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Composite pleomorphic xanthoastrocytoma-ganglioglioma (PXA-GG) is an extremely rare central nervous system neoplasm with 2 distinct but intermingled components. Whether this tumor represents a "collision tumor" of separate neoplasms or a monoclonal neoplasm with divergent evolution is poorly understood. Clinicopathologic studies and capture-based next generation sequencing were performed on extracted DNA from all available PXA-GG at 2 medical centers. Five PXA-GG were diagnosed in 1 male and 4 female patients ranging from 13 to 25 years in age. Four arose within the cerebral hemispheres; 1 presented in the cerebellar vermis. DNA was sufficient for analysis in 4 PXA components and 3 GG components. Four paired PXA and GG components harbored BRAF p.V600E hotspot mutations. The 4 sequenced PXA components demonstrated CDKN2A homozygous deletion by sequencing with loss of p16 (protein product of CDKN2A) expression by immunohistochemistry, which was intact in all assessed GG components. The PXA components also demonstrated more frequent copy number alterations relative to paired GG components. In one PXA-GG, shared chromosomal copy number alterations were identified in both components. Our findings support divergent evolution of the PXA and GG components from a common BRAF p.V600E-mutant precursor lesion, with additional acquisition of CDKN2A homozygous deletion in the PXA component as is typically seen in conventional PXA.

Introduction: The extent of meningioma resection is the most fundamental risk factor for recurrence, and exact knowledge of extent of resection is necessary for prognostication and for planning of adjuvant treatment. Currently used classifications are the EANO-grading and the Simpson grading. The former comprises radiological imaging with contrast-enhanced MRI and differentiation between “gross total removal” and “subtotal removal,” while the latter comprises a five-tiered differentiation of the surgeon’s impression of the extent of resection. The extent of resection of tumors is usually defined via analyses of resection margins but has until now not been implemented for meningiomas. PET/MRI imaging with 68Ga-DOTATOC allows more sensitive and specific imaging than MRI following surgery of meningiomas. Objective: To develop an objective grading system based on microscopic analyses of resection margins and sensitive radiological analyses to improve management of follow-up, adjuvant therapy, and prognostication of meningiomas. Based on the rationale of resection-margin analyses as gold standard and superior imaging performance of 68Ga DOTATOC PET, we propose “Copenhagen Grading” for meningiomas. Results: Copenhagen Grading was described for six pilot patients with examples of positive and negative findings on histopathology and DOTATOC PET scanning. The grading could be traceably implemented and parameters of grading appeared complementary. Copenhagen Grading is prospectively implemented as a clinical standard at Rigshospitalet, Copenhagen. Conclusion: Copenhagen Grading provided a comprehensive, logical, and reproducible definition of the extent of resection. It offers promise to be the most sensitive and specific imaging modality available for meningiomas. Clinical and cost-efficacy remain to be established during prospective implementation.

Large-scale molecular profiling studies in recent years have shown that central nervous system (CNS) tumors display a much greater heterogeneity in terms of molecularly distinct entities, cellular origins and genetic drivers than anticipated from histological assessment. DNA methylation profiling has emerged as a useful tool for robust tumor classification, providing new insights into these heterogeneous molecular classes. This is particularly true for rare CNS tumors with a broad morphological spectrum, which are not possible to assign as separate entities based on histological similarity alone. Here, we describe a molecularly distinct subset of predominantly pediatric CNS neoplasms (n = 60) that harbor PATZ1 fusions. The original histological diagnoses of these tumors covered a wide spectrum of tumor types and malignancy grades. While the single most common diagnosis was glioblastoma (GBM), clinical data of the PATZ1-fused tumors showed a better prognosis than typical GBM, despite frequent relapses. RNA sequencing revealed recurrent MN1:PATZ1 or EWSR1:PATZ1 fusions related to (often extensive) copy number variations on chromosome 22, where PATZ1 and the two fusion partners are located. These fusions have individually been reported in a number of glial/glioneuronal tumors, as well as extracranial sarcomas. We show here that they are more common than previously acknowledged, and together define a biologically distinct CNS tumor type with high expression of neural development markers such as PAX2, GATA2 and IGF2. Drug screening performed on the MN1:PATZ1 fusion-bearing KS-1 brain tumor cell line revealed preliminary candidates for further study. In summary, PATZ1 fusions define a molecular class of histologically polyphenotypic neuroepithelial tumors, which show an intermediate prognosis under current treatment regimens.

