Neurologic effects of cancer treatment Survivorship conference 2013
introduction• The arc of medical advance – Supportive care – Crude but sometimes effective – Artful and often effective• Survivor = courageous – Not all of this will be encouraging• Who I am – Simple country neurologist• Chemotherapy – PNS – CNS• Radiation therapy – PNS – CNS
chemotherapy-induced peripheral neuropathy• pain, weakness, or imbalance can develop• generally dose-dependent• generally reversible, BUT » symptoms can “coast” » some irreversible neuropathy can occur• risk is probably greater in people with pre-existing neuropathy• chemo affects structural & energy-producing elements in nerve cells
chemotherapy inducedperipheral neuropathy o vincristine » weakness is prominent » can cause autonomic and cranial nerve deficits o cis-platinum » accumulates in sensory nerve cells » imbalance and loss of sensation is prominent » can cause tinnitus, hearing loss o oxaliplatin » also accumulates in sensory nerve cells » acutely, cold-induced pain and tingling in throat and limbs » muscle cramps » painful neuropathy o taxanes » sensory loss and some weakness » can also cause autonomic dysfunction o bevacizumab o thalidomide
chemotherapy-inducedperipheral neuropathy• no generally accepted prevention• Ca/Mg infusions may have benefit (Oxaliplaten)• several other treatments have been investigated• glutathione• N-acetylcysteine• glutamine• oxcarbazepine• neurologic monitoring may help guide therapy• neurologic examination• QST• bumps• sweat testing
chemotherapy induced peripheral neuropathy• treatment of CIPN pain is difficult – most drugs that have been proven beneficial in painful diabetic neuropathy have had negative trials in CIPN – recent modestly positive trial with Duloxetine – topicals safe » baclofen/amitriptyline/ketamine study marginally positive » topical lidocaine – reasonable to try other medications used for neuropathy pain
“chemobrain”• a lot to learn yet; mechanisms under investigation• affects concentration, processing speed, and memory – patient-specific factors may contribute• treatment is symptomatic – general health measures – cognitive interventions – treatment of sleep disruption, anxiety, depression if present – consider medications
risks of chemotherapy in the CNS QuickTime™ and a decompressor • encephalopathy usually resolves within days are needed to see this picture. – ifosfamide – MTX • PRES • stroke (Bevacizumab, other VEGF inhibitors, L-asparaginase) • aseptic meningitis (esp with MTX or ara-C given IT) • spinal cord syndrome – ara-C • cerebellar syndrome – ara-C • paclitaxel acute pain syndrome – axial joints, days in duration • oxaliplaten cold sensitivity • ATRA (x-retinoic acid) pseudotumor-like syndrome – chronic CNS effects • leukoencephalopathy following MTX
effects of radiation therapy in CNS• can injure normal cells as well as tumor cells• inflammation• interruption of BBB
radiation-inducedperipheral nerve injury– typically causes gradually progressive weakness– develops months-years after radiation– progresses for years– blood thinners and steroids have been proposed– Pentoclo (pentoxyphylline/tocopherol/clodronate- prednisone)– optic nerve and nerves of head and neck can be affected after treatment of skull base or pituitary tumors » intravitreal bevacizumab
Short-term CNS risks of radiation therapy• acute syndromes (days-weeks) – acute encephalopathy » breakdown of BBB » swelling around brain tumors and exacerbation of tumor symptoms » headache, nausea• subacute syndromes (2 weeks – 4 months) – transient worsening of symptoms from brain tumors – somnolence – localized brain dysfunction affecting normal brain in field for extracranial tumors – subacute syndromes are due to transient demyelination » can mimic tumor progression » may improve with steroid therapy
long-term CNS risks with radiation therapy• radiation necrosis 3 mos – 2 years – when related to radiation for brain tumors, can be difficult to distinguish from tumor recurrence – surgery, steroids, Bevacizumab QuickTime™ and a decompressor are needed to see this picture.• spinal cord syndrome (Brown-Sequard)• cerebral atrophy, often with white matter change – can be associated with cognitive/memory symptoms• SMART syndrome – stroke-like migraine attacks after RT
long-term CNS risks with radiation therapy QuickTime™ and a decompressor are needed to see this picture.• delayed leukoencephalopathy – white matter (deeper brain structures) affected – can affect memory and personality – commonly related to methotrexate with radiation – attempts to treat with methylphenidate, donepizil• radiation-induced vasculopathy (stroke) – large blood vessels in neck (often head and neck tumors) – small blood vessels in brain (brain tumors) – radiation-induced cavernous malformations and aneurysms
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