Publications by authors named "Steven D Chang"

186 Publications

Microsurgical resection of foramen magnum meningioma: multi-institutional retrospective case series and proposed surgical risk scoring system.

J Neurooncol 2021 May 10. Epub 2021 May 10.

Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, 94305, USA.

Purpose: Foramen magnum meningiomas (FMMs) are a major surgical challenge, due to relevant surgical morbidity and mortality. The paper aims to review the clinical (symptomatic improvement, complication rate, length of hospital stay) and radiological outcome (completeness of resection) of microsurgical resection of FMMs, and to identify predictors of complications.

Methods: A multi-institutional retrospective review of prospectively maintained database of FMMs included 51 patients (74.5% females) with a median tumor volume of 8.18 cm (range, 1.77-57.9 cm) and median follow-up of 36 months (range, 0.30-180.0 months). Tumors were resected though suboccipital approach (58.8%) or posterior-lateral approaches (39.3%), including far-lateral, extreme lateral and transcondylar approaches.

Results: Gross-total resection (GTR) was achieved in 80.4% and 98% of cases did not present tumor regrowth or recurrence. Clinical symptoms improved in 34 patients (66.7%) and worsened in 5 (9.8%). The median length of hospital stay was 5 days. Mortality was null. Postoperative complications developed in 15 patients (29.4%), with cerebrospinal fluid leak (7.8%) and lower cranial nerves deficits (7.8%) as the most frequent. Craniospinal location (p = 0.03), location anterior to the dentate ligament (DL) (p = 0.02), involvement of vertebral artery (VA) (p = 0.03) were significantly associated with complication rate. These three elements allow calculating the Foramen Magnum Meningioma Risk Score (FRMMRS), to estimate the risk of post-operative complications.

Conclusion: Microsurgical resection allows for high GTR rate and low rate of tumor regrowth or recurrence, despite complications in one third of the patients. The FMMRS allows classifying FMMs and estimating the risk of post-operative complications.
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http://dx.doi.org/10.1007/s11060-021-03773-zDOI Listing
May 2021

The Stanford stereotactic radiosurgery experience on 7000 patients over 2 decades (1999-2018): looking far beyond the scalpel.

J Neurosurg 2021 Apr 2:1-17. Epub 2021 Apr 2.

Departments of1Neurosurgery and.

Objective: The CyberKnife (CK) has emerged as an effective frameless and noninvasive method for treating a myriad of neurosurgical conditions. Here, the authors conducted an extensive retrospective analysis and review of the literature to elucidate the trend for CK use in the management paradigm for common neurosurgical diseases at their institution.

Methods: A literature review (January 1990-June 2019) and clinical review (January 1999-December 2018) were performed using, respectively, online research databases and the Stanford Research Repository of patients with intracranial and spinal lesions treated with CK at Stanford. For each disease considered, the coefficient of determination (r2) was estimated as a measure of CK utilization over time. A change in treatment modality was assessed using a t-test, with statistical significance assessed at the 0.05 alpha level.

Results: In over 7000 patients treated with CK for various brain and spinal lesions over the past 20 years, a positive linear trend (r2 = 0.80) in the system's use was observed. CK gained prominence in the management of intracranial and spinal arteriovenous malformations (AVMs; r2 = 0.89 and 0.95, respectively); brain and spine metastases (r2 = 0.97 and 0.79, respectively); benign tumors such as meningioma (r2 = 0.85), vestibular schwannoma (r2 = 0.76), and glomus jugulare tumor (r2 = 0.89); glioblastoma (r2 = 0.54); and trigeminal neuralgia (r2 = 0.81). A statistically significant difference in the change in treatment modality to CK was observed in the management of intracranial and spinal AVMs (p < 0.05), and while the treatment of brain and spine metastases, meningioma, and glioblastoma trended toward the use of CK, the change in treatment modality for these lesions was not statistically significant.

Conclusions: Evidence suggests the robust use of CK for treating a wide range of neurological conditions.
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http://dx.doi.org/10.3171/2020.9.JNS201484DOI Listing
April 2021

Improved survival and disease control following pembrolizumab-induced immune-related adverse events in high PD-L1 expressing non-small cell lung cancer with brain metastases.

J Neurooncol 2021 Mar 7;152(1):125-134. Epub 2021 Jan 7.

Department of Neurosurgery, Stanford Medical Center, Palo Alto, CA, 94304, USA.

Introduction: Immune checkpoint inhibitors have become standard of care for many patients with non-small cell lung cancer (NSCLC). These agents often cause immune-related adverse events (IRAEs), which have been associated with increased overall survival (OS). Intracranial disease control and OS for patients experiencing IRAEs with metastatic NSCLC and brain metastases have not yet been described.

Methods: We performed a single-institution, retrospective review of patients with NSCLC and existing diagnosis of brain metastasis, who underwent pembrolizumab treatment and developed any grade IRAE. The primary outcome of the study was intracranial time to treatment failure (TTF), defined from time of pembrolizumab initiation to new intracranial disease progression or death. Kaplan-Meier and Cox proportional hazard analyses were performed.

Results: A total of 63 patients with NSCLC brain metastasis were identified, and 24 developed IRAEs. Patients with any grade IRAEs had longer OS (21 vs. 10 months, p = 0.004), systemic TTF (15 vs. 4 months, p < 0.001) and intracranial TTF (14 vs. 5 months, p = 0.001), relative to patients without IRAEs. Presence of IRAEs and high PD-L1 (≥ 50%), but not absent/moderate PD-L1 (0-49%), had a positive association for OS, systemic TTF, and intracranial TTF. Following multivariable analysis, IRAE experienced on pembrolizumab was an independent predictor of OS, systemic TTF, and intracranial TTF.

Conclusions: In our series of patients with NSCLC and brain metastases treated with pembrolizumab, IRAE presence was associated with a significant increase in OS, systemic TTF, and intracranial TTF. Future studies with increased cohorts will clarify how IRAEs should be interpreted among molecular subtypes.
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http://dx.doi.org/10.1007/s11060-020-03686-3DOI Listing
March 2021

Intracranial Autograft Fat Placement to Separate the Optic Chiasm from Tumor to Improve Stereotactic Radiotherapy Dosimetry.

World Neurosurg 2021 Feb 29;146:80-84. Epub 2020 Oct 29.

Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California, USA. Electronic address:

Background: Radiation therapy for intracranial lesions is constrained by dose to neurologic organs at risk.

Case Description: We report 2 cases, a newly diagnosed chondrosarcoma and a previously irradiated meningioma, with tumors that abutted the optic chiasm following subtotal resection. Definitive radiotherapy would have required either undercoverage of the tumor or treatment of the chiasm with doses posing an unacceptable risk of blindness. Therefore, the patients underwent open surgery with placement of an abdominal fat autograft to provide space between the tumor and the optic structures at risk. Patients received definitive fractionated stereotactic radiotherapy. For each patient, we retrospectively compared the treated plan (with fat autograft) to a second plan generated using the pre-autograft imaging, maintaining similar tumor coverage. For the chondrosarcoma, the fat autograft reduced the optic chiasm maximum dose by 21% (70.4 Gy to 55.3 Gy). For the reirradiated peri-optic meningioma, the optic chiasm maximum dose was reduced by 10% (50.8 Gy to 45.9 Gy), the left optic nerve by 17% (48.9 Gy to 40.4 Gy), and the right optic nerve by 30% (32.3 Gy to 22.6 Gy).

