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For: Dirven CM, Mooij JJ, Molenaar WM. Cerebellar pilocytic astrocytoma: a treatment protocol based upon analysis of 73 cases and a review of the literature. Childs Nerv Syst 1997;13:17-23. [PMID: 9083697 DOI: 10.1007/s003810050033] [Citation(s) in RCA: 92] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]

For:	Dirven CM, Mooij JJ, Molenaar WM. Cerebellar pilocytic astrocytoma: a treatment protocol based upon analysis of 73 cases and a review of the literature. Childs Nerv Syst 1997;13:17-23. [PMID: 9083697 DOI: 10.1007/s003810050033] [Citation(s) in RCA: 92] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]

Number

Cited by Other Article(s)

Rufus P, Chatterjee S. Second-look surgery in postoperative pediatric low-grade glioma. Childs Nerv Syst 2024;40:3135-3142. [PMID: 38970692 DOI: 10.1007/s00381-024-06516-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Accepted: 06/20/2024] [Indexed: 07/08/2024]

Nahar Metu CL, Sutihar SK, Sohel M, Zohora F, Hasan A, Miah MT, Rani Kar T, Hossain MA, Rahman MH. Unraveling the signaling mechanism behind astrocytoma and possible therapeutics strategies: A comprehensive review. Cancer Rep (Hoboken) 2023;6:e1889. [PMID: 37675821 PMCID: PMC10598261 DOI: 10.1002/cnr2.1889] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2023] [Revised: 07/09/2023] [Accepted: 07/28/2023] [Indexed: 09/08/2023] Open

Abstract

BACKGROUND

A form of cancer called astrocytoma can develop in the brain or spinal cord and sometimes causes death. A detailed overview of the precise signaling cascade underlying astrocytoma formation has not yet been revealed, although various factors have been investigated. Therefore, our objective was to unravel and summarize our current understanding of molecular genetics and associated signaling pathways with some possible therapeutic strategies for astrocytoma.

RECENT FINDINGS

In general, four different forms of astrocytoma have been identified in individuals, including circumscribed, diffuse, anaplastic, and multiforme glioblastoma, according to a recent literature review. All types of astrocytoma have a direct connection with some oncogenic signaling cascade. Common signaling is MAPK cascade, including Ras-Raf-ERK, up-regulated with activating EGFR/AKT/PTEN/mTOR and PDGFR. Recent breakthrough studies found that BRAF mutations, including KIAA1549: BRAF and BRAF V600E are responsible for astrocytoma progression. Additionally, cancer progression is influenced by mutations in some tumor suppressor genes, such as the Tp53/ATRX and MGMT mutant. As synthetic medications must cross the blood-brain barrier (BBB), modulating signal systems such as miRNA is the primary option for treating patients with astrocytoma. However, available surgery, radiation therapy, and experimental therapies such as adjuvant therapy, anti-angiogenic therapy, and EGFR-targeting antibody drug are the usual treatment for most types of astrocytoma. Similar to conventional anticancer medications, some phytochemicals slow tumor growth by simultaneously controlling several cellular proteins, including those involved in cell cycle regulation, apoptosis, metastatic spread, tyrosine kinase, growth factor receptor, and antioxidant-related proteins.

CONCLUSION

In conclusion, cellular and molecular signaling is directly associated with the development of astrocytoma, and a combination of conventional and alternative therapies can improve the malignancy of cancer patients.

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Willman M, Willman J, Figg J, Dioso E, Sriram S, Olowofela B, Chacko K, Hernandez J, Lucke-Wold B. Update for astrocytomas: medical and surgical management considerations. EXPLORATION OF NEUROSCIENCE 2023;2:1-26. [PMID: 36935776 PMCID: PMC10019464 DOI: 10.37349/en.2023.00009] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 12/10/2022] [Indexed: 02/25/2023]

Abstract

Astrocytomas include a wide range of tumors with unique mutations and varying grades of malignancy. These tumors all originate from the astrocyte, a star-shaped glial cell that plays a major role in supporting functions of the central nervous system (CNS), including blood-brain barrier (BBB) development and maintenance, water and ion regulation, influencing neuronal synaptogenesis, and stimulating the immunological response. In terms of epidemiology, glioblastoma (GB), the most common and malignant astrocytoma, generally occur with higher rates in Australia, Western Europe, and Canada, with the lowest rates in Southeast Asia. Additionally, significantly higher rates of GB are observed in males and non-Hispanic whites. It has been suggested that higher levels of testosterone observed in biological males may account for the increased rates of GB. Hereditary syndromes such as Cowden, Lynch, Turcot, Li-Fraumeni, and neurofibromatosis type 1 have been linked to increased rates of astrocytoma development. While there are a number of specific gene mutations that may influence malignancy or be targeted in astrocytoma treatment, O 6-methylguanine-DNA methyltransferase (MGMT) gene function is an important predictor of astrocytoma response to chemotherapeutic agent temozolomide (TMZ). TMZ for primary and bevacizumab in the setting of recurrent tumor formation are two of the main chemotherapeutic agents currently approved in the treatment of astrocytomas. While stereotactic radiosurgery (SRS) has debatable implications for increased survival in comparison to whole-brain radiotherapy (WBRT), SRS demonstrates increased precision with reduced radiation toxicity. When considering surgical resection of astrocytoma, the extent of resection (EoR) is taken into consideration. Subtotal resection (STR) spares the margins of the T1 enhanced magnetic resonance imaging (MRI) region, gross total resection (GTR) includes the margins, and supramaximal resection (SMR) extends beyond the margin of the T1 and into the T2 region. Surgical resection, radiation, and chemotherapy are integral components of astrocytoma treatment.

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Sletvold TP, Boland S, Schipmann S, Mahesparan R. Quality indicators for evaluating the 30-day postoperative outcome in pediatric brain tumor surgery: a 10-year single-center study and systematic review of the literature. J Neurosurg Pediatr 2023;31:109-123. [PMID: 36401544 DOI: 10.3171/2022.10.peds22308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Accepted: 10/12/2022] [Indexed: 11/26/2022]

Abstract

OBJECTIVE

Surgery is the cornerstone in the management of pediatric brain tumors. To provide safe and effective health services, quantifying and evaluating quality of care are important. To do this, there is a need for universal measures in the form of indicators reflecting quality of the delivered care. The objective of this study was to analyze currently applied quality indicators in pediatric brain tumor surgery and identify factors associated with poor outcome at a tertiary neurosurgical referral center in western Norway.

METHODS

All patients younger than 18 years of age who underwent surgery for an intracranial tumor at the Department of Neurosurgery at Haukeland University Hospital in Bergen, Norway, between 2009 and 2020 were included. The primary outcomes of interest were classic quality indicators: 30-day readmission, 30-day reoperation, 30-day mortality, 30-day nosocomial infection, and 30-day surgical site infection (SSI) rates; and length of stay. The secondary aim was the identification of risk factors related to unfavorable outcome. The authors also conducted a systematic literature review. Articles concerning pediatric brain tumor surgery reporting at least two quality indicators were of interest.