Large-scale molecular profiling studies in recent years have shown that central nervous system (CNS) tumors display a much greater heterogeneity in terms of molecularly distinct entities, cellular origins and genetic drivers than anticipated from histological assessment. DNA methylation profiling has emerged as a useful tool for robust tumor classification, providing new insights into these heterogeneous molecular classes. This is particularly true for rare CNS tumors with a broad morphological spectrum, which are not possible to assign as separate entities based on histological similarity alone. Here, we describe a molecularly distinct subset of predominantly pediatric CNS neoplasms (n = 60) that harbor PATZ1 fusions. The original histological diagnoses of these tumors covered a wide spectrum of tumor types and malignancy grades. While the single most common diagnosis was glioblastoma (GBM), clinical data of the PATZ1-fused tumors showed a better prognosis than typical GBM, despite frequent relapses. RNA sequencing revealed recurrent MN1:PATZ1 or EWSR1:PATZ1 fusions related to (often extensive) copy number variations on chromosome 22, where PATZ1 and the two fusion partners are located. These fusions have individually been reported in a number of glial/glioneuronal tumors, as well as extracranial sarcomas. We show here that they are more common than previously acknowledged, and together define a biologically distinct CNS tumor type with high expression of neural development markers such as PAX2, GATA2 and IGF2. Drug screening performed on the MN1:PATZ1 fusion-bearing KS-1 brain tumor cell line revealed preliminary candidates for further study. In summary, PATZ1 fusions define a molecular class of histologically polyphenotypic neuroepithelial tumors, which show an intermediate prognosis under current treatment regimens.

BACKGROUND: During the latest decades the hypothesis that the subjective experience of free will is determined by preconscious activity in the dominant dorsal medial frontal cortex (dMFC) has repeatedly challenged our commonly held concepts of moral responsibility. AIMS OF THE STUDY: To investigate whether dMFC activity determines the sense of free will and to investigate effects of resections in this area on Quality of life (QoL). METHODS: A cohort of nine patients affected by transient declines in speech and movement skills after surgery involving the left dMFC answered questions about their postoperative, subjective experiences of volition in relation to symptoms. In eight cases resections were performed as part of glioma surgery and in the ninth case a meningioma adjacent to the dMFC was resected. In addition, a QoL questionnaire was administrated before and after surgery. RESULTS: None of the patients perceived the transient disabilities related to surgery as associated with a loss or absence of volition. No declines in QoL were detected after surgery. Two QoL domains showed improved function (motor dysfunction and future uncertainty). CONCLUSIONS:The subjective sense of volition is not contingent on dMFC activity. Surgical resections of this area are not typically associated with declines in QoL.

BACKGROUND: During the latest decades the hypothesis that the subjective experience of free will is determined by preconscious activity in the dominant dorsal medial frontal cortex (dMFC) has repeatedly challenged our commonly held concepts of moral responsibility. AIMS OF THE STUDY: To investigate whether dMFC activity determines the sense of free will and to investigate effects of resections in this area on Quality of life (QoL). METHODS: A cohort of nine patients affected by transient declines in speech and movement skills after surgery involving the left dMFC answered questions about their postoperative, subjective experiences of volition in relation to symptoms. In eight cases resections were performed as part of glioma surgery and in the ninth case a meningioma adjacent to the dMFC was resected. In addition, a QoL questionnaire was administrated before and after surgery. RESULTS: None of the patients perceived the transient disabilities related to surgery as associated with a loss or absence of volition. No declines in QoL were detected after surgery. Two QoL domains showed improved function (motor dysfunction and future uncertainty). CONCLUSIONS:The subjective sense of volition is not contingent on dMFC activity. Surgical resections of this area are not typically associated with declines in QoL.

BACKGROUND: During the latest decades the hypothesis that the subjective experience of free will is determined by preconscious activity in the dominant dorsal medial frontal cortex (dMFC) has repeatedly challenged our commonly held concepts of moral responsibility. AIMS OF THE STUDY: To investigate whether dMFC activity determines the sense of free will and to investigate effects of resections in this area on Quality of life (QoL). METHODS: A cohort of nine patients affected by transient declines in speech and movement skills after surgery involving the left dMFC answered questions about their postoperative, subjective experiences of volition in relation to symptoms. In eight cases resections were performed as part of glioma surgery and in the ninth case a meningioma adjacent to the dMFC was resected. In addition, a QoL questionnaire was administrated before and after surgery. RESULTS: None of the patients perceived the transient disabilities related to surgery as associated with a loss or absence of volition. No declines in QoL were detected after surgery. Two QoL domains showed improved function (motor dysfunction and future uncertainty). CONCLUSIONS:The subjective sense of volition is not contingent on dMFC activity. Surgical resections of this area are not typically associated with declines in QoL.

BACKGROUND: During the latest decades the hypothesis that the subjective experience of free will is determined by preconscious activity in the dominant dorsal medial frontal cortex (dMFC) has repeatedly challenged our commonly held concepts of moral responsibility. AIMS OF THE STUDY: To investigate whether dMFC activity determines the sense of free will and to investigate effects of resections in this area on Quality of life (QoL). METHODS: A cohort of nine patients affected by transient declines in speech and movement skills after surgery involving the left dMFC answered questions about their postoperative, subjective experiences of volition in relation to symptoms. In eight cases resections were performed as part of glioma surgery and in the ninth case a meningioma adjacent to the dMFC was resected. In addition, a QoL questionnaire was administrated before and after surgery. RESULTS: None of the patients perceived the transient disabilities related to surgery as associated with a loss or absence of volition. No declines in QoL were detected after surgery. Two QoL domains showed improved function (motor dysfunction and future uncertainty). CONCLUSIONS:The subjective sense of volition is not contingent on dMFC activity. Surgical resections of this area are not typically associated with declines in QoL.

