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Complications After Stereotactic Radiosurgery
35
Complications After Stereotactic Radiosurgery BRUCE E. POLLOCK
HIGHLIGHTS • Complications after stereotactic radiosurgery relate primarily to either temporary or permanent radiation injury to the structures adjacent to the irradiated target. • Risk factors are history of prior irradiation, lesion size, lesion location, nonconformal dose planning, and radiation dose. • Reversible imaging changes (areas of increased signal on T2-weighted magnetic resonance imaging) are common and generally occur in the first 6 to 12 months after stereotactic radiosurgery. Most are asymptomatic and resolve without treatment, whereas patients with symptomatic reversible imaging changes can usually be managed with corticosteroid therapy. • Radiation necrosis (persistent areas of enhancement with adjacent edema) is much less common and represents permanent vascular damage with resultant immune response. Treatment of symptomatic patients can include corticosteroids, bevacizumab, hyperbaric oxygen therapy, or surgical resection. • Late adverse radiation effects develop 5 or more years after stereotactic radiosurgery and are characterized by perilesional edema or cyst formation. Symptomatic late adverse radiation effects frequently require surgical removal to improve the patient’s neurologic condition.
Introduction The concept of stereotactic radiosurgery (SRS) was developed by Lars Leksell from the Karolinska Institute in Stockholm, Sweden in 1951.1,2 SRS utilizes the principles of stereotactic localization combined with the precise delivery of radiation to an imagingdefined target. In the past 40 years, SRS has experienced exponential growth and has become an integral part of both neurosurgery and radiation oncology. Advances in neuroimaging and dose-planning software, together with the accumulated clinical experience of more than 1,000,000 treated patients to date, have made SRS safer and more effective for a wide variety of clinical indications.3–5 Whereas once SRS was available in only a few academic centers, now SRS is available to patients at both academic and community medical centers around the world. The goal of SRS is to deliver a clinically effective radiation dose to an imaging-defined target. At first, SRS was a single-fraction technique limited to the brain. Now SRS is defined as stereotactically delivered radiation in 1 to 5 fractions to both intracranial and extracranial targets. As with any radiation treatment, SRS aims to
damage the target more than the adjacent normal tissues. Two primary approaches are used to increase the therapeutic ratio in different types of radiation treatment. One, dose fractionation, exploits the differential radiosensitivity of normal and abnormal tissues. Typically, normal tissues are better able to repair sublethal DNA damage than tumors because of aberrant cell cycle control mechanisms in tumors. This is the rationale behind external beam radiation therapy (EBRT), whereby multiple small doses of radiation are delivered to the target and the adjacent normal tissue. Two, and in contrast to EBRT, single-fraction SRS achieves its therapeutic effect by minimizing the radiation delivered to the nearby normal structures by using highly conformal dose plans. Within several millimeters of the edge of the target, the radiation dose drops from a therapeutic level (10–25 Gy) to doses that approximate a single fraction of EBRT (2 Gy). Multisession SRS (2–5 fractions) theoretically takes advantage of both of these approaches by using conformal dose planning delivered in a small number of sessions.
Types of Radiation Complications Parenchymal Injury Imaging changes noted after SRS are common and can be divided into three categories. First, reversible imaging changes (RIC) (areas of increased signal on T2-weighted magnetic resonance imaging [MRI]) generally occur in the first 6 to 12 months after SRS (Fig. 35.1).6–8 Most are asymptomatic and resolve without treatment. Second, radiation necrosis (persistent areas of enhancement with adjacent edema) is much less common and represents permanent vascular damage with resultant immune response. Distinguishing between RIC, radiation necrosis, and tumor growth after SRS is important, and no imaging technique is perfect at guiding clinical decision-making.9 For small areas in asymptomatic patients, observation with repeat imaging is preferred. Comparison of the area on gadolinium-enhanced T1-weighted and T2-weighted MRI is commonly used after brain metastases SRS.10,11 Third, late adverse radiation effects (ARE) develop 5 or more years after SRS and are characterized by perilesional edema or cyst formation.12,13
Cranial Neuropathy Cranial nerve deficits after SRS of skull base lesions are uncommon.14–21 Most occur within the first year after SRS, but delayed injury can occur. Special somatic sensory nerves (optic, 203
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• Fig. 35.1
Axial T2-weighted magnetic resonance imaging (MRI) of a 58-year-old man who developed mild headaches 7 months after SRS of a recurrent posterior fossa pilocytic astrocytoma. The MRI showed edema throughout the right cerebellar hemisphere and mild mass effect on the fourth ventricle. The patient was started on corticosteroid therapy with resolution of his symptoms.
vestibulo-cochlear) are the most radiation sensitive, followed by the general somatic sensory nerves (trigeminal). The motor nerves are particularly radiation resistant.