RESULTS

The authors included 82 patients aged 0-17 years. The 30-day outcomes for unplanned reoperation, unplanned remission, mortality, nosocomial infection, and SSI were 9.8%, 14.6%, 0%, 6.1%, and 3.7%, respectively. Unplanned reoperation was associated with eloquent localization (p = 0.009), primary emergency surgery (p = 0.003), and CSF diversion procedures (p = 0.002). Greater tumor volume was associated with unplanned readmission (p = 0.008), nosocomial infection (p = 0.004), and CSF leakage (p = 0.005). In the systematic review, after full-text screening, 16 articles were included and provided outcome data for 1856 procedures. Overall, the 30-day mortality rate was low, varying from 0% to 9.3%. The 30-day reoperation rate varied from 1.5% to 12%. The SSI rate ranged between 0% and 3.9%, and 0% to 17.4% of patients developed CSF leakage. Four studies reported infratentorial tumor location as a risk factor for postoperative CSF leakage.

CONCLUSIONS

The 30-day outcomes in the authors' department were comparable to published outcomes. The most relevant factors related to unfavorable outcomes are tumor volume and location, both of which are not modifiable by the surgeon. This highlights the importance of risk adjustment. This evaluation of quality indicators reveals concerns related to the unclear and nonstandardized definitions of outcomes. Standardized outcome definitions and documentation in a large and multicentric database are needed in the future for further evaluation of quality indicators.

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Santos AN, Dieckmann C, Rauschenbach L, Oppong MD, Dinger TF, Deuschl C, Tippelt S, Fleischhack G, Schmidt B, Pierscianek D, Jabbarli R, Wrede KH, Müller O, Sure U, Dammann P. Long-term outcome after management of pilocytic astrocytoma in the posterior fossa in a pediatric population. IBRO Neurosci Rep 2022;13:388-392. [PMID: 36340442 PMCID: PMC9630615 DOI: 10.1016/j.ibneur.2022.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Revised: 10/01/2022] [Accepted: 10/04/2022] [Indexed: 11/06/2022] Open

Abstract

Background and purpose

To assess the impact of posterior fossa pilocytic astrocytoma (PA) removal in pediatric patients, with special focus on postoperative neurological outcome after repeated surgery for tumor remnants.

Methods

Our institutional database was screened for patients with PA treated between 2000 and 2019. Patients ≤ 18 years of age with complete clinical records, preoperative contrast enhanced magnetic resonance imaging (MRI) and postoperative follow-up time of ≥ 6 months were suitable for study inclusion. Functional outcome was quantified with the modified Ranking Scale (mRS) score and assessed at admission, at discharge and at every follow-up investigation. Predictors of hydrocephalus, cranial nerve deficits and tumor recurrence were evaluated.

Results

A total of 57 pediatric patients with a mean age of 7.7 ± 4.8 years were included in the analysis. 27 (47.3%) children suffered from hydrocephalus at diagnosis, out of which 19 (33.3%) required a subsequent VP-Shunt. 22 (39.3%) patients had a partial resection, of which 9 (40.9%) went through second-look surgery. 2 patients with initially radiological confirmation of complete resection, had a tumor recurrence at FU and needed second-look surgery. Among the children requiring second-look surgery, 7 (63.6%) had a complete resection. Favorable outcome (mRS≤2) after initial and second-look surgery was observed in 52 patients (91.2%). Univariate analysis identified tumor location in the floor of the 4th ventricle (p = 0.030), and repeated surgery for tumor remnant removal (p = 0.043) as predictors for post-operative cranial nerve deficits. Multivariate analysis confirmed this independent association. The incidence of tumor recurrence occurred more often in patients with previous partial resection (p = 0.009) as well as in lesions located in the cerebellar peduncles (p = 0.043). Partial resection remained an independent predictor after multivariate logistic regression analysis (p = 0.045).

Conclusions

Incomplete resection of posterior fossa PA is a risk factor for tumor recurrence and repeated surgery to remove tumor remnants increases the risk of new postoperative deficits. Thus, the risk of iatrogenic deterioration due to second look surgery should be implemented in the primary pre- and intraoperative decision-making.

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Sager O, Dincoglan F, Demiral S, Uysal B, Gamsiz H, Gumustepe E, Ozcan F, Colak O, Gursoy AT, Dursun CU, Tugcu AO, Dogru GD, Arslan R, Elcim Y, Gundem E, Dirican B, Beyzadeoglu M. Concise review of radiosurgery for contemporary management of pilocytic astrocytomas in children and adults. World J Exp Med 2022;12:36-43. [PMID: 35765513 PMCID: PMC9168785 DOI: 10.5493/wjem.v12.i3.36] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 03/09/2022] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open

Affiliation(s)

Omer Sager Department of Radiation Oncology, Gulhane Medical Faculty, University of Health Sciences, Ankara 0090, Turkey
Ferrat Dincoglan Department of Radiation Oncology, Gulhane Medical Faculty, University of Health Sciences, Ankara 0090, Turkey
Selcuk Demiral Department of Radiation Oncology, Gulhane Medical Faculty, University of Health Sciences, Ankara 0090, Turkey
Bora Uysal Department of Radiation Oncology, Gulhane Medical Faculty, University of Health Sciences, Ankara 0090, Turkey
Hakan Gamsiz Department of Radiation Oncology, Gulhane Medical Faculty, University of Health Sciences, Ankara 0090, Turkey
Esra Gumustepe Department of Radiation Oncology, Gulhane Medical Faculty, University of Health Sciences, Ankara 0090, Turkey
Fatih Ozcan Department of Radiation Oncology, Gulhane Medical Faculty, University of Health Sciences, Ankara 0090, Turkey
Onurhan Colak Department of Radiation Oncology, Gulhane Medical Faculty, University of Health Sciences, Ankara 0090, Turkey
Ahmet Tarik Gursoy Department of Radiation Oncology, Gulhane Medical Faculty, University of Health Sciences, Ankara 0090, Turkey
Cemal Ugur Dursun Department of Radiation Oncology, Gulhane Medical Faculty, University of Health Sciences, Ankara 0090, Turkey
Ahmet Oguz Tugcu Department of Radiation Oncology, Gulhane Medical Faculty, University of Health Sciences, Ankara 0090, Turkey
Galip Dogukan Dogru Department of Radiation Oncology, Gulhane Medical Faculty, University of Health Sciences, Ankara 0090, Turkey
Rukiyye Arslan Department of Radiation Oncology, Gulhane Medical Faculty, University of Health Sciences, Ankara 0090, Turkey
Yelda Elcim Department of Radiation Oncology, Gulhane Medical Faculty, University of Health Sciences, Ankara 0090, Turkey
Esin Gundem Department of Radiation Oncology, Gulhane Medical Faculty, University of Health Sciences, Ankara 0090, Turkey
Bahar Dirican Department of Radiation Oncology, Gulhane Medical Faculty, University of Health Sciences, Ankara 0090, Turkey
Murat Beyzadeoglu Department of Radiation Oncology, Gulhane Medical Faculty, University of Health Sciences, Ankara 0090, Turkey

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Elwatidy SM, Ahmed J, Bawazir MH, Alnasser A, Abanumy J, Al Shammari A, Alduhaish A, Malik SH, Elwatidy HS. Outcome of Childhood Cerebellar Pilocytic Astrocytoma: A Series With 20 Years of Follow Up. Cureus 2022;14:e22258. [PMID: 35350495 PMCID: PMC8933261 DOI: 10.7759/cureus.22258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/14/2022] [Indexed: 11/29/2022] Open

Abstract

Background: Cerebellar pilocytic astrocytoma (PCA) is one of the few CNS tumors that can be cured with gross-total removal (GTR). In this series, we had 39 patients diagnosed with cerebellar PCA, 27 patients (70%) had GTR, and mean follow-up period was 62 months with no tumor recurrence.

