Stereotactic radiosurgery for brain metastases

Stereotactic radiosurgery for brain metastases

Management of brain metastases typically includes radiotherapy (RT) with conventional fractionation and/or stereotactic radiosurgery (SRS). However, optimal indications and practice patterns for SRS remain unclear.

Significant heterogeneity exists in target volumes for postoperative stereotactic radiosurgery.

The use of radiosurgery as a first-line or salvage treatment for brain metastases continues to expand. As a focal, highly precise treatment option, stereotactic radiosurgery (SRS) provides many benefits, including a short treatment timeline, a low probability of normal tissue complication, and a high probability of treated lesion control 1).

Kann et al. sought to evaluate national practice patterns for patients with metastatic disease receiving brain RT. They queried the National Cancer Data Base (NCDB) for patients diagnosed with metastatic non-small cell lung cancer, breast cancer, colorectal cancer, or melanoma from 2004 to 2014 who received upfront brain RT. Patients were divided into SRS and non-SRS cohorts. Patient and facility-level SRS predictors were analyzed with chi-square tests and logistic regression, and uptake trends were approximated with linear regression. Survival by diagnosis year was analyzed with the Kaplan-Meier method. Results: Of 75,953 patients, 12,250 (16.1%) received SRS and 63,703 (83.9%) received non-SRS. From 2004 to 2014, the proportion of patients receiving SRS annually increased (from 9.8% to 25.6%; P<.001), and the proportion of facilities using SRS annually increased (from 31.2% to 50.4%; P<.001). On multivariable analysis, nonwhite race, nonprivate insurance, and residence in lower-income or less-educated regions predicted lower SRS use (P<.05 for each). During the study period, SRS use increased disproportionally among patients with private insurance or who resided in higher-income or higher-educated regions. From 2004 to 2013, 1-year actuarial survival improved from 24.1% to 49.6% for patients selected for SRS and from 21.0% to 26.3% for non-SRS patients (P<.001). Conclusions: This NCDB analysis demonstrates steadily increasing-although modest overall-brain SRS use for patients with metastatic disease in the United States and identifies several progressively widening sociodemographic disparities in the adoption of SRS. Further research is needed to determine the reasons for these worsening disparities and their clinical implications on intracranial control, neurocognitive toxicities, quality of life, and survival for patients with brain metastases 2).


With increased adoption of this approach also comes an increase in incidence of treatment failure. Radiosurgical failure, either due to tumor regrowth or radiation necrosis, can occur in about 10% to 15% of patients still alive at 1 yr 3).

Radiation necrosis (RN) may occur after treatment and is challenging to distinguish from local recurrence (LR).

PET is superior to computed tomography and magnetic resonance imaging in the differentiation between recurrence and radiation reaction/necrosis. However, temporary radiation effects may mask remaining tumor tissue, and repeat PET studies may sometimes be necessary 4).

There are a variety of salvage options available for patients with brain metastases who experience local failure after stereotactic radiosurgery (SRS). These options include resection,whole brain radiation therapy, laser interstitial thermotherapy, and repeat SRS. There is little data on the safety and efficacy of repeat SRS following local failure of a prior radiosurgical procedure.

Systematic Reviews


Using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was conducted using PubMed and Medline up to November 2016. A separate search was conducted for SRS for larger brain metastases.

Twenty-seven prospective study, critical reviews, metaanalysis, and published consensus guidelines were reviewed. Four key points came from these studies. First, there is no detriment to survival by withholding whole brain radiation (WBRT) in the upfront management of brain metastases with SRS. Second, while SRS on its own provides a high rate of local control (LC), WBRT may provide further increase in LC. Next, WBRT does provide distant brain control with less need for salvage therapy. Finally, the addition of WBRT does affect neurocognitive function and quality of life more than SRS alone. For larger brain metastases, surgical resection should be considered, especially when factoring lower LC with single-session radiosurgery. There is emerging data showing good LC and/or decreased toxicity with multisession radiosurgery.

A number of well-conducted prospective and meta-analyses studies demonstrate good LC, without compromising survival, using SRS alone for patients with a limited number of brain metastases. Some also demonstrated less impact on neurocognitive function with SRS alone. Practice guidelines were developed using these data with International Stereotactic Radiosurgery Society consensus 5).

Stereotactic radiosurgery (SRS) offers excellent local control for brain metastases (BM) with low rates of toxicity.

It avoids whole brain radiotherapy (WBRT)-associated morbidity.