Conclusions: We demonstrate the utility of abdominal fat autograft placement to maximize coverage of tumor while minimizing dose to intracranial organs at risk.
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http://dx.doi.org/10.1016/j.wneu.2020.10.110DOI Listing
February 2021

Efficacy and safety of embolization of dural arteriovenous fistulas via the ophthalmic artery.

Interv Neuroradiol 2020 Oct 26:1591019920969270. Epub 2020 Oct 26.

Division of Neuroimaging and Neurointervention, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.

Introduction: Dural arteriovenous fistulae (DAVF) are vascular lesions with arteriovenous shunting that may be treated with surgical obliteration or endovascular embolization. Some DAVF, such as anterior cranial fossa DAVF (AC-DAVF) derive their arterial supply from ophthalmic artery branches in nearly all cases, and trans-arterial embolization carries a risk of vision loss. We determined the efficacy and safety of trans-ophthalmic artery embolization of DAVF.

Materials And Methods: We performed a retrospective cohort study of all patients with DAVF treated by trans-ophthalmic artery embolization from 2012 to 2020. Primary outcome was angiographic cure of the DAVF. Secondary outcomes included vision loss, visual impairment, orbital cranial nerve injury, stroke, modified Rankin Scale at 90-days, and mortality.

Results: 12 patients met inclusion criteria (9 males; 3 females). 10 patients had AC-DAVF. Patient age was 59.7  ±  9.5 (mean ± SD) years. Patients presented with intracranial hemorrhage (4 patients), headache (4 patients), amaurosis fugax (1 patients), or were incidentally discovered (2 patients). DAVF Cognard grades were: II (1 patient), III (6 patients), and IV (5 patients). DAVF were embolized with Onyx (10 patients), nBCA glue (1 patient), and a combination of coils and Onyx (1 patient). DAVF cure was achieved in 11 patients (92%). No patients experienced vision loss, death, or permanent disability. One patient experienced a minor complication of blurry vision attributed to posterior ischemic optic neuropathy. 90-day mRS was 0 (10 patients) and 1 (2 patients).

Conclusions: Trans-ophthalmic artery embolization is an effective and safe treatment for DAVF.
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http://dx.doi.org/10.1177/1591019920969270DOI Listing
October 2020

Intracranial Tumor Control After Immune-Related Adverse Events and Discontinuation of Immunotherapy for Melanoma.

World Neurosurg 2020 Dec 24;144:e316-e325. Epub 2020 Aug 24.

Department of Neurosurgery, Stanford Medical Center, Palo Alto, California, USA. Electronic address:

Objective: Immunotherapy for patients with melanoma with brain metastasis has significantly improved outcomes; however, it has also been characterized by potentially dangerous immune-related adverse events (IRAEs). Several reports have suggested that these reactions can precede improved treatment responses. For intracranial disease control, we sought to identify if such an association exists.

Methods: We conducted a retrospective chart review of patients with melanoma who underwent immunotherapy treatment after diagnosis of brain metastasis. The study cohort was then stratified into 2 groups based on their history of developing an IRAE that prompted discontinuation of that regimen. The primary outcome variable included intracranial progression-free survival (PFS). Kaplan-Meier and Cox proportional hazard analyses were used to evaluate survival and predictors of outcomes.

Results: Fifty-two patients met the inclusion criteria, 17 of whom experienced severe IRAEs that led to discontinuation of immunotherapy. Median intracranial PFS was 19.9 versus 10.5 months (P = 0.053) in patients who did and did not experience severe IRAEs prompting discontinuation, respectively. No additional outcome benefits were identified for systemic PFS or overall survival (mean, 33.1 months and 27.6 months, respectively). Multivariable analysis identified BRAF mutation status as a negative prognosticator of brain progression (P = 0.013; hazard ratio, 3.90). Initial treatment with BRAF inhibitor was also a negative predictor of all-cause mortality (P = 0.015; hazard ratio, 10.73).

Conclusions: Immune-related adverse events may signify an underlying immunogenic response that has intracranial disease control benefits. Despite their associated side effects, immunotherapies continue to show promising outcomes as a first-line agent for melanoma with brain metastasis.
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http://dx.doi.org/10.1016/j.wneu.2020.08.124DOI Listing
December 2020

Evidence for endothelial-to-mesenchymal transition in human brain arteriovenous malformations.

Clin Transl Med 2020 Jun 21;10(2):e99. Epub 2020 Jun 21.

Stanford Neuromolecular Innovation Program, Department of Neurosurgery, Stanford University, Stanford, California.

Background: Brain arteriovenous malformations (AVMs) are rare, potentially devastating cerebrovascular lesions that can occur in both children and adults. AVMs are largely sporadic and the basic disease biology remains unclear, limiting advances in both detection and treatment. This study aimed to investigate human brain AVMs for endothelial-to-mesenchymal transition (EndMT), a process recently implicated in cerebral cavernous malformations (CCMs).

Methods: We used 29 paraffin-embedded and 13 fresh/frozen human brain AVM samples to profile expression of panels of EndMT-associated proteins and RNAs. CCMs, a cerebrovascular disease also characterized by abnormal vasculature, were used as a primary comparison, given that EndMT specifically contributes to CCM disease biology. AVM-derived cell lines were isolated from three fresh, surgical AVM samples and characterized by protein expression.

Results: We observed high collagen deposition, high PAI-1 expression, and expression of EndMT-associated transcription factors such as KLF4, SNAI1, and SNAI2 and mesenchymal-associated markers such as VIM, ACTA2, and S100A4. SMAD-dependent TGF-β signaling was not strongly activated in AVMs and this pathway may be only partially involved in mediating EndMT. Using serum-free culture conditions, we isolated myofibroblast-like cell populations from AVMs that expressed a unique range of proteins associated with mature cell types and with EndMT. Conditioned medium from these cells led to increased proliferation of HUVECs and SMCs.

Conclusions: Collectively, our results suggest a role for EndMT in AVM disease. This may lead to new avenues for disease models to further our understanding of disease mechanisms, and to the development of improved diagnostics and therapeutics.
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http://dx.doi.org/10.1002/ctm2.99DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403663PMC
June 2020

Stereotactic Radiosurgery for Resected Brain Metastases: Does the Surgical Corridor Need to be Targeted?

Pract Radiat Oncol 2020 Sep - Oct;10(5):e363-e371. Epub 2020 May 16.

Departments of Radiation Oncology, Stanford, California. Electronic address:

Purpose: Although consensus guidelines for postresection stereotactic radiosurgery (SRS) for brain metastases recommend the surgical corridor leading to the resection cavity be included in the SRS plan, no study has reported patterns of tumor recurrence based on inclusion or exclusion of the corridor as a target. We reviewed tumor control and toxicity outcomes of postresection SRS for deep brain metastases based on whether or not the surgical corridor was targeted.

Materials And Methods: We retrospectively reviewed patients who had resected brain metastases treated with SRS between 2007 and 2018 and included only "deep" tumors (defined as located ≥1.0 cm from the pial surface before resection).