BACKGROUND: During the latest decades the hypothesis that the subjective experience of free will is determined by preconscious activity in the dominant dorsal medial frontal cortex (dMFC) has repeatedly challenged our commonly held concepts of moral responsibility. AIMS OF THE STUDY: To investigate whether dMFC activity determines the sense of free will and to investigate effects of resections in this area on Quality of life (QoL). METHODS: A cohort of nine patients affected by transient declines in speech and movement skills after surgery involving the left dMFC answered questions about their postoperative, subjective experiences of volition in relation to symptoms. In eight cases resections were performed as part of glioma surgery and in the ninth case a meningioma adjacent to the dMFC was resected. In addition, a QoL questionnaire was administrated before and after surgery. RESULTS: None of the patients perceived the transient disabilities related to surgery as associated with a loss or absence of volition. No declines in QoL were detected after surgery. Two QoL domains showed improved function (motor dysfunction and future uncertainty). CONCLUSIONS:The subjective sense of volition is not contingent on dMFC activity. Surgical resections of this area are not typically associated with declines in QoL.

BACKGROUND: During the latest decades the hypothesis that the subjective experience of free will is determined by preconscious activity in the dominant dorsal medial frontal cortex (dMFC) has repeatedly challenged our commonly held concepts of moral responsibility. AIMS OF THE STUDY: To investigate whether dMFC activity determines the sense of free will and to investigate effects of resections in this area on Quality of life (QoL). METHODS: A cohort of nine patients affected by transient declines in speech and movement skills after surgery involving the left dMFC answered questions about their postoperative, subjective experiences of volition in relation to symptoms. In eight cases resections were performed as part of glioma surgery and in the ninth case a meningioma adjacent to the dMFC was resected. In addition, a QoL questionnaire was administrated before and after surgery. RESULTS: None of the patients perceived the transient disabilities related to surgery as associated with a loss or absence of volition. No declines in QoL were detected after surgery. Two QoL domains showed improved function (motor dysfunction and future uncertainty). CONCLUSIONS:The subjective sense of volition is not contingent on dMFC activity. Surgical resections of this area are not typically associated with declines in QoL.

Paediatric high-grade gliomas, including glioblastoma and anaplastic astrocytoma, make up 8%-12% of paediatric central nervous system tumours 1 and have poor prognosis, with 2-year survival less than 30% 2 and overall survival less than 10%. The only known prognostic factors in this population include extent of resection and tumour histological grade. We present the case of a 9-year-old boy with disseminated anaplastic astrocytoma treated with subtotal resection, craniospinal radiation and temozolomide, with 8-year survival despite metastatic disease at presentation and subtotal resection. Next generation cancer gene panel sequencing revealed an usual pattern of 12 amplifications and four mutations not previously described.

We present the case of a 13-year-old boy with a very unusual periventricular atypical central neurocytoma with unique molecular features treated with subtotal surgical resection and photon intensity-modulated radiotherapy. Histological features were most consistent with atypical central neurocytoma. However, next-generation sequencing analysis revealed a novel EWSR1-ATF1 gene fusion (EWSR1-ATF1) as well as a MUTYH mutation. The EWSR1-ATF1 raised the possibility of Ewing sarcoma or angiomatoid fibrous histiocytoma, however, FLI-1 immunohistochemistry was negative. MUTYH mutations have been reported in diffuse midline paediatric glioma. The role of EWSR1-ATF1 and MUTYH mutations in central nervous system tumours is not well established. We present the first case of EWSR1-ATF1 and MUTYH mutation in a rare paediatric atypical central neurocytoma. Further studies are indicated to elucidate the consequences of these gene alterations in the context of paediatric central nervous system tumours as well as to investigate the potential role for targeted therapies.

We present the case of a 13-year-old boy with a very unusual periventricular atypical central neurocytoma with unique molecular features treated with subtotal surgical resection and photon intensity-modulated radiotherapy. Histological features were most consistent with atypical central neurocytoma. However, next-generation sequencing analysis revealed a novel EWSR1-ATF1 gene fusion (EWSR1-ATF1) as well as a MUTYH mutation. The EWSR1-ATF1 raised the possibility of Ewing sarcoma or angiomatoid fibrous histiocytoma, however, FLI-1 immunohistochemistry was negative. MUTYH mutations have been reported in diffuse midline paediatric glioma. The role of EWSR1-ATF1 and MUTYH mutations in central nervous system tumours is not well established. We present the first case of EWSR1-ATF1 and MUTYH mutation in a rare paediatric atypical central neurocytoma. Further studies are indicated to elucidate the consequences of these gene alterations in the context of paediatric central nervous system tumours as well as to investigate the potential role for targeted therapies.