Objective: To assess the long-term outcome of childhood cerebellar PCA treated at our institute during the period 2000-2020 and to highlight our surgical protocol.

Methodology: Retrospective review of all patients under 18 years of age who were diagnosed with cerebellar PCA and had surgical excision between 2000 and 2020 at the Medical City of King Saud University.

Results: The study included 39 patients: 17 males and 22 females, the mean age was 8.4 years. Radiologically, the tumor was solid in eight patients, cystic in 15 patients, and mixed components were found in 16 patients. The lesion was located in the right cerebellar hemisphere in 12 patients, left cerebellar hemisphere in five patients, and midline 22 patients. The tumor size ranged from 2 to 7 cm in its greatest diameter, it was <5 cm in 13 patients and >5 cm in 26 patients. Thirty-one patients had preoperative hydrocephalus. GTR of the tumor was achieved in 27 patients and subtotal resection (STR) was done in 12 patients, 18 patients required permanent ventriculoperitoneal (V-P) shunt, and five patients had postoperative radiotherapy. Postoperative complications included infection in two patients, cerebellar mutism in two patients, and significant neurologic disability in four patients. The duration of follow-up ranged from 0 to 240 months (mean follow-up period: 62.0 months). The outcome at 10 years was good in 30 patients, fair in four patients, poor in four patients, and one patient died. Recurrence was documented in nine patients, seven of them had GTR and two had STR.

Conclusion: GTR, if achievable, is curative for childhood cerebellar PCA. Many posterior fossa surgical complications could be avoided with watertight dural closure. Although new dural substitutes are available we prefer using autologous grafts (pericranium). It is easy to harvest pericranial graft from the external ventricular drain (EVD) site. The insertion of EVD synchronously with GTR of the tumor and gradual weaning of EVD could avoid the insertion of V-P shunt.

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Khalafallah AM, Jimenez AE, Shah PP, Brem H, Mukherjee D. Effect of radiation therapy on overall survival following subtotal resection of adult pilocytic astrocytoma. J Clin Neurosci 2020;81:340-345. [PMID: 33222942 DOI: 10.1016/j.jocn.2020.10.020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Revised: 09/30/2020] [Accepted: 10/04/2020] [Indexed: 12/26/2022]

Park JH, Jung N, Kang SJ, Kim HS, Kim E, Lee HJ, Jung HR, Choe M, Shim YJ. Survival and Prognosis of Patients with Pilocytic Astrocytoma: A Single-Center Study. Brain Tumor Res Treat 2019;7:92-97. [PMID: 31686439 PMCID: PMC6829088 DOI: 10.14791/btrt.2019.7.e36] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Revised: 06/24/2019] [Accepted: 07/12/2019] [Indexed: 11/20/2022] Open

Maharaj A, Manoranjan B, Verhey LH, Fleming AJ, Farrokhyar F, Almenawer S, Singh SK, Yarascavitch B. Predictive measures and outcomes of extent of resection in juvenile pilocytic astrocytoma. J Clin Neurosci 2019;70:79-84. [PMID: 31466905 DOI: 10.1016/j.jocn.2019.08.066] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Accepted: 08/07/2019] [Indexed: 11/19/2022]

Tabash MA. Characteristics, survival and incidence rates and trends of pilocytic astrocytoma in children in the United States; SEER-based analysis. J Neurol Sci 2019;400:148-152. [PMID: 30953904 DOI: 10.1016/j.jns.2019.03.028] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2018] [Revised: 03/05/2019] [Accepted: 03/28/2019] [Indexed: 10/27/2022]

Chua J, Nafziger E, Leung D. Evidence-Based Practice: Temozolomide Beyond Glioblastoma. Curr Oncol Rep 2019;21:30. [PMID: 30835007 DOI: 10.1007/s11912-019-0783-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]

Villanueva KG, Rea ND, Krieger MD. Novel Surgical and Radiologic Risk Factors for Progression or Recurrence of Pediatric Pilocytic Astrocytoma. Pediatr Neurosurg 2019;54:375-385. [PMID: 31593969 DOI: 10.1159/000503110] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Accepted: 09/03/2019] [Indexed: 11/19/2022]

Vogt VL, Witt JA, Delev D, Grote A, von Lehe M, Becker AJ, Schramm J, Elger CE, Helmstaedter C. Cognitive features and surgical outcome of patients with long-term epilepsy-associated tumors (LEATs) within the temporal lobe. Epilepsy Behav 2018;88:25-32. [PMID: 30212725 DOI: 10.1016/j.yebeh.2018.08.028] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Revised: 08/21/2018] [Accepted: 08/22/2018] [Indexed: 11/18/2022]

Abstract

OBJECTIVE

The objective of the study was to evaluate cognitive and epilepsy-related features in 166 surgically treated patients with epilepsy with long-term epilepsy-associated tumors (LEATs) located in the temporal lobe.

METHOD

Pre- and postsurgical cognitive as well as the one-year seizure outcome of adult patients with histopathologically confirmed LEATs (28 grade-I dysembryoplastic neuroepithelial tumors (DNET), 95 grade-I gangliogliomas (GG), 24 grade-I pilocytic astrocytomas (PA), 9 grade-II pleomorphic xanthoastrocytoma (PXA), 10 grade-II diffuse astrocytoma (DA)) who underwent epilepsy surgery in Bonn/Germany between 1988 and 2012 were evaluated.

RESULTS

At baseline, tumor groups differed in regard to age at epilepsy onset and location within the temporal lobe. Postoperative seizure freedom was achieved most frequently (>77.8%) in DNET, GG, and DA, less often in PXA (62.5%) and the least in PA (56.5%). Preoperative memory was impaired in 67.1% of all patients, executive functions in 44.7%, and language in 45.5%. Patients with PA displayed the poorest cognitive performance. Individual significant memory decline that was observed in 27.1% of all patients was predicted by left-sided surgery, a mesial pathology, and extended hippocampal resection. Executive functions depended on antiepileptic drug (AED) load and remained stable (72.0%) or even improved (21.6%) after surgery. Language functions were unchanged in 89.5% of patients.

CONCLUSION

Patients with LEATs in the temporal lobe frequently show cognitive impairments. Predictors for pre- and postoperative cognition mostly correspond to what is known for temporal lobe epilepsy and resections in general. However, different tumor types appear to be associated with different cognitive and seizure outcomes with astrocytoma as the least benefitted group.

