Primary Extra-axial Glioblastoma: Case Report and Literature Review

Glioblastoma multiforme (GBM) is the most frequent and most aggressive primary brain tumor in adults,mainly located in the cerebral hemispheres. In the literature, few cases of primary GBM have been reported to have radiographic and intraoperative features of extra-axial lesions, leading to a diagnostic dilemma. Despite the advances in imaging modalities, the diagnosis of GBM can be challenging, and it is mainly based on the histopathologic confirmation of the excised tumor. We describe the case of a 76- year-old previously healthy female patient who presented to our hospital due to speech disturbances and cognitive impairment. The diagnosis of the tumor type on magnetic resonance imaging (MRI) was difficult, as the findings were suggestive of a malignant meningioma due to the heterogeneous enhancement of a dural-based mass with a dural tail sign. Moreover, the intraoperative findings revealed an extra-axial mass attached to the dura. A histological examination confirmed the diagnosis of glioblastoma with arachnoid infiltration. The patient underwent adjuvant radiotherapy and concomitant temozolomide treatment, she had clinical improvement postoperatively, and was stable during the six months of follow-up. Glioblastoma should be considered in the differential diagnosis of primary extra-axial mass with atypical and malignant features, especially in elderly patients.

Estudio de una cohorte uruguaya de pacientes portadores de Glioblastoma tratados con radioterapia y Temozolamida / Analysis of a Uruguayan cohort of patients with Glioblastoma treated with radiotherapy and Temozalamide

Objetivos: conocer la sobrevida a dos años de pacientes con diagnóstico de Glioblastoma multiforme (GBM) tratados con Temozolamida con cobertura del Fondo Nacional de Recursos (FNR), evaluar la seguridad del tratamiento y los factores pronósticos. Metodología: cohorte de pacientes portadores de GBM, tratados con Temozolamida entre mayo de 2009 y diciembre 2011. Fuente de información: base de datos del FNR. Resultados: Se incluyeron 81 pacientes. La mediana de sobrevida global fue de 18 meses. Vivos a dos años: 33 de los pacientes. El análisis multivariado encontró a la edad y al peor estado funcional del paciente como los factores de riesgo para mortalidad. 8 pacientes tuvieron efectos adversos severos. Discusión: Se presentan los primeros resultados nacionales vinculados al tratamiento combinado de los GBM. La sobrevida fue similar a la reportada en los estudios de referencia internacionales y mayor que la descripta para el tratamiento radiante exclusivo. El beneficio es mayor en aquellos pacientes jóvenes con buena capacidad funcional previa al inicio del tratamiento. Su seguridad fue considerada como aceptable.

Objectives: find out the two-year survival of patients diagnosed with Multiform Glioblastoma (MGB) treated with Temozolamide funded by the National Resource Fund (FNR), and evaluate the safety of therapy and prognostic factors. Methodology: cohort of patients with MGB, treated with Temozolamide between May 2009 and December 2011. Data source: database of the FNR. Results: the 81 patients included had a median overall survival of 18 months; 33 of them were still alive at two years. The multivariate analysis found that the patient’s age and functional status were the risk factors for mortality. Eight patients had severe adverse effects. Discussion: Presentation of the first national results related to the combined therapy of MGB. Survival was similar to that reported in the international reference studies and greater than that described for radiation therapy alone. Benefits were greater in young patients presenting with a good functional capacity before starting therapy. The safety of therapy was deemed acceptable.

Glioblastoma multiforme metastásico a ganglio linfático cervical: reporte de un caso y revisión de la literatura / Glioblastoma multiforme metastatic cervical lymph node: a case report and literature review

El Glioblastoma Multiforme (GBM) es el tumor cerebral primario más común en los adultos, la metástasis extra-craneal de GBM detectada clínicamente es bastante rara, debido a la ausencia de linfáticos en el cerebro y a la dificultad de los tumores en penetrar los vasos sanguíneos. Se producen entre el 0,2 a 2% según 10 reportado en la literatura disponible. Se reporta un caso de rara presentación de una paciente de 53 añ os con diagnóstico de Glioblastoma multiforme localizado en región interparietal derecha y otra lesion en region fronto-parietal derecha (multifocal). Se le realiza biopsia estereotáxica para diagnóstico y recibio tratamiento con radioterapia conformada en 3D al primario. Posteriormente a los 2 meses presenta metástasis linfática en ganglio cervical derecho, diagnosticado por citología y biopsia incisional. Así mismo se realiza revisión de la literatura. Se discuten el impacto de la cirugía en la diseminación tumoral y las posibles vías de diseminación.

