Vestibular Schwannoma Gamma Knife radiosurgery complications

Vestibular Schwannoma Gamma Knife radiosurgery complications

Patients treated with Stereotactic radiosurgery for vestibular schwannoma can have a similar complication profile to those treated with intracranial surgery. Vestibular Schwannoma Meta-analysis from early experience showed that 44% with serviceable hearing prior to treatment retained their ability after SRS, a statistically equivalent rate to the surgical data. This evidence also suggest that 37.9% of patients have other complications 1).


In the mid-1970s, early facial weakness occurred in 38% and facial numbness in 33%. This has gradually decreased to less than 2% in the 1990s. Preservation of hearing (unchanged or almost unchanged) is currently achieved in 65 to 70%. Tinnitus is rarely changed by the treatment. The risks of intracranial bleeding, infection, and CSF leak are avoided because of the non-invasive nature of the treatment. Hydrocephalus directly induced by the tumor occurred in 9.2% of patients. On the other hand, a treatment%related peritumoral reaction sufficient to block the CSF circulation and require shunt insertion was seen in only 1.4%. Based on experiences worldwide, the incidence of secondary neoplasia seems to be 0.1%. The effectiveness of GKR together with its low complication rate makes it a suitable treatment for anyone, regardless of age and general health 2).


Malignant transformation is possible 3). , and long-term post-SRS surveillance MRI is important 4).

Patients receiving > 13 Gy were significantly more likely to develop trigeminal neuropathy than those receiving < 13 Gy (p < 0.001) 5).

Pollack et al. described an acute facial and acoustic neuropathy following gamma knife surgery (GKS) for vestibular schwannoma (VS). This 39-year-old woman presenting with tinnitus underwent GKS for a small right-sided intracanalicular VS, receiving a maximal dose of 26 Gy and a tumor margin dose of 13 Gy to the 50% isodose line. Thirty-six hours following treatment she presented with nausea, vomiting, vertigo, diminished hearing, and a House-Brackmann Grade III facial palsy. She was started on intravenous glucocorticosteroid agents, and over the course of 2 weeks her facial function returned to House-Brackmann Grade I. Unfortunately, her hearing loss persisted. A magnetic resonance (MR) image obtained at the time of initial deterioration demonstrated a significant decrease in tumor enhancement but no change in tumor size or peritumoral edema. Subsequently, the patient experienced severe hemifacial spasms, which persisted for a period of 3 weeks and then progressed to a House-Brackmann Grade V facial palsy. During the next 3 months, the patient was treated with steroids and in time her facial function and hearing returned to baseline levels. Results of MR imaging revealed transient enlargement (3 mm) of the tumor, which subsequently returned to its baseline size. This change corresponded to the tumor volume increase from 270 to 336 mm3. The patient remains radiologically and neurologically stable at 10 months posttreatment. This is the first detailed report of acute facial and vestibulocochlear neurotoxicity following GKS for VS that improved with time. In addition, MR imaging findings were indicative of early neurotoxic changes. A review of possible risk factors and explanations of causative mechanisms is provided 6).

see Vestibular Schwannoma pseudoprogression.


1)

Kaylie DM, Horgan MJ, Delashaw JB, McMenomey SO. A meta-analysis comparing outcomes of microsurgery and gamma knife radiosurgery. Laryngoscope. 2000 Nov;110(11):1850-6. doi: 10.1097/00005537-200011000-00016. PMID: 11081598.
2)

Norén G. Long-term complications following gamma knife radiosurgery of vestibular schwannomas. Stereotact Funct Neurosurg. 1998 Oct;70 Suppl 1:65-73. doi: 10.1159/000056408. PMID: 9782237.
3)

Yanamadala V, Williamson RW, Fusco DJ, Eschbacher J, Weisskopf P, Porter RW. Malignant transformation of a vestibular schwannoma after gamma knife radiosurgery. World Neurosurg. 2013 Mar-Apr;79(3-4):593.e1-8. doi: 10.1016/j.wneu.2012.03.016. Epub 2012 Apr 2. PubMed PMID: 22480982.
4)

