**4. Chemotherapy**

Chemotherapy is an essential modality in the treatment of many childhood malignancies including brain tumors. A wide variety of chemotherapeutic agents proved to be effective for most types of brain tumors. The role of chemotherapy varies from delaying the RT timing to allow further development of brain functions in the young, stabilizing tumors, reducing radiation doses, or even avoiding RT altogether. Effective agents include many alkylating agents, vinca alkaloids, topoisomerase inhibitors, antimetabolites, and angiogenesis inhibitors.

Chemotherapy for brain tumors can be given by various routes, including orally, intrave‐ nously, intrathecally, and via an Ommaya reservoir. Furthermore, chemotherapy may be given as an adjuvant or as concomitant with radiotherapy, improved survival for many pediatric brain tumors including medulloblastoma, germ cell tumor, high-grade astrocytoma, and others. In other conditions, like ependymoma, chemotherapy may be used to increase resect ability of the tumor [49].

The blood-brain barrier is a dynamic interface separating the brain from the circulatory system. The blood-brain barrier regulates the transport of essential molecules from the circulation to the brain, protecting the brain from harmful chemicals. It limits the ability of many chemo‐ therapy agents to penetrate into the CNS. There are mechanisms such as blood-brain barrier disruption, intra-arterial chemotherapy injection, intrathecal chemotherapy administration, or intratumoral chemotherapy administration which were utilized to overcome the blood–brain barrier.

#### **4.1. Intrathecal chemotherapy**

Intrathecal administration of chemotherapy is another method of bypassing the blood-brain barrier to deliver chemotherapy within the CNS. Many agents have been investigated for a variety of brain tumors. Intrathecal liposomal cytarabine, mafosfamide, and etoposide were used in children with ependymoma, primitive neuroectodermal tumor, medulloblastoma, and atypical teratoid rhabdoid tumor [50].

#### **4.2. Intra-ommaya therapy**

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].

Chemotherapy is an essential modality in the treatment of many childhood malignancies including brain tumors. A wide variety of chemotherapeutic agents proved to be effective for most types of brain tumors. The role of chemotherapy varies from delaying the RT timing to allow further development of brain functions in the young, stabilizing tumors, reducing radiation doses, or even avoiding RT altogether. Effective agents include many alkylating agents, vinca alkaloids, topoisomerase inhibitors, antimetabolites, and angiogenesis inhibitors.

Chemotherapy for brain tumors can be given by various routes, including orally, intrave‐ nously, intrathecally, and via an Ommaya reservoir. Furthermore, chemotherapy may be given as an adjuvant or as concomitant with radiotherapy, improved survival for many pediatric brain tumors including medulloblastoma, germ cell tumor, high-grade astrocytoma, and others. In other conditions, like ependymoma, chemotherapy may be used to increase resect

The blood-brain barrier is a dynamic interface separating the brain from the circulatory system. The blood-brain barrier regulates the transport of essential molecules from the circulation to the brain, protecting the brain from harmful chemicals. It limits the ability of many chemo‐ therapy agents to penetrate into the CNS. There are mechanisms such as blood-brain barrier disruption, intra-arterial chemotherapy injection, intrathecal chemotherapy administration, or intratumoral chemotherapy administration which were utilized to overcome the blood–brain

Intrathecal administration of chemotherapy is another method of bypassing the blood-brain barrier to deliver chemotherapy within the CNS. Many agents have been investigated for a variety of brain tumors. Intrathecal liposomal cytarabine, mafosfamide, and etoposide were used in children with ependymoma, primitive neuroectodermal tumor, medulloblastoma, and

**4. Chemotherapy**

462 Neurooncology - Newer Developments

ability of the tumor [49].

**4.1. Intrathecal chemotherapy**

atypical teratoid rhabdoid tumor [50].

barrier.

Ommaya reservoirs were placed directly into the lateral ventricle to prevent repeated lumbar punctures for intrathecal chemotherapy. These provide easy access to the intrathecal space. Ommaya reservoirs have also been placed into the cysts of craniopharyngiomas in order to deliver chemotherapy agents intratumorally. The two agents that have previously been successfully utilized using this method of drug delivery are bleomycin and alpha interferon [51, 52].