Paediatric high-grade gliomas, including glioblastoma and anaplastic astrocytoma, make up 8%-12% of paediatric central nervous system tumours 1 and have poor prognosis, with 2-year survival less than 30% 2 and overall survival less than 10%. The only known prognostic factors in this population include extent of resection and tumour histological grade. We present the case of a 9-year-old boy with disseminated anaplastic astrocytoma treated with subtotal resection, craniospinal radiation and temozolomide, with 8-year survival despite metastatic disease at presentation and subtotal resection. Next generation cancer gene panel sequencing revealed an usual pattern of 12 amplifications and four mutations not previously described.

We present the case of a 13-year-old boy with a very unusual periventricular atypical central neurocytoma with unique molecular features treated with subtotal surgical resection and photon intensity-modulated radiotherapy. Histological features were most consistent with atypical central neurocytoma. However, next-generation sequencing analysis revealed a novel EWSR1-ATF1 gene fusion (EWSR1-ATF1) as well as a MUTYH mutation. The EWSR1-ATF1 raised the possibility of Ewing sarcoma or angiomatoid fibrous histiocytoma, however, FLI-1 immunohistochemistry was negative. MUTYH mutations have been reported in diffuse midline paediatric glioma. The role of EWSR1-ATF1 and MUTYH mutations in central nervous system tumours is not well established. We present the first case of EWSR1-ATF1 and MUTYH mutation in a rare paediatric atypical central neurocytoma. Further studies are indicated to elucidate the consequences of these gene alterations in the context of paediatric central nervous system tumours as well as to investigate the potential role for targeted therapies.

Paediatric high-grade gliomas, including glioblastoma and anaplastic astrocytoma, make up 8%-12% of paediatric central nervous system tumours 1 and have poor prognosis, with 2-year survival less than 30% 2 and overall survival less than 10%. The only known prognostic factors in this population include extent of resection and tumour histological grade. We present the case of a 9-year-old boy with disseminated anaplastic astrocytoma treated with subtotal resection, craniospinal radiation and temozolomide, with 8-year survival despite metastatic disease at presentation and subtotal resection. Next generation cancer gene panel sequencing revealed an usual pattern of 12 amplifications and four mutations not previously described.

Central nervous system tumors are the leading cause of cancer related death in children. Despite much progress in the field of pediatric neurooncology, modern combination treatment regimens often result in significant late effects, such as neurocognitive deficits, endocrine dysfunction, secondary malignancies, and a host of other chronic health problems. Precision medicine strategies applied to pediatric neurooncology target specific characteristics of individual patients' tumors to achieve maximal killing of neoplastic cells while minimizing unwanted adverse effects. Here, we review emerging trends and the current literature that have guided the development of new molecularly based classification schemas, promising diagnostic techniques, targeted therapies, and delivery platforms for the treatment of pediatric central nervous system tumors.