Kawashima M, Hasegawa H, Shin M, Shinya Y, Katano A, Saito N. Outcomes of stereotactic radiosurgery in young adults with vestibular schwannomas. J Neurooncol. 2021 Jul 9. doi: 10.1007/s11060-021-03803-w. Epub ahead of print. PMID: 34241770.
5)

Sughrue ME, Yang I, Han SJ, Aranda D, Kane AJ, Amoils M, Smith ZA, Parsa AT. Non-audiofacial morbidity after Gamma Knife surgery for vestibular schwannoma. J Neurosurg. 2013 Dec;119 Suppl:E4. Review. PubMed PMID: 25077327.
6)

Pollack AG, Marymont MH, Kalapurakal JA, Kepka A, Sathiaseelan V, Chandler JP. Acute neurological complications following gamma knife surgery for vestibular schwannoma. Case report. J Neurosurg. 2005 Sep;103(3):546-51. doi: 10.3171/jns.2005.103.3.0546. PMID: 16235688.

Gamma Knife radiosurgery for acromegaly

Gamma Knife radiosurgery for acromegaly

Numerous studies of radiosurgery for acromegaly have been carried out. These illustrate an overall remission rate of over 40%. Morbidity from radiosurgery is infrequent but can include cranial nerve palsies and hypopituitarism. Overall, stereotactic radiosurgery is a promising therapy for patients with acromegaly and deserves further study to refine its role in the treatment of affected patients 1).

GKS is an effective adjuvant treatment option for remnant tumors inside the cavernous sinus (CS) after transsphenoidal surgery (TSS). Maximal surgical resection leaving a minimal volume of remnants only inside the CS allows the safe and sufficient delivery of a radiation dose to tumors, thereby increasing the possibility of remission. However, the risk of new hypopituitarism and radiation necrosis should be considered when tumors inside the CS are treated with GKS 2).

Losa et al. performed a study to investigate, which would be the outcome of GKRS, independently on the response to somatostatin receptor ligand (SRL).

Design: Retrospectiveobservational study.

Patients: Ninety-six patients with active acromegaly were included.

Measurements: The cumulative probability of normalization of insulin-like growth factor 1 (IGF-1) levels after GKRS was assessed by the Kaplan-Meier method. The association of several clinical characteristics with GKRS outcomes was explored with the use of a Cox proportional-hazard model with the relative hazard ratio and 95% confidence interval (CI).

Results: Resistance to SRL occurred in 39 of the 96 patients (40.6%). After GKRS, patients resistant to SRL had a 5- and 10-year probability of remission of 40.7% (95% CI: 23.7%-57.7%) and 75.9% (95% CI: 57.9%-93.9%), respectively. Patients responding to SRL had a 5- and 10-year probability of remission of 46.8% (95% CI: 32.2%-61.4%) and 58.1% (95% CI: 41.5%-74.7%), respectively. The difference was not significant (p = .48 by the log-rank test). Multivariate Cox analysis confirmed that the only independent variables associated with GKRS outcome were basal growth hormone (GH; p = .001) and IGF-1 multiple of the upper limit of normal levels before GKRS (p = .013).

Conclusion: They demonstrate for the first time that the responsiveness to SRL has no effect on the probability to obtain remission of acromegaly after GKRS. The remission of disease occurred more frequently in patients who had lower GH and IGF-1 levels before GKRS 3).


Forty-two patients (minimum 6 months follow-up) were included. The mean marginal dose was 27.7 (median 28, 20-35), and the mean BED received by the tumor was 193.1 Gy2.47 (median 199.7, 64.1-237.1). Based on the median values, we divided the patients into the high tumor BED group (H-BEDtm, 199.7-237.1 Gy2.47, n = 12) and low BED one (L- BEDtm, 64.1-199.7 Gy2.47 , n = 10). The two groups did not differ by pre-therapeutic IGF-1 levels (p = .1) or by the prescribed dose (p = .6).