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Zhang J, Al-Nahari F, Wang ZF, Lin FH, Zhao YY, Xiao SY, Liu JM, Ke C, Chen ZH, Jiang Y, Yang M, Sai K, Wang J, Mou YG. Application of fluorescein sodium in the resection of vermis pilocytic astrocytomas. World J Surg Oncol 2017;15:46. [PMID: 28196488 PMCID: PMC5310027 DOI: 10.1186/s12957-017-1108-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2016] [Accepted: 01/25/2017] [Indexed: 11/21/2022] Open

Affiliation(s)

Ji Zhang Department of Neurosurgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation, Center for Cancer Medicine, 651 Dong Feng East Road, Guangzhou, 510060, China
Fuad Al-Nahari Department of Neurosurgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation, Center for Cancer Medicine, 651 Dong Feng East Road, Guangzhou, 510060, China
Zi-Feng Wang Department of Neurosurgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation, Center for Cancer Medicine, 651 Dong Feng East Road, Guangzhou, 510060, China
Fu-Hua Lin Department of Neurosurgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation, Center for Cancer Medicine, 651 Dong Feng East Road, Guangzhou, 510060, China
Yi-Yin Zhao Department of Neurosurgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation, Center for Cancer Medicine, 651 Dong Feng East Road, Guangzhou, 510060, China
Shi-Yin Xiao Department of Neurosurgery, The second affiliated hospital of Guangzhou medical university, Guangzhou, China
Jian-Min Liu Department of Neurosurgery, Department of Neurosurgery, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, China
Chao Ke Department of Neurosurgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation, Center for Cancer Medicine, 651 Dong Feng East Road, Guangzhou, 510060, China
Zheng-He Chen Department of Neurosurgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation, Center for Cancer Medicine, 651 Dong Feng East Road, Guangzhou, 510060, China
Yu Jiang Department of Anesthesiology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, 651 Dong Feng East Road, Guangzhou, 510060, China
Men Yang Department of Thoracic surgery, state Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, 651 Dong Feng East Road, Guangzhou, 510060, China
Ke Sai Department of Neurosurgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation, Center for Cancer Medicine, 651 Dong Feng East Road, Guangzhou, 510060, China
Jian Wang Department of Neurosurgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation, Center for Cancer Medicine, 651 Dong Feng East Road, Guangzhou, 510060, China
Yong-Gao Mou Department of Neurosurgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation, Center for Cancer Medicine, 651 Dong Feng East Road, Guangzhou, 510060, China.

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Giordano M, Arraez C, Samii A, Samii M, Di Rocco C. Neurosurgical tools to extend tumor resection in pediatric hemispheric low-grade gliomas: iMRI. Childs Nerv Syst 2016;32:1915-22. [PMID: 27659833 DOI: 10.1007/s00381-016-3177-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2016] [Accepted: 07/05/2016] [Indexed: 10/21/2022]

Yde CW, Sehested A, Mateu-Regué À, Østrup O, Scheie D, Nysom K, Nielsen FC, Rossing M. A new NFIA:RAF1 fusion activating the MAPK pathway in pilocytic astrocytoma. Cancer Genet 2016;209:440-444. [PMID: 27810072 DOI: 10.1016/j.cancergen.2016.09.002] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2016] [Revised: 08/24/2016] [Accepted: 09/08/2016] [Indexed: 12/21/2022]

Buder T, Deutsch A, Klink B, Voss-Böhme A. Model-Based Evaluation of Spontaneous Tumor Regression in Pilocytic Astrocytoma. PLoS Comput Biol 2015;11:e1004662. [PMID: 26658166 PMCID: PMC4675550 DOI: 10.1371/journal.pcbi.1004662] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Accepted: 11/17/2015] [Indexed: 11/19/2022] Open

Ryu HH, Jung TY, Lee GJ, Lee KH, Jung SH, Jung S, Baek HJ. Differences in the clinical courses of pediatric and adult pilocytic astrocytomas with progression: a single-institution study. Childs Nerv Syst 2015;31:2063-9. [PMID: 26293677 DOI: 10.1007/s00381-015-2887-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Accepted: 08/11/2015] [Indexed: 02/03/2023]

Abstract

PURPOSE

Pilocytic astrocytoma (PA) is a World Health Organization grade I neoplasm that generally follows a benign course. However, in some patients, PA exhibits an aggressive clinical course. Here, we examined the clinical course of pediatric and adult PAs with progression at a single institution.

METHODS

Between 1995 and 2013, 39 patients with PA were treated. Nineteen were pediatric patients (mean age, 12 years; range, 1-17 years) with a male-to-female patient ratio of 10:9, while 20 were adults (mean age, 36.4 years; range, 19-65 years) with a male-to-female ratio of 9:11. We analyzed and compared tumor location, extent of tumor resection, adjuvant treatment, and clinical course in all patients.

RESULTS

In the 19 pediatric patients, tumors were located in the cerebellar vermis, cerebellar hemisphere, optic pathways plus hypothalamus, hypothalamus, brainstem, and the temporal lobe in 6 (31.6%), 5 (26.3%), 3 (15.8%), 2 (10.5%), and 2 (10.5%) patients and 1 (5.3%) patient, respectively. The mass was totally, subtotally, or partially resected in 11 (57.9%), 2 (10.5%), and 4 (21.1%) patients, respectively; biopsies were performed in 2 (10.5%) patients. Immediate postoperative adjuvant treatment was carried out in 6 patients. Tumor progression was detected in 3 patients at 3.0, 4.6, and 5.2 years after treatment, respectively, without significant symptoms. In the 20 adult patients, tumors were located in the cerebellar hemisphere, cerebellar vermis, hypothalamus, brainstem, cerebral hemisphere, and lateral ventricle in 5 (25%), 4 (20%), 3 (15%), 3 (15%), 3 (15%), and 2 (10%) patients, respectively. The mass was totally, subtotally, or partially resected in 11 (55%) and 6 (30%) patients and 1 (5%) patient, respectively; biopsies were performed in 2 patients. Immediate adjuvant treatment was carried out in 2 patients. Progression was detected in 3 patients at 0.3, 0.9, and 2.5 years after treatment, respectively, with progressive neurologic symptoms. There was one case of disease-related mortality during follow-up among the adult patients.

CONCLUSION

Most of the PA cases evaluated in this study were benign. However, tumor progression in adult PAs followed a more aggressive clinical course than those in pediatric PAs.

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Penman CL, Faulkner C, Lowis SP, Kurian KM. Current Understanding of BRAF Alterations in Diagnosis, Prognosis, and Therapeutic Targeting in Pediatric Low-Grade Gliomas. Front Oncol 2015;5:54. [PMID: 25785246 PMCID: PMC4347423 DOI: 10.3389/fonc.2015.00054] [Citation(s) in RCA: 75] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Accepted: 02/16/2015] [Indexed: 12/19/2022] Open

Postoperative Surveillance Magnetic Resonance Imaging for Cerebellar Astrocytoma. Can J Neurol Sci 2014;36:707-12. [DOI: 10.1017/s0317167100008313] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]

Ait Khelifa-Gallois N, Laroussinie F, Puget S, Sainte- Rose C, Dellatolas G. Long-term functional outcome of patients with cerebellar pilocytic astrocytoma surgically treated in childhood. Brain Inj 2014;29:366-73. [DOI: 10.3109/02699052.2014.975281] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]

Vincent AJ, Singhal M, Johnstone PAS, Buchsbaum JC. Age-Related Changes in Frontal Lobe Anatomy Require Alternatives to Opposed Lateral Fields. Int J Part Ther 2014. [DOI: 10.14338/ijpt.13.00004.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open