Results: In 66 deep brain metastases in 64 patients, the surgical corridor was targeted in 43 (65%). There were no statistical differences in the cumulative incidences of progression at 12 months for targeting versus not targeting the corridor, respectively, for overall local failure 2% (95% confidence interval [CI], 0%-11%) versus 9% (95% CI, 1%-25%; P = .25), corridor failure 0% (95% CI, 0%-0%) versus 9% (95% CI, 1%-25%; P = .06), cavity failure 2% (95% CI, 0%-11%) versus 0% (95% CI, 0%-0%; P = .91), and adverse radiation effect 5% (95% CI, 1%-15%) versus 13% (95% CI, 3%-30%; P = .22). Leptomeningeal disease (7%; 95% CI, 2%-18%) versus 26% (95% CI, 10%-45%; P = .03) was higher in those without the corridor targeted.

Conclusions: Omitting the surgical corridor in postoperative SRS for resected brain metastases was not associated with statistically significant differences in corridor or cavity recurrence or adverse radiation effect. As seen in recent prospective trials of postresection SRS, the dominant pattern of progression is within the resection cavity; omission of the corridor would yield a smaller SRS volume that could allow for dose escalation to potentially improve local cavity control.
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http://dx.doi.org/10.1016/j.prro.2020.04.009DOI Listing
May 2020

Predictors of visual functional outcome following treatment for cavernous sinus meningioma.

J Neurosurg 2020 May 15:1-12. Epub 2020 May 15.

1Department of Neurosurgery, and.

Objective: Cavernous sinus meningioma (CSM) can affect visual function and require expeditious treatment to prevent permanent visual loss. Authors of this retrospective study sought to determine the factors associated with visual functional outcomes in CSM patients treated with surgery, stereotactic radiosurgery (SRS), or stereotactic radiation therapy (SRT), alone or in combination.

Methods: Consecutive patients with CSM who had presented at an academic tertiary care hospital from 2000 to 2018 were identified through retrospective chart review. Visual function-visual eye deficit (VED), optic disc (OD) appearance, intraocular pressure (IOP), and extraocular movement (EOM)-was assessed before and after treatment for CSM. VED with visual acuity (VA) ≤ 20/200 and visual field defect ≥ -11 dB, pale OD appearance in the ipsilateral or contralateral eye, increased ipsilateral IOP, and/or EOM restriction were defined as a poor visual functional outcome. Multivariable logistic regression was used to evaluate the associations between pretreatment visual functional assessment and posttreatment visual outcomes.

Results: The study cohort included 44 patients (73% female; median age 55 years), with a median clinical follow-up of 14 months. Ipsilateral VED improved, remained stable, or worsened, respectively, in 0%, 33.4%, and 66.6% of the patients after subtotal resection (STR) alone; in 52.6%, 31.6%, and 15.8% after STR plus radiation treatment; in 28.5%, 43.0%, and 28.5% after gross-total resection (GTR) alone; and in 56.3%, 43.7%, and 0% after radiation treatment (SRS or SRT) alone. Contralateral VED remained intact in all the patients after STR alone and those with radiation treatment (SRS or SRT) alone; however, it improved, remained stable, or worsened in 10.5%, 84.2%, and 5.3% after STR plus radiation treatment and in 43.0%, 28.5%, and 28.5% after GTR alone. EOM remained intact, fully recovered, remained stable, and worsened, respectively, in 0%, 50%, 50%, and 0% of the patients after STR alone; in 36.8%, 47.4%, 15.8%, and 0% of the patients after STR with radiation treatment; in 57.1%, 0%, 28.6%, and 14.3% of the patients after GTR alone; and in 56.2%, 37.5%, 6.3%, and 0% of the patients after radiation treatment (SRS or SRT) alone.In multivariable analyses adjusted for age, tumor volume, and treatment modality, initial ipsilateral poor VED (OR 10.1, 95% CI 1.05-97.2, p = 0.04) and initial ipsilateral pale OD appearance (OR 21.1, 95% CI 1.6-270.5, p = 0.02) were associated with poor ipsilateral VED posttreatment. Similarly, an initial pale OD appearance (OR 15.7, 95% CI 1.3-199.0, p = 0.03), initial poor VED (OR 21.7, 95% CI 1.2-398.6, p = 0.03), and a higher IOP in the ipsilateral eye (OR 55.3, 95% CI 1.7-173.9, p = 0.02) were associated with an ipsilateral pale OD appearance posttreatment. Furthermore, a higher initial ipsilateral IOP (OR 35.9, 95% CI 3.3-400.5, p = 0.004) was indicative of a higher IOP in the ipsilateral eye posttreatment. Finally, initial restricted EOM was indicative of restricted EOM posttreatment (OR 20.6, 95% CI 18.7-77.0, p = 0.02).

Conclusions: Pretreatment visual functional assessment predicts visual outcomes in patients with CSM and can be used to identify patients at greater risk for vision loss.
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http://dx.doi.org/10.3171/2020.2.JNS193009DOI Listing
May 2020

Stereotactic radiosurgery for head and neck paragangliomas: a systematic review and meta-analysis.

Neurosurg Rev 2021 Apr 21;44(2):741-752. Epub 2020 Apr 21.

Department of Neurosurgery, Stanford University School of Medicine, 300 Pasteur Drive, Edwards Bldg, Stanford, CA, USA.

Head and neck paragangliomas (HNPs) are rare, usually benign hyper vascularized neuroendocrine tumors that traditionally have been treated by surgery, with or without endovascular embolization, or, more recently stereotactic radiosurgery (SRS). The aim of our study is to determine the clinical and radiographic effectiveness of SRS for treatment of HNPs. A systematic search of electronic databases was performed, and 37 articles reporting 11,174 patients (1144 tumors) with glomus jugulare (GJT: 993, 86.9%), glomus tympanicum (GTT: 94, 8.2%), carotid body tumors (CBTs: 28, 2.4%), and glomus vagale (GVT: 16, 1.4%) treated with SRS definitively or adjuvantly were included. The local control (LC) was estimated from the pooled analysis of the series, and its association with SRS technique as well as demographic and clinical factors was analyzed. The median age was 56 years (44-69 years). With a median clinical and radiological follow-up of 44 months (9-161 months), LC was 94.2%. Majority of the patients (61.0%) underwent Gamma Knife Radiosurgery (GKS), but there was no statistically significant difference in LC depending upon the SRS technique (p = 0.9). Spearmen's correlation showed that LC was strongly and negatively correlated with multiple parameters, which included female gender (r = - 0.4, p = 0.001), right-sided tumor (r = - 0.3, p = 0.03), primary SRS (r = - 0.5, p ≤ 0.001), and initial clinical presentation of hearing loss (r = - 0.4, p = 0.001). To achieve a LC ≥ 90%, a median marginal dose (Gy) of 15 (range, 12-30 Gy) was required. The results corroborate that SRS in HNPs is associated with good clinical and radiological outcome.
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http://dx.doi.org/10.1007/s10143-020-01292-5DOI Listing
April 2021

Evaluating Surgical Resection Extent and Adjuvant Therapy in the Management of Gliosarcoma.

Front Oncol 2020 11;10:337. Epub 2020 Mar 11.

Department of Neurosurgery, Stanford University Medical Center, Stanford, CA, United States.

