Emanuela Binello, Sheryl Green, Isabelle M Germano

Surgical Neurology International 2012 3(3):118-126

Background: For patients with newly diagnosed high-grade gliomas (HGG), the current standard-of-care treatment involves surgical resection, followed by concomitant temozolomide (TMZ) and external beam radiation therapy (XRT), and subsequent TMZ chemotherapy. For patients with recurrent HGG, there is no standard of care. Stereotactic radiosurgery (SRS) is used to deliver focused, relatively large doses of radiation to a small, precisely defined target. Treatment is usually delivered in a single fraction, but may be delivered in up to five fractions. The role of SRS in the management of patients with HGG is not well established. Methods: The PubMed database was searched with combinations of relevant MESH headings and limits. Case reports and/or small case series were excluded. Attention was focused on overall median survival as an objective measure, and data were examined separately for newly diagnosed and recurrent HGG. Results: With respect to newly diagnosed HGG, there is strong evidence that addition of an SRS boost prior to standard XRT provides no survival benefit. However, recent retrospective evidence suggests a possible survival benefit when SRS is performed after XRT. With respect to recurrent HGG, there is suggestion that SRS may confer a survival benefit but with potentially higher complication rates. Newer studies are investigating the combination of SRS with targeted molecular agents. Controlled prospective clinical trials using advanced imaging techniques are necessary for a complete assessment. Conclusions: SRS has the potential to provide a survival benefit for patients with HGG. Further research is clearly warranted to define its role in the management of newly diagnosed and recurrent HGG.

http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=3;spage=118;epage=126;aulast=Binello

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Júlio Leonardo B. Pereira
http://lattes.cnpq.br/7687651239699170
http://www.neurocirurgiabr.com

Neurosurgical Focus, Volume 32, Issue 5, Page E18, May 2012.
Object Given the feasibility of curative surgical and endovascular therapy for cerebral dural arteriovenous fistulas (DAVFs), there is a relative paucity of radiosurgical series for these lesions as compared with their arteriovenous malformation counterparts. Methods The authors reviewed records of 56 patients with 70 cerebral DAVFs treated at their institution over the past 6 years. Ten DAVFs (14%) in 9 patients were treated with stereotactic radiosurgery (SRS), with follow-up obtained for 8 patients with 9 DAVFs. They combined their results with those obtained from a comprehensive review of the literature, focusing on obliteration rates, post-SRS hemorrhage rates, and other complications. Results In the authors’ group of 9 DAVFs, angiographic obliteration was seen in 8 cases (89%), and no post-SRS hemorrhage or complications were observed after a mean follow-up of 2.9 years. Combining the results in these cases with data obtained from their review of the literature, they found 558 DAVFs treated with SRS across 14 series. The overall obliteration rate was 71%; transient worsening occurred in 9.1% of patients, permanent worsening in 2.4% (including 1 death, 0.2% of cases), and post-SRS hemorrhage occurred in 1.6% of cases (4.8% of those with cortical venous drainage [CVD]). The obliteration rate for cavernous DAVFs was 84%, whereas the rates for transversesigmoid and for tentorial DAVFs were 58% and 59%, respectively (adjusted p values, pcav,TS = 1.98 × 10−4, pcav,tent = 0.032). Obliteration rates were greater for DAVFs without CVD (80%, compared with 60% for those with CVD, p = 7.59 × 10−4). Both transient worsening and permanent worsening were less common in patients without CVD than in those with CVD (3.4% vs 7.3% for transient worsening and 0.9% vs 2.4% for permanent worsening). Conclusions Stereotactic radiosurgery with or without adjunctive embolization is an effective therapy for DAVFs that are not amenable to surgical or endovascular monotherapy. It is best suited for lesions without CVD and for cavernous DAVFs.

http://thejns.org/doi/abs/10.3171/2012.1.FOCUS11354?ai=rw&mi=3ba5z2&af=R

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Júlio Leonardo B. Pereira
http://lattes.cnpq.br/7687651239699170
http://www.neurocirurgiabr.com