Менінгіома є найчастішою інтракраніальною пухлиною у дорослих. Часто епілепсія є основним клінічним проявом менінгіоми. Хірургічне лікування є методом вибору у пацієнтів з вперше діагностованими менінгіомами. Ранній результати операції та вплив операцій на симптоматичну епілепсію добре вивчені. Однак віддалені результати малодосліджені.Мета дослідження. Оцінити віддалені результати хірургічного лікування супратенторіальних менінгіом головного мозку та провести їх порівняння із ранніми. Дослідити динаміку симптоматичної епілепсії у цих пацієнтів.Матеріали та методи: Проведено ретроспективний аналіз перебігу захворювання у 110 пацієнтів із тотально видаленою супратенторіальною менінгіомою головного мозку. Оцінено віддалені результати ефективності хірургічного лікування. Середня тривалість спостереження становила 48 місяців (13-83).Результати: Неврологічний дефіцит в доопераційному періоді спостерігався у 50 пацієнтів; на момент виписки у 40, при оцінці в віддаленому період - у 12, з 36 оцінених. У двох пацієнтів мала місце гематома ложа видаленої пухлини. Післяопераційна летальність становила 1,8 % - два пацієнти із судинними ускладненнями. 30 із 40 пацієнтів, які мали епілепсію до операції стали вільними від нападів після втручання. У 10 з 40 пацієнтів епілепсія зберігалася.. В тому числі у 2-х пацієнтів через продовжений ріст менінгіоми. У 7 пацієнтів із 70, які не мали нападів до операції, виникли напади у ранньому та/або пізньому післяопераційному періоді з різних причин. 87 (79 %) пухлин були вискодиференційованими, анапластична менінігіома виявлена у 5 (4,5 %) пацієнтів.Висновок: Тотальне видалення менінгіоми дозволяє досягнути хороших віддалених результатів. В нашій серії випадків неврологічний дефіцит при тривалому спостереженні зберігся тільки у 12 (11 %) з 50 (45,4 %) пацієнтів, які мали його до операції. Симптоматична епілепсія регресувала у 75 % пацієнтів. Відмічалася поява нападів у 7 пацієнтів з 70 в кого епінападу до операції не спостерігалися. Гістолог, Менингиома является наиболее частой интракраниальной опухолью у взрослых. Часто эпилепсия является основным клиническим проявлением менингиомы. Хирургическое лечение является методом выбора у пациентов с впервые диагностированными менингиомами. Ранний результаты операции и влияние операций на симптоматическую эпилепсию хорошо изучены. Однако отдаленные результаты малоизученные.Цель исследования. Оценка отдаленных результатов хирургического лечения супратенториальных менингиом головного мозга и проведения их сравнение с ранними. Исследовать динамику симптоматической эпилепсии у этих пациентов.Материалы и методы: Проведен ретроспективный анализ течения заболевания у 110 пациентов с тотально удаленной супратенториальной менингиомой головного мозга. Оценены отдаленные результаты эффективности хирургического лечения. Средняя продолжительность наблюдения составила 48 месяцев (13-83).Результаты. Неврологический дефицит в дооперационном периоде наблюдался у 50 пациентов; на момент выписки в 40, при оценке в отдаленном период - в 12 из 36 оцененных. У двух пациентов имела место гематома ложа удаленной опухоли. Послеоперационная летальность составила 1,8 % - два пациента с сосудистыми осложнениями. 30 из 40 пациентов, которые имели эпилепсию до операции, стали свободными от приступов после хирургического лечения. В 10 из 40 пациентов эпилепсия сохранялась.. В том числе в 2-х пациентов в связи с продолженным ростом менингиомы. У 7 пациентов из 70, которые не имели приступов до операции, возникли приступы в раннем и/или позднем послеоперационном периоде по разным причинам. 87 (79 %) опухолей были высокодифернцированые, анапластическая менингиома выявлена у 5 (4,5 %) пациентов.Выводы: Тотальное удаление менингиомы позволяет достичь хороших отдаленных результатов. В нашей серии случаев неврологический дефицит при длительном наблюдении сохранился только у 12 (11 %) из 50 (45,4 %) пациентов, имевших его к операции. Симптоматическая эпилепсия регрессировал у 75 % пациентов. Отмечала, Meningioma is the most common intracranial tumor in adults. Often epilepsy is a major clinical manifestation of meningioma. Surgical treatment is a method of choice in patients with meningioma. The early results of the operation and the impact of operations on symptomatic epilepsy are well studied. However, long-term results are poorly investigated.Aim: We were interested in the evaluation of long-term results of surgical treatment of supratentorial meningiomas of the brain and their comparison with the early, as well as the dynamics of symptomatic epilepsy in these patients.Materials and methods: A retrospective analysis of the course of the disease was performed in 110 patients with totally removed supratentorial meningioma of the brain. The long-term results of the effectiveness of surgical treatment are evaluated. The average duration of observation was 48 months (13-83).Results: Neurological deficiency in the preoperative period was observed in 50 patients; at the time of discharge in 40, with an assessment in the distant period - in 12, out of 36 evaluated. Two patients had a hematoma in the removed tumor bed. Postoperative lethality was 1.8% - two patients with vascular complications. 30 of the 40 patients who had epilepsy before the operation became free of attacks after the intervention. In 10 of 40 patients, epilepsy remained. Including 2 patients due to continued growth of meningiomas. In 7 of the 70 patients who did not have attacks before surgery, there were early and / or late postoperative seizures for various reasons. 87 (79%) of tumors were highly differentiated, anaplastic meningioma was detected in 5 (4.5%) patientsConclusions: Total removal of meningiomas can achieve good long-term results. In our series of cases, only 12 (11%) of the neurological deficits with long-term observation were observed in 50 (45.4%) patients who had prior surgery. Symptomatic epilepsy was regressed in 75% of patients. There was an appearance of attacks in 7 patients w

Central nervous system tumors are the leading cause of cancer related death in children. Despite much progress in the field of pediatric neurooncology, modern combination treatment regimens often result in significant late effects, such as neurocognitive deficits, endocrine dysfunction, secondary malignancies, and a host of other chronic health problems. Precision medicine strategies applied to pediatric neurooncology target specific characteristics of individual patients' tumors to achieve maximal killing of neoplastic cells while minimizing unwanted adverse effects. Here, we review emerging trends and the current literature that have guided the development of new molecularly based classification schemas, promising diagnostic techniques, targeted therapies, and delivery platforms for the treatment of pediatric central nervous system tumors.

Despite the fact that they are not typically life-threatening, low-grade gliomas (LGGs) remain a significant clinical challenge in pediatric neuro-oncology due to comorbidities associated with these tumors and/or their treatments, and their propensity to multiply recurs. LGGs, in total the most common brain tumors arising in childhood, can often become a chronic problem requiring decades of management. The Second International Consensus Conference on Pediatric Low-Grade Gliomas held in Padua, Italy in 2016 was convened in an attempt to advance the pace of translating biological discoveries on LGGs into meaningful clinical benefit. Topics discussed included: the implications of our growing biological understanding of the genomics underlying these tumors; the assessment of the model systems available; the implications of the molecular and histopathologic differences between adult and pediatric diffuse gliomas; and steps needed to expedite targeted therapy into late-stage clinical trials for newly diagnosed cases. Methods for the diagnostic assessment of alterations in the Ras/mitogen-activated protein kinase pathway, typical for these tumors, were also considered. While the overall tone was positive, with a consensus that progress is being and will continue to be made, the scale of the challenge presented by this complex group of tumors was also acknowledged. The conclusions and recommendations of the meeting panel are provided here as an outline of current thinking and a basis for further discussion.

