Radiation Necrosis 11/29/2016. Disclosure statement. Memorial Sloan Kettering Cancer Center

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1 Radiation Necrosis Date: December 1 st, 2016 Wayne Quashie, MSN, CNS, ACNS-BC, AOCNS Clinical Nurse Specialist Neurology, Neurosurgery and Orthopedics Disclosure statement Presenter does not have any financial/commercial relationships to disclose Memorial Sloan Kettering Cancer Center 1

2 Objectives Identify the pathological mechanisms that contribute to radiation necrosis Explain the current treatments for radiation necrosis management State the possible potential role of stem cell and other novel approaches in radiation necrosis management Describe the nursing management of patients undergoing treatment for radiation necrosis Cancer Treatment-related neurotoxicity Central Nervous System Surgery Traumatic Ischemic Radiation Acute Early Delayed Late Delayed Chemotherapy Encephalopathy Intracranial hemorrhage Posterior reversible leukoencephalopathy Myelopathy Paraneoplastic disorders Chamberlain, 2010 Peripheral Nervous System Radiculopathy Plexopathy Myelopathy Neuropathy Myopathy Paraneoplastic disorders Why is this important? Disease symptomology vs. treatment toxicity Advances in systemic cancers therapies Increased survival Potential impact on quality of life Provides opportunities for additional research Neurological complications should be avoided rather than treated David A Rottenberg,

3 Case Study Case Study JD is a 61 year old male with a history of smoking, asthma and a history of seizures that started in CT scan at that time showed an abnormality in right posterior temporal lobe. Started on Phenytoin and Decadron. Seen in 2012 with generalized seizures with an aura of a headache sensation. CT scan done revealed an enhancing mass with edema in the right posterior temporal lobe. A CT of the chest also showed a lesion in the right hilar region. Radiographic Scan CT Scan MRI 3

4 Case Study cont d JD was diagnosed with NSCLC with brain metastasis. On 6/12 had SRS for the right parietal-temporal lesion. Currently being treated with Gemcitabine and Carboplatin. On Levatiracetam for seizure management Seen in 8/12, No evidence of brain disease evident with regular follow ups Seen 4/13 with reports of new morning headaches relieved with Acetaminophen MRI showed an enhancing abnormality at the surgical resection site. Compared to previous study, the area grew 38% (unidimensional) or 63% (two dimensional measurement) Radiographic Scan Case Study cont d May 2013 still reports seizure. Approx. 10 days ago, had an episode of slurred speech, disorientation and asymmetrical smile. In the emergency room, received increased doses of dexamethasone and Levetiracetam. In addition, his wife reports his auditory hallucinations PET showed mild hyper-metabolism in the area of metastasis and surgery. In addition, hyper-metabolism at the right medial temporal lobe is noted. He experiences significant changes in mood and depression with elevations in dexamethasone doses 4

5 Right parietal craniotomy performed in May Pathology showed completely necrotic tissue Cerebral Radiation Toxicity Acute Injury Sub-Acute Injury (early delayed injury) Delayed (late) Injury Rahmathulla, G., Marko, N.F., & Weil, R.J. ( 2013) Radiation Necrosis 5

6 Radiation Necrosis Can occur in cerebral hemispheres and spinal cord Incidence- difficult to determine Concurrent chemotherapy may play a role Increased risk within the first 2 years Brain tolerance dose (45-50Gy), increased risk with higher doses Stereotactic radiosurgery incidence as high as 50% Blongigen, B.J., Steinmetz, R.D, Levin, L., et al (2010); Suh, J.H. (2010); Rahmathulla, G., Marko, N.F., & Weil, R.J. ( 2013) Diagnosis Radiographic identification is limited Metabolic imaging and perfusion scans may aid in discrimination Tumor recurrence in conjunction with radiation necrosis delays correct identification Histo-pathological diagnosis Alexiou, G.A., Tsiouris, S., Kyritisis, A.P. et al (2009) Clinical Manifestations Asymptomatic vs. Symptomatic Increased intracranial pressure Cognitive dysfunction Focal neurological deficits 6

7 Pathophysiology Vascular injury Inflammatory response Radiation Necrosis Glial injury Enzymatic disturbances Neuronal injury Treatment Corticosteroids Mechanism of action Dexamethasone common Improvement of symptoms related to increased intracranial pressure (IICP) Decreased mineralocorticoid effect Dosing Side effects Nursing Management 7

8 Surgery Symptomatic patients Increased morbidity Nursing Management Hyperbaric Oxygen Therapy Tissue Hypoxia Vascular injury Mechanism of Action 8