Purpose: Radiosurgery has been successfully used in selected cases to avoid repeat whole-brain irradiation (WBI) in patients with multiple brain metastases of most solid tumor histological findings. Few data are available for the use of radiosurgery for small-cell lung cancer (SCLC).Methods and Materials: Between November 1999 and June 2009, 51 patients with SCLC and previous WBI and new brain metastases were treated with GammaKnife stereotactic radiosurgery (GKSRS). A median dose of 18 Gy (range, 10–24 Gy) was prescribed to the margin of each metastasis. Patients were followed with serial imaging. Patient electronic records were reviewed to determine disease-related factors and clinical outcomes after GKSRS. Local and distant brain failure rates, overall survival, and likelihood of neurologic death were determined based on imaging results. The Kaplan-Meier method was used to determine survival and local and distant brain control. Cox proportional hazard regression was performed to determine strength of association between disease-related factors and survival.Results: Median survival time for the entire cohort was 5.9 months. Local control rates at 1 and 2 years were 57% and 34%, respectively. Distant brain failure rates at 1 and 2 years were 58% and 75%, respectively. Fifty-three percent of patients ultimately died of neurologic death. On multivariate analysis, patients with stable (hazard ratio [HR] = 2.89) or progressive (HR = 6.98) extracranial disease (ECD) had worse overall survival than patients without evidence of ECD (p = 0.00002). Concurrent chemotherapy improved local control (HR = 89; p = 0.006).Conclusions: GKSRS represents a feasible salvage option in patients with SCLC and brain metastases for whom previous WBI has failed. The status of patients’ ECD is a dominant factor predictive of overall survival. Local control may be inferior to that seen with other cancer histological results, although the use of concurrent chemotherapy may help to improve this.

http://www.redjournal.org/article/PIIS0360301611036170/abstract?rss=yes

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Júlio Leonardo B. Pereira
http://lattes.cnpq.br/7687651239699170
http://www.neurocirurgiabr.com

Purpose: To determine the efficacy and safety of radiosurgery in patients with large brain metastases treated with radiosurgery.Patients and Methods: Eighty patients with large brain metastases (>14 cm3) were treated with radiosurgery between 1998 and 2009. The mean age was 59 ± 11 years, and 49 (61.3%) were men. Neurologic symptoms were identified in 77 patients (96.3%), and 30 (37.5%) exhibited a dependent functional status. The primary disease was under control in 36 patients (45.0%), and 44 (55.0%) had a single lesion. The mean tumor volume was 22.4 ± 8.8 cm3, and the mean marginal dose prescribed was 13.8 ± 2.2 Gy.Results: The median survival time from radiosurgery was 7.9 months (95% confidence interval [CI], 5.343–10.46), and the 1-year survival rate was 39.2%. Functional improvement within 1–4 months or the maintenance of the initial independent status was observed in 48 (60.0%) and 20 (25.0%) patients after radiosurgery, respectively. Control of the primary disease, a marginal dose of ≥11 Gy, and a tumor volume ≥26 cm3 were significantly associated with overall survival (hazard ratio, 0.479; p = .018; 95% CI, 0.261–0.880; hazard ratio, 0.350; p = .004; 95% CI, 0.171–0.718; hazard ratio, 2.307; p = .006; 95% CI, 1.274–4.180, respectively). Unacceptable radiation-related toxicities (Radiation Toxicity Oncology Group central nervous system toxicity Grade 3, 4, and 5 in 7, 6, and 2 patients, respectively) developed in 15 patients (18.8%).Conclusion: Radiosurgery seems to have a comparable efficacy with surgery for large brain metastases. However, the rate of radiation-related toxicities after radiosurgery should be considered when deciding on a treatment modality.

http://www.redjournal.org/article/PIIS0360301611028379/abstract?rss=yes

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Júlio Leonardo B. Pereira
http://lattes.cnpq.br/7687651239699170
http://www.neurocirurgiabr.com