Vascular Large vessel injury is uncommon after SRS, although cases of internal carotid artery occlusion and stroke have been reported after SRS of cavernous sinus meningiomas,19 and focal morphologic changes and aneurysm formation have been seen in the superior cerebellar artery in patients after trigeminal neuralgia SRS.22,23
Secondary Tumor Formation The most significant complication of any radiation-based procedure is the development of secondary tumors caused by irradiation. Cahan et al. reported 11 cases of bone sarcomas that arose after radiation treatment and outlined four criteria that are required before a secondary tumor could be deemed radiation induced.24 First, the second tumor must arise within the prior radiation field. Second, there must be an adequate latency between the radiation exposure and the development of the second tumor. Third, the secondary tumor must be histologically different from the original tumor. Fourth, the patient must not have a genetic predisposition for tumor development. Often it is difficult to separate cases that are more likely coincidental than radiation induced.25,26 The risk of radiation-induced tumors after SRS has been reported between 0% and 2.6% at 15 years and should not be used as a justification for choosing other treatment approaches over SRS for appropriate patients.27–29
Risk Factors for Radiation Complications The primary risk factors for ARE after SRS are a history of prior irradiation, large treatment volume, target location, poor (nonconformal) dose planning, and higher radiation doses. Numerous studies have correlated the chance of RIC after SRS with some measure of the radiation dose to the surrounding tissue and the location of the target.6,7,30 The most commonly cited parameter is
the 12-Gy volume that is the total volume in the treatment field that receives a radiation dose of 12 Gy or more.6 Patients with lesions in deep parenchymal locations (thalamus, basal ganglia, and brainstem) are more likely to develop neurologic deficits secondary to imaging changes noted on MRI. Advances in SRS technique including improved neuroimaging, better dose-planning software, and more precise radiation delivery devices have all contributed to a reduction in the incidence of ARE after SRS.3–5 In addition, medical knowledge based on the last 40 years has been instrumental in guiding clinical decision-making and proper patient selection for SRS. Patients with large lesions with symptomatic mass effect are rarely good candidates for SRS. One area that has received a great deal of attention is the risk of radiation-induced optic neuropathy (RION) after single-fraction SRS in the parasellar region. Early studies concluded that the risk of RION was increased if the radiation dose to the anterior visual pathways (optic nerves or chiasm) exceeded 8 Gy.31 However, more recent studies have shown that radiation doses of 10 to 14 Gy are well tolerated and have a low risk of RION (Fig. 35.2).15,17,18 Acceptance of this higher dose threshold for the anterior visual pathways increases the applicability and likely the effectiveness of single-fraction SRS for patients with lesions in the parasellar region. Volume-staged SRS (VS-SRS) is another approach that has reduced the risk of ARE in arteriovenous malformation (AVM) SRS. Although SRS is an accepted treatment option for patients with small- to moderate-sized intracranial AVM, SRS is generally recommended only for AVM with a diameter of 3 cm or less (approximately 14 cm3). Over the past 20 years, a number of centers have performed VS-SRS for patients with large-volume AVM.32–35 Volume staging of large AVM into multiple radiosurgical sessions permits a higher radiation dose to be delivered to the entire AVM volume while reducing the radiation exposure to the adjacent brain. Early papers have shown that VS-SRS permits large-volume intracranial AVM to be treated with a low rate of ARE. More work on escalating dose and decreasing the treatment volume per stage is needed to determine whether this will increase the rate of obliteration with this technique.