Gliosarcomas are clinically aggressive tumors, histologically distinct from glioblastoma. Data regarding the impact of extent of resection and post-operative adjuvant therapy on gliosarcoma outcomes are limited. Patients with histologically confirmed gliosarcoma diagnosed between 1999 and 2019 were identified. Clinical, molecular, and radiographic data were assembled based on historical records. Comparisons of categorical variables used Pearson's Chi-square and Fisher's exact test while continuous values were compared using the Wilcoxon signed-rank test. Survival comparisons were assessed using Kaplan-Meier statistics and Cox regressions. Seventy-one gliosarcoma patients were identified. Secondary gliosarcoma was not associated with worse survival when compared to recurrent primary gliosarcoma (median survival 9.8 [3.8 to 21.0] months vs. 7.6 [1.0 to 35.7], = 0.7493). On multivariable analysis, receipt of temozolomide (HR = 0.02, 95% CI 0.001-0.21) and achievement of gross total resection (GTR; HR = 0.13, 95% CI 0.02-0.77) were independently prognostic for improved progression-free survival (PFS) while only receipt of temozolomide was independently associated with extended overall survival (OS) (HR = 0.03, 95% CI 0.001-0.89). In patients receiving surgical resection followed by radiotherapy and concomitant temozolomide, achievement of GTR was significantly associated with improved PFS (median 32.97 [7.1-79.6] months vs. 5.45 [1.8-26.3], = 0.0092) and OS (median 56.73 months [7.8-104.5] vs. 14.83 [3.8 to 29.1], = 0.0252). Multimodal therapy is associated with improved survival in gliosarcoma. Even in patients receiving aggressive post-operative multimodal management, total surgical removal of macroscopic disease remains important for optimal outcomes.
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http://dx.doi.org/10.3389/fonc.2020.00337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078164PMC
March 2020

Stereotactic Radiosurgery for Benign Spinal Tumors.

Neurosurg Clin N Am 2020 Apr 6;31(2):231-235. Epub 2020 Feb 6.

Department of Neurosurgery, Stanford University, 300 Pasteur Drive, Stanford, CA 94305, USA. Electronic address:

Benign spinal tumors are rare clinical conditions, including meningiomas, schwannomas, and neurofibromas. Although these tumors are usually treated with open surgical resection, spinal stereotactic radiosurgery may be a safe and effective alternative to surgery in selected patients.
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http://dx.doi.org/10.1016/j.nec.2019.12.003DOI Listing
April 2020

Local control and toxicity outcomes of stereotactic radiosurgery for spinal metastases of gastrointestinal origin.

J Neurosurg Spine 2020 Mar 6:1-8. Epub 2020 Mar 6.

Departments of1Radiation Oncology and.

Objective: Colorectal cancer (CRC) and other gastrointestinal (GI) cancers are believed to have greater radioresistance than other histologies. The authors report local control and toxicity outcomes of stereotactic radiosurgery (SRS) to spinal metastases from GI primary cancers.

Methods: A retrospective single-center review was conducted of patients with spinal metastases from GI primary cancers treated with SRS from 2004 to 2017. Patient demographics and lesion characteristics were summarized using medians, interquartile ranges (IQRs), and proportions. Local failure (LF) was estimated using the cumulative incidence function adjusted for the competing risk of death and compared using Gray's test for equality. Multivariable analyses were conducted using Cox proportional hazard models, adjusting for death as a competing risk, on a per-lesion basis. Patients were stratified in the Cox model to account for repeated measures for clustered outcomes. Median survival was calculated using the Kaplan-Meier method.

Results: A total of 74 patients with 114 spine lesions were included in our analysis. The median age of the cohort was 62 years (IQR 53-70 years). Histologies included CRC (46%), hepatocellular carcinoma (19%), neuroendocrine carcinoma (13%), pancreatic carcinoma (12%), and other (10%). The 1- and 2-year cumulative incidence rates of LF were 24% (95% confidence interval [CI] 16%-33%) and 32% (95% CI 23%-42%), respectively. Univariable analysis revealed that older age (p = 0.015), right-sided primary CRCs (p = 0.038), and single fraction equivalent dose (SFED; α/β = 10) < 20 Gy (p = 0.004) were associated with higher rates of LF. The 1-year cumulative incidence rates of LF for SFED < 20 Gy10 versus SFED ≥ 20 Gy10 were 35% and 7%, respectively. After controlling for gross tumor volume and prior radiation therapy to the lesion, SFED < 20 Gy10 remained independently associated with worse LF (hazard ratio 2.92, 95% CI 1.24-6.89, p = 0.014). Toxicities were minimal, with pain flare observed in 6 patients (8%) and 15 vertebral compression fractures (13%).

Conclusions: Spinal metastases from GI primary cancers have high rates of LF with SRS at a lower dose. This study found that SRS dose is a significant predictor of failure and that prescribed SFED ≥ 20 Gy10 (biological equivalent dose ≥ 60 Gy10) is associated with superior local control.
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http://dx.doi.org/10.3171/2020.1.SPINE191260DOI Listing
March 2020

A phase I/II trial of 5-fraction stereotactic radiosurgery with 5-mm margins with concurrent temozolomide in newly diagnosed glioblastoma: primary outcomes.

Neuro Oncol 2020 08;22(8):1182-1189

Department of Radiation Oncology, Stanford University, Stanford, California, USA.

Background: We sought to determine the maximum tolerated dose (MTD) of 5-fraction stereotactic radiosurgery (SRS) with 5-mm margins delivered with concurrent temozolomide in newly diagnosed glioblastoma (GBM).

Methods: We enrolled adult patients with newly diagnosed glioblastoma to 5 days of SRS in a 3 + 3 design on 4 escalating dose levels: 25, 30, 35, and 40 Gy. Dose limiting toxicity (DLT) was defined as Common Terminology Criteria for Adverse Events grades 3-5 acute or late CNS toxicity, including adverse radiation effect (ARE), the imaging correlate of radiation necrosis.

Results: From 2010 to 2015, thirty patients were enrolled. The median age was 66 years (range, 51-86 y). The median target volume was 60 cm3 (range, 14.7-137.3 cm3). DLT occurred in 2 patients: one for posttreatment cerebral edema and progressive disease at 3 weeks (grade 4, dose 40 Gy); another patient died 1.5 weeks following SRS from postoperative complications (grade 5, dose 40 Gy). Late grades 1-2 ARE occurred in 8 patients at a median of 7.6 months (range 3.2-12.6 mo). No grades 3-5 ARE occurred. With a median follow-up of 13.8 months (range 1.7-64.4 mo), the median survival times were: progression-free survival, 8.2 months (95% CI: 4.6-10.5); overall survival, 14.8 months (95% CI: 10.9-19.9); O6-methylguanine-DNA methyltransferase hypermethylated, 19.9 months (95% CI: 10.5-33.5) versus 11.3 months (95% CI: 8.9-17.6) for no/unknown hypermethylation (P = 0.03), and 27.2 months (95% CI: 11.2-48.3) if late ARE occurred versus 11.7 months (95% CI: 8.9-17.6) for no ARE (P = 0.08).

Conclusions: The per-protocol MTD of 5-fraction SRS with 5-mm margins with concurrent temozolomide was 40 Gy in 5 fractions. ARE was limited to grades 1-2 and did not statistically impact survival.
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http://dx.doi.org/10.1093/neuonc/noaa019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594571PMC
August 2020

Stereotactic Radiosurgery for Resected Brain Metastases: Single-Institutional Experience of Over 500 Cavities.