Glioblastoma multiforme (GBM) is the most common and most aggressive primary brain tumor in adults. The presence of extra-cranial GBM metastasis is very rare, because the absence of brain lympha- tics and the difficulty of tumors cells to penetrate into blood vessels, occurring only between 0.2 to 2% of the cases reported in the available literature. A case of extreme rarity is presented: A female 53 year old patient, with diagnosis ofGliobastoma multiforme localized in the right interparietal region and another lesion in the rightfrontal-parietal region (multifocal). She underwent diagnostic stereotactic biopsy and was treated with 3D conformal radiotherapy in the primary. Two months later the patient presents lymphatic metastasis in the right cervical lymph node, diagnosed by cytology and incisional biopsy. A review of the literature is presented. The impacts of surgery in tumor dissemination and possible tumor dissemination schemes are discussed.

Interfractional Variation of Radiation Target and Adaptive Radiotherapy for Totally Resected Glioblastoma

This study aimed to evaluate the effects of volume adapted re-planning for radiotherapy (RT) after gross total resection (GTR) for glioblastoma. Nineteen patients with glioblastoma who underwent GTR and postoperative RT were analyzed. The volumes of the surgical cavity on computed tomography (CT) obtained one day after GTR (CT0), the first RT simulation CT (sim-CT1), and the second simulation CT for the boost RT plan (sim-CT2) were compared. The boost RT plan was based on the surgical cavity observed on the sim-CT2 (boost RTP2) and was compared with that based on the surgical cavity observed on the sim-CT1 (boost RTP1). The volume reduction ratios were 14.4%-51.3% (median, 29.0%) between CT0 and sim-CT1 and -7.9%-71.9% (median, 34.9%) between sim-CT1 and sim-CT2 (P < 0.001). The normal brain volumes in boost RTP1 were significantly reduced in boost RTP2, especially at high dose levels. Target volume in sim-CT2 which was not covered with the boost RTP1, developed in five cases (26.3%). The surgical cavity volume was reduced following surgery in patients with glioblastoma who underwent GTR. The application of volume-adapted re-planning during RT could decrease the irradiated volume of normal brain and prevent a target miss for boost RT.

Glioblastoma multiforme cerebral hemisférico: análisis de sobrevida de 65 casos tratados en el Departamento de Oncología del Hospital de Clínicas, desde 1980 a 2000 / Glioblastoma multiforme in the cerebral hemisphere: survival analysis of 65 cases seen at the Oncology Department of the Clínicas Hospital from 1980 through 2000

Introducción: el glioblastoma multiforme (GBM) representa la forma más agresiva de los gliomas. La sobrevida a cinco años con el tratamiento quirúrgico exclusivo es nula. El agregado radioterapia (RT) y quimioterapia (QT) prolongan la so-brevida. Objetivo: evaluar el impacto del tratamiento en la sobrevida de pacientes portadores de GBM.Pacientes y métodos: se incluyeron los pacientes con diagnóstico histológico de GBM asistidos en la Unidad de Neuro-Oncología del Hospital de Cínicas, de 1980 a 2000. Se recabaron datos patronímicos, clínicos, paraclínicos y evolutivos de las historias clínicas. Se calculó la sobrevida mediante el método de Kaplan Meier y Mantel Cox.Resultados: se estudiaron 65 pacientes con una edad mediana de 58 años (rango: 6-79). Recibieron cirugía 100%(completa en 22 pacientes, subtotal en 9, parcial en 32 y biopsia en 2). El 92% recibió RT posoperatoria y 25% QT. La mediana de sobrevida fue de 46,6 semanas y la sobrevida global al año fue de 28%. La probabilidad de sobrevida al año fue 0 en los pacientes que recibieron cirugía exclusiva; 0,23 en los que se agregó RT, y 0,62 en los tratados con QT (p=0,0001). El análisis multivariable identificó como variables independientes: el tratamiento multimodal incluyendo quimioterapia(p=0,003) y buen estado neurológico posoperatorio (p=0,007).Conclusiones: la mediana de sobrevida de esta serie fue similar a lo descrito en la literatura, existiendo una sobrevida mayor en los pacientes con buen estado neurológico tratadoscon cirugía seguida de RT y QT.

