•Methods of irradiation:

–Conventional external irradiation

–Three-dimensional irradiation with precise boundary between the irradiated field and the adjacent tissue

–Stereotactic irradiation (gamma knife) used for small tumors

–Brachytherapy or interstitial irradiation by transient implantation of radioisotopes

–Radiotherapy in combination with hyperthermia

9.11.3 Chemotherapy (for Details of Special Tumor Types See Below)

•Chemotherapy depends on tumor type, age, and location

•Efficacy and penetration depend on vascularization of the tumor

•High-dose chemotherapy with or without support by autologous stem cell transplantation, especially in children below the age of 3 years

•Palliative chemotherapy:

–May induce transient remission

–Increases the quality of life

–The benefits of chemotherapy or other treatments must be balanced by consideration of the toxicities

•Intrathecal chemotherapy via lumbar puncture, Rickham or Ommaya reservoir; limited value due to low penetration of drug from cerebral fluid to brain tissue when leptomeningeal disease is not present

•Future directions:

–Adoptive immunotherapy with interleukin-2 or lymphokine-activated T-cell vaccination, or by monoclonal antibodies

–Gene transfer therapy via virus-mediated delivery systems

°Targeted tumor receptor inhibition

°Antibody conjugated to immunotoxin

°Stimulation of tumor-specific antigen immune responses using dendritic cell vaccines

–Reduction of tumor-induced angiogenesis

°Blocking of signaling pathways

9.12Special Tumor Types

For general aspects of brain tumors, see above

9.12.1 Astrocytic Tumors

9.12.1.1 Incidence

•Most frequent tumor of childhood

•Infratentorial area (cerebellar tumor) or supratentorial (cerebral hemisphere or midline tumors) occurrence

•Mean age of patients: 6–9 years

•Males more frequently affected than females

9.12.1.2 Radiological Diagnosis

CT and MRI

• Hypodense zone with weak enhancement

• Often calcification present

9.12.1.3 Characteristics of Low-Grade Astrocytoma (LGA I and II)

•Variable nomenclature:

–Supratentorial: fibrillary mixed xanthochromic, pilocytic astrocytoma, oligodendroglioma, or ganglioglioma

–Infratentorial (cerebellar): pilocytic (80%), and fibrillary diffuse astrocytoma (15–20%)

•Therapy:

•Surgical procedure:

–Degree of tumor removal is dependent on location, and tumor size and infiltration, which defines the prognosis and the watch and wait approach; in relapsing low-grade astrocytoma, again tumor removal should be considered

–The goal of surgery is to remove as much tumor as is safe

•Radiotherapy:

–In children with subtotal resection, consider watch and wait approach of involved-field radiotherapy is used

–In inoperable tumors, stereotactic radiotherapy may be an option

•Chemotherapy:

–In children with inoperable low-grade astrocytoma and in those below the age of 3 years

–Effective drugs alone or in combination include: vincristine, carboplatin, nitrosourea, cyclophosphamide, temozolomide

–Response rate 65–75%

9.12.1.4 Characteristics of High-Grade Astrocytoma (HGA III/IV)

•Synonyms: anaplastic astrocytoma, glioblastoma multiforme, mixed oligodendroglioma

•Therapy and prognosis

–Depending on degree of resectability, infiltration in adjacent brain tissue is frequent

–Radiotherapy results in short-term, mostly partial remission

–Multiagent chemotherapy prolongs the survival time, with variable long-term remission

–Effective drugs alone or in combination: cisplatin, carboplatin, cyclophosphamide, ifosfamide, etoposide, topotecan, procarbazine, temozolomide, lomustine (CCNU), carmustine (BCNU)

9.12.2Optic–Hypothalamic Glioma

9.12.2.1 Incidence

•Three to five percent of intracranial tumors, two-thirds manifesting within the first 5 years of life

•About 35% of children with neurofibromatosis

Extension of optic–hypothalamic glioma

•Optic nerve only

•Frontal part of chiasma

•Posterior parts of chiasma and hypothalamus with involvement of frontal lobes, thalamus, and other midline structures

9.12.2.2 Pathology

• Mostly astrocytoma I–II; pilocytic, occasionally fibrillary histology

9.12.2.3Clinical Presentation

• Progressive loss of vision

• Bilateral loss of vision by involvement of chiasma

• Exophthalmos in frontal involvement of the optic nerve

• Visual field deficiency variable, depending on tumor location and extension

• Fundoscopy: papillary weakness or optic nerve atrophy

– More aggressive course observed commonly in infants compared to older children

9.12.2.4Radiological Diagnosis

•MRI or CT: weak enhancement in peripheral chiasmatic tumor, moderate enhancement in chiasmatic tumor (i.e., higher degree of malignancy)

9.12.2.5 Histology

• Biopsy if diagnosis is unclear (in children with neurofibromatosis, usually unnecessary)

9.12.2.6 Therapy and Prognosis

•Radical resection rarely possible

•Chemotherapy: in small children and/or in children with extensive tumor of the chiasmatic hypothalamus region