Radiation Necrosis Medication
- Author: Michael J Schneck, MD, MBA; more...
Medical therapy focuses on 2 mechanisms: controlling vasogenic edema and/or controlling vessel thrombosis.
Steroid therapy has only a temporary role in relieving neurologic decompensation and deficits. It relieves any symptomology related to vasogenic edema and disruption of the blood-brain barrier. While administering steroid therapy, the clinician must implement another medical or surgical therapy to treat radiation necrosis and to protect the patient from long-term complications.
Glucocorticoids such as dexamethasone have potent anti-inflammatory effects in many disorders. In addition to metabolic effects, they modify immune system response. Lacks salt-retaining property of hydrocortisone.
Patients can be switched from an IV to PO regimen in a 1:1 ratio.
Because radiation necrosis pathophysiology involves vessel thrombosis and subsequent occlusion, anticoagulant use has been proposed. To date, few case studies have addressed use in this condition; the evidence for anticoagulation is very limited. Patients with radiation necrosis may also be at risk of intracranial hemorrhage, further limiting the presumptive benefits of this therapy. In most of these studies, histologic verification of radiation necrosis was present. Patients received 6 mo of IV heparin, then warfarin with aPTT and PT adjusted to 1.5 times the control. Patients had significant resolution of deficits. When anticoagulation was stopped, symptoms reemerged. Almost immediate resolution of symptoms occurred when anticoagulation was restarted. Before starting anticoagulation therapy, careful diagnostic evaluation and management are needed.
Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis. Check aPTT after the first 6 h, then periodically q4-6h in early treatment. Dosage is therapeutic when aPTT is adjusted to 1.5 times normal.
Inhibits synthesis of vitamin K-dependent clotting factors (II, VII, IX, X) and anticoagulants (proteins C and S). Vitamin K is a cofactor for postribosomal synthesis of vitamin K-dependent clotting factors, which promote synthesis of gamma-carboxyglutamic acid (necessary for proper coagulation). Reportedly interferes with vitamin K epoxide regeneration. Peak anticoagulant effect is 72-96 h. Like other anticoagulants, warfarin has no effect on a preexisting thrombus.
Individualize dose in response to PT/INR and therapeutic goal. Periodic determination of PT/INR is required.
Agents in this category are used to decrease blood supply to a tumor by inhibiting angiogenesis.[25, 26]
A recombinant, humanized antibody that inhibits vascular endothelial growth factor (VEGF). VEGF has a significant role in angiogenesis and maintenance of existing blood vessels. By inhibiting VEGF, the antibody would interfere with the blood supply to a tumor, which is thought to be critical to tumor metastasis. By preventing VEGF from reaching leaky capillaries that are associated with brain swelling, bevacizumab may also help in radiation necrosis.
Fifteen patients with malignant brain tumors were treated with bevacizumab or bevacizumab combination n in one study.
Lai R, Abrey LE, Rosenblum MK, DeAngelis LM. Treatment-induced leukoencephalopathy in primary CNS lymphoma: a clinical and autopsy study. Neurology. 2004 Feb 10. 62(3):451-6. [Medline].
Liu AK, Macy ME, Foreman NK. Bevacizumab as therapy for radiation necrosis in four children with pontine gliomas. Int J Radiat Oncol Biol Phys. 2009 Nov 15. 75(4):1148-54. [Medline].
Barajas RF Jr, Chang JS, Segal MR, Parsa AT, McDermott MW, Berger MS, et al. Differentiation of recurrent glioblastoma multiforme from radiation necrosis after external beam radiation therapy with dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging. Radiology. 2009 Nov. 253(2):486-96. [Medline]. [Full Text].
Levin VA, Bidaut L, Hou P, et al. Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system. Int J Radiat Oncol Biol Phys. 2011 Apr 1. 79(5):1487-95. [Medline]. [Full Text].
Plimpton SR, Stence N, Hemenway M, Hankinson TC, Foreman N, Liu AK. Cerebral Radiation Necrosis in Pediatric Patients. Pediatr Hematol Oncol. 2013 May 7. [Medline].
Kureshi SA, Hofman FM, Schneider JH, Chin LS, Apuzzo ML, Hinton DR. Cytokine expression in radiation-induced delayed cerebral injury. Neurosurgery. 1994 Nov. 35(5):822-9; discussion 829-30. [Medline].
Langleben DD, Segall GM. PET in differentiation of recurrent brain tumor from radiation injury. J Nucl Med. 2000 Nov. 41(11):1861-7. [Medline].