Int J Radiat Oncol Biol Phys 2020 03 27;106(4):764-771. Epub 2019 Nov 27.

Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California. Electronic address:

Purpose: Postoperative stereotactic radiosurgery (SRS) has less detrimental effect on cognition and quality of life compared with whole brain radiation therapy (WBRT) and is increasingly used for resected brain metastases (BMs). Postoperative SRS techniques are not standardized, and there is a concern for a different pattern of failure after postoperative SRS compared with WBRT. We aim to study the efficacy, toxicity, and failure pattern of postoperative SRS.

Methods And Materials: We retrospectively reviewed outcomes of patients with resected BMs treated with postoperative SRS between 2007 and 2018. Overall survival and cumulative incidences of local failure, overall distant intracranial failure (distant parenchymal failure, nodular leptomeningeal disease [nLMD], classical leptomeningeal disease [cLMD]), and adverse radiation effect were reported. Neurologic death was determined for patients with leptomeningeal disease (LMD).

Results: A total of 442 patients with 501 resected BMs were treated over 475 total SRS courses. Median clinical follow-up and overall survival after SRS were 10.1 months (interquartile range, 3.6-20.7 months) and 13.9 months (95% confidence interval [CI], 11.8-15.2 months), respectively. At 12 months, event rates were 7% (95% CI, 5%-10%) for local failure, 9% (95% CI, 7%-12%) for adverse radiation effect, 44% (95% CI, 40%-49%) for overall distant intracranial failure, 37% (95% CI, 33%-42%) for distant parenchymal failure, and 13% (95% CI, 10%-17%) for LMD. The overall incidence of LMD was 15.8% (53% cLMD, 46% nLMD). cLMD was associated with shorter survival than nLMD (2.0 vs 11.2 months, P < .01) and a higher proportion of neurologic death (67% vs 41%, P = .02). A total of 15% of patients ultimately received WBRT.

Conclusions: We report the largest clinical experience of postoperative SRS for resected BMs, showing excellent local control and low toxicity. Intracranial failure was predominantly distant, with a rising incidence of LMD.
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http://dx.doi.org/10.1016/j.ijrobp.2019.11.022DOI Listing
March 2020

Stereotactic Radiosurgery for Large Benign Intracranial Tumors.

World Neurosurg 2020 Feb 9;134:e172-e180. Epub 2019 Oct 9.

Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California, USA.

Background: Historically, it is stated that large intracranial tumors, herein defined as a maximum dimension of ≥3 cm or tumor volume ≥14.2 cm, are not candidates for stereotactic radiosurgery (SRS). We report outcomes of patients with large benign intracranial tumors treated with SRS.

Methods: With institutional review board approval, we retrospectively identified 74 patients with large benign intracranial tumors (59 meningiomas, 9 vestibular schwannomas, and 6 glomus jugulare tumors) treated with robotic SRS (2007-2018). Patients received definitive SRS in 47.3% of the cases, adjuvant to surgical resection in 44.6%, and salvage after past radiation treatment in 8.1%. A median tumor volume of 16.0 cm (range, 10.1-65.5 cm) received a median dose of 24.0 Gy (range, 14.0-30.0 Gy) in a median of 3 fractions (range, 1-5), for a median single fraction equivalent dose (with alpha/beta of 3) of 14.8 Gy (range, 11.3-18.0 Gy). The Kaplan-Meier estimate of tumor local control (LC) was calculated from date of SRS.

Results: With a median clinical follow-up of 32.8 months (range, 0.6-125.9 months) and median radiologic follow-up of 28.5 months (range, 0.6-121.4 months), LC was 96.5% (95% confidence interval, 92.4%-100%) at 3 years and 91.7% (95% confidence interval, 87.6%-95.7%) at 5 years. Adverse radiation effect (ARE) was seen in 10 patients (13.5%) at a median of 13.5 months (range, 7.8-34.5 months). ARE occurred in 9% of those with prior treatment compared with 5% who were radiation-naïve (P = 0.23). With 236.4 person-years of follow-up, no secondary malignancies were seen.

Conclusions: Despite the historical adage, we find that SRS provides high rates of LC for these large tumors, with rates of ARE similar to historical reports of SRS for smaller benign tumors.
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http://dx.doi.org/10.1016/j.wneu.2019.10.005DOI Listing
February 2020

Stereotactic Radiosurgery for Pediatric and Adult Intracranial and Spinal Ependymomas.

Stereotact Funct Neurosurg 2019 7;97(3):189-194. Epub 2019 Oct 7.

Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California, USA.

Objective/background: We report efficacy and toxicity outcomes with stereotactic radiosurgery (SRS) for intracranial and spinal ependymoma.

Methods: We analyzed adult and pediatric patients with newly diagnosed or recurrent intracranial or spinal ependymoma lesions treated with SRS at our institution. Following SRS, local failure (LF) was defined as failure within or adjacent to the SRS target volume, while distant failure (DF) was defined as failure outside of the SRS target volume. Time to LF and DF was analyzed using competing risk analysis with death as a competing risk.Overall survival (OS) was calculated from the date of first SRS to the date of death or censored at the date of last follow-up using the Kaplan-Meier method.

Results: Twenty-one patients underwent SRS to 40 intracranial (n = 30) or spinal (n = 10) ependymoma lesions between 2007 and 2018, most commonly with 18 or 20 Gy in 1 fraction. Median follow-up for all patients after first SRS treatment was 54 months (range 2-157). The 1-year, 2-year, and 5-year rates of survival among patients with initial intracranial ependymoma were 86, 74, and 52%, respectively. The 2-year cumulative incidences of LF and DF after SRS among intracranial ependymoma patients were 25% (95% CI 11-43) and 42% (95% CI 22-60), respectively. No spinal ependymoma patient experienced LF, DF, or death within 2 years of SRS. Three patients had adverse radiation effects.

Conclusions: SRS is a viable treatment option for intracranial and spinal ependymoma with excellent local control and acceptable toxicity.
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http://dx.doi.org/10.1159/000502653DOI Listing
February 2020

Ultrasmall theranostic gadolinium-based nanoparticles improve high-grade rat glioma survival.

J Clin Neurosci 2019 Sep 4;67:215-219. Epub 2019 Jul 4.

Biomedical Beamline, European Synchrotron Radiation Facility, CS40220, F38043 Grenoble Cedex 9, France.