Treatment of Radiation Complications In neurologically stable patients, follow-up after SRS consists of periodic clinical examination and MRI. For patients with metastatic brain disease or primary brain tumors, this is usually performed every 3 months for the first year, then less frequently thereafter. Patients with AVM and most benign tumors (meningiomas, vestibular schwannoma, pituitary adenoma, glomus tumor) now undergo MRI between 6 and 12 months after SRS, then every 1 to 2 years. MRI review consists of lesion response, determination of RIC, and new tumor formation. In asymptomatic patients, areas of increased signal on T2-weighted MRI adjacent to the treated lesion are followed, and further imaging is recommended. Most resolve without treatment, but patients with symptomatic RIC can usually be managed with corticosteroid therapy. Patients with symptomatic radiation necrosis can also be managed most times with corticosteroid therapy, but sometimes they cannot be successfully weaned off steroids, and other treatments are required. Treatment of persistent radiation necrosis can include bevacizumab, hyperbaric oxygen therapy, or surgical resection.9,36–38 For patients with late ARE, again observation with serial imaging is recommended if they are asymptomatic.12,13 Patients with symptomatic late ARE frequently require surgical removal to improve the patient’s neurologic condition.
CHAPTER 35 Complications After Stereotactic Radiosurgery
205
• Fig. 35.2
Dose plan for a 52-year-old woman with a recurrent nonfunctioning pituitary adenoma after two prior transsphenoidal resections. The tumor margin dose was 15 Gy. The maximum dose to the right and left optic nerves was 13.2 and 13.4 Gy, respectively.
SURGICAL REWIND
My Worst Case The patient was a 51-year-old man who had undergone complete resection of a left-sided 6-cm parasagittal fronto-parietal WHO grade II meningioma (Fig. 35.3). Postoperatively he did well but continued to have intermittent partial motor seizures. Follow-up MRI performed 7 months after surgery showed a tumor recurrence measuring 28 mm in greatest dimension. After discussing the options of repeat resection, EBRT, or SRS, the patient decided to proceed with SRS. Gamma Knife SRS was performed using 17 isocenters of radiation to cover a volume of 10.2 cm3. The tumor margin dose was 16 Gy. Three months after SRS, he began to have more frequent seizures, and MRI showed slight tumor enlargement and adjacent edema. His anticonvulsant medications were increased, and he was placed on corticosteroid therapy. Over the next 5 months, he was not able to discontinue corticosteroid therapy without worsening headaches and more seizure activity. In addition, he developed steroid-induced diabetes mellitus and had a pulmonary embolus. He was started on bevacizumab therapy with improvement in the vasogenic edema. The bevacizumab therapy was stopped after 3 doses, and he was tapered off corticosteroids. Within several weeks, he started having more seizures again, and MRI showed the tumor to
A
B • Fig. 35.3
be larger with significant edema and mass effect. The patient underwent repeat tumor resection 15 months after SRS. A near-complete tumor resection was achieved, but he had a right-sided hemiparesis that required inpatient rehabilitation therapy. Within several weeks, his strength improved to normal, he was able to discontinue corticosteroid therapy, and he had no further seizure activity. One month after his second resection, he was treated with EBRT (59.4 Gy/33 fractions). The decisions in this patient’s management that contributed to his difficult course relate primarily to the timing and use of EBRT and SRS. It could be argued that EBRT given after his initial surgery may have prevented tumor recurrence and the need for SRS. However, the patient was not operated on at our center, and the usefulness of postoperative EBRT after complete removal of WHO grade II meningiomas remains controversial. In my opinion, the greater error was proceeding with SRS for a tumor >10 cm3 in a location that is very high risk for ARE.39,40 In retrospect, repeat surgical resection would have been a better option than SRS for this rapidly enlarging tumor. The lesson to learn is that poor patient selection cannot be overcome by advances in SRS technique.
C
Coronal postgadolinium magnetic resonance imaging (MRI) and dose plan of a 51-year-old man who underwent SRS for a recurrent WHO grade II meningioma. (A) MRI 3 months after initial resection showing no gross evidence of tumor. (B) Dose plan at the time of SRS 7 months after initial resection. (C) MRI 15 months after SRS shows the tumor to be increased in size with adjacent edema and mass effect.
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NEUROSURGICAL SELFIE MOMENT Major complications after contemporary SRS are uncommon, and most can be well managed by experienced physicians. The risks of ARE are greater in patients with a history of prior radiation treatment, large treatment volumes, and nonconformal dose plans. Late ARE can occur after both AVM and benign tumor SRS, emphasizing the need for ongoing MRI follow-up many years after SRS. The risk of radiation-induced tumors after single-fraction SRS is very low and should not be used as a reason to choose alternative treatment strategies for appropriate patients.