Among childhood cancer survivors, increased stroke risk after cranial radiation therapy may be caused by radiation-induced arteriopathy, but limited data exist to support this hypothesis. Herein, we assess the timing and presence of cerebral arteriopathy identified by magnetic resonance angiography (MRA) after cranial radiation therapy in childhood brain tumor survivors. In a cohort of 115 pediatric brain tumor survivors, we performed chart abstraction and prospective annual follow-up to assess the presence of large vessel cerebral arteriopathy by MRA. We identified 10 patients with cerebral arteriopathy. The cumulative incidence of arteriopathy 5 years post-cranial radiation therapy was 5.4% (CI 0.6%-10%) and 10 years was 16% (CI 4.6%-26%). One patient had an arterial ischemic stroke 2.4 years post-cranial radiation therapy in the distribution of a radiation-induced stenotic artery. We conclude that large vessel arteriopathies can occur within a few years of cranial radiation therapy and can become apparent on MRA in under a year.

While magnetic resonance imaging (MRI) is the gold-standard imaging modality for diagnosis of intracranial neoplasia, computed tomography (CT) remains commonly used for diagnosis and therapeutic planning in veterinary medicine. Despite the routine use of both imaging modalities, comparison of CT and MRI has not been described in the canine patient. A retrospective study was performed to evaluate CT and MRI studies of 15 dogs with histologically confirmed glioma. Multiple lesion measurements were obtained, including two-dimensional and volumetric dimensions in pre-contrast and post-contrast images. Similar measurement techniques were compared between CT and MRI. The glioma type (astrocytoma or oligodendroglioma) and grade (high or low) were predicted on CT and MRI independently. With the exception of the comparison between CT pre-contrast volume to T2-weighted MRI volume, no other statistical differences between CT and MRI measurements were identified. Overall accuracy for tumor grade (high or low) was 46.7 and 53.3% for CT and MRI, respectively. For predicted tumor type, accuracy of CT was 53.3% and MRI and MRI 60%. Based on the results of this study, both CT and MRI contrast measurement techniques are considered equivalent options for lesion mensuration. Given the low-to-moderate predictability of CT and MRI in glioma diagnosis, histopathology remains necessary for accurate diagnosis of canine brain tumors.

While magnetic resonance imaging (MRI) is the gold-standard imaging modality for diagnosis of intracranial neoplasia, computed tomography (CT) remains commonly used for diagnosis and therapeutic planning in veterinary medicine. Despite the routine use of both imaging modalities, comparison of CT and MRI has not been described in the canine patient. A retrospective study was performed to evaluate CT and MRI studies of 15 dogs with histologically confirmed glioma. Multiple lesion measurements were obtained, including two-dimensional and volumetric dimensions in pre-contrast and post-contrast images. Similar measurement techniques were compared between CT and MRI. The glioma type (astrocytoma or oligodendroglioma) and grade (high or low) were predicted on CT and MRI independently. With the exception of the comparison between CT pre-contrast volume to T2-weighted MRI volume, no other statistical differences between CT and MRI measurements were identified. Overall accuracy for tumor grade (high or low) was 46.7 and 53.3% for CT and MRI, respectively. For predicted tumor type, accuracy of CT was 53.3% and MRI and MRI 60%. Based on the results of this study, both CT and MRI contrast measurement techniques are considered equivalent options for lesion mensuration. Given the low-to-moderate predictability of CT and MRI in glioma diagnosis, histopathology remains necessary for accurate diagnosis of canine brain tumors.

While magnetic resonance imaging (MRI) is the gold-standard imaging modality for diagnosis of intracranial neoplasia, computed tomography (CT) remains commonly used for diagnosis and therapeutic planning in veterinary medicine. Despite the routine use of both imaging modalities, comparison of CT and MRI has not been described in the canine patient. A retrospective study was performed to evaluate CT and MRI studies of 15 dogs with histologically confirmed glioma. Multiple lesion measurements were obtained, including two-dimensional and volumetric dimensions in pre-contrast and post-contrast images. Similar measurement techniques were compared between CT and MRI. The glioma type (astrocytoma or oligodendroglioma) and grade (high or low) were predicted on CT and MRI independently. With the exception of the comparison between CT pre-contrast volume to T2-weighted MRI volume, no other statistical differences between CT and MRI measurements were identified. Overall accuracy for tumor grade (high or low) was 46.7 and 53.3% for CT and MRI, respectively. For predicted tumor type, accuracy of CT was 53.3% and MRI and MRI 60%. Based on the results of this study, both CT and MRI contrast measurement techniques are considered equivalent options for lesion mensuration. Given the low-to-moderate predictability of CT and MRI in glioma diagnosis, histopathology remains necessary for accurate diagnosis of canine brain tumors.