We formulated an ultra-small, gadolinium-based nanoparticle (AGuIX) with theranostic properties to simultaneously enhance MRI tumor delineation and radiosensitization in a glioma model. The 9L glioma cells were orthotopically implanted in 10-week-old Fischer rats. The intra-tumoral accumulation of AGuIX was quantified using MRI T1-maps. Rats randomized to intervention cohorts were subsequently treated with daily temozolomide for five consecutive days before radiotherapy treatment. Collectively, a series of 32 rats were divided into untreated (n = 7), temozolomide-only (n = 7), temozolomide and MRT (n = 9), AGuIX and MRT (n = 7), and triple therapy (temozolomide, AGuIX NPs, and MRT; n = 9) cohorts. AGuIX nanoparticles achieved a maximum intra-tumoral concentration (expressed as concentration of Gd3+) at 1 h after intravenous injection, reaching a mean of 227.9 ± 60 μM. This was compared to concentrations of 10.5 ± 9.2 μM and 62.9 ± 24.7 μM in the contralateral hemisphere and cheek, respectively. There was a slower washout in the intra-tumor region, with sustained tumor-to-contralateral ratio of AGuIX, up to 14-fold, for each time point. The combination of AGuIX or temozolomide with MRT improved the median survival time (40 days) compared to the MeST of control rats (25 days) (p < 0.002). There was a trend towards further increased survival when the three treatments were combined (MeST of 46 days). This study demonstrated the selective accumulation of AGuIX in high grade glioma, as well as the potential survival benefits when combined with chemoradiation.
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http://dx.doi.org/10.1016/j.jocn.2019.05.065DOI Listing
September 2019

Clinical Efficacy of Frameless Stereotactic Radiosurgery in the Management of Spinal Metastases From Thyroid Carcinoma.

Spine (Phila Pa 1976) 2019 Oct;44(20):E1188-E1195

Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA.

Study Design: A retrospective data review.

Objective: To evaluate the efficacy of CyberKnife (CK) stereotactic radiosurgery (SRS) for thyroid spinal metastasis (SMs).

Summary Of Background Data: Thyroid carcinoma is an infrequent cause of SM. The absolute efficacy of SRS generally and CK in particular remains poorly characterized for thyroid SM. The current study is the first to specifically evaluate the efficacy of CK SRS for thyroid SMs.

Methods: A retrospective review of patients at our institution between 2003 and 2013 was done. Details about tumor location, radiographic findings before and after CK SRS, tumor recurrence, prescription isodose level, total and maximum dose, number of fractions, and gross tumor volume coverage were similarly collected. For comparison with other studies, the biologically effective dose and the equivalent total dose in 2 Gy fractions were calculated. Each patient was assessed for survival and local disease control from the time of the first CK session and survival analysis was carried out using the Kaplan-Meier method. Risk factors for local failure were assessed using multivariate logistic regression.

Results: A total of 12 patients with 32 spinal metastases from thyroid carcinoma that were treated with CK SRS were identified. Survival for 1, 2, and 3 years was 55%, 44%, and 33%, and local control was 67%, 56%, and 34% respectively. The study found that the single strongest factor associated with local control was prior radiotherapy (β-coefficient -27.72, P = 0.01). No complications occurred in the immediate or late follow-up period.

Conclusion: This was the first study to specifically investigate the efficacy of CK for treatment of thyroid SMs. Our findings suggest that CK can be safely used to treat spinal SMs from thyroid cancer and is associated with a high rate of local control.

Level Of Evidence: 4.
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http://dx.doi.org/10.1097/BRS.0000000000003087DOI Listing
October 2019

Stereotactic Radiosurgery in Large Intracranial Meningiomas: A Systematic Review.

World Neurosurg 2019 Sep 19;129:269-275. Epub 2019 Jun 19.

Department of Neurosurgery, Stanford University School of Medicine, Stanford, California, USA.

Gross total resection of large intracranial meningiomas (LIMs) can be challenging and cause significant morbidity and mortality. The aim of this systematic review is to determine the clinical effectiveness and safety of stereotactic radiosurgery (SRS) either as primary or adjuvant therapy for LIMs with tumors ≥2.5 cm in maximum dimension (tumor volume ≥8.1 cm). A total of 452 tumors in 496 patients (350 female [69.3%] and 146 male [30.6%]) with median age 60 years (48-65 years) were included. The median tumor volume at the time of diagnosis was 16.7 cm (10-53.3 cm). The tumors typically were located in the skull base (77.2%), whereas only 14.6% were in the supratentorial space. The median follow-up after SRS was 54 months (18-90 months). In total, 87.8% of patients were treated with single-session (SS) Gamma Knife radiosurgery (GKS), whereas the remaining 12.1% patients received non-SS GKS. Of 452 LIMs assessed for clinical response, 45.1% showed improvement and 15.7% deteriorated after SRS. Radiographic tumor control at last follow-up (2-7.5 years) ranged from 84% to 100%. Overall, radiation-induced toxicity occurred in 23% of patients, with the most common adverse effect being cranial nerve neuropathy (5.5%) and peritumoral edema (5.3%). Subgroup analysis revealed that there is 2-fold greater likelihood of improvement in clinical symptoms in patients with non-SS GKS than SS GKS (odds ratio 2.47; 95% confidence interval 1.38-4.44; P = 0.002). SRS is safe and effective in the treatment of LIMs as primary or adjuvant treatment. Further prospective studies are required to validate our results.
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http://dx.doi.org/10.1016/j.wneu.2019.06.064DOI Listing
September 2019

Stereotactic radiosurgery versus stereotactic radiotherapy in the management of intracranial meningiomas: a systematic review and meta-analysis.

Neurosurg Focus 2019 06;46(6):E2

1Department of Neurosurgery, Stanford University School of Medicine, Palo Alto; and.

OBJECTIVEStereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) have been used as a primary treatment or adjuvant to resection in the management of intracranial meningiomas (ICMs). The aim of this analysis is to compare the safety and long-term efficacy of SRS and SRT in patients with primary or recurrent ICMs.METHODSA systematic review of the literature comparing SRT and SRS in the same study was conducted using PubMed, the Cochrane Library, Google Scholar, and EMBASE from January 1980 to December 2018. Randomized controlled trials, case-control studies, and cohort studies (prospective and retrospective) analyzing SRS versus SRT for the treatment of ICMs in adult patients (age > 16 years) were included. Pooled and subgroup analyses were based on the fixed-effect model.RESULTSA total of 1736 patients from 12 retrospective studies were included. The treatment modality used was: 1) SRS (n = 306), including Gamma Knife surgery (n = 36), linear accelerator (n = 261), and CyberKnife (n = 9); or 2) SRT (n = 1430), including hypofractionated SRT (hFSRT, n = 268) and full-fractionated SRT (FSRT, n = 1162). The median age of patients at the time of treatment was 59 years. The median follow-up duration after treatment was 35.5 months. The median tumor volumes at the time of treatment with SRS, hFSRT, and FSRT were 2.84 cm3, 5.45 cm3, and 12.75 cm3, respectively. The radiographic tumor control at last follow-up was significantly worse in patients who underwent SRS than SRT (odds ratio [OR] 0.47, 95% confidence interval [CI] 0.27-0.82, p = 0.007) with 7% less volume of tumor shrinkage (OR 0.93, 95% CI 0.61-1.40, p = 0.72). Compared to SRS, the radiographic tumor control was better achieved by FSRT (OR 0.46, 95% CI 0.26-0.80, p = 0.006) than by hFSRT (OR 0.81, 95% CI 0.21-3.17, p = 0.76). Moreover, SRS leads to a significantly higher risk of clinical neurological worsening during follow-up (OR 2.07, 95% CI 1.06-4.06, p = 0.03) and of immediate symptomatic edema (OR 4.58, 95% CI 1.67-12.56, p = 0.003) with respect to SRT. SRT could produce a better progression-free survival at 4-10 years compared to SRS, but this was not statistically significant (p = 0.29).CONCLUSIONSSRS and SRT are both safe options in the management of ICMs. However, SRT carries a better radiographic tumor control rate and a lower incidence of posttreatment symptomatic worsening and symptomatic edema, with respect to SRS. However, further prospective studies are still needed to validate these results.
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http://dx.doi.org/10.3171/2019.3.FOCUS1970DOI Listing
June 2019

Efficacy and toxicity of particle radiotherapy in WHO grade II and grade III meningiomas: a systematic review.

