Complications of Cancer Therapy

Complications of Cancer Therapy

Jasmin Jo

David Schiff


Neurologic complications of cancer therapy are relatively common and may be disabling. Understanding these complications may mitigate or halt progression of injury to the nervous system through early recognition and prompt management. In this chapter, we will discuss neurotoxicities associated with the various agents used in the treatment of cancer.


Cranial and spinal radiation used to treat primary or secondary central nervous system (CNS) tumors as well as for prophylaxis in certain systemic malignancies is a recognized cause of neurologic complications. The cranial and peripheral nerves are also vulnerable to adverse effects when included in the radiation field for CNS or non-CNS tumors. The risk for radiation injury increases with higher total dose and fractions, larger treatment volume, and coadministration of chemotherapy. Patients younger than 10 and older than 70 years old are more susceptible to complications of radiotherapy (RT).


Tissue injury from RT is categorized in sequential stages: acute (<1 month), early-delayed (1 to 6 months), and late-delayed reactions (>6 months). The timing is helpful in predicting reversibility of tissue damage. Capillary injury and leakiness leading to edema is the mechanism during acute injury. Late injury is generally associated with permanent tissue damage. In the brain and spinal cord, the proposed mechanism for late effects is a combination of vascular injury involving the small- and medium-sized vessels, demyelination with loss of oligodendrocytes, and immunologic response to antigens released from damaged glial cells. The pathologic end state is radiation necrosis, involving coagulation necrosis and gross demyelination. Tissue atrophy is seen upon long-term follow-up. Table 105.1 summarizes RT injuries and their corresponding manifestations based on location.

TABLE 105.1 Neurologic Complications of Radiotherapy

Symptoms according to Sites





Spinal Cord

Cranial Nerves

Peripheral Nerves


<1 mo

BBB disruption Edema

Acute encephalopathy Pseudoprogression



1-6 mo

Edema Demyelination

Somnolence syndrome Transient cognitive impairment Pseudoprogression

Lhermitte sign

Painless visual loss Tongue weakness Hearing loss Anosmia

Transient plexopathy Pain


>6 mo

Vascular injury Demyelination Necrosis Cellular loss

Focal radionecrosis Leukoencephalopathy Cognitive impairment Dementia

Brown-Séquard syndrome Spastic paraplegia

Hearing loss Visual loss Lower CN palsies

Irreversible plexopathy Myokymia on EMG

BBB, blood-brain barrier; CN, cranial nerves; EMG, electromyography.


Cytotoxic chemotherapeutic agents may cause toxic effects to the peripheral and central nervous system, often leading to reduction or cessation of treatment. The severity depends on the treatment dose, duration, route, existing comorbidities, and coadministration of other neurotoxic agents.


The mechanism of chemotherapy-induced peripheral neuropathy (CIPN) depends on the cytotoxic agents used. Antimitotic agents, such as vinca alkaloids and taxanes, disrupt microtubule-based axonal transport leading to length-dependent axonal injury. Platinum agents such as cisplatin cause neuropathy by apoptosis of sensory neurons in dorsal root ganglion, whereas oxaliplatin additionally causes transient Na-gated channel dysfunction resulting in altered nerve excitability, particularly refractoriness. Despite the presence of the blood-brain barrier (BBB), the CNS remains susceptible to neurotoxicity effects if the protective barrier is breached by direct effects of tumor through endothelium damage or by RT, if the agent crosses the intact BBB, or if the agents are administered directly to the cerebrospinal fluid (CSF) or into the cerebral vasculature. Chemotherapy can also cause damage to neural progenitor cells responsible for neurogenesis and maintenance of white matter integrity.


Central Nervous System

Chemotherapy agents such as ifosfamide, high-dose methotrexate, and procarbazine can cause acute toxicities occurring during or few days after treatment, characterized by confusion, hallucination, seizures, and drowsiness. A cerebellar syndrome may develop from high-dose cytarabine. Intrathecal (IT) methotrexate and cytarabine can cause aseptic meningitis and myelopathy. IT vincristine causes severe neurotoxicity that is nearly always fatal and must be avoided. Posterior reversible encephalopathy syndrome (PRES), manifesting as acute or subacute onset of headache, seizures, confusion, and visual changes, has been reported from cisplatin, cyclophosphamide, high-dose corticosteroids, and gemcitabine. Chronic leukoencephalopathy, characterized by progressive personality change, dementia, ataxia, and incontinence, may occur months to years following methotrexate, especially when given during or soon after whole brain RT. Therefore, whole brain RT should be administered after systemic or IT methotrexate.

Peripheral Nervous System

CIPN typically presents with symmetric distal paresthesia, loss of proprioception and vibratory sense, and loss of ankle reflexes. Distal motor weakness and autonomic dysfunction including atonic bladder, impotence, and orthostatic hypotension may also occur with certain agents (Table 105.2). Vestibulocochlear toxicity, with hearing loss, vertigo, and ataxia, is associated with cisplatin. Acute cold-induced dysesthesia involving the distal extremities, throat, mouth, or face occur commonly with oxaliplatin.

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Jul 27, 2016 | Posted by in NEUROLOGY | Comments Off on Complications of Cancer Therapy

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