References 1. Leksell L. The stereotactic method and radiosurgery of the brain. Acta Chir Scand. 1951;102:316–319. 2. Leksell L. Stereotactic radiosurgery. J Neurol Neurosurg Psychiatry. 1983;46:797–803. 3. Flickinger JC, Kondziolka D, Pollock BE, et al. Evolution in technique for vestibular schwannoma radiosurgery and effect on outcome. Int J Radiat Oncol Biol Phys. 1996;36:275–280. 4. Nagy G, Rowe JG, Radatz MWR, et al. A historical analysis of single-staged Gamma Knife radiosurgical treatment for large arteriovenous malformations: evolution and outcomes. Acta Neurochir. 2012;154:383–394. 5. Pollock BE, Link MJ, Stafford SL, et al. Stereotactic radiosurgery for arteriovenous malformations: the effect of treatment period on patient outcomes. Neurosurgery. 2016;78:499–509. 6. Flickinger JC, Kondziolka D, Lunsford LD, et al. Development of a model to predict permanent symptomatic post-radiosurgery injury for arteriovenous malformation patients. Int J Radiat Oncol Biol Phys. 2000;46:1143–1148. 7. Kano H, Flickinger JC, Tonetti D, et al. Estimating the risks of adverse radiation effects after Gamma Knife radiosurgery for arteriovenous malformations. Stroke. 2017;48:84–90. 8. Yen CP, Matsumoto JA, Wintermark M, et al. Radiation-induced imaging changes following Gamma Knife surgery for cerebral arteriovenous malformations. J Neurosurg. 2013;118:63–73. 9. Chao ST, Ahluwalia MS, Barnett GH, et al. Challenges with the diagnosis and treatment of cerebral radiation necrosis. Int J Radiat Oncol Biol Phys. 2013;87:449–457. 10. Dequesada IM, Quisling RG, Yachnis A, et al. Can standard magnetic resonance imaging reliably distinguish recurrent tumor from radiation necrosis after radiosurgery for brain metastases? A radiographicpathologic study. Neurosurgery. 2008;63:898–904. 11. Kano H, Kondziolka D, Lobato-Polo J, et al. T1/T2 matching to differentiate tumor growth from radiation effects after stereotactic radiosurgery. Neurosurgery. 2010;66:486–492. 12. Pan H, Sheehan J, Stroila M, et al. Late cyst formation following Gamma Knife surgery of arteriovenous malformations. J Neurosurg. 2005;102(suppl):124–127. 13. Pollock BE, Link MJ, Branda ME, et al. Incidence and management of late adverse radiation effects after arteriovenous malformation radiosurgery. Neurosurgery. 2017;81(6):928–934. 14. Carlson ML, Jacob JT, Pollock BE, et al. Long-term hearing outcomes following low-dose stereotactic radiosurgery for vestibular schwannoma: patterns of hearing loss and variables influencing audiometric decline. J Neurosurg. 2013;118:579–587. 15. Hasegawa T, Kobayashi T, Kida Y. Tolerance of the optic apparatus in single-fraction irradiation using stereotactic radiosurgery: evaluation in 100 patients with craniopharyngioma. Neurosurgery. 2010;66:688–695. 16. Kano H, Park KJ, Kondziolka D, et al. Does prior microsurgery improve or worsen the outcomes of stereotactic radiosurgery for cavernous sinus meningiomas? Neurosurgery. 2013;73:401–410. 17. Leavitt JA, Stafford SL, Link MJ, et al. Long-term evaluation of radiation-induced optic neuropathy after single-fraction stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2013;87:524–527.