Neurosurg Focus 2019 06;46(6):E12

1Department of Neurosurgery, Stanford Health Care, Palo Alto.

OBJECTIVEAdjuvant radiotherapy has become a common addition to the management of high-grade meningiomas, as immediate treatment with radiation following resection has been associated with significantly improved outcomes. Recent investigations into particle therapy have expanded into the management of high-risk meningiomas. Here, the authors systematically review studies on the efficacy and utility of particle-based radiotherapy in the management of high-grade meningioma.METHODSA literature search was developed by first defining the population, intervention, comparison, outcomes, and study design (PICOS). A search strategy was designed for each of three electronic databases: PubMed, Embase, and Scopus. Data extraction was conducted in accordance with the PRISMA guidelines. Outcomes of interest included local disease control, overall survival, and toxicity, which were compared with historical data on photon-based therapies.RESULTSEleven retrospective studies including 240 patients with atypical (WHO grade II) and anaplastic (WHO grade III) meningioma undergoing particle radiation therapy were identified. Five of the 11 studies included in this systematic review focused specifically on WHO grade II and III meningiomas; the others also included WHO grade I meningioma. Across all of the studies, the median follow-up ranged from 6 to 145 months. Local control rates for high-grade meningiomas ranged from 46.7% to 86% by the last follow-up or at 5 years. Overall survival rates ranged from 0% to 100% with better prognoses for atypical than for malignant meningiomas. Radiation necrosis was the most common adverse effect of treatment, occurring in 3.9% of specified cases.CONCLUSIONSDespite the lack of randomized prospective trials, this review of existing retrospective studies suggests that particle therapy, whether an adjuvant or a stand-alone treatment, confers survival benefit with a relatively low risk for severe treatment-derived toxicity compared to standard photon-based therapy. However, additional controlled studies are needed.
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http://dx.doi.org/10.3171/2019.3.FOCUS1967DOI Listing
June 2019

Adverse Radiation Effect and Disease Control in Patients Undergoing Stereotactic Radiosurgery and Immune Checkpoint Inhibitor Therapy for Brain Metastases.

World Neurosurg 2019 Jun 20;126:e1399-e1411. Epub 2019 Mar 20.

Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California, USA. Electronic address:

Background: Immune checkpoint inhibitors (ICIs) and stereotactic radiosurgery (SRS) are increasingly used together to manage brain metastases (BMs). We assessed adverse radiation effect, disease control, and overall survival in patients with BMs who received SRS with anticytotoxic T-lymphocyte-associated protein 4 and/or anti- programmed cell death protein receptor/ligand therapies.

Methods: We retrospectively reviewed the records of patients with intact or resected BMs treated with SRS and ICIs within 5 months of SRS between 2010 and 2018. Patients were defined as receiving concurrent SRS and ICI if a dose of ICI was given within 4 weeks of SRS. Local failure, distant intracranial failure, extracranial failure, and adverse radiation effect were assessed using cumulative incidence rates and competing risk regressions with death as a competing risk. Overall survival was assessed using the Kaplan-Meier method and Cox proportional hazards models.

Results: A total of 97 patients with 580 BMs were included in our analysis. Competing risk analyses showed that concurrent SRS-ICI therapy is associated with higher rates of adverse radiation effect (6.4% vs. 2.0% at 1 year; multivariable hazard ratio [HR], 4.47; 95% confidence interval [CI], 1.57-12.73; P = 0.005), lower rates of extracranial failure (69.7% vs. 80.8% at 1 year; multivariable HR, 0.60; 95% CI, 0.42-0.87; P = 0.007), and better overall survival (48.6% vs. 25.4% at 1 year; multivariable HR, 0.57; 95% CI, 0.33-0.99; P = 0.044) compared with nonconcurrent therapy. SRS-ICI timing was not associated with local failure or distant intracranial failure.

Conclusions: Concurrent SRS-ICI therapy has a tolerable adverse event profile and may improve extracranial disease control and overall survival, supporting concurrent use in the management of BMs.
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http://dx.doi.org/10.1016/j.wneu.2019.03.110DOI Listing
June 2019

Magnetic Particle Imaging in Neurosurgery.

World Neurosurg 2019 05 8;125:261-270. Epub 2019 Feb 8.

Department of Neurosurgery, Stanford University, Stanford, California, USA.

Background: Magnetic particle imaging (MPI) is a novel radiation-free tomographic imaging method that provides a background-free, signal attenuation-free, direct quantification of the spatial distribution of superparamagnetic iron-oxide nanoparticles (SPIONs) with high temporal resolution (milliseconds), high spatial resolution (<1 mm), and extreme sensitivity (μmol). The technique is based on nonlinear magnetization of the SPIONs when exposed to an oscillating magnetic field. MPI was first described in 2001. Since then, the technique has been applied to experimental imaging of diseases affecting different organs in the human body. The aim of this paper is to review the potential applications of MPI in the field of neurosurgery.

Methods: A nonsystematic review of the existing literature on the use of MPI in neurosurgical diseases was performed.

Results: MPI has been used for the detection of locoregional invasion of brain tumors, tracking, and monitoring the viability of neural stem cells implanted for neuroregenerative purposes, diagnosis of cerebral ischemia, and diagnosis and morphofunctional assessment of brain aneurysms.

Conclusions: MPI is at a preclinical stage. In the future, human-sized MPI scanners, along with the optimal toxicity profile of SPIONs will allow diagnostic applications in neurosurgical diseases.
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http://dx.doi.org/10.1016/j.wneu.2019.01.180DOI Listing
May 2019

Radiographic Rate and Clinical Impact of Pseudarthrosis in Spine Radiosurgery for Metastatic Spinal Disease.

Cureus 2018 Nov 25;10(11):e3631. Epub 2018 Nov 25.

Department of Neurosurgery, Stanford University School of Medicine, Stanford, USA.

Purpose Pseudarthrosis within the spine tumor population is increased from perioperative radiation and complex stabilization for invasive and recurrent pathology. We report the radiographic and clinical rates of pseudarthrosis following multiple courses of instrumented fusion and perioperative stereotactic radiosurgery (SRS). Methods We performed a single institution review of 418 patients treated with non-isocentric SRS for spine between October 2002 and January 2013, identifying those with spinal instrumentation and greater than six months of follow-up. Surgical history, radiation planning, and radiographic outcomes were documented. Results Eleven patients who met criteria for inclusion underwent 21 sessions of spinal SRS and 16 instrumented operations. Radiographic follow-up was 48.9 months; 3/11 (27%) were with radiographic hardware failure, and one (9%) separate case ultimately warranted externalization due to tumor recurrence. SRS was administered to treat progression of disease in 12/21 (57%) procedures, and residual lesions in 7/11 (64%) procedures. Following first and second SRS, 8/11 (73%) and 2/7 (29%) patients were with symptomatic improvement, respectively. Conclusion Risk of pseudarthrosis following SRS for patients with oncologic spinal lesions will become increasingly apparent with the optimized management of and survival from spinal pathologies. We highlight how the need for local control outpaces the risk of instrumentation failure.
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http://dx.doi.org/10.7759/cureus.3631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349573PMC
November 2018

Silicon Valley new focus on brain computer interface: hype or hope for new applications?

