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Central Nervous System Tumors Central Nervous System Tumors Central Nervous System Tumors Authors: Ayda G. Nambayan, DSN, RN, St. Jude Children’s Research Hospital Erin Gafford, Pediatric Oncology Education Student, St. Jude Children’s Research Hospital; Nursing Student, School of Nursing, Union University Content Reviewed by: Daniel H. Alderete, MD, Hospital Nacional de Pediatría J.P. Garrahan, Argentina Cure4Kids Release Date: 1 September 2006 Central nervous system (CNS) tumors are the second most common malignancy in children and the most common cause of cancer mortality in this population. CNS tumors comprise approximately 17% of all childhood malignancies; and the incidence has steadily increased over the last decade. The most common histologic types of pediatric brain tumors are the gliomas, which arise from the glial tissue of the brain. Gliomas include mainly astrocytomas, ependymomas. The other important group comprises embryonal tumors, such as medulloblastoma and supratentorial primitive neuroectodermal tumors ( PNETs). The diversity of the tumors requires distinct therapeutic strategies and multimodal therapies, which have significant long term residual and late effects. Risk Factors: Though the cause of CNS tumors is largely unknown, the occurrence is associated with certain (A – 1) familial and hereditary syndromes. Other identified risk factors include ionizing radiation (cranial radiation) and environmental agents (industrial and chemical toxins, exposure to paint, solvents and electromagnetic fields). CNS tumors are also associated with other malignancies (embryonal CNS tumors-Atypical teratoid/ rhabdoid tumor- with renal tumors). Classification System: Because of the histologic diversity of CNS tumors, several (A – 2) classification systems have been developed. One widely accepted classification system (Bailey and Cushing) is based on different cell types, their developmental stages, and the corresponding tumors that arise from them. Current classification systems include World Health Organization (WHO) and Russell and Rubinstein, both based on Bailey and Cushing’s morphologic and histogenetic concepts. Another classification system, based on the premise that glial tumor cells become progressively anaplastic (Kernohan and Associates) uses a grading classification system that reflects the degree of anaplasia (Grade I – IV). Module 13 - Document 7 Page 1 of 13 Central Nervous System Tumors Clinical Signs and Symptoms: The neurologic dysfunction resulting from a brain tumor depends on the age, premorbid developmental level of the child, and site of origin (supratentorial and infratentorial). However, earlier manifestations of brain tumors are usually associated with increased intracranial pressure (IICP). IICP can result from compression and/or infiltration of the CNS structures and by obstruction of cerebrospinal fluid (CSF) flow. The classic IICP symptom triad includes morning headaches, generally relieved by vomiting and lethargy. Patients may also have papilledema, mental status changes (behavior, temperament, and levels of consciousness) and seizures. Varying degrees of hydrocephalus are also present in many patients. IICP is generally subtle, sub-acute and non-specific. In school age children, IICP may be manifested by a decline in academic performance, fatigue, personality changes, and vague intermittent headaches, present in the morning and becoming less intense through the day. Younger children might experience irritability, anorexia, and delayed developmental, intellectual, and motor abilities. When cranial sutures are still open, macrocephaly and “(A – 3) sunset sign” might be observed. Clinical Signs and Symptoms of Infratentorial (Brain stem and cerebellar) Tumors Brain Stem Lesions: Cranial nerve palsies (especially III, IV, VI, VII and IX) Clumsiness, uncoordinated walk Personality changes Drowsiness, Hearing loss Cerebellar Lesions: Clumsy, uncoordinated walk, swaying, staggering gait Dizziness, tremors, difficulty coordinating speech Double vision, nystagmus Clinical Signs and Symptoms of Supratentorial Tumors Signs and symptoms depend on the size and location of the tumor, and can be nonspecific, non- localizing and might precede IICP. Morning headaches that recede during the day Seizures that can be grand mal or petit mal Upper motor neuron signs including hemiparesis, hyper-reflexia, and clonus with associated sensory losses Frontal lobe tumors are often associated with behavioral problems and personality changes; IICP without obvious focal deficits Hypothalamic tumors causing diencephalic syndrome: failure to thrive and emaciation in a seemingly euphoric child with increased appetite. Module 13 - Document 7 Page 2 of 13 Central Nervous System Tumors Visual Symptoms: absence or significant