18. Pollock BE, Link MJ, Leavitt JL, et al. Dose-volume analysis of radiation-induced optic neuropathy after single-fraction stereotactic radiosurgery. Neurosurgery. 2014;75:456–460. 19. Pollock BE, Stafford SL, Link MJ, et al. Single-fraction radiosurgery of benign cavernous sinus meningiomas. J Neurosurg. 2013;119: 675–682. 20. Sheehan JP, Starke RM, Mathieu D, et al. Gamma Knife radiosurgery for the management of nonfunctioning pituitary adenomas: a multicenter study. J Neurosurg. 2013;119:446–456. 21. Skeie BS, Enger PO, Skeie GO, et al. Gamma Knife surgery of meningiomas involving the cavernous sinus: long-term follow-up of 100 patients. Neurosurgery. 2010;66:661–669. 22. Chen JC, Chao K, Rahimian J. De novo superior cerebellar artery aneurysm following radiosurgery for trigeminal neuralgia. J Clin Neurosci. 2017;38:87–90. 23. Maher CO, Pollock BE. Radiation induced vascular injury after stereotactic radiosurgery for trigeminal neuralgia. Surg Neurol. 2000;54:189–193. 24. Cahan WG, Woodard HQ, Higonbotham NL, et al. Sarcoma arising in irradiated bone. Report of 11 cases. Cancer. 1948;1:3–29. 25. Carlson ML, Glasgow AE, Jacob JT, et al. The short- and intermediateterm risk of second neoplasms after diagnosis and treatment of unilateral vestibular schwannoma: analysis of 9,460 cases. Int J Radiat Oncol Biol Phys. 2016;95(4):1149–1157. 26. Rowe J, Grainger A, Walton L, et al. Risk of malignancy after Gamma Knife stereotactic radiosurgery. Neurosurgery. 2007;60:60–66. 27. Patel TR, Chiang VL. Secondary neoplasms after stereotactic radiosurgery. World Neurosurg. 2014;81:594–599. 28. Pollock BE, Link MJ, Stafford SL, et al. The risk of radiation-induced tumors or malignant transformation after single-fraction intracranial radiosurgery: results based on a 25-year experience. Int J Radiat Oncol Biol Phys. 2017;97(5):919–923. 29. Starke RM, Yen CP, Chen CJ, et al. An updated assessment of the risk of radiation-induced neoplasia after radiosurgery of arteriovenous malformations. World Neurosurg. 2014;82:395–401. 30. Voges J, Treuer H, Lehrke R, et al. Risk analysis of LINAC radiosurgery in patients with arterio-venous malformations (AVM). Acta Neurochir. 1997;68:118–123. 31. Tishler RB, Loeffler JS, Lunsford LD, et al. Tolerance of cranial nerves of the cavernous sinus to radiosurgery. Int J Radiat Oncol Biol Phys. 1993;27:215–221. 32. Kano H, Kondziolka D, Flickinger JC, et al. Stereotactic radiosurgery for arteriovenous malformations, part 6: multistaged volumetric management of large arteriovenous malformations. J Neurosurg. 2012;116:54–65. 33. Nagy G, Grainger A, Hodgson T, et al. Staged volume radiosurgery of large arteriovenous malformations improves outcome by reducing the rate of adverse radiation effects. Neurosurgery. 2017;80: 180–192. 34. Pollock BE, Link MJ, Stafford SL, et al. Volume-staged stereotactic radiosurgery for intracranial arteriovenous malformations: outcomes based on an 18-year experience. Neurosurgery. 2017;80(4):543–550. 35. Seymour ZA, Sneed PK, Gupta N, et al. Volume-staged radiosurgery for large arteriovenous malformations: an evolving paradigm. J Neurosurg. 2016;124:163–174. 36. Boothe D, Young R, Yamada Y, et al. Bevacizumab as a treatment for radiation necrosis of brain metastases post stereotactic radiosurgery. Neuro Oncol. 2013;15:1257–1263. 37. Kohshi K, Imada H, Nomoto S, et al. Successful treatment of radiation-induced brain necrosis by hyperbaric oxygen therapy. J Neurol Sci. 2003;209:115–117. 38. Levin VA, Bidaut L, Hou P, et al. Randomized double-blind placebocontrolled trial of bevacizumab therapy for radiation necrosis of the central nervous system. Int J Radiat Oncol Biol Phys. 2011;79:1487–1495. 39. Bledsoe JM, Link MJ, Stafford SL, et al. Radiosurgery for large volume (>10 cc) benign meningiomas. J Neurosurg. 2010;112:951–956. 40. Pollock BE, Stafford SL, Link MJ, et al. Single-fraction radiosurgery of benign intracranial meningiomas. Neurosurgery. 2012;71:604–613.
