Monday, July 30, 2012

Multidrug resistance proteins expression in glioma patients with epilepsy

Abstract  
Epilepsy occurs in glioma, especially in low-grade glioma (LGG), but also in glioblastoma (GBM). In about 20 % of patients pharmacological treatment with anti-epileptic drugs (AEDs) fails. Refractory epilepsy is a multifactorial phenomenon not yet completely understood. The multidrug resistance phenotype was initially associated to P-glycoprotein (Pgp), an ATP-dependent transporter belonging to the same superfamily of multidrug resistance-associated proteins (MRPs). Glutathione-S-transferase-π (GST-π) is also involved in refractory epilepsy. In the present work we investigated the expression of Pgp, MRP1, MRP3 and GST-π in surgical specimens obtained from 35 patients with glioma and epilepsy. We observed MRP1 expression in tumor and endothelial cells (EC), MRP3 and Pgp expression mainly in ECs and GST-π predominantly in tumor cells (TC). MRP1 and MRP3 were more expressed in high grade glioma (HGG) than in LGG. In 6 cases we could compare tumor and periphery detecting the same MRP1 and Pgp expression, while MRP3 was mainly expressed in the tumor. We observed a trend of a better outcome in seizure control associated with a lower expression of MRP1 and MRP3. MRP3 was statistically more expressed in TCs of HGG than LGG (p = 0.0401) and more expressed in tumor than in periphery, in agreement with recent works that identify MRP3 as a potential target in GBM. Moreover, MRP3 was investigated in association with refractory epilepsy for the first time in our study and it was less expressed in patients with complete response to AEDs (p = 0.0550). Our preliminary data show an association between multidrug resistance transporters and refractory epilepsy in glioma.

  • Content Type Journal Article
  • Category Clinical Study - Patient Study
  • Pages 1-7
  • DOI 10.1007/s11060-012-0946-9
  • Authors
    • Chiara Calatozzolo, Department of Neuropathology, Fondazione IRCCS Istituto Neurologico "C. Besta", Via Celoria 11, 20133 Milan, Italy
    • Bianca Pollo, Department of Neuropathology, Fondazione IRCCS Istituto Neurologico "C. Besta", Via Celoria 11, 20133 Milan, Italy
    • Andrea Botturi, Department of Neuro-oncology, Fondazione IRCCS Istituto Neurologico "C. Besta", Via Celoria 11, 20133 Milan, Italy
    • Loredana Dinapoli, Center for Brain Tumor-related Epilepsy, Istituto Nazionale Tumori "Regina Elena", Via Elio Chianesi 53, 00144 Rome, Italy
    • Mariantonia Carosi, Department of Pathology, Istituto Nazionale Tumori "Regina Elena", Via Elio Chianesi 53, 00144 Rome, Italy
    • Andrea Salmaggi, Department of Neuro-oncology, Fondazione IRCCS Istituto Neurologico "C. Besta", Via Celoria 11, 20133 Milan, Italy
    • Marta Maschio, Center for Brain Tumor-related Epilepsy, Istituto Nazionale Tumori "Regina Elena", Via Elio Chianesi 53, 00144 Rome, Italy





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Identification of a novel population in high-grade oligodendroglial tumors not deleted on 1p/19q usi

Abstract  
Oligodendroglial tumors (ODTs) are primary tumors of the central nervous system that show recurrent codeletion of whole chromosome arms 1p and 19q. Non-1p/19q-deleted high-grade ODTs can present other genetic aberrations, CDKN2A deletion (9p21.3), EGFR amplification (7p11.2) and/or chromosome 10 loss, which are associated with a poor prognosis. The identification of these abnormalities allowed drafting a histo-molecular classification. The aim of this study was to precisely identify, using array CGH, the genomic hallmarks of these tumors, particularly those that are not deleted on 1p/19q. We studied 14 formalin-fixed paraffin-embedded high-grade ODTs using pangenomic oligonucleotide array CGH with an average resolution of 22.3 kb. The 1p/19q codeletion was found in five anaplastic oligodendrogliomas. The three genomic aberrations carrying a poor prognosis were found, most often associated, in five out of nine tumors not deleted on 1p/19q. In addition, four recurrent copy number alterations, involving genes that participate to cell growth and cycle, were found to be strongly associated in five tumors not deleted on 1p/19q: gain or amplification at 1q32.1 (MDM4, PIK3C2B genes), 12q14.1 (CDK4 gene), 12q14.3-q15 (MDM2 gene) and homozygous deletion at 22q13.1 (APOBEC3B gene). MDM2, MDM4, CDK4 and PIK3C2B are known for potentially being amplified or overexpressed in high-grade gliomas. However, the involvement of APOBEC3B, coding for mRNA edition enzyme, is described here for the first time. Our results show a strong association between these four alterations. Therefore, this can open a perspective for a novel subgroup in high-grade ODTs not deleted on 1p/19q.

  • Content Type Journal Article
  • Category Clinical Study
  • Pages 1-9
  • DOI 10.1007/s11060-012-0909-1
  • Authors
    • Matthieu Talagas, Faculté de Médecine et des Sciences de la Santé, Université de Brest, Brest, France
    • Pascale Marcorelles, Service d'Anatomie Pathologique, CHRU Brest, Hôpital Morvan, Brest, France
    • Arnaud Uguen, Faculté de Médecine et des Sciences de la Santé, Université de Brest, Brest, France
    • Sylvia Redon, Institut National de la Santé et de la Recherche Médicale (INSERM), U1078, Brest, France
    • Isabelle Quintin-Roué, Service d'Anatomie Pathologique, CHRU Brest, Hôpital Morvan, Brest, France
    • Sebastian Costa, Service d'Anatomie Pathologique, CHRU Brest, Hôpital Morvan, Brest, France
    • Claude Férec, Faculté de Médecine et des Sciences de la Santé, Université de Brest, Brest, France
    • Frédéric Morel, Faculté de Médecine et des Sciences de la Santé, Université de Brest, Brest, France
    • Phong Dam Hieu, Faculté de Médecine et des Sciences de la Santé, Université de Brest, Brest, France
    • Marc De Braekeleer, Faculté de Médecine et des Sciences de la Santé, Université de Brest, Brest, France





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A prospective phase II single-institution trial of sunitinib for recurrent malignant glioma

Abstract  
Single-agent sunitinib, an oral small molecule inhibitor of multiple tyrosine kinase receptors, was evaluated for treatment of patients with recurrent glioblastoma (GB) and anaplastic astrocytoma (AA). Fourteen AA and 16 GB patients, all previously treated with surgery, radiotherapy, and temozolomide, were enrolled in a prospective phase II study at either first or second relapse. Patients were treated with daily sunitinib for 4 consecutive weeks, followed by a 2-week break. For AA patients, the most common side effects were fatigue (86 %), diarrhea (43 %), hand-foot syndrome (36 %), neutropenia (36 %), thrombocytopenia (36 %), and nausea (29 %). In the GB cohort, the most common side effects were fatigue (56 %), diarrhea (44 %), neutropenia (31 %), and thrombocytopenia (25 %). Six of 14 (43 %) AA and 5 of 16 (31 %) GB patients experienced grade 3 or greater toxicities. Five patients discontinued study due to drug toxicities. There were no partial or complete responses in either cohort; 8/14 (57 %) AA and 5/16 (31 %) GB patients had stable disease at the first planned assessment. Progression-free survival at 6 months was 21.5 % (AA) and 16.7 % (GB). Median overall survival was 12.1 months (AA) and 12.6 months (GB). These results are comparable to those reported in the literature in patients treated with standard cytotoxic therapies. This is the largest reported trial of sunitinib in recurrent malignant astrocytic gliomas to date, as well as contains the largest AA cohort. Nonetheless, sunitinib did not demonstrate significant anti-glioma activity in patients with recurrent malignant astrocytic gliomas.