Mandiwanza T, Kaliaperumal C, Khalil A, Sattar M, Crimmins D, Caird J. Suprasellar pilocytic astrocytoma: one national centre's experience. Childs Nerv Syst 2014;30:1243-8. [PMID: 24566674 DOI: 10.1007/s00381-014-2374-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2013] [Accepted: 01/28/2014] [Indexed: 12/01/2022]

Reis GF, Bloomer MM, Perry A, Phillips JJ, Grenert JP, Karnezis AN, Tihan T. Pilocytic astrocytomas of the optic nerve and their relation to pilocytic astrocytomas elsewhere in the central nervous system. Mod Pathol 2013;26:1279-87. [PMID: 23702730 DOI: 10.1038/modpathol.2013.79] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2012] [Revised: 02/24/2013] [Accepted: 02/27/2013] [Indexed: 12/13/2022]

Strauss I, Jonas-Kimchi T, Bokstein F, Blumenthal D, Roth J, Sitt R, Wilson J, Ram Z. Gliomas of the posterior fossa in adults. J Neurooncol 2013;115:401-9. [PMID: 23979683 DOI: 10.1007/s11060-013-1231-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2013] [Accepted: 08/18/2013] [Indexed: 11/25/2022]

Steinbok P, Mangat JS, Kerr JM, Sargent M, Suryaningtyas W, Singhal A, Cochrane D. Neurological morbidity of surgical resection of pediatric cerebellar astrocytomas. Childs Nerv Syst 2013;29:1269-75. [PMID: 23715810 DOI: 10.1007/s00381-013-2171-z] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2013] [Accepted: 05/16/2013] [Indexed: 11/30/2022]

Differential expression and methylation of brain developmental genes define location-specific subsets of pilocytic astrocytoma. Acta Neuropathol 2013;126:291-301. [PMID: 23660940 DOI: 10.1007/s00401-013-1124-7] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2013] [Revised: 04/30/2013] [Accepted: 05/01/2013] [Indexed: 10/26/2022]

Loh JK, Lieu AS, Chai CY, Hwang SL, Kwan AL, Wang CJ, Howng SL. Arrested growth and spontaneous tumor regression of partially resected low-grade cerebellar astrocytomas in children. Childs Nerv Syst 2013;29:2051-5. [PMID: 23632690 PMCID: PMC3825417 DOI: 10.1007/s00381-013-2113-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2013] [Accepted: 04/11/2013] [Indexed: 11/30/2022]

Outcome of Patients With Pilocytic Astrocytoma and Leptomeningeal Dissemination. Int J Radiat Oncol Biol Phys 2012;84:350-4. [DOI: 10.1016/j.ijrobp.2011.12.044] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2011] [Accepted: 12/08/2011] [Indexed: 11/23/2022]

Gnekow AK, Falkenstein F, von Hornstein S, Zwiener I, Berkefeld S, Bison B, Warmuth-Metz M, Driever PH, Soerensen N, Kortmann RD, Pietsch T, Faldum A. Long-term follow-up of the multicenter, multidisciplinary treatment study HIT-LGG-1996 for low-grade glioma in children and adolescents of the German Speaking Society of Pediatric Oncology and Hematology. Neuro Oncol 2012;14:1265-84. [PMID: 22942186 DOI: 10.1093/neuonc/nos202] [Citation(s) in RCA: 180] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open

Abstract

The Hirntumorstudien (HIT)-LGG-1996 protocol offered a comprehensive treatment strategy for pediatric patients with low-grade glioma (LGG), ie, observation, surgery, adjuvant radiotherapy, and chemotherapy to defer the start of irradiation in young children. In this current study, we sought to determine clinical factors for progression and survival. Between October 1, 1996 and March 31, 2004, 1031 patients were prospectively recruited into an observation arm (n = 668) and a nonsurgical arm stratifying 12 months of vincristine-carboplatin chemotherapy (n = 216) and conventional radiotherapy/brachytherapy (n = 147) in an age-dependent manner. Median patient age was 6.9 years; 28 patients had diencephalic syndrome, 44 had dissemination, and 108 had neurofibromatosis type 1(NF-1). Main tumor location was the supratentorial midline (40.4%), and the main histology was pilocytic astrocytoma (67.9%). Following a median observation of 9.3 years, 10-year overall survival (OS) was 0.94 and 10-year event-free survival (EFS) was 0.47. Ten-year progression-free survival was 0.62 following radiotherapy and 0.44 following chemotherapy. Sixty-one of 216 chemotherapy patients received radiotherapy 0.3-8.7 years after initial diagnosis. By multivariate analysis, diencephalic syndrome and incomplete resection were found to be unfavorable factors for OS and EFS, age ≥11 years for OS, and supratentorial midline location for EFS. Dissemination, age <1 year, and nonpilocytic histology were unfavorable factors for progression following radiotherapy (138 patients); and diencephalic syndrome, dissemination, and age ≥11 years were unfavorable factors following chemotherapy (210 patients). NF-1 patients and boys experienced prolonged tumor stabilization with chemotherapy. A nationwide multimodal treatment strategy is feasible for pediatric LGG. Extended follow-up yielded results comparable to single-institution series for the treatment groups. Three-quarters of surviving chemotherapy patients have not yet received radiation therapy. Infants with or without diencephalic syndrome and dissemination bear the highest risk for death and progression following diagnosis or treatment.

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Biologic tumor behavior in pilocytic astrocytomas. Childs Nerv Syst 2012;28:375-89. [PMID: 22246337 DOI: 10.1007/s00381-011-1676-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2011] [Accepted: 12/29/2011] [Indexed: 10/14/2022]

Johnson DR, Brown PD, Galanis E, Hammack JE. Pilocytic astrocytoma survival in adults: analysis of the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. J Neurooncol 2012;108:187-93. [PMID: 22367412 DOI: 10.1007/s11060-012-0829-0] [Citation(s) in RCA: 97] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2011] [Accepted: 02/15/2012] [Indexed: 10/28/2022]

Lin A, Rodriguez FJ, Karajannis MA, Williams SC, Legault G, Zagzag D, Burger PC, Allen JC, Eberhart CG, Bar EE. BRAF alterations in primary glial and glioneuronal neoplasms of the central nervous system with identification of 2 novel KIAA1549:BRAF fusion variants. J Neuropathol Exp Neurol 2012;71:66-72. [PMID: 22157620 PMCID: PMC4629834 DOI: 10.1097/nen.0b013e31823f2cb0] [Citation(s) in RCA: 120] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open

Wisoff JH, Sanford RA, Heier LA, Sposto R, Burger PC, Yates AJ, Holmes EJ, Kun LE. Primary neurosurgery for pediatric low-grade gliomas: a prospective multi-institutional study from the Children's Oncology Group. Neurosurgery 2011;68:1548-54; discussion 1554-5. [PMID: 21368693 DOI: 10.1227/neu.0b013e318214a66e] [Citation(s) in RCA: 168] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open