Results: The mean follow-up period was 62.5 months (median 60.5, 9-127). The probability of IGF-1 normalization was 65% at 3 years and 72.4% at 4 years, remaining stable until last follow-up. Twenty-two (52.4%) patients had complete endocrine remission in absence of any Somatostatin analogs. Actuarial rates were 33% at 3 years and 57.4% at 7 years, further remaining stable during the follow-up course. In univariate analysis, the only statistically significant parameter was pre-therapeutic serum IGF-1 and IGF-1 index (p = .01). Five patients (5/26, 19.3%) without previous hypopituitarism developed new pituitary insufficiency. H-BEDtm was associated with higher rates of endocrine remission compared with L-BEDtm, with an actuarial probability of 70.2% versus 48.2% at 9 years, although this did not reach statistical significance (p > .05).

The study confirms that SRS by Gamma Knife is safe and effective for GH-secreting PA. Pre therapeutic serum levels of IGF-1 were the only statistically significant parameters for endocrine remission 4).


A retrospective analysis of hormonal, radiological, and ophthalmologic data collected in a predefined protocol from 1994 to 2009. The mean age at treatment was 42.3 years (range 22-67 yy). 103 acromegalic patients participated in the study. The median follow-up was 71 months (IQ range 43-107). All patients were treated with GK for residual or recurrent GH-secreting adenoma. Results. Sixty-three patients (61.2%) reached the main outcome of the study. The rate of remission was 58.3% at 5 years (95% CI 47.6-69.0%). Other 15 patients (14.6%) were in remission after GK while on treatment with somatostatin analogs. No serious side effects occurred after GK. Eight patients (7.8%) experienced a new deficit of pituitary function. New cases of hypogonadism, hypothyroidism and hypoadrenalism occurred in 4 of 77 patients (5.2%), 3 of 95 patients (3.2%), and 6 of 100 patients at risk (6.0%), respectively. Conclusion. In a highly selected group of acromegalic patients, GK treatment had good efficacy and safety 5).


Thirty acromegalic patients (14 women and 16 men) entered a prospective study of GK treatment. Most were surgical failures, whereas in 3 GK was the primary treatment. Imaging of the adenoma and target coordinates identification were obtained by high-resolution magnetic resonance imaging. All patients were treated with multiple isocenters (mean, 8; range, 3-11). The 50% isodose was used in 27 patients (90%). The mean margin dose was 20 Gy (range, 15-35), and the dose to the visual pathways was always less than 8 Gy. After a median follow-up of 46 months (range, 9-96), IGF-I fell from 805 micro g/liter (median; interquartile range, 640-994) to 460 micro g/liter (interquartile range, 217-654; P = 0.0002), and normal age-matched IGF-I levels were reached in 7 patients (23%). Mean GH levels decreased from 10 micro g/liter (interquartile range, 6.4-15) to 2.9 micro g/liter (interquartile range, 2-5.3; P < 0.0001), reaching levels below 2.5 micro g/liter in 11 (37%). The rate of persistently pathological hormonal levels was still 70% at 5 yr by Kaplan-Meier analysis. The median volume was 1.43 ml (range, 0.20-3.7). Tumor shrinkage (at least 25% of basal volume) occurred after 24 months (range, 12-36) in 11 of 19 patients (58% of assessable patients). The rate of shrinkage was 79% at 4 yr. In no case was further growth observed. Only 1 patient complained of side effects (severe headache and nausea immediately after the procedure, with full recovery in a few days with steroid therapy). Anterior pituitary failures were observed in 2 patients, who already had partial hypopituitarism, after 2 and 6 yr, respectively. No patient developed visual deficits. GK is a valid adjunctive tool in the management of acromegaly that controls GH/IGF-I hypersecretion and tumor growth, with shrinkage of adenoma and no recurrence of the disease in the considered observation period and with low acute and chronic toxicity 6).