  • Content Type Journal Article
  • Category Clinical Study
  • Pages 1-8
  • DOI 10.1007/s11060-012-0943-z
  • Authors
    • Edward Pan, Department of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr., Tampa, FL 33612-9416, USA
    • Daohai Yu, Department of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr., Tampa, FL 33612-9416, USA
    • Binglin Yue, Department of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr., Tampa, FL 33612-9416, USA
    • Lisa Potthast, Department of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr., Tampa, FL 33612-9416, USA
    • Sajeel Chowdhary, Department of Neuro-Oncology, Florida Hospital Cancer Institute, Orlando, FL, USA
    • Pamela Smith, Department of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr., Tampa, FL 33612-9416, USA
    • Marc Chamberlain, Department of Neurology and Neurological Surgery, Seattle Cancer Care Alliance, Seattle, WA, USA





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The influence of surgery on quality of life in patients with intracranial meningiomas: a prospective

Abstract  
Meningiomas may influence both survival and neurological functions. Studies assessing the impact of surgery on health-related quality of life (HRQL) remain absent. In this prospective study we aimed to describe HRQL dynamics before and after surgery in patients with meningiomas. HRQL assessments were performed using EuroQol-5D (EQ-5D), a generic HRQL instrument. All adult patients with suspected intracranial meningioma from 2007 through 2011 were eligible for inclusion, and 54 patients were included after informed consent. All patients received a histopathological diagnosis of meningioma. The average preoperative EQ-5D index value (±SD) was 0.69 ± 0.26. The mean improvement 6 weeks after surgery was 0.06 (95 % CI, −0.03 to 0.16; p = 0.161) and the mean long term improvement was 0.09 (95 % CI, 0.00–0.17; p = 0.040). Surgery reduced pain/discomfort and anxiety/depression and improved the capability of performing usual activities. Clinically significant improvement at long-term assessment was noted in 25 patients (49 %) while a significant deterioration was reported in 10 patients (20 %). Patients who reported postoperative worsening of HRQL were also reporting better preoperative scores, suggesting a possible ceiling effect of EQ-5D in some of these patients. In our patients a modest average improvement in HRQL was seen after surgery for meningioma. About half of the patients reported a clinical important improvement at the late follow-up assessment. This improvement was mainly observed in the domains usual activities, pain/discomfort and anxiety/depression. However, one in five patients fared worse on late follow-up assessment, a figure of particular importance when treating asymptomatic meningiomas.

  • Content Type Journal Article
  • Category Clinical Study
  • Pages 1-8
  • DOI 10.1007/s11060-012-0947-8
  • Authors
    • Asgeir S. Jakola, Department of Neurosurgery, St. Olavs University Hospital, 7006 Trondheim, Norway
    • Michel Gulati, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway
    • Sasha Gulati, Department of Neurosurgery, St. Olavs University Hospital, 7006 Trondheim, Norway
    • Ole Solheim, Department of Neurosurgery, St. Olavs University Hospital, 7006 Trondheim, Norway





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Patterns of care and outcomes of patients with pleomorphic xanthoastrocytoma: a SEER analysis

Abstract  
To study the clinical characteristics, treatment approach and outcome of pleomorphic xanthoastrocytoma (PXA), patients were identified using the National Cancer Intitute's Surveillance, Epidemiology, and End Results (SEER) database. A total of 214 patients were identified with PXA using the November 2010 submission. Patient demographics, tumor characteristics, extent of surgical resection, the use of radiotherapy, and overall survival were evaluated. Overall survival for PXA was then compared to that of pilocytic astrocytoma, oligodendroglioma, ependymom and glioblastoma also using the SEER database. Kaplan–Meier, univariate and multivariate analyses were performed. The majority of patients were found to be young adults with the most common tumor location being temporal lobe. Surgery was performed on most (95 %) patients, while 25 % of patients received radiation therapy. Five and 10 year overall survival rates were 75 and 67 %, respectively. Grade was only available for a limited number of patients but appeared to affect prognosis. Patients with grade IV tumors had a median overall survival of 45 months, whereas median survival was not reached for grade I–III patients. On multivariate analysis, male gender and increasing age were associated with worse overall survival (p values 0.05 and <0.006, respectively). Extent of resection trended towards significance in favor of gross total resection. PXA is a rare diagnosis that affects young adults. Surgical resection is the primary modality of treatment with an overall good prognosis. Elderly patients, those with higher grade disease and patients with incomplete resections may have a worse prognosis. The role of radiation therapy for PXA remains unclear but is more often used for patients with high grade tumors. Compared to other common brain tumors, PXA's appear to fare worse than pilocytic astrocytoma and oligodendroglioma, especially in younger patients. However, even high grade PXA patients have significantly better overall survival compared to glioblastoma.

  • Content Type Journal Article
  • Category Clinical Study
  • Pages 1-6
  • DOI 10.1007/s11060-012-0939-8
  • Authors
    • Stephanie M. Perkins, Department of Radiation Oncology, Vanderbilt University Medical Center, Pierce Ave B1003, 2220, Nashville, TN 37232, USA
    • Nandita Mitra, Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA
    • Wan Fei, Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA
    • Eric T. Shinohara, Department of Radiation Oncology, Vanderbilt University Medical Center, Pierce Ave B1003, 2220, Nashville, TN 37232, USA





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Sunday, July 29, 2012

Quantum Computing: A Prime Modality in Neurosurgery’s Future

Publication year: 2012
Source:World Neurosurgery
Brian Lee, Charles Y. Liu, Michael L.J. Apuzzo
Objective With each significant development in the field of neurosurgery, our dependence upon computers, small and large, has continuously increased. From something as mundane as bipolar cautery to sophisticated intraoperative navigation with real-time MRI-assisted surgical guidance, both technologies, however simple or complex, require computational processing power to function. The next frontier for neurosurgery involves developing a greater understanding of the brain and furthering our capabilities as surgeons to directly affect brain circuitry and function. Methods This has come in the form of implantable devices which can electronically and nondestructively influence the cortex and nuclei with the purpose of restoring neuronal function and improving quality of life. Results We are now transitioning from devices that are turned on and left alone, such as vagus nerve stimulators (VNS) and deep brain stimulators (DBS), to "smart" devices that can listen and react to the body as the situation may dictate. Conclusion The development of quantum computers and their potential to be thousands, if not millions of times faster than current "classical" computers, will significantly affect the neurosciences, especially the field of neurorehabilitation and neuromodulation. Quantum computers may advance our understanding of the neural code, and in turn, better develop and program implantable neural devices. When quantum computers reach the point where we can actually implant such devices in patients, the possibilities of what can be done to interface and restore neural function will be limitless.