9 Hyperbaric Oxygen (HBO) Therapy Chubaet al, (1997) 10 children with brain necrosis. All patients initially improved. Four died from disease and 5 of the remaining 6 sustained improvement Feldmeierand Hampson (2002) systematic review supported the beneficial use of HBO in different types of radiation injuries Cihanet. al (2009) Pt with PCNSL developed radiation necrosis who failed steroid therapy and refused surgery. HBO resulted in clinical and radiographic improvement Hyperbaric oxygen therapy Regimen sessions at atm 60 sessions (3 months), then 50 sessions (2.5 months) Advantages - Reduction in steroid dose -Symptom and imaging improvement - Used to treat symptom recurrence Cihan, Y.B., Uzun, G., Yildiz, S. & Donmez, H. (2009); Na, A., Haghigi, N. & Drummond, K.J. (2014) Side Effects Ear pain Sinusitis Lower seizure threshold Tumor progression Chuba, P.J., Aronin, P., Bhambhani, K. et al (1997); Feldmeier, J.J. & Hampson, N.B. (2002); Na, A., Haghigi, N. & Drummond, K.J. (2014) 9

10 Biologic Agents Vascular injury VEGF expression Bevacizumab Monoclonal antibody against VEGF Used to treat a variety of cancers Side effects include hypertension, increased risk of thromboembolic events, hemorrhage and hypersensitivity Dosage: 5-10 mg/kg every two weeks (up to 4-8 cycles) Retrospective study of 15 patients treated with Bevacizumab (single agent and combination) Radiation necrosis diagnosed in 8 patients Noted change in post gadolinium and FLAIR images post treatment 10

11 Fourteen (14) patients with confirmed radiation necrosis randomized to two treatment groups: Bevacizumab or placebo No response noted in placebo group 100% of all patients who received Bevacizumab responded (5 /5 randomized and 7/7 cross-over) Radiographic and symptom response Only 2 patients experienced a recurrence of RN median of 10 months Laser Interstitial Thermal Therapy (LITT) Focused laser energy at target area Treatment planning involves 3 zones Case reports are promising May be an option for high risk patients Rahmathulla, G., Marko, N.F., & Weil, R.J. ( 2013) 11

12 Nerve Growth Factor The future The future From human embryonic stem cells, isolated oligodendrocytes progenitors were transplanted Repair major white matter tracts resulting in structural and functional repair Behavioral testing showed complete recovery of cognitive function Additional transplantation in the cerebellum resulted in recovery of motor deficits Piao, J., et al (2015), vol. 16,

13 Nursing Management Assess neurological baseline to detect changes Monitor for complications from treatment Implement home services as needed Evaluate compliance with medications and treatment plan Educate patient and caregiver regarding self care strategies Future research Increase knowledge regarding the pathophysiology of radiation necrosis Continue to improve technology regarding radiation therapy More rigorous research on current treatment options Research exploring other possibilities Summary 13

14 References Chamberlain, M. (2010). Neurotoxicity of cancer treatment. Current Oncology Reports, 12, Chuba, PJ, Aronin, P., Bhambhani, K., et al. (1997). Hyperbaric oxygen therapy for radiation-induced brain injury in children. Cancer, 80, Cihan, Y., Uzun, G, Yildiz, S., & Donmez, H. (2009). Hyperbaric oxygen therapy for radiation induced brain necrosis in a patient with primary central nervous system lymphoma. Journal of Surgical Oncology, 100, Feldmeier, J. & Hampson, N. (2002). A systematic review of the literature reporting the application of hyperbaric oxygen prevention and treatment of delayed radiation injuries: An evidence based approach. Undersea and Hyperbaric Medical Society, 29, 4-30 Gonzalez, J., Kumar, A., Conrad, C., & Levin, V. (2007) Effect of bevacizumab on radiation necrosis of the brain. International journal of Radiation Oncology, Biology and Physics, 67, (2), Levin, V, Bidaut, L, Hou, P., Kumar, A., Wefel, J., et al (2011) Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system. International journal of Radiation Oncology, Biology and Physics, 79,(5), Murovic, J.A. & Chang, S.D. (2015). The pathophysiology of cerebral radiation necrosis and the role of laser interstitial thermal therapy. World Neurosurgery, 83, Na, A., Haghigi, N., & Drummond, K.J. (2014). Cerebral radiation necrosis. Asia-Pacific Journal of Clinical Oncology, 10, Piao, J., Major, T, Auyeung, G., Policarpio, E., Menon, J., et. al (2015) Human embryonic stem cell-derived oligodendrocyte progenitors remyelinatethe brain and rescue behavioral deficits following radiation. Cell Stem Cell, 16, Rahmathulla, G., Marko, N.F., & Weil, R. (2013) Cerebral radiation necrosis: a review of the pathobiology, diagnosis and management considerations. Journal of Clinical Neuroscience, 20, Rahmathulla, G., Recinos, P., Valerio, J., et al. (2012). Laser interstitial thermal therapy for focal cerebral radiation necrosis: a case report and literature review. Stereotactic Functional Neurosurgery, 90, Rottenberg, DA Neurological complications of cancer treatment. (1991), Butterworth-Heinemann, Minnesota Wang, X.S.,, Ying, H.M., He, X.Y., Zhou, Z.R. Wu, Y.R. & Hu, C.S. (2016) Treatment of cerebral radiation necrosis with nerve growth factor: a prospective, randomized, controlled phase II study. Radiotherapy and Oncology, 120, Wayne Quashie quashiew@mskcc.org 14