage, the clinician will be able to define the target volumes as well as critical struc‐ tures. Other modalities such as MRI can be co-registered with the CT data for better determi‐ nation of the target volumes. Two main basic issues are essential for treatment planning: the identification of the topography and geometry of the diseased tissue and the correct segmen‐ tation of the anatomy of normal tissues. The International Commission on Radiation Units and Measurements (ICRU) has defined evolving standard definitions for radiotherapy target volumes. Their recent recommendations [39] include:

**2.** Moderate sedation/analgesia.

For the two-dimensional (2D) RT, the procedure is a clinical anatomical decision-making process, determining the tumor location as well as the proximity of critical normal tissues. Setting up two orthogonal radiation beam fields on an X-ray simulator with bony anatomy provides the bulk of the guidance. The target was identified on a planar X-ray, and areas not to be treated were blocked, originally with lead or cerrobend alloy, converting a square or a rectangular beam offered by the machine into an irregularly shaped beam, at least in two directions. Bony anatomy visualized on plain radiographs was the primary method of determining field placement using orthogonal, and occasionally oblique or vertex fields. The uncertainty in target determination with this rudimentary method mandated the incorpora‐ tion of error as a significant element in the radiation field design, generally resulting in large volumes being irradiated [37]. The tremendous advancement in computers and telecommu‐ nication allowed more complex treatment planning systems (TPS). Technical advances such as multileaf collimation (MLC), digitally reconstructed radiographs (DRRs), and electronic portal imaging (EPI) greatly contributed to the integration of three-dimensional conformal radiation therapy (3DCRT) effective delivery. The planning process for 3DCRT is significant‐ ly more complex than for conventional RT. Therefore, multiple well-coordinated steps are taken by the different categories of radiation oncology team; radiation technologist, dosimet‐ rist, physicist, and radiation oncologist. With the advancement in CT technology, it became possible to incorporate 3D data for both normal organ at risk and tumor into treatment planning systems. This results not only to delineate targets accurately but also to calculate radiation doses efficiently from multiple beams through multiple directions, and to block out (and save) normal tissue more effectively, thus yielding a more conformal 3D radiation

The initial step of the planning process is to place the patient in a reproducible position that optimizes treatment of the entire tumor volume while sparing surrounding critical struc‐ tures. Variable customizable immobilization devices may be used, including thermoplastic facemasks, alpha cradles, and vacuum mattresses. It is important to ensure that these devices are comfortable, reproducible, and sustainable along the whole radiotherapy treatment. Upon the optimal position of the patient, localization (determining points of origin through a laser device) is determined and marks are placed. With the patient in the treatment position, CT images of the area of interest are obtained and the data are transferred to the planning system. At this stage, the clinician will be able to define the target volumes as well as critical struc‐ tures. Other modalities such as MRI can be co-registered with the CT data for better determi‐ nation of the target volumes. Two main basic issues are essential for treatment planning: the identification of the topography and geometry of the diseased tissue and the correct segmen‐ tation of the anatomy of normal tissues. The International Commission on Radiation Units and

**3.** Deep sedation/analgesia.

**4.** General anesthesia.

458 Neurooncology - Newer Developments

plan.

**3.1. Immobilization and imaging**


Once a satisfactory plan is generated, digital reconstructive radiograms (DRRs) correspond‐ ing to the planned radiation fields are obtained. These DRRs typically display field shapes and tumor volumes and the standard radiographic anatomical information. Using a complex 3D plan, MLC allows for rapid change of field shape under computer control, dramatically shortening the time needed to treat a patient. A verification simulation can be performed to check the validity and accuracy of the fields. This can be performed with the use of an electronic

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 deal with intra-fractional movements.

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 dose to that for the well-known conventional fractionation.

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 conventional RT [41]. Furthermore, decreasing the cumulative dose of *cis*-platinum or usage of efficient less ototoxic drug is preferable for better hearing integrity.