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Saturday, July 28, 2012

Novel pathological abnormalities of deep brain structures including dysplastic neurons in anterior s

Journal of Neurosurgery: Pediatrics, Volume 0, Issue 0, Page 1-9, Ahead of Print.
Object Some patients are not seizure free even after epileptogenic cortical resection. The authors recently described a case of frontal lobe epilepsy cured after the resection of periventricular white matter and striatum, in which dysplastic neurons were revealed. The authors attempted to confirm similar cases. Methods They reviewed the records of 8 children with frontal lobe epilepsy who had daily (7) or monthly (1) seizures and underwent resections including deep brain structures. Results Five patients underwent multiple resections. Neuroimaging of the deep structures showed the transmantle sign in 3 patients, ictal hyperperfusion in 6, reduced iomazenil uptake in 2, and spike dipole clustering in 6. All patients became seizure free postoperatively. Focal cortical dysplasia of various types was diagnosed in all patients. Dysmorphic neurons were found in the cortex and subcortical white matter of 5 patients. The striatum was verified in 3 patients in whom dysmorphic neurons were scattered. In the periventricular white matter, prominent astrocytosis was evident in all cases. Conclusions Pathological abnormalities such as dysmorphic neurons and astrocytosis in deep brain structures would play a key role in epileptogenesis.





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Endoscopic Resection of Colloid Cysts: Use of a Dual-Instrument Technique and an Anterolateral Approach



Publication year: 2012 Source:World NeurosurgeryDavid A. Wilson, David J. Fusco, Scott D. Wait, Peter Nakaji Objective: Endoscopic approaches are increasingly utilized to treat third ventricular colloid cysts but have been associated with lower rates of complete cyst wall resection. Our objective was to assess the results of colloid cyst resection via an anterolateral endoscopic approach with a dual-instrument technique, with an emphasis on completeness of cyst wall resection. Methods: A retrospective review of the senior author’s experience with 22 colloid cysts treated with endoscopic resection since 2004 was performed. Initial cyst size, completeness of resection, postoperative radiographic residual, recurrence at follow-up, need for reoperation, and neurological morbidity were assessed. All cysts were approached from an anterolateral trajectory with two instruments working in concert through a single endoscope. Results: Of 22 patients, near-total resection was obtained in 95%. In 3 cases a very small, radiographically occult residual was left. Complete cyst wall resection was therefore obtained in 18 (82%). There were no cases of recurrence at follow-up in any patient. No patients required craniotomy or underwent re-resection. 15 of 16 (94%) patients with long-term clinical follow-up remained stable or improved. Conclusion: High rates of complete colloid cyst resection, with low morbidity, are possible with an anterolateral endoscopic approach with dual-instrument technique. These results support the findings of other endoscopists that show how technical modifications to traditional endoscopic approaches can produce favorable results.
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Endoscopic Resection of Colloid Cysts: Use of a Dual-Instrument Technique and an Anterolateral Appro

Publication year: 2012
Source:World Neurosurgery
David A. Wilson, David J. Fusco, Scott D. Wait, Peter Nakaji
Objective: Endoscopic approaches are increasingly utilized to treat third ventricular colloid cysts but have been associated with lower rates of complete cyst wall resection. Our objective was to assess the results of colloid cyst resection via an anterolateral endoscopic approach with a dual-instrument technique, with an emphasis on completeness of cyst wall resection. Methods: A retrospective review of the senior author's experience with 22 colloid cysts treated with endoscopic resection since 2004 was performed. Initial cyst size, completeness of resection, postoperative radiographic residual, recurrence at follow-up, need for reoperation, and neurological morbidity were assessed. All cysts were approached from an anterolateral trajectory with two instruments working in concert through a single endoscope. Results: Of 22 patients, near-total resection was obtained in 95%. In 3 cases a very small, radiographically occult residual was left. Complete cyst wall resection was therefore obtained in 18 (82%). There were no cases of recurrence at follow-up in any patient. No patients required craniotomy or underwent re-resection. 15 of 16 (94%) patients with long-term clinical follow-up remained stable or improved. Conclusion: High rates of complete colloid cyst resection, with low morbidity, are possible with an anterolateral endoscopic approach with dual-instrument technique. These results support the findings of other endoscopists that show how technical modifications to traditional endoscopic approaches can produce favorable results.






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Endoscopic Resection of Colloid Cysts: Use of a Dual-Instrument Technique and an Anterolateral Approach


Endoscopic Resection of Colloid Cysts: Use of a Dual-Instrument Technique and an Anterolateral Approach

Publication year: 2012
Source:World Neurosurgery
David A. Wilson, David J. Fusco, Scott D. Wait, Peter Nakaji
Objective: Endoscopic approaches are increasingly utilized to treat third ventricular colloid cysts but have been associated with lower rates of complete cyst wall resection. Our objective was to assess the results of colloid cyst resection via an anterolateral endoscopic approach with a dual-instrument technique, with an emphasis on completeness of cyst wall resection. Methods: A retrospective review of the senior author's experience with 22 colloid cysts treated with endoscopic resection since 2004 was performed. Initial cyst size, completeness of resection, postoperative radiographic residual, recurrence at follow-up, need for reoperation, and neurological morbidity were assessed. All cysts were approached from an anterolateral trajectory with two instruments working in concert through a single endoscope. Results: Of 22 patients, near-total resection was obtained in 95%. In 3 cases a very small, radiographically occult residual was left. Complete cyst wall resection was therefore obtained in 18 (82%). There were no cases of recurrence at follow-up in any patient. No patients required craniotomy or underwent re-resection. 15 of 16 (94%) patients with long-term clinical follow-up remained stable or improved. Conclusion: High rates of complete colloid cyst resection, with low morbidity, are possible with an anterolateral endoscopic approach with dual-instrument technique. These results support the findings of other endoscopists that show how technical modifications to traditional endoscopic approaches can produce favorable results.

Original Page: http://www.sciencedirect.com/science?_ob=GatewayURL&_origin=IRSSSEARCH&_method=citationSearch&_piikey=S1878875012007929&_version=1&md5=d4682cda020e1f3d36aa3a9974d68539

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Solitary cerebral metastasis from transitional cell carcinoma after a 14-year remission of urinary b

J Manuel Sarmiento, Matt S Wi, Zhe Piao, Eric S Stiner

Surgical Neurology International 2012 3(1):82-82

Background: Brain metastases are the most common adult brain tumors, frequently arising from primary tumors in the lung, breast, skin, kidneys, and colon. Transitional cell carcinoma (TCC), the most common type of urinary bladder cancer, is a rare cause of brain metastasis with an ominous prognosis. Case Description: A 68-year-old female presented with right-sided paresis and focal motor seizures of her right upper and lower extremities 14 years after being diagnosed and treated for primary TCC of the urinary bladder with gemcitabine-based chemotherapy. MRI imaging revealed a 3.1 &#215; 3.1 &#215; 2.7 cm heterogeneously enhancing mass located along the posterior aspect of the left frontal convexity. The lesion was accessed using a transsulcal approach and was surgically debulked along the motor cortex with motor strip mapping, followed by adjuvant whole-brain radiation therapy. Pathological examination confirmed metastatic carcinoma with features of TCC, a rare entity among metastatic brain tumors. Conclusion: Brain metastases may present several years later in patients with TCC of the urinary bladder who have been treated with surgery and chemotherapy. Chemotherapeutic agents that penetrate the blood-brain barrier, such as gemcitabine, may delay development of cerebral metastasis from primary TCC of the urinary bladder.