Sikkema AH, de Bont ESJM, Molema G, Dimberg A, Zwiers PJ, Diks SH, Hoving EW, Kamps WA, Peppelenbosch MP, den Dunnen WFA. Vascular endothelial growth factor receptor 2 (VEGFR-2) signalling activity in paediatric pilocytic astrocytoma is restricted to tumour endothelial cells. Neuropathol Appl Neurobiol 2011;37:538-48. [PMID: 21208252 DOI: 10.1111/j.1365-2990.2011.01160.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]

Hallemeier CL, Pollock BE, Schomberg PJ, Link MJ, Brown PD, Stafford SL. Stereotactic radiosurgery for recurrent or unresectable pilocytic astrocytoma. Int J Radiat Oncol Biol Phys 2011;83:107-12. [PMID: 22019245 DOI: 10.1016/j.ijrobp.2011.05.038] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2011] [Revised: 03/28/2011] [Accepted: 05/08/2011] [Indexed: 12/31/2022]

Ogiwara H, Bowman RM, Tomita T. Long-term Follow-up of Pediatric Benign Cerebellar Astrocytomas. Neurosurgery 2011;70:40-7; discussion 47-8. [DOI: 10.1227/neu.0b013e31822ff0ed] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open

Abstract Abstract BACKGROUND The long-term prognosis of cerebellar astrocytomas needs to be reviewed. OBJECTIVE To elucidate the factors influencing tumor recurrence or progression and to determine how long these patient with cerebellar astrocytomas require surveillance with neuroimaging. METHODS A retrospective review of 101 children surgically treated for a cerebellar astrocytoma and followed up for < 10 years was performed. RESULTS Mean follow-up was 18.4 years. Total resection confirmed by postoperative imaging was performed in 51 patients (50.5%; group A). Twenty-three patients (22.8%) had surgical total resection; however, equivocal residual tumor was found on postoperative imaging (group B). Subtotal resection leaving a portion of brainstem or cerebellar peduncle was performed in 27 patients (26.7; group C). Of these 50 residual tumors, 16 (32%) showed spontaneous regression and 8 (16%) showed arrested growth. Radiographic recurrence or progression was noted in 29 patients (28.7%). Only 3 of 51 patients (5.9%) of group A with total resection had recurrence, whereas 26 of 50 residual tumors (52%; groups B and C) progressed. The only factor affecting recurrence or progression by multivariate analysis was the extent of surgical resection. All tumor recurrence or progression except for 1 (96.6%) occurred within 8 years from the original surgery (range, 2–132 months). CONCLUSIONS Overall prognosis of cerebellar astrocytomas is good; the 10-year survival rate was 100% and recurrence- or progression-free rate was 71.3% in our cohort. Almost half of residual tumors showed spontaneous regression or arrested growth in the long term. Eight to 10 years is considered to be a reasonable follow-up period by neuroimaging. Collapse

Forbes JA, Mobley BC, O’Lynnger TM, Cooper CM, Ghiassi M, Hanif R, Pearson MM. Pediatric cerebellar pilomyxoid-spectrum astrocytomas. J Neurosurg Pediatr 2011;8:90-6. [PMID: 21721894 PMCID: PMC3779306 DOI: 10.3171/2011.4.peds1115] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]

Abstract

OBJECT

Pediatric cerebellar astrocytomas with pilomyxoid features include classic pilomyxoid astrocytomas (PMAs) and intermediate pilomyxoid tumors (IPTs). Since the original description of PMA in 1999, most reports in the literature have described PMAs arising from the hypothalamic/chiasmatic region. To the authors' knowledge, PMAs arising from the posterior fossa have not been discussed in the neurosurgical literature. Intermediate pilomyxoid tumors, or tumors with pathological features of both pilocytic astrocytoma (PA) and PMA, have only recently been described. In this article, the authors present 2 cases that fall within the spectrum of pediatric cerebellar PMA-including a classic PMA and an intermediate pilomyxoid tumor. The authors compare the radiological presentation, surgical results, and postoperative course to findings in a cohort of 15 patients with cerebellar PAs.

METHODS

Between 2003 and 2010, 2 patients with pilomyxoid-spectrum astrocytomas underwent treatment at Vanderbilt Children's Hospital. One was a 22-month-old girl who presented with progressive gait disturbance and falls. The other was a 4-year-old girl who presented with ataxia and generalized weakness. In a retrospective review of pediatric cerebellar neoplasms resected by the senior author during this period, these tumors comprised 4% of cerebellar neoplasms and approximately 10% of cerebellar glial neoplasms.

RESULTS

Both patients were treated with midline suboccipital craniotomy for resection. In both cases, tumor invasion anteriorly into the brainstem prevented gross-total resection. the patient in Case 1 was placed on chemotherapy following pathological diagnosis and later developed definitive evidence of leptomeningeal dissemination (LD) 3 years after the operation. The patient in Case 2 was placed on chemotherapy after exhibiting progressive evidence of local recurrence (findings were negative for LD) 12 months following resection.

CONCLUSIONS

Pediatric patients with cerebellar pilomyxoid-spectrum astrocytomas appear to suffer higher rates of local recurrence and LD than pediatric patients with cerebellar PAs.

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Anagnostopoulos AK, Dimas KS, Papathanassiou C, Braoudaki M, Anastasiadou E, Vougas K, Karamolegou K, Kontos H, Prodromou N, Tzortzatou-Stathopoulou F, Tsangaris GT. Proteomics Studies of Childhood Pilocytic Astrocytoma. J Proteome Res 2011;10:2555-65. [DOI: 10.1021/pr200024m] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]

Affiliation(s)

Athanasios K. Anagnostopoulos Proteomics Research Unit, Center of Basic Research II, Biomedical Research Foundation of the Academy of Athens, Athens, Greece Hematology/Oncology Unit, First Department of Pediatrics, University of Athens, Aghia Sophia Children’s Hospital, Athens, Greece
Konstantinos S. Dimas Pharmacology Division, Center of Basic Research I, Biomedical Research Foundation of the Academy of Athens, Athens, Greece
Chrissa Papathanassiou Hematology/Oncology Unit, First Department of Pediatrics, University of Athens, Aghia Sophia Children’s Hospital, Athens, Greece
Maria Braoudaki Hematology/Oncology Unit, First Department of Pediatrics, University of Athens, Aghia Sophia Children’s Hospital, Athens, Greece University Research Institute for the Study and Treatment of Childhood Genetic and Malignant Diseases, University of Athens, Aghia Sophia Children’s Hospital, Athens, Greece
Ema Anastasiadou Proteomics Research Unit, Center of Basic Research II, Biomedical Research Foundation of the Academy of Athens, Athens, Greece
Konstantinos Vougas Proteomics Research Unit, Center of Basic Research II, Biomedical Research Foundation of the Academy of Athens, Athens, Greece
Kalliopi Karamolegou Hematology/Oncology Unit, First Department of Pediatrics, University of Athens, Aghia Sophia Children’s Hospital, Athens, Greece
Harry Kontos “Genomedica” Molecular Diagnostics Laboratory, Piraeus, Greece
Neofytos Prodromou Department of Neurosurgery, Aghia Sophia Children’s Hospital, Athens, Greece
Fotini Tzortzatou-Stathopoulou University Research Institute for the Study and Treatment of Childhood Genetic and Malignant Diseases, University of Athens, Aghia Sophia Children’s Hospital, Athens, Greece
George Th. Tsangaris Proteomics Research Unit, Center of Basic Research II, Biomedical Research Foundation of the Academy of Athens, Athens, Greece