Complications After Stereotactic Radiosurgery BRUCE E. POLLOCK
HIGHLIGHTS • Complications after stereotactic radiosurgery relate primarily to either temporary or permanent radiation injury to the structures adjacent to the irradiated target. • Risk factors are history of prior irradiation, lesion size, lesion location, nonconformal dose planning, and radiation dose. • Reversible imaging changes (areas of increased signal on T2-weighted magnetic resonance imaging) are common and generally occur in the first 6 to 12 months after stereotactic radiosurgery. Most are asymptomatic and resolve without treatment, whereas patients with symptomatic reversible imaging changes can usually be managed with corticosteroid therapy. • Radiation necrosis (persistent areas of enhancement with adjacent edema) is much less common and represents permanent vascular damage with resultant immune response. Treatment of symptomatic patients can include corticosteroids, bevacizumab, hyperbaric oxygen therapy, or surgical resection. • Late adverse radiation effects develop 5 or more years after stereotactic radiosurgery and are characterized by perilesional edema or cyst formation. Symptomatic late adverse radiation effects frequently require surgical removal to improve the patient’s neurologic condition.
Introduction The concept of stereotactic radiosurgery (SRS) was developed by Lars Leksell from the Karolinska Institute in Stockholm, Sweden in 1951.1,2 SRS utilizes the principles of stereotactic localization combined with the precise delivery of radiation to an imagingdefined target. In the past 40 years, SRS has experienced exponential growth and has become an integral part of both neurosurgery and radiation oncology. Advances in neuroimaging and dose-planning software, together with the accumulated clinical experience of more than 1,000,000 treated patients to date, have made SRS safer and more effective for a wide variety of clinical indications.3–5 Whereas once SRS was available in only a few academic centers, now SRS is available to patients at both academic and community medical centers around the world. The goal of SRS is to deliver a clinically effective radiation dose to an imaging-defined target. At first, SRS was a single-fraction technique limited to the brain. Now SRS is defined as stereotactically delivered radiation in 1 to 5 fractions to both intracranial and extracranial targets. As with any radiation treatment, SRS aims to
damage the target more than the adjacent normal tissues. Two primary approaches are used to increase the therapeutic ratio in different types of radiation treatment. One, dose fractionation, exploits the differential radiosensitivity of normal and abnormal tissues. Typically, normal tissues are better able to repair sublethal DNA damage than tumors because of aberrant cell cycle control mechanisms in tumors. This is the rationale behind external beam radiation therapy (EBRT), whereby multiple small doses of radiation are delivered to the target and the adjacent normal tissue. Two, and in contrast to EBRT, single-fraction SRS achieves its therapeutic effect by minimizing the radiation delivered to the nearby normal structures by using highly conformal dose plans. Within several millimeters of the edge of the target, the radiation dose drops from a therapeutic level (10–25 Gy) to doses that approximate a single fraction of EBRT (2 Gy). Multisession SRS (2–5 fractions) theoretically takes advantage of both of these approaches by using conformal dose planning delivered in a small number of sessions.
Types of Radiation Complications Parenchymal Injury Imaging changes noted after SRS are common and can be divided into three categories. First, reversible imaging changes (RIC) (areas of increased signal on T2-weighted magnetic resonance imaging [MRI]) generally occur in the first 6 to 12 months after SRS (Fig. 35.1).6–8 Most are asymptomatic and resolve without treatment. Second, radiation necrosis (persistent areas of enhancement with adjacent edema) is much less common and represents permanent vascular damage with resultant immune response. Distinguishing between RIC, radiation necrosis, and tumor growth after SRS is important, and no imaging technique is perfect at guiding clinical decision-making.9 For small areas in asymptomatic patients, observation with repeat imaging is preferred. Comparison of the area on gadolinium-enhanced T1-weighted and T2-weighted MRI is commonly used after brain metastases SRS.10,11 Third, late adverse radiation effects (ARE) develop 5 or more years after SRS and are characterized by perilesional edema or cyst formation.12,13
Cranial Neuropathy Cranial nerve deficits after SRS of skull base lesions are uncommon.14–21 Most occur within the first year after SRS, but delayed injury can occur. Special somatic sensory nerves (optic, 203
204 SE C T I O N 2
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• Fig. 35.1
Axial T2-weighted magnetic resonance imaging (MRI) of a 58-year-old man who developed mild headaches 7 months after SRS of a recurrent posterior fossa pilocytic astrocytoma. The MRI showed edema throughout the right cerebellar hemisphere and mild mass effect on the fourth ventricle. The patient was started on corticosteroid therapy with resolution of his symptoms.
vestibulo-cochlear) are the most radiation sensitive, followed by the general somatic sensory nerves (trigeminal). The motor nerves are particularly radiation resistant.