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Endoscopic Resection of Colloid Cysts: Use of a Dual-Instrument Technique and an Anterolateral Appro

Publication year: 2012
Source:World Neurosurgery
David A. Wilson, David J. Fusco, Scott D. Wait, Peter Nakaji
Objective: Endoscopic approaches are increasingly utilized to treat third ventricular colloid cysts but have been associated with lower rates of complete cyst wall resection. Our objective was to assess the results of colloid cyst resection via an anterolateral endoscopic approach with a dual-instrument technique, with an emphasis on completeness of cyst wall resection. Methods: A retrospective review of the senior author's experience with 22 colloid cysts treated with endoscopic resection since 2004 was performed. Initial cyst size, completeness of resection, postoperative radiographic residual, recurrence at follow-up, need for reoperation, and neurological morbidity were assessed. All cysts were approached from an anterolateral trajectory with two instruments working in concert through a single endoscope. Results: Of 22 patients, near-total resection was obtained in 95%. In 3 cases a very small, radiographically occult residual was left. Complete cyst wall resection was therefore obtained in 18 (82%). There were no cases of recurrence at follow-up in any patient. No patients required craniotomy or underwent re-resection. 15 of 16 (94%) patients with long-term clinical follow-up remained stable or improved. Conclusion: High rates of complete colloid cyst resection, with low morbidity, are possible with an anterolateral endoscopic approach with dual-instrument technique. These results support the findings of other endoscopists that show how technical modifications to traditional endoscopic approaches can produce favorable results.






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Friday, July 27, 2012

Confira Traumatismo Crânio-Encefálico (TCE)

Traumatismo Crânio-Encefálico (TCE)

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Monday, July 23, 2012

Cancer Immunoediting in Malignant Glioma

imageSignificant work from many laboratories over the last decade in the study of cancer immunology has resulted in the development of the cancer immunoediting hypothesis. This contemporary framework of the naturally arising immune system–tumor interaction is thought to comprise 3 phases: elimination, wherein immunity subserves an extrinsic tumor suppressor function and destroys nascent tumor cells; equilibrium, wherein tumor cells are constrained in a period of latency under immune control; and escape, wherein tumor cells outpace immunity and progress clinically. In this review, we address in detail the relevance of the cancer immunoediting concept to neurosurgeons and neuro-oncologists treating and studying malignant glioma by exploring the de novo immune response to these tumors, how these tumors may persist in vivo, the mechanisms by which these cells may escape/attenuate immunity, and ultimately how this concept may influence our immunotherapeutic approaches. ABBREVIATIONS: APC, antigen-presenting cell CTL, cytotoxic T lymphocyte DC, dendritic cell eGFR, endothelial growth factor receptor IL, interleukin IFN, interferon-γ MHC, major histocompatibility complex MICA/B, MHC class I chain-related A/B NK, natural killer PD-L1, programmed death receptor ligand 1 RAG2, recombinase activating gene 2 STAT3, signal transducer and activator of transcription 3 TGF-β, transforming growth factor-β TIL, tumor-infiltrating lymphocyte Treg, regulatory T cell ULBP, UL16-binding protein





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Ciência Hoje faz 30 anos

Em julho de 1982, um grupo de pesquisadores brasileiros materializou um sonho ousado, ao lançar a primeira revista de divulgação científica brasileira comandada por cientistas. Movidos quase que somente pela vontade, superaram a inexperiência e responderam ao cenário político e social que se apresentava.

Em meio a um momento de grande agitação política, a CH buscou estimular a divulgação





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Sunday, July 22, 2012

Butterfly glioblastomas: a retrospective review and qualitative assessment of outcomes

Abstract  
To address a paucity of literature and treatment guidelines regarding the management of butterfly glioblastomas, we performed a ten year retrospective analysis of data from twenty-three consecutive patients treated for this disease at a single institution. Clinical characteristics and outcomes were assessed. Median age was 59 years; 52 % were female; median preoperative Karnofsky performance score (KPS) was 80. Twelve patients underwent biopsy and eleven underwent surgical decompression. The median tumor volume for the biopsy group was 60.6 cm3 and for the surgically decompressed group 40.5 cm3. In the biopsy group, five patients received adjuvant therapy but one died prior to its completion; two died prior to the initiation of adjuvant therapy and five were lost to follow up. In the surgical decompression group, seven patients received adjuvant therapy, one died prior to the initiation of adjuvant therapy, two were treated with palliative measures only, and one was lost to follow up. Kaplan–Meier estimates of overall median post surgical-survival of the whole group was 180 days, the biopsy group 48 days, and the surgically decompressed group 265 days (p = 0.14). Our results show that there was a higher median survival in the surgically decompressed group; but a direct correlation could not be established, and that the median KPS did not improve in either group after treatment. A larger multicenter review is required to quantitatively assess the factors, including tumor biomarkers that are associated with patient outcome.

  • Content Type Journal Article
  • Category Clinical Study
  • Pages 1-9
  • DOI 10.1007/s11060-012-0926-0
  • Authors
    • Kristine Dziurzynski, Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, 1400 Holcombe Blvd., Unit 442, Houston, TX 77030, USA
    • David Blas-Boria, Neurology Section, Department of Internal Medicine, University of Puerto Rico, San Juan, PR, USA
    • Dima Suki, Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, 1400 Holcombe Blvd., Unit 442, Houston, TX 77030, USA
    • Daniel P. Cahill, Department of Neurosurgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA
    • Sujit S. Prabhu, Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, 1400 Holcombe Blvd., Unit 442, Houston, TX 77030, USA
    • Vinay Puduvalli, Department of Neurooncology, The University of Texas M.D. Anderson Cancer Center, 1400 Holcombe Blvd., Unit 442, Houston, TX, USA
    • Nicholas Levine, Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, 1400 Holcombe Blvd., Unit 442, Houston, TX 77030, USA





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Improvements in site-specific quality of life 6 months after endoscopic anterior skull base surgery:

Journal of Neurosurgery, Volume 0, Issue 0, Page 1-9, Ahead of Print.
Object Endoscopic skull base surgery (ESBS) is a minimal-access technique that provides an alternative to traditional approaches. Patient-reported outcomes are becoming increasingly important in measuring the success of surgical interventions. Endoscopic skull base surgery may lead to improvements in quality of life (QOL) since natural orifices are used to reach the pathology; however, sinonasal QOL may be negatively affected. The purpose of this study was to assess the impact of ESBS on both site-specific QOL, using the Anterior Skull Base Questionnaire (ASBQ), and sinonasal-related QOL, using the Sino-Nasal Outcome Test (SNOT-22). Methods Consecutive patients from a tertiary referral center who were undergoing ESBS were prospectively enrolled in this study. All patients completed the ASBQ and SNOT-22 preoperatively as well as at regular intervals after ESBS. Results Sixty-six patients were included in the study, and 57.6% of them had pituitary adenoma. There was no significant decline or improvement in the ASBQ-measured QOL at 3 and 6 weeks after ESBS, but there were significant improvements at 12 weeks and 6 months postoperatively (p < 0.05). Improvements were noted in all but one ASBQ subdomain at 12 weeks and 6 months postsurgery (p < 0.05). Preoperative QOL was significantly worse in patients who had undergone revision surgery and significantly improved postoperatively in patients who underwent gross-total resection (p < 0.05). Scores on the SNOT-22 worsened at 3 weeks postoperatively and returned to baseline thereafter. The presence of a nasoseptal flap or a graft-donor site did not contribute to a decreased QOL. Conclusions Endoscopic skull base surgery is associated with an improvement in postoperative site-specific QOL as compared with the preoperative QOL. Short-term improvements are greater if gross-total resection is achieved. Sinonasal QOL transiently declines and then returns to preoperative baseline levels. Endoscopic skull base surgery is a valuable tool in the neurosurgical management of anterior skull base pathology, leading to improvements in site-specific QOL.