149 patients with GH-secreting pituitary adenoma, 97 males and 52 females, aged 42.8 (12-72 years), with a course of 6-240 months (72.5 months) and with the mean volume of tumor of 2.36 cm(3) (0.11-12.7 cm(3)) were treated by GKS. The mean dose to tumor margin was 20.87 Gy (10-30 Gy). 124 of them were followed up for 30 months (6-72 months).

The serum GH returned normal in 74 patients (64.9%) and declined in comparison with the level before radiosurgery in 23 patients (18.5%). The tumor volume was reduced in 84 patients (67.7%) and remained unchanged in 124 patients (32.4%). Ambiopia appeared in one patient. No other complication was found during the follow-up.

GKS is safe and effective on the treatment of GH-secreting pituitary adenoma 7).


1)

Rolston JD, Blevins LS Jr. Gamma knife radiosurgery for acromegaly. Int J Endocrinol. 2012;2012:821579. doi: 10.1155/2012/821579. Epub 2012 Feb 13. PMID: 22518132; PMCID: PMC3296174.
2)

Kim EH, Oh MC, Chang JH, Moon JH, Ku CR, Chang WS, Lee EJ, Kim SH. Postoperative Gamma Knife radiosurgery for cavernous sinus-invading growth hormone-secreting pituitary adenomas. World Neurosurg. 2017 Nov 16. pii: S1878-8750(17)31966-6. doi: 10.1016/j.wneu.2017.11.043. [Epub ahead of print] PubMed PMID: 29155347.
3)

Losa M, Resmini E, Barzaghi LR, Albano L, Bailo M, Webb SM, Mortini P. Resistance to first-generation somatostatin receptor ligands does not impair the results of gamma knife radiosurgery in acromegaly. Clin Endocrinol (Oxf). 2021 Jul 4. doi: 10.1111/cen.14547. Epub ahead of print. PMID: 34219264.
4)

Balossier A, Tuleasca C, Cortet-Rudelli C, Soto-Ares G, Levivier M, Assaker R, Reyns N. Gamma Knife radiosurgery for acromegaly: Evaluating the role of the biological effective dose associated with endocrine remission in a series of 42 consecutive cases. Clin Endocrinol (Oxf). 2021 Mar;94(3):424-433. doi: 10.1111/cen.14346. Epub 2020 Oct 10. PMID: 32984972.
5)

Franzin A, Spatola G, Losa M, Picozzi P, Mortini P. Results of gamma knife radiosurgery in acromegaly. Int J Endocrinol. 2012;2012:342034. doi: 10.1155/2012/342034. Epub 2012 Feb 19. PMID: 22518119; PMCID: PMC3296167.
6)

Attanasio R, Epaminonda P, Motti E, Giugni E, Ventrella L, Cozzi R, Farabola M, Loli P, Beck-Peccoz P, Arosio M. Gamma-knife radiosurgery in acromegaly: a 4-year follow-up study. J Clin Endocrinol Metab. 2003 Jul;88(7):3105-12. doi: 10.1210/jc.2002-021663. PMID: 12843150.
7)

Wang MH, Liu P, Liu AL, Luo B, Sun SB. [Efficacy of gamma knife radiosurgery in treatment of growth hormone-secreting pituitary adenoma]. Zhonghua Yi Xue Za Zhi. 2003 Dec 10;83(23):2045-8. Chinese. PubMed PMID: 14703413.

Gamma Knife radiosurgery for cavernous malformation


Gamma Knife radiosurgery for cavernous malformation

Stereotactic radiosurgery (SRS) is a therapeutic option for repeatedly hemorrhagic cavernous malformations (CMs) located in areas deemed to be high risk for resection. During the latency period of 2 or more years after SRS, recurrent hemorrhage remains a persistent risk until the obliterative process has finished. The pathological response to SRS has been studied in relatively few patients.