This report describes the methodology, diagnostic yield, and adverse events (AE) associated with frame-based stereotactic brain biopsies (FBSB) obtained from 26 dogs with solitary forebrain lesions. Medical records were reviewed from dogs that underwent FBSB using two stereotactic headframes designed for use in small animals and compatible with computed tomographic (CT) and magnetic resonance (MR) imaging. Stereotactic plans were generated from MR and CT images using commercial software, and FBSB performed both with (14/26) and without intraoperative image guidance. Records were reviewed for diagnostic yield, defined as the proportion of biopsies producing a specific neuropathological diagnosis, AE associated with FBSB, and risk factors for the development of AE. Postprocedural AE were evaluated in 19/26 dogs that did not proceed to a therapeutic intervention immediately following biopsy. Biopsy targets included intra-axial telencephalic masses (24/26), one intra-axial diencephalic mass, and one extra-axial parasellar mass. The median target volume was 1.99 cm(3). No differences in patient, lesion, or outcome variables were observed between the two headframe systems used or between FBSB performed with or without intraoperative CT guidance. The diagnostic yield of FBSB was 94.6%. Needle placement error was a significant risk factor associated with procurement of non-diagnostic biopsy specimens. Gliomas were diagnosed in 24/26 dogs, and meningioma and granulomatous meningoencephalitis in 1 dog each. AE directly related to FBSB were observed in a total of 7/26 (27%) of dogs. Biopsy-associated clinical morbidity, manifesting as seizures and transient neurological deterioration, occurred in 3/19 (16%) of dogs. The case fatality rate was 5.2% (1/19 dogs), with death attributable to intracranial hemorrhage. FBSB using the described apparatus was relatively safe and effective at providing neuropathological diagnoses in dogs with focal forebrain lesions.

What makes a high-quality biomarker experiment? The success of personalized medicine hinges on the answer to this question. Unfortunately, as many commentators have now emphasized, the quality of most biomarker experiments to date has been quite low. Although the technical side of this problem has received considerable attention, the philosophical issues remain largely unexplored. In this paper, I argue that understanding what constitutes a high-quality biomarker experiment requires some fundamental shifts in how we think about the epistemology, ontology, and methodology of clinical translation., ¿Qué convierte a un experimento con biomarcadores en un experimento de gran calidad? El éxito de la medicina personalizada depende de la respuesta a esta pregunta. En este artículo sostengo que el juicio sobre la calidad de los experimentos con biomarcadores está mediado por el problema de la subdeterminación teórica, es decir, la red de teorías biológicas y patofisiológicas que motivan un experimento con biomarcadores es lo bastante complicada como para frustrar a menudo una interpretación válida de los resultados experimentales. A partir de un caso de desarrollo de diagnóstico con biomarcadores, defiendo que el problema de la subdeterminación puede ser superado con mayor coordinación en la trayectoria de investigación sobre el biomarcador. Después sugiero un enfoque para evaluar la coordinación a lo largo de una trayectoria de investigación. Por último concluyo que lo que hace que un experimento con biomarcadores tenga una alta calidad debe dirimirse en función de la contribución epistémica que aquél realiza sobre este esfuerzo investigador coordinado.

Despite various treatment strategies being available, recurrent high-grade gliomas (r-HGG) are difficult to manage. To obtain local control, radiosurgery (SRS) reirradiation has been considered as potential treatment. In the present study, a retrospective analysis was performed on r-HGG patients treated with salvage single- (s-SRS) or multi-fraction SRS (m-SRS). The aim of this study was to evaluate the effectiveness of salvage SRS in terms of overall survival (OS); toxicity was analyzed as well. Between 2004 May and 2011 December, 128 r-HGG patients (161 lesions) treated with CyberKnife(®) SRS reirradiation were retrospectively analyzed. Toxicity was graded according to Radiation Therapy Oncology Group and by Common Terminology Criteria for Adverse Events v.3 criteria. OS from the diagnosis date and OS from reirradiation were estimated using the Kaplan-Meier method. Median follow-up was 9 months (range 15 days-82 months). All patients completed SRS without high-grade toxicity. Radiation necrosis was observed in seven patients (6 %) with large volume lesions. The median survival from initial diagnosis was 32 months. The 1-, 2-, and 3-years survival rates from diagnosis were 95, 62, and 45 % respectively. Median survival following SRS was 11.5 months. The 1-, 2-, and 3-years survival rate following SRS was 48, 20, and 17 % respectively. On multivariate analysis, age <40 years, salvage surgery before SRS, and other post-SRS therapies (second-line chemotherapy and/or surgery) were found to significantly improve survival (p = 0.03). SRS represents a safe and feasible option to treat r-HGG patients with low complication rates and potential survival benefit