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A single spinal lesion arising from an intradural meningioma contiguous with an extradural lymphoma

Journal of Neurosurgery: Spine, Volume 0, Issue 0, Page 1-5, Ahead of Print.
The authors describe here a unique case of contiguous, synchronous meningioma and lymphoma in the spinal column. Both tumors were present at the same vertebral level, one intradural and the other extradural. A patient presented with bilateral leg pain, acute weakness, and sensory loss in the lower extremities. Magnetic resonance imaging revealed an intradural mass at T6–7 with ambiguous boundaries relative to the thecal sac and compressing the spinal cord. The patient underwent resection of the epidural and intradural mass at T6–7. Histopathology revealed the epidural specimen to be a double-hit B-cell lymphoma and the intradural mass to be a transitional meningioma. Postoperatively, the patient did well, with an immediate return of strength and sensation. A postoperative MR image showed complete resection of the intradural mass. The authors suggest that biopsy may be prudent in patients with known systemic lymphoma presenting with a spinal lesion that has unclear boundaries relative to the thecal sac prior to commencing radiation and chemotherapy.





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Pediatric incidental brain tumors: a growing treatment dilemma

Journal of Neurosurgery: Pediatrics, Volume 0, Issue 0, Page 1-7, Ahead of Print.
Object Rising numbers of MRI studies performed during evaluations for pediatric disorders have contributed to a significant increase in the number of incidentally found brain tumors. Currently, there is very little literature on the nature of and the preferred treatment for these incidental brain tumors. In this paper the authors review their experience diagnosing and treating these lesions in children as well as the current literature on this topic. Methods Records from 2 centers were reviewed for incidentally found brain tumors, treatment approaches, and outcomes for both surgical and nonsurgical cohorts. Results Forty-seven children (30 males and 17 females) with a mean age of 8.6 years were found to have incidental brain lesions suspected to be neoplasms. Twenty-five underwent surgery and 22 were observed. Two children in the observation group required surgery at a later stage. Tumor pathology in 24 patients was benign. Only 3 patients had high-grade tumors. All nonsurgically treated lesions were presumed to be low-grade tumors and were followed up for 25 ± 20 months. Conclusions The discovery of incidental brain tumors on MRI in children poses an increasing challenge. Additional studies are needed to determine the significance as well as the optimal management strategies in this situation.





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The incomplete infrastructure for interhospital patient transfer

imageObjective: Interhospital transfer of critically ill patients is a common part of their care. This article sought to review the data on the current patterns of use of interhospital transfer and identify systematic barriers to optimal integration of transfer as a mechanism for improving patient outcomes and value of care. Data Source: Narrative review of medical and organizational literature. Summary: Interhospital transfer of patients is common, but not optimized to improve patient outcomes. Although there is a wide variability in quality among hospitals of nominally the same capability, patients are not consistently transferred to the highest quality nearby hospital. Instead, transfer destinations are selected by organizational routines or non-patient-centered organizational priorities. Accomplishing a transfer is often quite difficult for sending hospitals. But once a transfer destination is successfully found, the mechanics of interhospital transfer now appear quite safe. Conclusion: Important technological advances now make it possible to identify nearby hospitals best able to help critically ill patients, and to successfully transfer patients to those hospitals. However, organizational structures have not yet developed to insure that patients are optimally routed, resulting in potentially significant excess mortality.





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Thursday, July 19, 2012

Pilot study of systemic and intrathecal mafosfamide followed by conformal radiation for infants with

Abstract  
A pilot study to investigate the feasibility of the addition of intrathecal (IT) mafosfamide to a regimen of concomitant multi-agent systemic chemotherapy followed by conformal radiation therapy (RT) for children <3 years with newly diagnosed embryonal CNS tumors was performed. Ninety-three newly diagnosed infants and children (<3 years) with embryonal CNS tumors were enrolled. Twenty weeks of systemic multi-agent chemotherapy commenced within 35 days of surgery. Patients without CSF flow obstruction (n = 71) received IT mafosfamide (14 mg) with chemotherapy. Localized (M0) patients with SD or better subsequently received RT followed by 20 additional weeks of chemotherapy. Second look surgery was encouraged prior to RT if there was an incomplete surgical resection at diagnosis. 71 evaluable patients with normal CSF flow received IT Mafosfamide with systemic chemotherapy; patients with M + disease were removed from protocol therapy at 20 weeks and those with PD at the time of progression. One and 5-year progression free survival (PFS) and overall survival (OS) for the cohort of 71 evaluable patients were 52 ± 6.5 % and 33 ± 13 %, and 67 ± 6.2 % and 51 ± 11 %, respectively. The 1-year Progression Free Survival (PFS) for M0 patients with medulloblastoma (MB, n = 20), supratentorial primitive neuroectodermal tumor (PNET, n = 9), and atypical teratoid rhabdoid tumor (ATRT, n = 12) was 80 ± 7 %, 67 ± 15 % and 27 ± 13 % and 5-year PFS was 65 ± 19 %, 37 ± 29 %, and 0 ± 0 %, respectively. The addition of IT mafosfamide to systemic chemotherapy in infants with embryonal CNS tumors was feasible. The PFS for M0 patients appears comparable to or better than most prior historical comparisons and was excellent for those receiving conformal radiotherapy.

  • Content Type Journal Article
  • Category Clinical Study - Patient Study
  • Pages 1-7
  • DOI 10.1007/s11060-012-0929-x
  • Authors
    • Susan M. Blaney, Texas Children's Cancer Center, Baylor College of Medicine, 6621 Fannin; CC 1410.00, Houston, TX 77030, USA
    • Mehmet Kocak, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
    • Amar Gajjar, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
    • Murali Chintagumpala, Texas Children's Cancer Center, Baylor College of Medicine, 6621 Fannin; CC 1410.00, Houston, TX 77030, USA
    • Thomas Merchant, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
    • Mark Kieran, Dana-Farber Cancer Institute and Children's Hospital Boston, Boston, MA 02115, USA
    • Ian F. Pollack, Children's Hospital of Pittsburgh, Pittsburgh, PA 15213, USA
    • Sri Gururangan, Duke University Medical Center, Durham, NC 27710, USA
    • Russ Geyer, Children's Hospital and Medical Center, Seattle, WA 98105, USA
    • Peter Phillips, Children's Hospital of Philadelphia, Philadelphia, PA 191044, USA
    • Roger E. McLendon, Duke University Medical Center, Durham, NC 27710, USA
    • Roger Packer, Children's National Medical Center, Washington, D.C., 20010 USA
    • Stewart Goldman, Children's Memorial Hospital, Chicago, IL 60614, USA
    • Anu Banerjee, University of California, San Francisco, CA 94143, USA
    • Richard Heideman, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
    • James M. Boyett, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
    • Larry Kun, St. Jude Children's Research Hospital, Memphis, TN 38105, USA





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Patient decision aids for cancer treatment

Abstract

BACKGROUND:

Although patient decision aids (pDAs) are effective, widespread use of pDAs for cancer treatment has not been achieved. The objectives of this study were to perform a systematic review to identify alternate types of decision support interventions (DSIs) for cancer treatment and a meta-analysis to compare the effectiveness of these DSIs to pDAs.