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Gronych J, Korshunov A, Bageritz J, Milde T, Jugold M, Hambardzumyan D, Remke M, Hartmann C, Witt H, Jones DTW, Witt O, Heiland S, Bendszus M, Holland EC, Pfister S, Lichter P. An activated mutant BRAF kinase domain is sufficient to induce pilocytic astrocytoma in mice. J Clin Invest 2011;121:1344-8. [PMID: 21403401 DOI: 10.1172/jci44656] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2010] [Accepted: 01/19/2011] [Indexed: 11/17/2022] Open

Sie M, de Bont ESJM, Scherpen FJG, Hoving EW, den Dunnen WFA. Tumour vasculature and angiogenic profile of paediatric pilocytic astrocytoma; is it much different from glioblastoma? Neuropathol Appl Neurobiol 2011;36:636-47. [PMID: 20704656 DOI: 10.1111/j.1365-2990.2010.01113.x] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]

Abstract

AIMS

Pilocytic astrocytomas are the most frequent brain tumours in children. Because of their high vascularity, this study aimed to obtain insights into potential angiogenic related therapeutic targets in these tumours by characterization of the vasculature and the angiogenic profile. In this study 59 paediatric pilocytic astrocytomas were compared with 62 adult glioblastomas, as a prototype of tumour angiogenesis.

METHODS

Microvessel density, vessel maturity in terms of basement membrane and pericyte coverage, and turnover of both endothelial and tumour cells, and vascular endothelial growth factor (VEGF) expression were evaluated in tumour tissue, immunohistochemically stained with, respectively, CD34, collagen IV, smooth muscle actin, Ki67/CD34, caspase-3/CD34 and VEGF(-A-D). As an indicator for vessel stability the angiopoietin (ANGPT)-1/ANGPT-2 balance was calculated using Real Time RT-PCR.

RESULTS

Pilocytic astrocytoma and glioblastoma showed similar fractions of vessels covered with basement membrane and pericytes. Overlapping ANGPT-1/ANGPT-2 balance and VEGF-A expression were found. Pilocytic astrocytoma had fewer but wider vessels compared with glioblastoma. Turnover of endothelial and tumour cells were relatively lower in pilocytic astrocytoma. Within pilocytic astrocytoma, higher ANGPT-1/ANGPT-2 balance was correlated with fewer apoptotic endothelial cells. Lower numbers of vessels were correlated with higher VEGF-A expression.

CONCLUSIONS

Despite the fact that pilocytic astrocytoma showed a different vessel architecture compared with glioblastoma, a critical overlap in vessel immaturity/instability and the angiogenic profile was seen between both tumours. These findings suggest encouraging possibilities for targeting angiogenesis (for instance with anti-VEGF) as a therapeutic strategy in pilocytic astrocytoma.

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Rodriguez EF, Scheithauer BW, Giannini C, Rynearson A, Cen L, Hoesley B, Gilmer-Flynn H, Sarkaria JN, Jenkins S, Long J, Rodriguez FJ. PI3K/AKT pathway alterations are associated with clinically aggressive and histologically anaplastic subsets of pilocytic astrocytoma. Acta Neuropathol 2011;121:407-20. [PMID: 21113787 DOI: 10.1007/s00401-010-0784-9] [Citation(s) in RCA: 104] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2010] [Revised: 10/24/2010] [Accepted: 11/16/2010] [Indexed: 12/22/2022]

Abstract

Pilocytic astrocytomas (PA) are well-differentiated gliomas having a favorable prognosis when compared with other diffuse or infiltrative astrocytomas. Molecular genetic abnormalities and activation of signaling pathways associated with clinically aggressive PA and histologically anaplastic PA have not been adequately studied. We performed molecular genetic, gene expression, and immunohistochemical studies using three PA subsets, including conventional PA (n = 43), clinically aggressive/recurrent PA (n = 24), and histologically anaplastic PA (n = 25). A clinical diagnosis of NF1 was present in 28% of anaplastic PA. Molecular cytogenetic studies demonstrated heterozygous PTEN/10q and homozygous p16 deletions in 6/19 (32%) and 3/15 (20%) cases of anaplastic PA, respectively, but in neither of the two other groups. BRAF duplication was identified in 33% of sporadic anaplastic PA and 63% of cerebellar examples. BRAF (V600E) mutation was absent in four (of 4) sporadic cases lacking duplication. IDH1(R132H) immunohistochemistry was negative in 16 (of 16) cases. Neither PDGFRA nor EGFR amplifications were present. pERK staining levels were similar among the three PA subsets, but a stepwise increase in cytoplasmic pAKT and to a lesser extent pS6 immunoreactivity was noted by immunohistochemistry in aggressive PA groups. This was particularly true in histologically anaplastic PA when compared with conventional PA (p < 0.001 and p = 0.005, respectively). In addition, PTEN expression at the mRNA level was decreased in histologically anaplastic PA when compared to the other groups (p = 0.05). In summary, activation of the PI3K/AKT in addition to MAPK/ERK signaling pathways may underlie biological aggressiveness in PA. Specifically, it may mediate the increased proliferative activity observed in histologically anaplastic PA.

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Kurwale NS, Suri V, Suri A, Sarkar C, Gupta DK, Sharma BS, Mahapatra AK. Predictive factors for early symptomatic recurrence in pilocytic astrocytoma: does angiogenesis have a role to play? J Clin Neurosci 2011;18:472-7. [PMID: 21292490 DOI: 10.1016/j.jocn.2010.04.055] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2009] [Revised: 04/12/2010] [Accepted: 04/14/2010] [Indexed: 11/19/2022]

Abstract

We studied predictive factors with respect to angiogenesis and proliferative indices for early symptomatic recurrences in patients with pilocytic astrocytoma (PA). One hundred and eighteen patients who underwent surgery for PA were divided into non-recurrent and early symptomatic recurrence groups to analyze clinicoradiological and immunohistopathological (n=33) parameters. Patients with non-recurrent tumors presented with symptoms for a mean duration of 10.2 ± 9.1 months while those with recurrent tumors presented slightly earlier (6.9 ± 4.5 months). Common tumor locations were the cerebellum (38.1%), optic chiasm (27.9%), supratentorial region (19.4%) and brainstem (9.3%). Recurrent tumors were mostly located in the cerebellum (44%) and brainstem (33%). Strong contrast enhancement was noted in 70 (59.3%) tumors, while 48 (40.7%) showed poor contrast. Resection was complete in 53% of patients while near total excision was achieved for the remaining patients. Cellularity and pleomorphism were similar in both groups. Extensive endothelial proliferation was observed in 18.1% of patients while the remainder showed a focal pattern. Diffuse vascular endothelial growth factor (VEGF) expression was observed in 36.3% of patients while 63.6% showed mild-to-moderate focal expression. Endothelial proliferation and VEGF expression were more pronounced in patients with non-recurrent tumors, but this was not statistically significant. MIB-I labeling indices were similar (1-5%) for both groups. Symptomatic recurrences were common in infratentorial PAs. Radiology, histopathology and proliferative indices did not offer any prognostic information. Angiogenesis markers such as endothelial proliferation and VEFG expression did not predict early symptomatic recurrence. Diffuse VEGF expression and endothelial proliferation were observed in tumors that showed strong contrast enhancement.