Cheng KM, Chan CM, Fu YT, Ho LC, Cheung FC, Law CK. Acute hemorrhage in late radiation necrosis of the temporal lobe: report of five cases and review of the literature. J Neurooncol. 2001 Jan. 51(2):143-50. [Medline].
Ruben JD, Dally M, Bailey M, Smith R, McLean CA, Fedele P. Cerebral radiation necrosis: incidence, outcomes, and risk factors with emphasis on radiation parameters and chemotherapy. Int J Radiat Oncol Biol Phys. 2006 Jun 1. 65(2):499-508. [Medline].
Shah R, Vattoth S, Jacob R, Manzil FF, O'Malley JP, Borghei P, et al. Radiation necrosis in the brain: imaging features and differentiation from tumor recurrence. Radiographics. 2012 Sep-Oct. 32(5):1343-59. [Medline].
Asao C, Korogi Y, Kitajima M, et al. Diffusion-weighted imaging of radiation-induced brain injury for differentiation from tumor recurrence. AJNR Am J Neuroradiol. 2005 Jun-Jul. 26(6):1455-60. [Medline].
Dequesada IM, Quisling RG, Yachnis A, Friedman WA. Can standard magnetic resonance imaging reliably distinguish recurrent tumor from radiation necrosis after radiosurgery for brain metastases? A radiographic-pathological study. Neurosurgery. 2008 Nov. 63(5):898-903; discussion 904. [Medline].
Reddy K, Westerly D, Chen C. MRI patterns of T1 enhancing radiation necrosis versus tumour recurrence in high-grade gliomas. J Med Imaging Radiat Oncol. 2013 Jun. 57(3):349-55. [Medline].
Miyashita M, Miyatake S, Imahori Y, Yokoyama K, Kawabata S, Kajimoto Y, et al. Evaluation of fluoride-labeled boronophenylalanine-PET imaging for the study of radiation effects in patients with glioblastomas. J Neurooncol. 2008 Sep. 89(2):239-46. [Medline].
Xiangsong Z, Weian C. Differentiation of recurrent astrocytoma from radiation necrosis: a pilot study with 13N-NH3 PET. J Neurooncol. 2007 May. 82(3):305-11. [Medline].
Mogard J, Kihlstrom L, Ericson K, Karlsson B, Guo WY, Stone-Elander S. Recurrent tumor vs radiation effects after gamma knife radiosurgery of intracerebral metastases: diagnosis with PET-FDG. J Comput Assist Tomogr. 1994 Mar-Apr. 18(2):177-81. [Medline].
Kahn D, Follett KA, Bushnell DL, et al. Diagnosis of recurrent brain tumor: value of 201Tl SPECT vs 18F-fluorodeoxyglucose PET. AJR Am J Roentgenol. 1994 Dec. 163(6):1459-65. [Medline].
Chung JK, Kim YK, Kim SK, et al. Usefulness of 11C-methionine PET in the evaluation of brain lesions that are hypo- or isometabolic on 18F-FDG PET. Eur J Nucl Med Mol Imaging. 2002 Feb. 29(2):176-82. [Medline].
Rock JP, Hearshen D, Scarpace L, et al. Correlations between magnetic resonance spectroscopy and image-guided histopathology, with special attention to radiation necrosis. Neurosurgery. 2002 Oct. 51(4):912-9; discussion 919-20. [Medline].
Chuba PJ, Aronin P, Bhambhani K, et al. Hyperbaric oxygen therapy for radiation-induced brain injury in children. Cancer. 1997 Nov 15. 80(10):2005-12. [Medline].
Ashamalla HL, Thom SR, Goldwein JW. Hyperbaric oxygen therapy for the treatment of radiation-induced sequelae in children. The University of Pennsylvania experience. Cancer. 1996 Jun 1. 77(11):2407-12. [Medline].
Levin VA, Bidaut L, Hou P, Kumar AJ, Wefel JS, Bekele BN, et al. Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system. Int J Radiat Oncol Biol Phys. 2011 Apr 1. 79 (5):1487-95. [Medline].
Boothe D, Young R, Yamada Y, Prager A, Chan T, Beal K. Bevacizumab as a treatment for radiation necrosis of brain metastases post stereotactic radiosurgery. Neuro Oncol. 2013 Sep. 15 (9):1257-63. [Medline].
Glantz MJ, Burger PC, Friedman AH, Radtke RA, Massey EW, Schold SC Jr. Treatment of radiation-induced nervous system injury with heparin and warfarin. Neurology. 1994 Nov. 44(11):2020-7. [Medline].