Gamma Knife radiosurgery (GKRS) has been used to treat cavernous malformations (CMs) located in basal ganglia and thalamus. However, previous reports are limited by small patient population.

Hu et al. retrospectively reviewed the clinical and radiological data of 53 patients with CMs of basal ganglia and thalamus who underwent GKRS at West China Medical Center between May 2009 and July 2018. All patients suffered at least once bleeding before GKRS. The mean volume of these lesions was 1.77 cm3, and the mean marginal dose was 13.2 Gy. After treatment, patients were followed to determine the change in symptom and hemorrhage event.

The mean follow-up period was 52.1 months (6.2-104.3 months). The calculated annual hemorrhage rate (AHR) was 48.5% prior to GKRS and 3.0% after treatment (p < 0.001). The Kaplan-Meier analysis revealed that 2-, 3-, and 5-year hemorrhage-free survival were 88, 80.9, and 80.9%, respectively. Preexisting symptoms were resolved in 11 patients, improved in 14, and stable in 5. Only 2 patients (3.8%) developed new neurological deficit.

This study suggests that AHR after GKRS was comparable to the recorded AHR of natural history (3.1-4.1%) in previous studies. GKRS is a safe and effective treatment modality for CMs of basal ganglia and thalamus. Considering the relative insufficient understanding of natural history of CMs, future study warrants longer follow-up 1)

Wen et al., from the West China Hospital performed a meta-analysis is to evaluate the clinical efficacy of gamma knife radiosurgery for treating cavernous malformation.

PUBMEDOVID EMBASE, and OVID MEDLINE electronic databases are searched. The primary outcome is hemorrhage rate and this meta-analysis is performed with REVMAN 5.3.

9 studies are included in this meta-analysis. The overall RR of hemorrhage rate of pre-GKRS and post-GKRS is 6.08(95% CI: 5.04-7.35). The overall RR is 3.03(95% CI: 2.65-4.11) between the hemorrhage rate of pre-GKRS and the first 2 years of post-radiosurgery, and the overall RR is 12.13 (95% CI: 1.73-85.07) comparing pre-GKRS with 2 years after GKRS. There is no significant difference of the hemorrhage rate between the first 2 years of post-radiosurgery and 2 years after GKRS (RR =2.81, 95% CI: 0.20-13.42). The neurological deficiency is the commonest radiosurgery related complications.

Patients with cerebral CMs, especially who were deep seated and surgically inaccessible, seems to benefit from GKRS due to a reduction of annual hemorrhage rate in the first 2 years, and after that time, despite of a number of cases that suffer from negative side effects of radiation 2).

Between 1993 and 2018, 261 patients with 331 symptomatic CCMs were treated by GKS. The median age was 39.9 years and females were predominant (54%). The median volume of CCMs was 3.1 mL. The median margin dose was 11.9 Gy treat to a median isodose level of 59%. Median clinical and imaging follow-up times were 69 and 61 months, respectively. After the initial hemorrhage that led to CCM diagnosis, 136 hemorrhages occurred in the period prior to GKS (annual incidence = 23.6%). After GKS, 15 symptomatic hemorrhages occurred within the first 2 years of follow-up (annual incidence = 3.22%), and 37 symptomatic hemorrhages occurred after the first 2 years of follow-up (annual incidence = 3.16%). Symptomatic radiation-induced complication was encountered in 8 patients (3.1%). Mortality related to GKS occurred in 1 patient (0.4%). In conclusion, GKS decreased the risk of hemorrhage in CCM patients presenting with symptomatic hemorrhage. GKS is a viable alternative treatment option for patients with surgically-inaccessible CCMs or significant medical comorbidities 3).


Shin et al. aimed to gain insight into the effect of SRS on CM and to propose possible mechanisms leading to recurrent hemorrhages following SRS.