Studies have clearly established the safety and efficacy of single-dose SRS. However, as patient survival has increased, the recurrence of tumors and the development of metastases to new sites within the brain have made it desirable to repeat treatments over time. The cumulative toxicity of multi-isocenter, multiple treatments has not been well defined.

Postoperative stereotactic radiosurgery to the resection cavity safely and effectively augments local control of large brain metastases. Patients with <4 metastases and controlled systemic disease have significantly lower rates of distant brain failure (DBF) and are ideal treatment candidates 6).

In patients with limited brain metastases from non small cell lung cancer (NSCLC), SRS is an effective treatment associated with high local control rate with low morbidity. When performed in isolation, close follow-up is mandatory and radiosurgery can be renewed as salvage treatment for distant brain progression, limiting the use of WBRT 7).

Significant tumor volume reduction by 6 or 12 weeks post-SRS was associated with long-term local control.

For patients at low risk of distant intracranial failure (such as those with systemic disease control) with early, robust volumetric response, it may reasonable to lengthen imaging intervals to maximize clinical utility.

Although it is necessary to validate the findings in a larger, prospective series, the results are encouraging that a robust early volumetric response is associated with sustained local control for metastatic brain lesions 8).

Gamma Knife radiosurgery (GKRS) offers a high rate of tumor control and good survival benefits in both new and recurrent patients with MBT. Thus, GKRS is an effective treatment option for new patients with MBT, as well as an adjuvant therapy in patients with recurrent MBT. 9) 10).

There appears to be no consensus regarding the optimal treatment strategy among patients with >3 brain metastases, and practice patterns are heterogeneous. Radiation oncologists, especially high-volume CNS specialists, are treating significantly more brain metastases with SRS than what currently is recommended by published consensus guidelines. Providers struggle with patients with a moderate intracranial disease burden. Further prospective studies are needed to support these practice patterns and guide decision making 11).

Case series

Patients (n = 41) undergoing single-fraction Gamma Knife SRS following surgical resection of brain metastases from 2011 to 2017 were retrospectively reviewed. SRS included the entire contrast-enhancing cavity with heterogeneity in inclusion of the surgical tract and no routine margin along the dura or clinical target volume margin. Follow-up MR imaging was fused with SRS plans to assess patterns of failure.

The median follow-up was 11.1 months with a median prescription of 18 Gy. There were 5 local failures: infield (n = 3, 60%), surgical tract (n = 1, 20%), and marginal > 5 mm from the resection cavity (n = 1, 20%). No marginal failures < 5 mm or dural margin failures were noted. For deep lesions (n = 13), 62% (n = 8) had the entire tract covered. The only tract recurrence was in a deep lesion without coverage of the surgical tract (n = 1/5).

In this small preliminary experience, despite no routine inclusion of the dural tract or bone flap, no failures were noted in these locations. Omission of the surgical tract in deep lesions may increase failure rates 12).



Nieder C, Grosu AL, Gaspar LE. Stereotactic radiosurgery (SRS) for brain metastases: a systematic review. Radiat Oncol. 2014 Jul 12;9:155. doi: 10.1186/1748-717X-9-155. Review. PubMed PMID: 25016309; PubMed Central PMCID: PMC4107473.

Kann BH, Park HS, Johnson SB, Chiang VL, Yu JB. Radiosurgery for Brain Metastases: Changing Practice Patterns and Disparities in the United States. J Natl Compr Canc Netw. 2017 Dec;15(12):1494-1502. doi: 10.6004/jnccn.2017.7003. PubMed PMID: 29223987.

Sneed PK, Mendez J, Vemer-van den Hoek JG, Seymour ZA, Ma L, Molinaro AM, Fogh SE, Nakamura JL, McDermott MW. Adverse radiation effect after stereotactic radiosurgery for brain metastases: incidence, time course, and risk factors. J Neurosurg. 2015 Aug;123(2):373-86. doi: 10.3171/2014.10.JNS141610. Epub 2015 May 15. PubMed PMID: 25978710.

Ericson K, Kihlström L, Mogard J, Karlsson B, Lindquist C, Widén L, Collins VP, Stone-Elander S. Positron emission tomography using 18F-fluorodeoxyglucose in patients with stereotactically irradiated brain metastases. Stereotact Funct Neurosurg. 1996;66 Suppl 1:214-24. PubMed PMID: 9032864.