Wong ET, Huberman M, Lu XQ, Mahadevan A. Bevacizumab reverses cerebral radiation necrosis. J Clin Oncol. 2008 Dec 1. 26(34):5649-50. [Medline].
Gonzalez J, Kumar AJ, Conrad CA, Levin VA. Effect of bevacizumab on radiation necrosis of the brain. Int J Radiat Oncol Biol Phys. 2007 Feb 1. 67(2):323-6. [Medline].
Buchpiguel CA, Alavi JB, Alavi A, Kenyon LC. PET versus SPECT in distinguishing radiation necrosis from tumor recurrence in the brain. J Nucl Med. 1995 Jan. 36(1):159-64. [Medline].
Cerghet M, Redman B, Junck L, Forman J, Rogers LR. Prolonged survival after multifocal brain radiation necrosis associated with whole brain radiation for brain metastases: case report. J Neurooncol. 2008 Oct. 90(1):85-8. [Medline].
Chen W. Clinical applications of PET in brain tumors. J Nucl Med. 2007 Sep. 48(9):1468-81. [Medline].
de Vries B, Taphoorn MJ, van Isselt JW, Terhaard CH, Jansen GH, Elsenburg PH. Bilateral temporal lobe necrosis after radiotherapy: confounding SPECT results. Neurology. 1998 Oct. 51(4):1183-4. [Medline].
Deshmukh A, Scott JA, Palmer EL, Hochberg FH, Gruber M, Fischman AJ. Impact of fluorodeoxyglucose positron emission tomography on the clinical management of patients with glioma. Clin Nucl Med. 1996 Sep. 21(9):720-5. [Medline].
Ishikawa M, Kikuchi H, Miyatake S, Oda Y, Yonekura Y, Nishizawa S. Glucose consumption in recurrent gliomas. Neurosurgery. 1993 Jul. 33(1):28-33. [Medline].
Kumar AJ, Leeds NE, Fuller GN, et al. Malignant gliomas: MR imaging spectrum of radiation therapy- and chemotherapy-induced necrosis of the brain after treatment. Radiology. 2000 Nov. 217(2):377-84. [Medline].
Lee AW, Foo W, Chappell R, et al. Effect of time, dose, and fractionation on temporal lobe necrosis following radiotherapy for nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 1998 Jan 1. 40(1):35-42. [Medline].
McPherson CM, Warnick RE. Results of contemporary surgical management of radiation necrosis using frameless stereotaxis and intraoperative magnetic resonance imaging. J Neurooncol. 2004 May. 68(1):41-7. [Medline].
Nelson MD Jr, Soni D, Baram TZ. Necrosis in pontine gliomas: radiation induced or natural history?. Radiology. 1994 Apr. 191(1):279-82. [Medline].
Nelson SJ, Huhn S, Vigneron DB, et al. Volume MRI and MRSI techniques for the quantitation of treatment response in brain tumors: presentation of a detailed case study. J Magn Reson Imaging. 1997 Nov-Dec. 7(6):1146-52. [Medline].
Olivero WC, Dulebohn SC, Lister JR. The use of PET in evaluating patients with primary brain tumours: is it useful?. J Neurol Neurosurg Psychiatry. 1995 Feb. 58(2):250-2. [Medline].
Omuro AM, Leite CC, Mokhtari K, Delattre JY. Pitfalls in the diagnosis of brain tumours. Lancet Neurol. 2006 Nov. 5(11):937-48. [Medline].
Packer RJ, Zimmerman RA, Kaplan A, et al. Early cystic/necrotic changes after hyperfractionated radiation therapy in children with brain stem gliomas. Data from the Childrens Cancer Group. Cancer. 1993 Apr 15. 71(8):2666-74. [Medline].
Peterson K, Clark HB, Hall WA, Truwit CL. Multifocal enhancing magnetic resonance imaging lesions following cranial irradiation. Ann Neurol. 1995 Aug. 38(2):237-44. [Medline].
Posner JB. Side effects of radiation therapy. Neurologic Complications of Cancer. No. 54. Philadelphia, Pa: FA Davis; 1995. 311-37.
Rizzoli HV, Pagnanelli DM. Treatment of delayed radiation necrosis of the brain. A clinical observation. J Neurosurg. 1984 Mar. 60(3):589-94. [Medline].
Slizofski WJ, Krishna L, Katsetos CD, et al. Thallium imaging for brain tumors with results measured by a semiquantitative index and correlated with histopathology. Cancer. 1994 Dec 15. 74(12):3190-7. [Medline].