Vascular Large vessel injury is uncommon after SRS, although cases of internal carotid artery occlusion and stroke have been reported after SRS of cavernous sinus meningiomas,19 and focal morphologic changes and aneurysm formation have been seen in the superior cerebellar artery in patients after trigeminal neuralgia SRS.22,23
Secondary Tumor Formation The most significant complication of any radiation-based procedure is the development of secondary tumors caused by irradiation. Cahan et al. reported 11 cases of bone sarcomas that arose after radiation treatment and outlined four criteria that are required before a secondary tumor could be deemed radiation induced.24 First, the second tumor must arise within the prior radiation field. Second, there must be an adequate latency between the radiation exposure and the development of the second tumor. Third, the secondary tumor must be histologically different from the original tumor. Fourth, the patient must not have a genetic predisposition for tumor development. Often it is difficult to separate cases that are more likely coincidental than radiation induced.25,26 The risk of radiation-induced tumors after SRS has been reported between 0% and 2.6% at 15 years and should not be used as a justification for choosing other treatment approaches over SRS for appropriate patients.27–29
Risk Factors for Radiation Complications The primary risk factors for ARE after SRS are a history of prior irradiation, large treatment volume, target location, poor (nonconformal) dose planning, and higher radiation doses. Numerous studies have correlated the chance of RIC after SRS with some measure of the radiation dose to the surrounding tissue and the location of the target.6,7,30 The most commonly cited parameter is
the 12-Gy volume that is the total volume in the treatment field that receives a radiation dose of 12 Gy or more.6 Patients with lesions in deep parenchymal locations (thalamus, basal ganglia, and brainstem) are more likely to develop neurologic deficits secondary to imaging changes noted on MRI. Advances in SRS technique including improved neuroimaging, better dose-planning software, and more precise radiation delivery devices have all contributed to a reduction in the incidence of ARE after SRS.3–5 In addition, medical knowledge based on the last 40 years has been instrumental in guiding clinical decision-making and proper patient selection for SRS. Patients with large lesions with symptomatic mass effect are rarely good candidates for SRS. One area that has received a great deal of attention is the risk of radiation-induced optic neuropathy (RION) after single-fraction SRS in the parasellar region. Early studies concluded that the risk of RION was increased if the radiation dose to the anterior visual pathways (optic nerves or chiasm) exceeded 8 Gy.31 However, more recent studies have shown that radiation doses of 10 to 14 Gy are well tolerated and have a low risk of RION (Fig. 35.2).15,17,18 Acceptance of this higher dose threshold for the anterior visual pathways increases the applicability and likely the effectiveness of single-fraction SRS for patients with lesions in the parasellar region. Volume-staged SRS (VS-SRS) is another approach that has reduced the risk of ARE in arteriovenous malformation (AVM) SRS. Although SRS is an accepted treatment option for patients with small- to moderate-sized intracranial AVM, SRS is generally recommended only for AVM with a diameter of 3 cm or less (approximately 14 cm3). Over the past 20 years, a number of centers have performed VS-SRS for patients with large-volume AVM.32–35 Volume staging of large AVM into multiple radiosurgical sessions permits a higher radiation dose to be delivered to the entire AVM volume while reducing the radiation exposure to the adjacent brain. Early papers have shown that VS-SRS permits large-volume intracranial AVM to be treated with a low rate of ARE. More work on escalating dose and decreasing the treatment volume per stage is needed to determine whether this will increase the rate of obliteration with this technique.