METHODS:

The inclusion criteria for the study were: 1) all published studies using a randomized, controlled trial design, and 2) DSIs involving treatment decision-making for breast, prostate, colorectal, and/or lung cancer. For this analysis, DSIs were classified as pDAs if: 1) one reported outcome measure mapped onto the International Patient Decision Aids Standards Collaboration effectiveness criterion, and 2) the DSI was evaluated relative to standard consultation. Random effects models were used to compare the effectiveness of pDAs relative to other identified DSIs for reported outcomes.

RESULTS:

A total of 71 studies were reviewed, and 24 met the inclusion criteria. Overall, there were no significant differences in knowledge, satisfaction, anxiety, or decisional conflict scores between pDAs and other DSIs.

CONCLUSIONS:

This study showed that the effectiveness of other DSIs, including question prompt lists and audiorecording of the consultation, is similar to pDAs. This is important because it may be that these less complex DSIs may be all that is necessary to achieve similar outcomes as pDAs for cancer treatment. Cancer 2012. © 2012 American Cancer Society.






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Wednesday, July 11, 2012

Reirradiation of recurrent meningioma

Publication year: 2012
Source:Journal of Clinical Neuroscience
Andrzej P. Wojcieszynski, Nitin Ohri, David W. Andrews, James J. Evans, Adam P. Dicker, Maria Werner-Wasik
Management of meningioma includes observation, resection, and radiation therapy (RT). For patients with recurrent disease, similar options exist. However, the control rate following a second course of RT for recurrent disease is unknown. We reviewed an institutional database of patients with meningioma treated with stereotactic radiosurgery or fractionated stereotactic RT who underwent a second course for recurrent disease. Cox regression model was used for analysis. Variables tested included tumor volume, RT type, tumor grade, age at diagnosis, time to progression, and interval between RT. Eleven of 19 patients (58%) experienced disease progression. Median time to second progression was 10months. Freedom from progression at one year was lower in patients with grade II or III tumors compared to those with grade 1 or unknown histology (17% compared to 92%, p =0.0054). Cox regression showed that a grade II–III tumor affects progression-free survival (PFS), with a hazard ratio of 5.37 (p =0.011). Median time to progression (MTP) for patients with grade II–III tumors was eight months. MTP was not reached for patients with grade 1/unknown tumors. Reirradiation for recurrent meningioma yields modest tumor control rates but for patients with grade II or III tumors, outcomes are poor.






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18 F-FDG PET-CT during chemo-radiotherapy in patients with non-small cell lung cancer: the early met

Background: To evaluate the metabolic changes on 18 F-fluoro-2-deoxyglucose positron emissiontomography integrated with computed tomography (18 F-FDG PET-CT) performed before,during and after concurrent chemo-radiotherapy in patients with locally advanced non-smallcell lung cancer (NSCLC); to correlate the metabolic response with the delivered radiationdose and with the clinical outcome. Methods: Twenty-five NSCLC patients candidates for concurrent chemo-radiotherapy underwent 18 FFDGPET-CT before treatment (pre-RT PET-CT), during the third week (during-RT PETCT)of chemo-radiotherapy, and 4 weeks from the end of chemo-radiotherapy (post-RT PETCT).The parameters evaluated were: the maximum standardized uptake value (SUVmax) ofthe primary tumor, the SUVmax of the lymph nodes, and the Metabolic Tumor Volume(MTV). Results: SUVmax of the tumor and MTV significantly (p=0.0001, p=0.002, respectively) decreasedearlier during the third week of chemo-radiotherapy, with a further reduction 4 weeks fromthe end of treatment (p<0.0000, p<0.0002, respectively). SUVmax of lymph nodes showed atrend towards a reduction during chemo-radiotherapy (p=0.06) and decreased significantly(p=0.0006) at the end of treatment. There was a significant correlation (r=0.53, p=0.001)between SUVmax of the tumor measured at during-RT PET-CT and the total dose ofradiotherapy reached at the moment of the scan. Disease progression free survival wassignificantly (p=0.01) longer in patients with complete metabolic response measured at post-RT PET-CT. Conclusions: In patients with locally advanced NSCLC, 18 F-FDG PET-CT performed during and aftertreatment allows early metabolic modifications to be detected, and for this SUVmax is themore sensitive parameter. Further studies are needed to investigate the correlation betweenthe metabolic modifications during therapy and the clinical outcome in order to optimize thetherapeutic strategy. Since the metabolic activity during chemo-radiotherapy correlates withthe cumulative dose of fractionated radiotherapy delivered at the moment of the scan, specialattention should be paid to methodological aspects, such as the radiation dose reached at thetime of PET.





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Brain Tumors Traced To Stem Cells In Developing Brain

Stem cells that come from a specific part of the developing brain help fuel the growth of brain tumors caused by an inherited condition, researchers at Washington University School of Medicine in St. Louis report...





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Being at home may soothe terminally ill cancer patients

For patients with terminal cancer who have exhausted all treatment options, being as comfortable and relaxed as possible during their final days often becomes a priority. Staying out of the hospital may be key to attaining that frame of mind, a new study suggests.





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Prescription dose and fractionation predict improved survival after stereotactic radiotherapy for br

Background: Brainstem metastases represent an uncommon clinical presentation that is associated with apoor prognosis. Treatment options are limited given the unacceptable risks associated withsurgical resection in this location. However, without local control, symptoms includingprogressive cranial nerve dysfunction are frequently observed. The objective of this studywas to determine the outcomes associated with linear accelerator-based stereotacticradiotherapy or radiosurgery (SRT/SRS) of brainstem metastases. Methods: We retrospectively reviewed 38 tumors in 36 patients treated with SRT/SRS betweenFebruary 2003 and December 2011. Treatment was delivered with the CyberknifeTM orTrilogyTM radiosurgical systems. The median age of patients was 62 (range: 28-89). Primarypathologies included 14 lung, 7 breast, 4 colon and 11 others. Sixteen patients (44%) hadreceived whole brain radiation therapy (WBRT) prior to SRT/SRS; ten had received priorSRT/SRS at a different site (28%). The median tumor volume was 0.94 cm3 (range: 0.01-4.2)with a median prescription dose of 17 Gy (range: 12-24) delivered in 1-5 fractions. Results: Median follow-up for the cohort was 3.2 months (range: 0.4-20.6). Nineteen patients (52%)had an MRI follow-up available for review. Of these, one patient experienced local failurecorresponding to an actuarial 6-month local control of 93%. Fifteen of the patients withavailable follow-up imaging (79%) experienced intracranial failure outside of the treatmentvolume. The median time to distant intracranial failure was 2.1 months. Six of the 15 patientswith distant intracranial failure (40%) had received previous WBRT. The actuarial overallsurvival rates at 6- and 12-months were 27% and 8%, respectively. Predictors of survivalincluded Graded Prognostic Assessment (GPA) score, greater number of treatment fractions,and higher prescription dose. Three patients experienced acute treatment-related toxicityconsisting of nausea (n = 1) and headaches (n = 2) that resolved with a short-course ofdexamethasone. Conclusion: SRT/SRS for brainstem metastases is safe and achieves a high rate of local control. We foundhigher GPA as well as greater number of treatment fractions and higher prescription dose tobe correlated with improved overall survival. Despite this approach, prognosis remains poorand distant intracranial control remains an issue, even in patients previously treated withWBRT.