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Forbes JA, Chambless LB, Smith JG, Wushensky CA, Lebow RL, Alvarez J, Pearson MM. Use of T2 signal intensity of cerebellar neoplasms in pediatric patients to guide preoperative staging of the neuraxis. J Neurosurg Pediatr 2011;7:165-74. [PMID: 21284463 PMCID: PMC3777739 DOI: 10.3171/2010.11.peds10312] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]

Abstract

OBJECT

The question of whether to obtain routine or selective preoperative imaging of the neuraxis in pediatric patients with cerebellar neoplasms remains a controversial topic. Staging of the neuraxis is generally considered beneficial in patients with neoplasms associated with an elevated risk of leptomeningeal dissemination (LD). When these studies are obtained preoperatively, there is a decrease in the number of false-positive images related to debris in the immediate postoperative period. Additionally, knowledge of the extent of spread has the potential to affect the risk/benefit analysis of aggressive resection. Although the majority of pediatric neurosurgeons surveyed choose to obtain selective preoperative imaging of the neuraxis in cases of cerebellar neoplasms "with findings suggestive of high-grade pathology," an evidence-based protocol in the literature is lacking. The goal of this study was to assess radiological characteristics of tumors with an elevated risk of LD and identify a method to help guide preoperative imaging of the neuraxis.

METHODS

The authors first reviewed the literature to gain an appreciation of the risk of LD of pediatric cerebellar neoplasms based on underlying histopathology and/or grade. Available evidence indicates preoperative imaging of the neuraxis in patients with Grade I tumors to be of questionable utility. In contrast, evidence suggested that preoperative imaging of the neuraxis in patients with Grades II-IV neoplasms was clinically warranted. The authors then evaluated an extensive base of neuroradiological literature to identify possible MR imaging and/or CT findings with the potential to differentiate Grade I from higher-grade neoplasms in pediatric patients. They analyzed the preoperative radiological findings in 50 pediatric patients who had undergone craniotomy for resection of cerebellar neoplasms at Vanderbilt Children's Hospital since 2003 with reference to 7 chosen radiological criteria. Logistic regression models were fit using radiological features to determine the best predictors of Grades II-IV tumors. Receiver operating characteristic methods were used to identify diagnostic properties of the best predictors.

RESULTS

The relative T2 signal intensity (RT2SI), an indirect measure of the water content of the solid component of the tumor, was best able to identify neoplasms with an elevated risk of LD. An RT2SI value of 0.71 was selected by the authors as the best operating point on the curve. Of the 31 neoplasms retrospectively designated as hypointense T2-weighted lesions (RT2SI ≤ 0.71), 30 (97%) were Grade II or higher. All medulloblastomas, ependymomas, and high-grade (Grades III and IV) neoplasms were hypointense T2-weighted lesions. Of the 19 T2-weighted hyperintense neoplasms (RT2SI > 0.71), 16 (84%) were Grade I and 3 were Grade II.

CONCLUSIONS

Measurement of the RT2SI can help predict Grade II-IV tumors at an elevated risk of leptomeningeal spread and guide staging of the neuraxis. Pediatric patients with cerebellar neoplasms found to have an RT2SI of less than or equal to 0.71 are recommended for neuraxis imaging prior to surgery.

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U-King-Im JM, Taylor MD, Raybaud C. Posterior fossa ependymomas: new radiological classification with surgical correlation. Childs Nerv Syst 2010;26:1765-72. [PMID: 20680298 DOI: 10.1007/s00381-010-1251-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2010] [Accepted: 07/21/2010] [Indexed: 11/26/2022]

Slatter T, Gifford-Garner J, Wiles A, Tan X, Chen YJ, MacFarlane M, Sullivan M, Royds J, Hung N. Pilocytic astrocytomas have telomere-associated promyelocytic leukemia bodies without alternatively lengthened telomeres. THE AMERICAN JOURNAL OF PATHOLOGY 2010;177:2694-700. [PMID: 21037079 DOI: 10.2353/ajpath.2010.100468] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]

Dorward IG, Luo J, Perry A, Gutmann DH, Mansur DB, Rubin JB, Leonard JR. Postoperative imaging surveillance in pediatric pilocytic astrocytomas. J Neurosurg Pediatr 2010;6:346-52. [PMID: 20887107 DOI: 10.3171/2010.7.peds10129] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]

Abstract

OBJECT

Currently there is no consensus regarding the frequency of neuroimaging following gross-total resection (GTR) of pilocytic astrocytoma (PA) in children. Whereas several reports recommend no postoperative imaging, one study proposed surveillance MR imaging studies to detect delayed recurrences.

METHODS

The records of 40 consecutive pediatric patients who underwent GTR of infratentorial PAs were examined. All had follow-up duration of ≥ 2 years. Patients underwent early (< 48 hours) postoperative MR imaging, followed by surveillance imaging at 3-6 months, 1 year, and variably thereafter. The classification of GTR was based on a lack of nodular enhancement on early postoperative MR imaging. Demographic, clinical, and pathological variables were analyzed with respect to recurrence status. Univariate and multivariate analyses were performed to evaluate the association between pathological variables and recurrence-free survival (RFS).

RESULTS

Of 13 patients demonstrating new nodular enhancement on MR imaging at 3-6 months, the disease progressed in 10, with a median time to recurrence of 6.4 months (range 2-48.2 months). At last follow-up, 29 patients had no recurrence, whereas in 1 additional patient the tumor recurred at 48 months, despite the absence of a new contrast-enhancing nodule at 3-6 months (for a total of 11 patients with recurrence). No demographic variable was associated with recurrence. Nodular enhancement on MR imaging at 3-6 months was significantly associated with recurrence in both univariate (p < 0.0001) and multivariate (p = 0.0015) analyses. Among the pathological variables, a high Ki 67 labeling index (LI) was similarly significantly associated with RFS in both univariate (p = 0.0016) and multivariate (p = 0.034) analyses. Multivariate models that significantly predicted RFS included a risk score incorporating Ki 67 LI and CD68 positivity (p = 0.0022), and a similar risk score combining high Ki 67 LI with the presence of nodular enhancement on initial surveillance MR imaging (p < 0.0001).

CONCLUSIONS

Surveillance MR imaging at 3-6 months after resection predicts tumor recurrence following GTR. One patient suffered delayed recurrence, arguing against a "no imaging" philosophy. The data also highlight the pathological variables that can help categorize patients into groups with high or low risk for recurrence. Larger series are needed to confirm these associations.

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Horbinski C, Hamilton RL, Nikiforov Y, Pollack IF. Association of molecular alterations, including BRAF, with biology and outcome in pilocytic astrocytomas. Acta Neuropathol 2010;119:641-9. [PMID: 20044755 DOI: 10.1007/s00401-009-0634-9] [Citation(s) in RCA: 109] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2009] [Revised: 12/23/2009] [Accepted: 12/24/2009] [Indexed: 12/25/2022]

Spontaneous malignant transformation of a supratentorial pilocytic astrocytoma. Neurocirugia (Astur) 2010;21:245-52. [DOI: 10.1016/s1130-1473(10)70084-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]