Chao ST, De Salles A, Hayashi M, Levivier M, Ma L, Martinez R, Paddick I, Régis J, Ryu S, Slotman BJ, Sahgal A. Stereotactic Radiosurgery in the Management of Limited (1-4) Brain Metasteses: Systematic Review and International Stereotactic Radiosurgery Society Practice Guideline. Neurosurgery. 2017 Nov 3. doi: 10.1093/neuros/nyx522. [Epub ahead of print] PubMed PMID: 29126142.

Ling DC, Vargo JA, Wegner RE, Flickinger JC, Burton SA, Engh J, Amankulor N, Quinn AE, Ozhasoglu C, Heron DE. Postoperative stereotactic radiosurgery to the resection cavity for large brain metastases: clinical outcomes, predictors of intracranial failure, and implications for optimal patient selection. Neurosurgery. 2015 Feb;76(2):150-7. doi: 10.1227/NEU.0000000000000584. PubMed PMID: 25549189.

Zairi F, Ouammou Y, Le Rhun E, Aboukais R, Blond S, Vermandel M, Deken V, Devos P, Reyns N. Relevance of gamma knife radiosurgery alone for the treatment of non-small cell lung cancer brain metastases. Clin Neurol Neurosurg. 2014 Oct;125:87-93. doi: 10.1016/j.clineuro.2014.07.030. Epub 2014 Jul 27. PubMed PMID: 25108698.

Sharpton SR, Oermann EK, Moore DT, Schreiber E, Hoffman R, Morris DE, Ewend MG. The Volumetric Response of Brain Metastases After Stereotactic Radiosurgery and Its Post-treatment Implications. Neurosurgery. 2014 Jan;74(1):9-16. doi: 10.1227/NEU.0000000000000190. PubMed PMID: 24077581.

Bir SC, Ambekar S, Nanda A. Long term outcome of Gamma Knife radiosurgery for metastatic brain tumors. J Clin Neurosci. 2014 Dec;21(12):2122-8. doi: 10.1016/j.jocn.2014.05.015. Epub 2014 Jul 25. PubMed PMID: 25065951.

Bir SC, Ambekar S, Bollam P, Nanda A. Long-term outcome of gamma knife radiosurgery for metastatic brain tumors originating from lung cancer. Surg Neurol Int. 2014 Sep 5;5(Suppl 8):S396-403. doi: 10.4103/2152-7806.140197. eCollection 2014. PubMed PMID: 25289169; PubMed Central PMCID: PMC4173307.

Sandler KA, Shaverdian N, Cook RR, Kishan AU, King CR, Yang I, Steinberg ML, Lee P. Treatment trends for patients with brain metastases: Does practice reflect the data? Cancer. 2017 Feb 8. doi: 10.1002/cncr.30607. [Epub ahead of print] PubMed PMID: 28178376.

McDermott DM, Hack JD, Cifarelli CP, Vargo JA. Tumor Cavity Recurrence after Stereotactic Radiosurgery of Surgically Resected Brain Metastases: Implication of Deviations from Contouring Guidelines. Stereotact Funct Neurosurg. 2019 Feb 14:1-7. doi: 10.1159/000496156. [Epub ahead of print] PubMed PMID: 30763944.

Brain Dock

Brain Dock

The Brain Dock is the “Ningen Dock for the brain”. The Ningen Dock is a complete medical check, but does not include in-depth inspections of the brain. Since brain diseases are very difficult to treat, it is very important to prevent or find a predictor without fail. Brain Dock can detect a brain aneurysm, brain tumor, unruptured brain aneurysm, Asymptomatic brain infarction, and so on.

They recommend middle-aged and elderly people to have Brain Dock once to feel safe.

Group Medical Treatment Corporate Foundation Meiri-kai Gyotoku General Hospital.

A total of 4070 healthy adults 22 years or older (mean age [± SD] 50.6 ± 11.0 years; 41.9% women) who underwent a brain examination known as “Brain Dock” in the central Tokyo area between April 2014 and March 2015 were checked for unruptured saccular aneurysm using 3T MRI/MRA.

The following types of cases were excluded:

1) protrusions with a maximum diameter < 2 mm at locations other than arterial bifurcations.

2) conical protrusions at arterial bifurcations with a diameter < 3 mm.

3) cases of suspected aneurysms with unclear imaging of the involved artery.

When an aneurysm was definitively diagnosed, the case was included in the aneurysm group.

Imaizumi et al., also investigated the relationship between aneurysm occurrence and risk factors (age, sex, smoking history, hypertension, diabetes, and hyperlipidemia).

