CNS complications of cancer therapy

Radiation, cytotoxic chemotherapy and biologic and targeted therapies have recognized in the CNS side effects.

Central nervous system complications of cancer therapy are increased as modalities of treatment are combined.

Radiation to the CNS may be associated with acute, or delayed effects ranging from weeks to months or years.

Acute complications of radiation include acute encephalopathy with headaches, nausea, vomiting, and somnolence and potentially focal neurologic deficits.

Acute radiation symptoms typically develop during the first few days of radiation and are the result of increased intracranial pressure from disruption of the blood brain barrier and development of cerebral edema.

Cerebral edema may result in herniation and death on a rare occasion.

Symptoms occur more frequently with large radiation fractions and in patients with a large mass tumor effect.

Acute radiation effects on the CNS are uncommon low dose fractions, but patients may experience fatigue, headache and nausea.

Acute effects following radiosurgery occur in approximately 2.2% of patients.

Early delayed complications occurring within a few months of radiation manifested by drowsiness and fatigue, nausea, irritability, and headache and occasional fever with transient papilledema.

The above symptoms of early delayed complications are referred to as the somnolence syndrome, and is more common in children and adults.

Early delayed complications include transient worsening of focal deficits, such as can occur with brain tumors with demyelination from injury to oligodendrocytes.

With early delayed complications corticosteroids can speed recovery.

With early delayed complications transient cognitive decline may occur with impaired memory and attention: these cognitive disturbances resolve over weeks to months.

In glioblastoma treated patients with radiation and temozolomide enhanced lesion progression may occur in 30% of patients, on MRI examination, in the first few months as a result of treatment rather than tumor growth.

The above process is referred to as “pseudo-progression” (Brandsma D).

Radionecrosis findings surgical resection or consistent with pseudo-progression.

In general, acute and early delayed effects of radiation are reversible.

Late delayed complications of radiation to the CNS, occurring months or even years after radiotherapy are often progressive and are irreversible.

Radionecrosis is areaction to radiation that primarily affects white matter of the brain or spinal cord.

Radionecrosis produces cell necrosis and vascular injury, axonal and oligodendrocyte loss, with gliosis and demyelinization.

Radionecrosis pathological changes occur within a year and a half of radiation, but can develop years or even decades following treatment.

Radionecrosis symptoms relate to edema and mass effect, focal progressive neurologic deficits, seizures, or increased intracranial pressure.

Clinical presentation and MRI findings in the radionecrosis are often indistinguishable from tumor progression.

Imaging techniques have the difficulty distinguishing between radiation necrosis and tumor recurrence, the lesions frequently are coexistent and it is difficult to jawline between the 2 different lesions.

Radionecrosis is seen following external beam radiation but may be more frequent with stereotactic radiosurgery and brachytherapy.

Incidence increases extent, volume and dose of radiation, especially above 65 Gy.

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