Table 2.
Summary of Main Treatment Adverse Events in Long-Term Brain Tumor Survivors
| Category | Complication | Timing of onset | Frequency at long term, % | Clinical symptoms | Risk factors | MRI findings | Treatment |
|---|---|---|---|---|---|---|---|
| Nonfocal CNS | Cognition impairment | 3-4 mo to ≥ 2 y after initiated treatment | 50%-90% | Cognitive functions decline, especially in attention | Surgery in eloquent areas ChT RT (WBRT and SRS) Supportive treatment (AEDs) |
Changes in periventricular white matter, ventricular dilation, cortical atrophy, loss of hippocampal volume | Cognitive rehabilitation Hippocampal sparing Memantine |
| Fatigue | Usually appears during active treatment (40%-80%) | 20%-30% | Physical, emotional, and mental exhaustion | Progression of tumor, anemia, endocrine dysfunction, emotional distress, comorbidities | Not applicable | Aerobic exercise Psychosocial intervention Methylphenidate and modafinil (uncertain) |
|
| Endocrinopathies | 10-20 y | 43%-93% | GH deficiency > hypothyroidism > hypogonadism > ACTH deficiency > hyperprolactinemia | RT Surgical resection of hypothalamus and pituitary gland ChT (rarely) |
Not applicable | Supplementary treatment according to guidelines, except for GHD replacement (uncertain) | |
| Focal CNS | Cerebrovascular disorders | 3-4 y (RT) During active treatment (ChT) |
25% related to RT 1% related to ChT |
Focal neurological deficits | RT ChT (MTX, 5-fluorouracil, platinum compounds, L-asparaginase, BVZ) |
Stroke, lacunar lesions, vascular occlusive disease (Moyamoya syndrome), and vascular malformations, carotid stenosis | Adapted from stroke guidelines therapy in noncancer adult patients |
| Cerebral radiation necrosis | 3 mo to 10 y after RT | 5-%7% (HGG) 14%-24% (BMs) |
Asymptomatic or focal neurological deficits | RT | Focal area of contrast-enhancement on T1-weighted, lower rCBV levels, higher Lact/Cr and lower Cho/Cr ratios, nuclear medicine studies (amino acid tracers) | Clinical and radiographic monitoring (if asymptomatic) Oral corticosteroids or BVZ (if neurological symptoms) |
|
| SMART syndrome | ≥ 20 y | Rare | Headache (migraine-like attacks), seizures (mostly generalized seizures), transient stroke-like deficits | RT | Diffuse unilateral cortical (parieto-occipital) gadolinium enhancement of cerebral gyri | Symptomatic headache treatment | |
| Peripheral nervous system | Cranial neuropathies | 3 mo to 9 y | 57%-60% (cochlea damage and RION) | Cochlea damage > RION > vagal, recurrent laryngeal, hypoglossal, sympathetic nerve neuropathies | RT (skull base, parasellar region, posterior cranial fossa) ChT (platinum, vincristine) |
RION (focal enhancement of intracranial optic nerve) | Dose reduction Symptomatic treatment |
| CIPNs | During active treatment, right after last cycle | 20%-30% (platinum compounds) | Sensory, motor, autonomic polyneuropathy | ChT (platinum compounds, vincristine) Hereditary neuropathies |
Not applicable | Dose reduction Symptomatic treatment | |
| Secondary neoplasms | Secondary neoplasms | 25-30 y | 11%-20% | Asymptomatic, focal neurological deficits, seizures, hematological malignancies | RT ChT (leukemogenic agents: temozolomide, carmustine or lomustine) Genetic predisposition (NF1) |
Meningiomas, gliomas, malignant schwannomas, sarcomas | Oncological treatment |
Abbreviations: ACTH, adrenocorticotropic hormone; AEDs, antiepileptic drugs; BMs, brain metastases; BVZ, bevacizumab; Cho, choline; ChT, chemotherapy; CIPNs, chemotherapy-induced peripheral neuropathies; Cr, creatine; GH, growth hormone; GHD, growth hormone deficiency; HGG, high-grade gliomas; Lact, lactate; NF1, neurofibromatosis type 1; MTX, methotrexate; RION, radiation-induced optic neuropathy; rCBV, relative cerebral blood volume; RT, radiotherapy; SMART, stroke-like migraine attacks after radiation therapy; SRS, stereotactic radiosurgery; WBRT, whole-brain radiotherapy.
SMART syndrome (not including peri-ictal pseudoprogression and acute late-onset encephalopathy after radiotherapy syndrome as presented in detail in Table 1).