What makes a high-quality biomarker experiment? The success of personalized medicine hinges on the answer to this question. Unfortunately, as many commentators have now emphasized, the quality of most biomarker experiments to date has been quite low. Although the technical side of this problem has received considerable attention, the philosophical issues remain largely unexplored. In this paper, I argue that understanding what constitutes a high-quality biomarker experiment requires some fundamental shifts in how we think about the epistemology, ontology, and methodology of clinical translation., ¿Qué convierte a un experimento con biomarcadores en un experimento de gran calidad? El éxito de la medicina personalizada depende de la respuesta a esta pregunta. En este artículo sostengo que el juicio sobre la calidad de los experimentos con biomarcadores está mediado por el problema de la subdeterminación teórica, es decir, la red de teorías biológicas y patofisiológicas que motivan un experimento con biomarcadores es lo bastante complicada como para frustrar a menudo una interpretación válida de los resultados experimentales. A partir de un caso de desarrollo de diagnóstico con biomarcadores, defiendo que el problema de la subdeterminación puede ser superado con mayor coordinación en la trayectoria de investigación sobre el biomarcador. Después sugiero un enfoque para evaluar la coordinación a lo largo de una trayectoria de investigación. Por último concluyo que lo que hace que un experimento con biomarcadores tenga una alta calidad debe dirimirse en función de la contribución epistémica que aquél realiza sobre este esfuerzo investigador coordinado.

This report describes the methodology, diagnostic yield, and adverse events (AE) associated with frame-based stereotactic brain biopsies (FBSB) obtained from 26 dogs with solitary forebrain lesions. Medical records were reviewed from dogs that underwent FBSB using two stereotactic headframes designed for use in small animals and compatible with computed tomographic (CT) and magnetic resonance (MR) imaging. Stereotactic plans were generated from MR and CT images using commercial software, and FBSB performed both with (14/26) and without intraoperative image guidance. Records were reviewed for diagnostic yield, defined as the proportion of biopsies producing a specific neuropathological diagnosis, AE associated with FBSB, and risk factors for the development of AE. Postprocedural AE were evaluated in 19/26 dogs that did not proceed to a therapeutic intervention immediately following biopsy. Biopsy targets included intra-axial telencephalic masses (24/26), one intra-axial diencephalic mass, and one extra-axial parasellar mass. The median target volume was 1.99 cm(3). No differences in patient, lesion, or outcome variables were observed between the two headframe systems used or between FBSB performed with or without intraoperative CT guidance. The diagnostic yield of FBSB was 94.6%. Needle placement error was a significant risk factor associated with procurement of non-diagnostic biopsy specimens. Gliomas were diagnosed in 24/26 dogs, and meningioma and granulomatous meningoencephalitis in 1 dog each. AE directly related to FBSB were observed in a total of 7/26 (27%) of dogs. Biopsy-associated clinical morbidity, manifesting as seizures and transient neurological deterioration, occurred in 3/19 (16%) of dogs. The case fatality rate was 5.2% (1/19 dogs), with death attributable to intracranial hemorrhage. FBSB using the described apparatus was relatively safe and effective at providing neuropathological diagnoses in dogs with focal forebrain lesions.

This report describes the methodology, diagnostic yield, and adverse events (AE) associated with frame-based stereotactic brain biopsies (FBSB) obtained from 26 dogs with solitary forebrain lesions. Medical records were reviewed from dogs that underwent FBSB using two stereotactic headframes designed for use in small animals and compatible with computed tomographic (CT) and magnetic resonance (MR) imaging. Stereotactic plans were generated from MR and CT images using commercial software, and FBSB performed both with (14/26) and without intraoperative image guidance. Records were reviewed for diagnostic yield, defined as the proportion of biopsies producing a specific neuropathological diagnosis, AE associated with FBSB, and risk factors for the development of AE. Postprocedural AE were evaluated in 19/26 dogs that did not proceed to a therapeutic intervention immediately following biopsy. Biopsy targets included intra-axial telencephalic masses (24/26), one intra-axial diencephalic mass, and one extra-axial parasellar mass. The median target volume was 1.99 cm(3). No differences in patient, lesion, or outcome variables were observed between the two headframe systems used or between FBSB performed with or without intraoperative CT guidance. The diagnostic yield of FBSB was 94.6%. Needle placement error was a significant risk factor associated with procurement of non-diagnostic biopsy specimens. Gliomas were diagnosed in 24/26 dogs, and meningioma and granulomatous meningoencephalitis in 1 dog each. AE directly related to FBSB were observed in a total of 7/26 (27%) of dogs. Biopsy-associated clinical morbidity, manifesting as seizures and transient neurological deterioration, occurred in 3/19 (16%) of dogs. The case fatality rate was 5.2% (1/19 dogs), with death attributable to intracranial hemorrhage. FBSB using the described apparatus was relatively safe and effective at providing neuropathological diagnoses in dogs with focal forebrain lesions.