Publication year: 2012
Source:World Neurosurgery
Bente Sandvei Skeie, Per Øyvind Enger, Jan Brøgger, Jeremy Christopher Ganz, Frits Thorsen, Jan Ingeman Heggdal, Paal-Henning Pedersen
Objective The optimal management of patients with recurrent glioblastoma multiforme (GBM) is a subject of controversy. These patients may be candidates for both reoperation, and/or Gamma Knife Surgery (GKS). Few studies have addressed the role of GKS for relapsing gliomas and the results have not been compared with reoperation. In order to validate the efficacy and safety of GKS, we compared the survival and complication rates of GKS and reoperation for recurrent GBMs. Methods We retrospectively reviewed 77 consecutive patients with histopathologically confirmed GBMs retreated for recurrent GBM between 1996 and 2007. Thirty-two patients underwent GKS, 26 reoperation and 19 both procedures. Results Median time from second intervention to tumor progression was longer after GKS than after resection, p=0.009. Median survival after retreatment was 12 months for the 51 patients receiving GKS compared to 6 months for reoperation only (p=0.001, HR 2.4), and 19 months vs. 16 months from the time of primary diagnosis (p=0.021, HR 1.8). A multivariate analysis adjustied for possible confounding factors (tumor volume, RPA-class, neurological deficits, time to recurrence, adjuvant therapy and tumor location), showed significantly longer survival for patients treated with GKS both from retreatment (p=0.013, HR 4.1) and primary diagnosis (p= 0.002, HR 5.8). The adjusted results were still significant after separate analysis according to tumor volume < 5 cm³, 5-20 cm³ and >20 cm³. The complications rate was 9.8% after GKS and 25.2 % after reoperation. Conclusion GKS may be an alternative to open surgery for small GBMs at the time of recurrences with a significantly lower complication rate and a possible survival benefit compared with reoperation.

http://www.sciencedirect.com/science?_ob=GatewayURL&_origin=IRSSSEARCH&_method=citationSearch&_piikey=S1878875012004421&_version=1&md5=061b9a3896e367cd48cfc4c296599706

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Júlio Leonardo B. Pereira
http://lattes.cnpq.br/7687651239699170
http://www.neurocirurgiabr.com

Abstract The objective of the study is to define the tumor control rate and complications associated with stereotactic radiosurgery (SRS) for patients with recurrent intracranial ependymoma. Retrospective review of 26 patients (49 tumors) having SRS between 1990 and 2008. Twenty-five patients (96 %) had undergone one or more craniotomies; one patient underwent SRS for a metastatic tumor after resection of a spinal ependymoma. Nineteen patients (73 %) had received cranial external beam radiotherapy (median dose, 54 Gy). Eight patients (31 %) were less than 18 years old. The median target volume was 2.2 cm3 (range, 0.3–66.6); the median tumor margin dose was 18 Gy (range, 12–24). The median follow-up after SRS was 3.1 years (range, 3 months–13.1 years). The median overall survival after SRS was 5.5 years. The 1-year and 3-year survival rates were 96 and 69 %, respectively. Local tumor control (LC) was achieved in 33 of 49 lesions (67 %) with a median time to progression of 14.7 months (range, 2.9 months–11.2 years). The 1-year and 3-year progression-free survival rates were 80 and 66 %, respectively. The 1-year and 3-year LC rate was 85 and 72 %, respectively. On univariate analysis, higher tumor grade was associated with worse OS (grade 3–4, 27 % vs grade 2, 82 %, p = 0.04). Seven patients (27 %) had distant tumor progression and two patients (8 %) had symptomatic radiation necrosis after SRS. SRS for recurrent intracranial ependymoma provided good LC and may improve survival for patients with limited recurrent disease after prior treatment.

• Content Type Journal Article
• Category Clinical Study
• Pages 1-6
• DOI 10.1007/s11060-012-0851-2
• Authors
  • Michael C. Stauder, Department of Radiation Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
  • Nadia NI Laack, Department of Radiation Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
  • Kamran A. Ahmed, Mayo Medical School, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
  • Michael J. Link, Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA
  • Paula J. Schomberg, Department of Radiation Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
  • Bruce E. Pollock, Department of Radiation Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA

• Journal Journal of Neuro-Oncology
• Online ISSN 1573-7373
• Print ISSN 0167-594X

http://www.springerlink.com/content/n16425g475807283/

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Júlio Leonardo B. Pereira
http://lattes.cnpq.br/7687651239699170
http://www.neurocirurgiabr.com

Journal of Neurosurgery, Volume 0, Issue 0, Page 1-5, Ahead of Print.
Object Despite the controversy over the clinical significance of Gamma Knife surgery (GKS) for refractory mesial temporal lobe epilepsy (MTLE), the modality has attracted attention because it is less invasive than resection. The authors report long-term outcomes for 7 patients, focusing in particular on the long-term complications. Methods Between 1996 and 1999, 7 patients with MTLE underwent GKS. The 50% marginal dose covering the medial temporal structures was 18 Gy in 2 patients and 25 Gy in the remaining 5 patients. Results High-dose treatment abolished the seizures in 2 patients and significantly reduced them in 2 others. One patient in this group was lost to follow-up. However, 2 patients presented with symptomatic radiation necrosis (SRN) necessitating resection after 5 and 10 years. One patient who did not need necrotomy continued to show radiation necrosis on MRI after 10 years. One patient died of drowning while swimming in the sea 1 year after GKS, before seizures had disappeared completely. Conclusions High-dose treatment resulted in sufficient seizure control but carried a significant risk of SRN after several years. Excessive target volume was considered as a reason for delayed necrosis. Drawbacks such as a delay in seizure control and the risk of SRN should be considered when the clinical significance of this treatment is evaluated.