One hundred eighty-eight aneurysms were identified in 176 individuals (detection rate 4.32%), with the detection rate for women being significantly higher (6.2% vs 3.0%, p < 0.001). The average age in the aneurysm group was significantly higher than in the patients in whom aneurysms were not detected (53.0 ± 11.1 vs 50.5 ± 11.0 years). The detection rate tended to increase with age. The detection rates were 3.6% for people in their 30s, 3.5% for those in their 40s, 4.1% for those in their 50s, 6.9% for those in their 60s, and 6.8% for those in their 70s. Excluding persons in their 20s and 80s-age groups in which no aneurysms were discovered-the detection rate in women was higher in all age ranges. Of the individuals with aneurysms, 12 (6.81%) had multiple cerebral aneurysms; no sex difference was observed with respect to the prevalence of multiple aneurysms. Regarding aneurysm size, 2.0-2.9 mm was the most common size range, with 87 occurrences (46.3%), followed by 3.0-3.9 mm (67 [35.6%]) and 4.0-4.9 mm (20 [10.6%]). The largest aneurysm was 13 mm. Regarding location, the internal carotid artery (ICA) was the most common aneurysm site, with 148 (78.7%) occurrences. Within the ICA, C1 was the site of 46 aneurysms (24.5%); C2, 57 (30.3%); and C3, 29 (15.4%). The aneurysm detection rates for C2, C3, and C4 were 2.23%, 1.23%, and 0.64%, respectively, for women and 0.68%, 0.34%, and 0.21%, respectively, for men; ICA aneurysms were significantly more common in women than in men (5.27% vs 2.20%, p < 0.001). Multivariate logistic regression analysis revealed that age (p < 0.001, OR 1.03, 95% CI 1.01-1.04), female sex (p < 0.001, OR 2.28, 95% CI 1.64-3.16), and smoking history (p = 0.011, OR 1.52, 95% CI 1.10-2.11) were significant risk factors for aneurysm occurrence

In this study, both female sex and older age were independently associated with an increased aneurysm detection rate. Aneurysms were most common in the ICA, and the frequency of aneurysms in ICA sites was markedly higher in women 1).

Kuroiwa et al., analyzed cases of small brain ischemic lesions found in examinees of a brain dock (neurological health screening center). Small cerebral infarction was found in 17 % of the examinees (733 cases). White matter lesions were found in 24 %. Infarctions were located in the cortex or subcortical white matter in 31 % and in the basal ganglia in 44 % of cases. Infratentorial infarction was found in 1.6 %.

They developed an animal model of small infarction in the cortex or basal ganglia induced by photothrombosis in rodents. Sprague Dawley rats or Mongolian gerbils were anesthetized and photothrombotic infarction was induced in the left caudate nucleus or parietal cortex by light exposure via an optic fiber and intravenous Rose Bengal dye injection. Histological examination revealed development of a small spherical infarction surrounding the tip of the optic fiber. The lesion turned to a cyst by 6 weeks after lesioning. Neurological deficits were found in animals both with cortical and caudate infarction. Behavioral changes in an open field test differed with the lesion site. Neurological deficits were sustained longer in animals with larger infarctions. Thus, photothrombotic infarction is useful for analyzing location-dependent and size-dependent neurological and neuropathological changes after cerebral infarction. 2).

A cross-sectional study included 1,414 adults without neurological disorders who underwent health-screening tests of the brain, referred to as the “Brain Dock,” in our center. The MMSE scores were compared between age groups (40-44, 45-49, 50-54, 55-59, 60-64, 65-69, or ≥70 years) and educational levels [the low education level group (6-12 years) and the high education level group (≥13 years)].

The median age was 59 years, and 763 (54%) were women. There was no significant difference in the MMSE total score between women and men. The stepwise method of the multiple linear regression analysis confirmed that a higher age [β value, -0.129; standard error (S.E.), 0.020; p<0.001], low education level (6-12 years) (β value, -0.226; S.E., 0.075; p=0.003), and women (β values, 0.148; S.E., 0.066; p=0.024) was significantly associated with decreased MMSE score. In general, both the percentile scores and mean scores decreased with aging and were lower in the low education level group than in the high education level group. The degree of decrement in scores with age was stronger in the low education level group than in the high education level group.

The provided data for age- and education-specific reference norms will be useful for both clinicians and investigators who perform comprehensive brain examinations to assess the cognitive function of subjects 3).

Dot-like low intensity spots (a dot-like hemosiderin spot: dotHS) on T2*-weighted MR images (T2*WI), which is regarded as a sensitive method for hemosiderin detection, have been histologically diagnosed as old microbleeds associated with microangiopathies. The clinical significance of the dotHS, however, is still under debate. Therefore, we investigated the factors associated with dotHS.