During a 13-year interval between 2001 and 2013, bleeding recurred in 9 patients with CMs that had been treated using Gamma Knife surgery at the authors’ institution. Microsurgical removal was subsequently performed in 5 of these patients, who had recurrent hemorrhages between 4 months and 7 years after SRS. Specimens from 4 patients were available for analysis and used for this report.

Histopathological analysis demonstrated that vascular sclerosis develops as early as 4 months after SRS. In the samples from 2 to 7 years after SRS, sclerotic vessels were prominent, but there were also vessels with incomplete sclerosis as well as some foci of neovascularization.

Recurrent bleeding after SRS for CM could be related to incomplete sclerosis of the vessels, but neovascularization may also play a role 4).


From 1994 to 2001, 92 patients with 114 CMs were treated by GKS and then followed up for 2-8 years (mean 4.1+/-1.9). We analyzed the MRI features of CMs bleeding, efficacy of GKS, and the complications of treatment. Six pathological specimens after radiosurgery (1 from our group, 5 from other centers) were also assayed.

Among 43 patients who were treated by GKS to control their epilepsy, epileptic paroxysm was alleviated in 36 patients (83.7%), including 12 (27.9%) seizure-free. Rebleeding was confirmed in 9 patients (9.8%) by neuroimage, one of whom died. Transient symptomatic radiation edema occurred in 7 cases (7.6%) within 6-12 months after radiosurgery, and one patient underwent open surgery for cerebral decompression. The main pathological changes of cavernoma were coagulation necrosis and the vessels obliterated gradually after radiosurgery.

It is feasible to treat small and surgically high risk CMs by radiosurgery. The treatment has to be prudent in an acute bleeding and symptomatic progression. Optimal treatment timing and dose planning are prerequisites to reduce radiation-related complications. GKS is safe and effective to control the epilepsy caused by CMs, and also to bring down the rebleeding rate after a latency interval of several years 5).

Gamma knife radiosurgery for brainstem cavernous malformation.


1)

Hu YJ, Zhang LF, Ding C, Tian Y, Chen J. Gamma Knife Radiosurgery for Cavernous Malformations of Basal Ganglia and Thalamus: A Retrospective Study of 53 Patients. Stereotact Funct Neurosurg. 2021 Jun 9:1-8. doi: 10.1159/000510108. Epub ahead of print. PMID: 34107485.
2)

Wen R, Shi Y, Gao Y, Xu Y, Xiong B, Li D, Gong F, Wang W. The efficacy of gamma knife radiosurgery for cavernous malformation: a meta-analysis and review. World Neurosurg. 2018 Dec 21. pii: S1878-8750(18)32869-9. doi: 10.1016/j.wneu.2018.12.046. [Epub ahead of print] Review. PubMed PMID: 30583131.
3)

Lee CC, Wang WH, Yang HC, Lin CJ, Wu HM, Lin YY, Hu YS, Chen CJ, Chen YW, Chou CC, Liu YT, Chung WY, Shiau CY, Guo WY, Hung-Chi Pan D, Hsu SPC. Gamma Knife radiosurgery for cerebral cavernous malformation. Sci Rep. 2019 Dec 24;9(1):19743. doi: 10.1038/s41598-019-56119-1. PMID: 31874979; PMCID: PMC6930272.
4)

Shin SS, Murdoch G, Hamilton RL, Faraji AH, Kano H, Zwagerman NT, Gardner PA, Lunsford LD, Friedlander RM. Pathological response of cavernous malformations following radiosurgery. J Neurosurg. 2015 Oct;123(4):938-44. doi: 10.3171/2014.10.JNS14499. Epub 2015 Jun 19. PubMed PMID: 26090838.
5)

Liu AL, Wang CC, Dai K. [Gamma knife radiosurgery for cavernous malformations]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2005 Feb;27(1):18-21. Chinese. PMID: 15782486.
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