delay in papillary reflex, nonconsensual response in the companion eye, hemianopsia, and uni- or bilateral nystagmus. Parinaud’s syndrome due to compression of the midbrain, pineal area tumors: poor upward gaze Slightly dilated pupils that react to accommodation but not to light Clinical Signs of the Spinal Cord and Cauda Equina Tumors Often caused by a metastatic lesion from a primary CNS tumor, especially of the primitive neuroectodermal and germ cell varieties. Local tenderness in the spine Back or radicular pain Bowel and/or bladder dysfunction Focal extremity weakness and sensory loss Diagnostic Workup: Complete history of the illness including length of the symptoms, pain, fatigue, weakness, neurological changes (developmental delays, morning vomiting, headache, seizures, visual changes, ataxia), and a review of potential predisposing factors and hereditary syndromes. Physical exam including growth and development, cranial nerve exam, gait, strength, sensory exam, coordination, deep tendon reflexes, head circumference, mental status CT with or without contrast detects 95% of CNS lesions Spinal imaging and CSF cytologic evaluations to determine best treatment plan MRI with or without enhancement is the procedure of choice in a child who is medically stable and able to cooperate Magnetic resonance angiography is used if there is concern over the vascularity of the tumor Positive emission tomography reflects brain metabolism and distinguishes between recurrent, residual tumor and radionecrosis. Bone marrow aspirates and bone scans are done in cases of medulloblastoma, only if patients have symptoms Tumor markers (blood and/or CSF) in pineal and suprasellar tumors (germ cell tumors) Treatment: A major goal of therapy is the removal of an extensive portion of the tumor by surgical resection, while preserving neurological function. Patients require a comprehensive evaluation at diagnosis to determine the intended initial treatment strategy, which can include radiotherapy and chemotherapy, depending on the tumor histology and age of the patient. Current (A – 4) neurosurgical techniques permit complete surgical resection, debulking, and/or biopsy of the tumor, often resulting in symptomatic relief. Module 13 - Document 7 Page 3 of 13 Central Nervous System Tumors Radiation has always played a major role in the treatment of CNS tumors, and improvements in delivery of this therapy, such as hyperfractionated, stereotactic, brachytherapy, and conformal field radiation therapy now minimize the effects on normal tissue within the radiation field. Hyperfractionated RT allows a higher total dose of radiation into the tumor by administration of smaller doses twice a day with a 4- to 6-hour rest between each dose. (A – 5) Chemotherapy is usually used as neoadjuvant and/or adjuvant treatment given before, during, and after radiation therapy, or as salvage therapy in cases of tumor recurrence or progression. Chemotherapy can be used as a single agent or in combination with other chemotherapeutic drugs to produce maximum effects. Chemotherapy is also used in infants and children less than 3 years old in order to delay or avoid radiation therapy until the child is older. This prevents the deleterious side-effects in the CNS tissues. The presence of the blood-brain-barrier (BBB) reduces the penetration of chemotherapy agents into the CNS, and thus impacts drug delivery strategies. In areas where the BBB is disrupted, water soluble chemotherapy (alkylators and platinum based agents) can be more efficient, while liposoluble agents seem to be more efficacious in areas of intact BBB. Regional therapy (carotid artery, intrathecal and intraventricular infusions) enhances drug penetration by increasing tumor drug exposure without increasing systemic toxicity. The disadvantage of this method is that although systemic toxicity is reduced, focal and diffuse CNS toxicity is common. High-dose systemic therapy with autologous bone marrow rescue is most applicable to patients whose tumors are sensitive to conventional dose treatment, to patients with minimal residual disease after surgery or prior to therapy, and patients with relapsed disease. Future Directions: Despite the irregular characteristic of the BBB in CNS tumors, it still poses a challenge to the treatment of CNS tumors. Studies have demonstrated that hyperosmolar agents (mannitol) increase CNS and CSF drug levels, offering potential improvement in clinical response. However, increased drug levels can also enhance CNS toxicity, similar to those seen in regional therapy. The use of monoclonal products–(antibodies) given intrathecally may have some promise. Clinical investigations demonstrated greater tumor-antibody accessibility and specific binding. Monoclonal antibodies also have selective
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