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Isthmin inhibits glioma growth through antiangiogenesis in vivo

Abstract  
Among glioma treatment strategies, antiangiogenesis emerges as a meaningful and feasible treatment approach for inducing long-term survival. Isthmin is a gene highly expressed in the isthmus of the midbrain–hindbrain organizer in Xenopus, and has recently been identified as a novel angiogenesis inhibitor. However, the potential of isthmin on the glioma angiogenesis has not been well studied. In the present study, we demonstrated that the recombinant adenovirus isthmin (Ad-isthmin) could inhibit VEGF-stimulated endothelial cell proliferation and induce apoptosis through a caspase-dependent pathway. In addition, Ad-isthmin significantly suppressed glioma growth through antiangiogenesis without apparent side effects. Taken together, our results demonstrated that isthmin could act as a novel angiogenesis inhibitor and might be utilized in the glioma antiangiogenesis therapy.

  • Content Type Journal Article
  • Category Laboratory Investigation
  • Pages 1-8
  • DOI 10.1007/s11060-012-0910-8
  • Authors
    • Bangqing Yuan, Department of Neurosurgery, The 476th Hospital of Fuzhou General Hospital, Fuzhou, 350025 Fujian, China
    • Ronghua Xian, Department of Neurosurgery, The 476th Hospital of Fuzhou General Hospital, Fuzhou, 350025 Fujian, China
    • Jianfang Ma, Department of Neurosurgery, The 476th Hospital of Fuzhou General Hospital, Fuzhou, 350025 Fujian, China
    • Yujian Chen, Department of Neurosurgery, The 476th Hospital of Fuzhou General Hospital, Fuzhou, 350025 Fujian, China
    • Chuangan Lin, Department of Neurosurgery, The 476th Hospital of Fuzhou General Hospital, Fuzhou, 350025 Fujian, China
    • Yaoming Song, Department of Cardiovascular Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 China





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Stress Management May Prevent MS Lesions

Findings of a new study suggest an anti-inflammatory effect of a cognitive stress management intervention on occurrence of new lesions on imaging.
Medscape Medical News





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Saturday, July 7, 2012

Necrosis After Craniospinal Irradiation: Results From a Prospective Series of Children With Central

Purpose: Necrosis of the central nervous system (CNS) is a known complication of craniospinal irradiation (CSI) in children with medulloblastoma and similar tumors. We reviewed the incidence of necrosis in our prospective treatment series.Patients and Methods: Between 1996 and 2009, 236 children with medulloblastoma (n = 185) or other CNS embryonal tumors (n = 51) received postoperative CSI followed by dose-intense cyclophosphamide, vincristine, and cisplatin. Average risk cases (n = 148) received 23.4 Gy CSI, 36 Gy to the posterior fossa, and 55.8 Gy to the primary; after 2003, the treatment was 23.4 Gy CSI and 55.8 Gy to the primary. All high-risk cases (n = 88) received 36-39.6 Gy CSI and 55.8 Gy primary. The primary site clinical target volume margin was 2 cm (pre-2003) or 1 cm (post-2003). With competing risk of death by any cause, we determined the cumulative incidence of necrosis.Results: With a median follow-up of 52 months (range, 4-163 months), eight cases of necrosis were documented. One death was attributed. The median time to the imaging evidence was 4.8 months and to symptoms 6.0 months. The cumulative incidence at 5 years was 3.7% ± 1.3% (n = 236) for the entire cohort and 4.4% ± 1.5% (n = 196) for infratentorial tumor location. The mean relative volume of infratentorial brain receiving high-dose irradiation was significantly greater for patients with necrosis than for those without: ≥50 Gy (92.12% ± 4.58% vs 72.89% ± 1.96%; P=.0337), ≥52 Gy (88.95% ± 5.50% vs 69.16% ± 1.97%; P=.0275), and ≥54 Gy (82.28% ± 7.06% vs 63.37% ± 1.96%; P=.0488), respectively.Conclusions: Necrosis in patients with CNS embryonal tumors is uncommon. When competing risks are considered, the incidence is 3.7% at 5 years. The volume of infratentorial brain receiving greater than 50, 52, and 54 Gy, respectively, is predictive for necrosis.





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Fractionated Proton Radiotherapy for Benign Cavernous Sinus Meningiomas

Purpose: To evaluate the efficacy of fractionated proton radiotherapy for a population of patients with benign cavernous sinus meningiomas.Methods and Materials: Between 1991 and 2002, 72 patients were treated at Loma Linda University Medical Center with proton therapy for cavernous sinus meningiomas. Fifty-one patients had biopsy or subtotal resection; 47 had World Health Organization grade 1 pathology. Twenty-one patients had no histologic verification. Twenty-two patients received primary proton therapy; 30 had 1 previous surgery; 20 had more than 1 surgery. The mean gross tumor volume was 27.6 cm3; mean clinical target volume was 52.9 cm3. Median total doses for patients with and without histologic verification were 59 and 57 Gy, respectively. Mean and median follow-up periods were 74 months.Results: The overall 5-year actuarial control rate was 96%; the control rate was 99% in patients with grade 1 or absent histologic findings and 50% for those with atypical histology. All 21 patients who did not have histologic verification and 46 of 47 patients with histologic confirmation of grade 1 tumor demonstrated disease control at 5 years. Control rates for patients without previous surgery, 1 surgery, and 2 or more surgeries were 95%, 96%, and 95%, respectively.Conclusions: Fractionated proton radiotherapy for grade 1 cavernous sinus meningiomas achieves excellent control rates with minimal toxicities, regardless of surgical intervention or use of histologic diagnosis. Disease control for large lesions can be achieved by primary fractionated proton therapy.





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Early Clinical Outcomes Demonstrate Preserved Cognitive Function in Children With Average-Risk Medul

Purpose: To report on acute toxicity, longitudinal cognitive function, and early clinical outcomes in children with average-risk medulloblastoma.Methods and Materials: Twenty children ≥5 years of age classified as having average-risk medulloblastoma were accrued on a prospective protocol of hyperfractionated radiation therapy (HFRT) alone. Radiotherapy was delivered with two daily fractions (1 Gy/fraction, 6 to 8 hours apart, 5 days/week), initially to the neuraxis (36 Gy/36 fractions), followed by conformal tumor bed boost (32 Gy/32 fractions) for a total tumor bed dose of 68 Gy/68 fractions over 6 to 7 weeks. Cognitive function was prospectively assessed longitudinally (pretreatment and at specified posttreatment follow-up visits) with the Wechsler Intelligence Scale for Children to give verbal quotient, performance quotient, and full-scale intelligence quotient (FSIQ).Results: The median age of the study cohort was 8 years (range, 5–14 years), representing a slightly older cohort. Acute hematologic toxicity was mild and self-limiting. Eight (40%) children had subnormal intelligence (FSIQ <85), including 3 (15%) with mild mental retardation (FSIQ 56–70) even before radiotherapy. Cognitive functioning for all tested domains was preserved in children evaluable at 3 months, 1 year, and 2 years after completion of HFRT, with no significant decline over time. Age at diagnosis or baseline FSIQ did not have a significant impact on longitudinal cognitive function. At a median follow-up time of 33 months (range, 16–58 months), 3 patients had died (2 of relapse and 1 of accidental burns), resulting in 3-year relapse-free survival and overall survival of 83.5% and 83.2%, respectively.Conclusion: HFRT without upfront chemotherapy has an acceptable acute toxicity profile, without an unduly increased risk of relapse, with preserved cognitive functioning in children with average-risk medulloblastoma.