F1000Res 2018 21;7:1327. Epub 2018 Aug 21.

Department of Neurosurgery, Stanford University Medical Center, Brighton, USA.

In the last year there has been increasing interest and investment into developing devices to interact with the central nervous system, in particular developing a robust brain-computer interface (BCI). In this article, we review the most recent research advances and the current host of engineering and neurological challenges that must be overcome for clinical application. In particular, space limitations, isolation of targeted structures, replacement of probes following failure, delivery of nanomaterials and processing and understanding recorded data. Neural engineering has developed greatly over the past half-century, which has allowed for the development of better neural recording techniques and clinical translation of neural interfaces. Implementation of general purpose BCIs face a number of constraints arising from engineering, computational, ethical and neuroscientific factors that still have to be addressed. Electronics have become orders of magnitude smaller and computationally faster than neurons, however there is much work to be done in decoding the neural circuits. New interest and funding from the non-medical community may be a welcome catalyst for focused research and development; playing an important role in future advancements in the neuroscience community.
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http://dx.doi.org/10.12688/f1000research.15726.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343225PMC
November 2019

Arterial-spin labeling MRI identifies residual cerebral arteriovenous malformation following stereotactic radiosurgery treatment.

J Neuroradiol 2020 Feb 15;47(1):13-19. Epub 2019 Jan 15.

Department of Radiology, Neuroimaging and Neurointervention Division, Stanford University Hospital, 300, Pasteur Drive, Stanford, CA 94305, US.

Background And Purpose: Brain arteriovenous malformation (AVM) treatment by stereotactic radiosurgery (SRS) is effective, but AVM obliteration following SRS may take two years or longer. MRI with arterial-spin labeling (ASL) may detect brain AVMs with high sensitivity. We determined whether brain MRI with ASL may accurately detect residual AVM following SRS treatment.

Materials And Methods: We performed a retrospective cohort study of patients who underwent brain AVM evaluation by DSA between June 2010 and June 2015. Inclusion criteria were: (1) AVM treatment by SRS, (2) follow-up MRI with ASL at least 30 months after SRS, (3) DSA within 3 months of the follow-up MRI with ASL, and (4) no intervening AVM treatment between the MRI and DSA. Four neuroradiologists blindly and independently reviewed follow-up MRIs. Primary outcome measure was residual AVM indicated by abnormal venous ASL signal.

Results: 15 patients (12 females, mean age 29 years) met inclusion criteria. There were three posterior fossa AVMs and 12 supratentorial AVMs. Spetzler-Martin (SM) Grades were: SM1 (8%), SM2 (33%), SM3 (17%), SM4 (25%), and SM5 (17%). DSA demonstrated residual AVM in 10 patients. The pooled sensitivity, specificity, positive predictive value, and negative predictive value of venous ASL signal for predicting residual AVM were 100% (95% CI: 0.9-1.0), 95% (95% CI: 0.7-1.0), 98% (95% CI: 0.9-1.0), and 100% (95% CI: 0.8-1.0), respectively. High inter-reader agreement as found by Fleiss' Kappa analysis (k = 0.92; 95% CI: 0.8-1.0; P < 0.0001).

Conclusions: ASL is highly sensitive and specific in the detection of residual cerebral AVM following SRS treatment.
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http://dx.doi.org/10.1016/j.neurad.2018.12.004DOI Listing
February 2020

Brain metastases.

Nat Rev Dis Primers 2019 01 17;5(1). Epub 2019 Jan 17.

Department of Neurosurgery, University of California-Davis, School of Medicine, Sacramento, CA, USA.

An estimated 20% of all patients with cancer will develop brain metastases, with the majority of brain metastases occurring in those with lung, breast and colorectal cancers, melanoma or renal cell carcinoma. Brain metastases are thought to occur via seeding of circulating tumour cells into the brain microvasculature; within this unique microenvironment, tumour growth is promoted and the penetration of systemic medical therapies is limited. Development of brain metastases remains a substantial contributor to overall cancer mortality in patients with advanced-stage cancer because prognosis remains poor despite multimodal treatments and advances in systemic therapies, which include a combination of surgery, radiotherapy, chemotherapy, immunotherapy and targeted therapies. Thus, interest abounds in understanding the mechanisms that drive brain metastases so that they can be targeted with preventive therapeutic strategies and in understanding the molecular characteristics of brain metastases relative to the primary tumour so that they can inform targeted therapy selection. Increased molecular understanding of the disease will also drive continued development of novel immunotherapies and targeted therapies that have higher bioavailability beyond the blood-tumour barrier and drive advances in radiotherapies and minimally invasive surgical techniques. As these discoveries and innovations move from the realm of basic science to preclinical and clinical applications, future outcomes for patients with brain metastases are almost certain to improve.
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http://dx.doi.org/10.1038/s41572-018-0055-yDOI Listing
January 2019

In Reply: Commentary: Peritumoral Edema/Tumor Volume Ratio: A Strong Survival Predictor for Posterior Fossa Metastases.

Neurosurgery 2019 03;84(3):E232

Department of Neurosurgery Stanford University Stanford, California.

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http://dx.doi.org/10.1093/neuros/nyy574DOI Listing
March 2019

Milestones in stereotactic radiosurgery for the central nervous system.

J Clin Neurosci 2019 Jan 26;59:12-19. Epub 2018 Oct 26.

Department of Neurosurgery, Stanford University School of Medicine, Stanford Health Care and Stanford Children's Health, Stanford Neuroscience Health Center, 213 Quarry Road, Palo Alto, CA 94304-5979, United States.

Introduction: Since Lars Leksell developed the first stereotactic radiosurgery (SRS) device in 1951, there has been growth in the technologies available and clinical indications for SRS. This expansion has been reflected in the medical literature, which is built upon key articles and institutions that have significantly impacted SRS applications. Our aim was to identify these prominent works and provide an educational tool for training and further inquiry.

Method: A list of search phrases relating to central nervous system applications of stereotactic radiosurgery was compiled. A topic search was performed using PubMed and Scopus databases. The journal, year of publication, authors, treatment technology, clinical subject, study design and level of evidence for each article were documented. Influence was proposed by citation count and rate.

Results: Our search identified a total of 10,211 articles with the top 10 publications overall on the study of SRS spanning 443-1313 total citations. Four articles reported on randomized controlled trials, all of which evaluated intracranial metastases. The most prominent subtopics included SRS for arteriovenous malformation, glioblastoma, and acoustic neuroma. Greatest representation by treatment modality included Gamma Knife, LINAC, and TomoTherapy.

Conclusions: This systematic reporting of the influential literature on SRS for intracranial and spinal pathologies underscores the technology's rapid and wide reaching clinical applications. Moreover the findings provide an academic guide to future health practitioners and engineers in their study of SRS for neurosurgery.
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http://dx.doi.org/10.1016/j.jocn.2018.09.029DOI Listing
January 2019