http://thejns.org/doi/abs/10.3171/2012.2.JNS111296?ai=ru&mi=0&af=R

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Júlio Leonardo B. Pereira
http://lattes.cnpq.br/7687651239699170
http://www.neurocirurgiabr.com

The development of radiologic criteria for the assessment of response to treatment in high-grade gliomas (HGGs) has evolved considerably over the past few decades since the original response criteria based on computed tomography imaging. Accuracy and objectivity in the assessment of response to treatment of HGGs is necessary for altering treatment regimens, establishing accurate provider communication, and improving the quality of clinical trials. Future studies assessing emerging advanced neuroimaging techniques will facilitate the development of even more accurate evidence-based radiologic response criteria.

http://www.neurosurgery.theclinics.com/article/PIIS1042368012000071/abstract?rss=yes

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Júlio Leonardo B. Pereira
http://lattes.cnpq.br/7687651239699170
http://www.neurocirurgiabr.com

Radiotherapy has become a part of the standard treatment of high-grade gliomas. Studies have shown that high-dose radiation results in more effective tumor control but at the cost of radionecrosis and other radiation-related side effects. Despite advancing techniques in stereotaxy and precise radiotherapy delivery techniques, studies published for stereotactic radiosurgical treatment of high-grade gliomas have not been unanimous, with large trials showing no survival benefit compared with conventional conformal radiotherapy. New imaging modalities have been studied with the hope to improve accuracy in the planning of radiosurgical treatments. However, further large scale studies are needed to confirm these results.

http://www.neurosurgery.theclinics.com/article/PIIS1042368012000046/abstract?rss=yes

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Júlio Leonardo B. Pereira
http://lattes.cnpq.br/7687651239699170
http://www.neurocirurgiabr.com

Safety and Efficacy of Stereotactic Radiosurgery and Adjuvant Bevacizumab in Patients With Recurrent Malignant Gliomas

Purpose: Patients with recurrent malignant gliomas treated with stereotactic radiosurgery (SRS) and multiagent systemic therapies were reviewed to determine the effects of patient- and treatment-related factors on survival and toxicity.Methods and Materials: A retrospective analysis was performed on patients with recurrent malignant gliomas treated with salvage SRS from September 2002 to March 2010. All patients had experienced progression after treatment with temozolomide and radiotherapy. Salvage SRS was typically administered only after multiple postchemoradiation salvage systemic therapies had failed.Results: 63 patients were treated with SRS for recurrent high-grade glioma; 49 patients had World Health Organization (WHO) Grade 4 disease. Median follow-up was 31 months from primary diagnosis and 7 months from SRS. Median overall survival from primary diagnosis was 41 months for all patients. Median progression-free survival (PFS) and overall survival from SRS (OS-SRS) were 6 and 10 months for all patients, respectively. The 1-year OS-SRS for patients with Grade 4 glioma who received adjuvant (concurrent with or after SRS) bevacizumab was 50% vs. 22% for patients not receiving adjuvant bevacizumab (p = 0.005). Median PFS for patients with a WHO Grade 4 glioma who received adjuvant bevacizumab was 5.2 months vs. 2.1 months for patients who did not receive adjuvant bevacizumab (p = 0.014). Karnofsky performance status (KPS) and age were not significantly different between treatment groups. Treatment-related Grade 3/4 toxicity for patients receiving and not receiving adjuvant BVZ was 10% and 14%, respectively (p = 0.58).On multivariate analysis, the relative risk of death and progression with adjuvant bevacizumab was 0.37 (confidence interval [CI] 0.17–0.82) and 0.45 (CI 0.21–0.97). KPS >70 and age <50 years were significantly associated with improved survival.Conclusions: The combination of salvage radiosurgery and bevacizumab to treat recurrent malignant gliomas is well tolerated and seems to be associated with improved outcomes. Prospective multiinstitutional studies are required to determine efficacy and long-term toxicity with this approach.