Treatment of Radiation Complications In neurologically stable patients, follow-up after SRS consists of periodic clinical examination and MRI. For patients with metastatic brain disease or primary brain tumors, this is usually performed every 3 months for the first year, then less frequently thereafter. Patients with AVM and most benign tumors (meningiomas, vestibular schwannoma, pituitary adenoma, glomus tumor) now undergo MRI between 6 and 12 months after SRS, then every 1 to 2 years. MRI review consists of lesion response, determination of RIC, and new tumor formation. In asymptomatic patients, areas of increased signal on T2-weighted MRI adjacent to the treated lesion are followed, and further imaging is recommended. Most resolve without treatment, but patients with symptomatic RIC can usually be managed with corticosteroid therapy. Patients with symptomatic radiation necrosis can also be managed most times with corticosteroid therapy, but sometimes they cannot be successfully weaned off steroids, and other treatments are required. Treatment of persistent radiation necrosis can include bevacizumab, hyperbaric oxygen therapy, or surgical resection.9,36–38 For patients with late ARE, again observation with serial imaging is recommended if they are asymptomatic.12,13 Patients with symptomatic late ARE frequently require surgical removal to improve the patient’s neurologic condition.
CHAPTER 35 Complications After Stereotactic Radiosurgery
205
• Fig. 35.2
Dose plan for a 52-year-old woman with a recurrent nonfunctioning pituitary adenoma after two prior transsphenoidal resections. The tumor margin dose was 15 Gy. The maximum dose to the right and left optic nerves was 13.2 and 13.4 Gy, respectively.
SURGICAL REWIND
My Worst Case The patient was a 51-year-old man who had undergone complete resection of a left-sided 6-cm parasagittal fronto-parietal WHO grade II meningioma (Fig. 35.3). Postoperatively he did well but continued to have intermittent partial motor seizures. Follow-up MRI performed 7 months after surgery showed a tumor recurrence measuring 28 mm in greatest dimension. After discussing the options of repeat resection, EBRT, or SRS, the patient decided to proceed with SRS. Gamma Knife SRS was performed using 17 isocenters of radiation to cover a volume of 10.2 cm3. The tumor margin dose was 16 Gy. Three months after SRS, he began to have more frequent seizures, and MRI showed slight tumor enlargement and adjacent edema. His anticonvulsant medications were increased, and he was placed on corticosteroid therapy. Over the next 5 months, he was not able to discontinue corticosteroid therapy without worsening headaches and more seizure activity. In addition, he developed steroid-induced diabetes mellitus and had a pulmonary embolus. He was started on bevacizumab therapy with improvement in the vasogenic edema. The bevacizumab therapy was stopped after 3 doses, and he was tapered off corticosteroids. Within several weeks, he started having more seizures again, and MRI showed the tumor to
A
B • Fig. 35.3
be larger with significant edema and mass effect. The patient underwent repeat tumor resection 15 months after SRS. A near-complete tumor resection was achieved, but he had a right-sided hemiparesis that required inpatient rehabilitation therapy. Within several weeks, his strength improved to normal, he was able to discontinue corticosteroid therapy, and he had no further seizure activity. One month after his second resection, he was treated with EBRT (59.4 Gy/33 fractions). The decisions in this patient’s management that contributed to his difficult course relate primarily to the timing and use of EBRT and SRS. It could be argued that EBRT given after his initial surgery may have prevented tumor recurrence and the need for SRS. However, the patient was not operated on at our center, and the usefulness of postoperative EBRT after complete removal of WHO grade II meningiomas remains controversial. In my opinion, the greater error was proceeding with SRS for a tumor >10 cm3 in a location that is very high risk for ARE.39,40 In retrospect, repeat surgical resection would have been a better option than SRS for this rapidly enlarging tumor. The lesson to learn is that poor patient selection cannot be overcome by advances in SRS technique.
C
Coronal postgadolinium magnetic resonance imaging (MRI) and dose plan of a 51-year-old man who underwent SRS for a recurrent WHO grade II meningioma. (A) MRI 3 months after initial resection showing no gross evidence of tumor. (B) Dose plan at the time of SRS 7 months after initial resection. (C) MRI 15 months after SRS shows the tumor to be increased in size with adjacent edema and mass effect.
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SE C T I O N 2
Cranial Complications
NEUROSURGICAL SELFIE MOMENT Major complications after contemporary SRS are uncommon, and most can be well managed by experienced physicians. The risks of ARE are greater in patients with a history of prior radiation treatment, large treatment volumes, and nonconformal dose plans. Late ARE can occur after both AVM and benign tumor SRS, emphasizing the need for ongoing MRI follow-up many years after SRS. The risk of radiation-induced tumors after single-fraction SRS is very low and should not be used as a reason to choose alternative treatment strategies for appropriate patients.
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