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Survival Benefit for Pediatric Patients With Recurrent Ependymoma Treated With Reirradiation

Purpose: The outcome of recurrent ependymoma in children is dismal. Reirradiation has been proposed as an effective modality for ependymoma at relapse. However, the toxicity and outcome benefits of this approach have not been well established.Methods and Materials: We conducted a retrospective population-based study of all patients with recurrent ependymoma treated between 1986 and 2010 in our institution. Demographic, treatment, and outcome data were analyzed for the entire cohort.Results: Of 113 patients with intracranial ependymoma, 47 patients relapsed. At the time of relapse, 29 patients were treated with surgical resection and/or chemotherapy, and 18 patients received full-dose (≥54 Gy focal and/or craniospinal) reirradiation with or without surgery at recurrence. Reirradiation was tolerated well with no severe acute complications noticed. Three-year overall survival was 7% ± 6% and 81% ± 12% for nonreirradiated and reirradiated patients, respectively (p < 0.0001). Time to second progression after reirradiation was significantly longer than time to first progression. This surprising phenomenon was associated with improved progression-free survival for tumors with evidence of DNA damage (n = 15; p = 0.002). At a mean follow-up of 3.73 years, only 2/18 patients had endocrine dysfunction, and 1 patient required special education support. However, a decline in intellectual function from pre- to postreirradiation assessment was observed.Conclusions: Reirradiation is an effective treatment that may change the natural history of recurrent ependymoma in children. However, this change may be associated with increased neurocognitive toxicity. Additional follow-up is needed to determine the risk of late recurrence, secondary radiation-induced tumors, and long-term functional outcome of these patients.





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Fractionated Stereotactic Radiotherapy of Vestibular Schwannomas Accelerates Hearing Loss

Objective: To evaluate long-term tumor control and hearing preservation rates in patients with vestibular schwannoma treated with fractionated stereotactic radiotherapy (FSRT), comparing hearing preservation rates to an untreated control group. The relationship between radiation dose to the cochlea and hearing preservation was also investigated.Methods and Materials: Forty-two patients receiving FSRT between 1997 and 2008 with a minimum follow-up of 2 years were included. All patients received 54 Gy in 27-30 fractions during 5.5-6.0 weeks. Clinical and audiometry data were collected prospectively. From a "wait-and-scan" group, 409 patients were selected as control subjects, matched by initial audiometric parameters. Radiation dose to the cochlea was measured using the original treatment plan and then related to changes in acoustic parameters.Results: Actuarial 2-, 4-, and 10-year tumor control rates were 100%, 91.5%, and 85.0%, respectively. Twenty-one patients had serviceable hearing before FSRT, 8 of whom (38%) retained serviceable hearing at 2 years after FSRT. No patients retained serviceable hearing after 10 years. At 2 years, hearing preservation rates in the control group were 1.8 times higher compared with the group receiving FSRT (P=.007). Radiation dose to the cochlea was significantly correlated to deterioration of the speech reception threshold (P=.03) but not to discrimination loss.Conclusion: FSRT accelerates the naturally occurring hearing loss in patients with vestibular schwannoma. Our findings, using fractionation of radiotherapy, parallel results using single-dose radiation. The radiation dose to the cochlea is correlated to hearing loss measured as the speech reception threshold.





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Single-fraction Radiosurgery for Presumed Intracranial Meningiomas: Efficacy and Complications From

Purpose: To define the rate of tumor control and factors associated with radiation-related complications after single-fraction radiosurgery (SRS) for patients with imaging defined intracranial meningiomas.Materials and Methods: Retrospective review of 251 patients (192 women, 59 men) having SRS for imaging-defined intracranial meningiomas between 1990 and 2008. Excluded were patients with radiation-induced tumors, meningiomatosis, or neurofibromatosis. The mean patient age was 58.6 ± 13.4 years. The majority of tumors involved the skull base/tentorium (n = 210, 83.7%). The mean treatment volume was 7.7 ± 6.2 cm3; the mean tumor margin dose was 15.8 ± 2.0 Gy. Follow-up (mean, 62.9 ± 43.9 months) was censored at last evaluation (n = 224), death (n = 22), or tumor resection (n = 5).Results: No patient died from tumor progression or radiation-related complications. Tumor size decreased in 181 patients (72.1%) and was unchanged in 67 patients (26.7%). Three patients (1.2%) had in-field tumor progression noted at 28, 145, and 150 months, respectively. No patient had a marginal tumor progression. The 3- and 10-year local control rate was 99.4%. One patient had distant tumor progression at 105 months and underwent repeat SRS. Thirty-one patients (12.4%) had either temporary (n = 8, 3.2%) or permanent (n = 23, 9.2%) symptomatic radiation-related complications including cranial nerve deficits (n = 14), headaches (n = 5), hemiparesis (n = 5), new/worsened seizure (n = 4), cyst-formation (n = 1), hemifacial spasm (n = 1), and stroke (n = 1). The 1- and 5-year complication rates were 8.3% and 11.5%, respectively. Radiation-related complications were associated with convexity/falx tumors (HR = 2.8, 95% CI 1.3–6.1, p = 0.009) and increasing tumor volume (HR = 1.05, 95% CI 1.0–1.1, p = 0.04) on multivariate analysis. No patient developed a radiation-induced tumor.Conclusions: Single-fraction SRS at the used dose range provides a high rate of tumor control for patients with imaging defined intracranial meningiomas. However, treatment failures were noted after 10 years emphasizing the need for long-term imaging follow-up after meningioma SRS.





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International Spine Radiosurgery Consortium Consensus Guidelines for Target Volume Definition in Spi

Purpose: Spinal stereotactic radiosurgery (SRS) is increasingly used to manage spinal metastases. However, target volume definition varies considerably and no consensus target volume guidelines exist. This study proposes consensus target volume definitions using common scenarios in metastatic spine radiosurgery.Methods and Materials: Seven radiation oncologists and 3 neurological surgeons with spinal radiosurgery expertise independently contoured target and critical normal structures for 10 cases representing common scenarios in metastatic spine radiosurgery. Each set of volumes was imported into the Computational Environment for Radiotherapy Research. Quantitative analysis was performed using an expectation maximization algorithm for Simultaneous Truth and Performance Level Estimation (STAPLE) with kappa statistics calculating agreement between physicians. Optimized confidence level consensus contours were identified using histogram agreement analysis and characterized to create target volume definition guidelines.Results: Mean STAPLE agreement sensitivity and specificity was 0.76 (range, 0.67-0.84) and 0.97 (range, 0.94-0.99), respectively, for gross tumor volume (GTV) and 0.79 (range, 0.66-0.91) and 0.96 (range, 0.92-0.98), respectively, for clinical target volume (CTV). Mean kappa agreement was 0.65 (range, 0.54-0.79) for GTV and 0.64 (range, 0.54-0.82) for CTV (P<.01 for GTV and CTV in all cases). STAPLE histogram agreement analysis identified optimal consensus contours (80% confidence limit). Consensus recommendations include that the CTV should include abnormal marrow signal suspicious for microscopic invasion and an adjacent normal bony expansion to account for subclinical tumor spread in the marrow space. No epidural CTV expansion is recommended without epidural disease, and circumferential CTVs encircling the cord should be used only when the vertebral body, bilateral pedicles/lamina, and spinous process are all involved or there is extensive metastatic disease along the circumference of the epidural space.Conclusions: This report provides consensus guidelines for target volume definition for spinal metastases receiving upfront SRS in common clinical situations.





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