Horita et al., investigated 209 healthy volunteers in our hospital (sex: 106 males, 103 females; age: 38 to 78 years old, mean age: 56.4 +/- 8.3 years old) using “Brain Dock”, a formalized screening system for asymptomatic brain diseases. The Odds ratio (OR) was estimated from multiple logistic regression analyses using the dotHS and variables.

T2*WI demonstrated dotHS in 7.7% of volunteers, and the mean number of dotHS was 0.16 +/- 0.78. The hemosiderin was preferentially deposited in the basal ganglia and thalamus. Age > or = 65 years old (OR: 5.9; 95% confidence interval [CI]: 1.4-25.9; p = 0.02), hypertension (OR: 7.0; 95% CI: 1.4-34.7; p = 0.02), and headache (OR: 5.8; 95% CI: 1.4-24.6; p = 0.02) were all found to be independently associated with dotHS.

The dotHS was significantly associated with several factors, including age, hypertension and headache 4).



Imaizumi Y, Mizutani T, Shimizu K, Sato Y, Taguchi J. Detection rates and sites of unruptured intracranial aneurysms according to sex and age: an analysis of MR angiography-based brain examinations of 4070 healthy Japanese adults. J Neurosurg. 2018 Apr 1:1-6. doi: 10.3171/2017.9.JNS171191. [Epub ahead of print] PubMed PMID: 29624149.

Kuroiwa T, Tabata H, Xi G, Hua Y, Schallert T, Keep RF. Analysis of Small Ischemic Lesions in the Examinees of a Brain Dock and Neurological Examination of Animals Subjected to Cortical or Basal Ganglia Photothrombotic Infarction. Acta Neurochir Suppl. 2016;121:93-7. doi: 10.1007/978-3-319-18497-5_16. PubMed PMID: 26463929.

Yakushiji Y, Horikawa E, Eriguchi M, Nanri Y, Nishihara M, Hirotsu T, Hara H. Norms of the Mini-Mental state Examination for Japanese subjects that underwent comprehensive brain examinations: the Kashima Scan Study. Intern Med. 2014;53(21):2447-53. Epub 2014 Nov 1. PubMed PMID: 25366002.

Horita Y, Imaizumi T, Niwa J, Yoshikawa J, Miyata K, Makabe T, Moriyama R, Kurokawa K, Mikami M, Nakamura M. [Analysis of dot-like hemosiderin spots using brain dock system]. No Shinkei Geka. 2003 Mar;31(3):263-7. Japanese. PubMed PMID: 12684979.

Effect of trauma center designation in severe traumatic brain injury outcome

Effect of trauma center designation in severe traumatic brain injury outcome

Trauma center designation is significantly associated with functional independence (FI) and independent expression (IE) (defined as a functional independence measure component of 4) after severe traumatic brain injury, but not moderate traumatic brain injuryProspective study is warranted to verify and explore factors contributing to this discrepancy 1).

Patients with severe traumatic brain injury treated in American College of Surgeons (ACS)-designated level 1 trauma centers have better survival rates and outcomes than those treated in ACS-designated level 2 trauma center2).

In 2019 a study showed superior functional outcomes and lower mortality rates in patients undergoing a neurosurgical procedurefor severe traumatic brain injury in level 1 trauma center3).



Brown JB, Stassen NA, Cheng JD, Sangosanya AT, Bankey PE, Gestring ML. Trauma center designation correlates with functional independence after severe but not moderate traumatic brain injury. J Trauma. 2010 Aug;69(2):263-9. doi: 10.1097/TA.0b013e3181e5d72e. PubMed PMID: 20699734.

DuBose JJ, Browder T, Inaba K, Teixeira PG, Chan LS, Demetriades D. Effect of trauma center designation on outcome in patients with severe traumatic brain injury. Arch Surg. 2008 Dec;143(12):1213-7; discussion 1217. doi: 10.1001/archsurg.143.12.1213. PubMed PMID: 19075174.

Chalouhi N, Mouchtouris N, Saiegh FA, Starke RM, Theofanis T, Das SO, Jallo J. Comparison of Outcomes in Level I vs Level II Trauma Centers in Patients Undergoing Craniotomy or Craniectomy for Severe Traumatic Brain Injury. Neurosurgery. 2019 Jan 24. doi: 10.1093/neuros/nyy634. [Epub ahead of print] PubMed PMID: 30690608.
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