Introduction: glioblastoma multiforme (GBM) is the most agressive kind of gliomas. The 5-year survival rate for exclusive surgical treatment is null. Additional chemotherapy and radiotherapy increases survival.Objective: to evaluate the impact of treatment in the survival of patients suffering from GBM.Method: patients with a histological diagnosis of GBM who were seen at the Neuro-Oncology Unit of the Clínicas Hospital, from 1980 through 2000. Clinical, paraclinical and patronymic data was collected, the same as information on the evolution of medical records. Survival rates were calculated through the Kaplan Meier and Mantel Cox method. Results: 65 patients with an average age of 58 years old were studied, (range: 6-79). All of them underwent surgery (complete in 22 patients, subtotal in 9, partial in 32 and biopsy in 2 patients). Ninety two percent of patients were treated with radiotherapy and 25% with chemotherapy. Median survival was 46.6 weeks and global survival one year after was 28%. The probability for survival one year after was 0 in patients who were treated only with surgery; 0.23 in those who also received radiotherapy and 0.62 with chemotherapy QT (p=0,0001).Multivariable analysis identified the following independent variables: multimodal treatment including chemotherapy (p=0,003) and a good postoperative general condition (p=0,007). Conclusions: median survival in this series was similar to that described in literature, there existing a longer survival rate for patients with a good neurologic condition who are treated with radiotherapy and chemotherapy after surgery.

Introdução: o glioblastoma multiforme (GBM) é a forma mais agressiva dos gliomas. A sobrevida a os cinco anos é nula quando o paciente recebe exclusivamente tratamento cirúrgico. Observa-se um aumento da sobrevida quando ademais da cirurgia se agrega radioterapia (RT) e quimioterapia (QT).Objetivo: avaliar o impacto do tratamento na sobrevida de pacientes portadores de GBM. Pacientes e métodos: foram incluídos todos os pacientes com diagnóstico histológico de GBM atendidos na Unidade de Neuro-Oncologia do Hospital de Clínicas, de 1980 a 2000. Dos prontuários dos pacientes foram coletados os dados de identificação, clínicos, resultados de exames e estudos e os relacionados com a evo-lução do caso. A sobrevida foi calculada utilizando o método de Kaplan Meier e Mantel Cox.Resultados: foram estudados 65 pacientes com idade média de 58 anos (rango: 6-79 anos). Todos os pacientes (100%) foram submetidos à cirurgia (completa em 22 pacientes, subtotal em 9, parcial em 32 e biopsia em 2). Noventa e dois por centos (92%) receberam RT pós-operatória e 25% QT. A mediana de sobrevida foi de 46,6 semanas e a sobrevida global aos 12 meses foi de 28%. A probabilidade de sobrevida aos 12 meses foi zero nos pacientes que foram submetidos exclusivamente à cirurgia; 0,23 nos que se agregaram RT, e 0,62 nos tratados com QT (p=0,0001). A análise multivariada identificou como variáveis independentes: o tratamento multimodal incluindo quimioterapia (p=0,003) e bom estado neurológico pós-operatório (p=0,007).Conclusões: a mediana de sobrevida desta serie foi similar às descritas na literatura, existindo uma sobrevida maior nos pacientes com bom estado neurológico tratados com cirurgia seguida de RT e QT.

Glioblastoma: experiência uni-institucional com 48 pacientes tratados com cirurgia, radioterapia e quimioterapia / Glioblastoma: single institutional experience with 48 patients treated with surgery, radiotherapy and chemotherapy

OBJETIVO: Identificar fatores prognósticos e avaliar a evolução clínica de pacientes com diagnósticode glioblastoma submetidos a cirurgia e radioterapia, com ou sem quimioterapia adjuvante. MATERIAL E MÉTODO: trabalho retrospectivo com 48 pacientes portadores de glioblastoma tratadosno período de 1997 a 2007. Todos os pacientes foram classificados segundo critérios do recursive partitioning analysis (RPA). RESULTADOS: Observaram-se predominância do sexo feminino, idade maior ou igual a 50 anos, performance status maior ou igual a 70, e as classes mais prevalentes,de acordo com a classificação RPA, foram a V e VI. Em 72,9% dos pacientes foi realizada ressecção parcial da lesão e em 27,1%, ressecção subtotal ou total. Quimioterapia foi administrada em47,9% dos pacientes e a dose de radioterapia foi de 50û60 Gy em 72,9% dos casos. A sobrevida global mediana observada foi de 52 semanas. CONCLUSÃO: Os dados obtidos mostram que a sobrevida global de pacientes portadores de glioblastoma foi semelhante aos resultados encontrados na literatura e dependente de fatores como a adição de quimioterapia, dose de radioterapia eíndice de Karnofsky.

OBJECTIVE: To identify prognostic factors and evaluate the clinicaloutcome of patients with glioblastoma treated with surgery and radiotherapy combined or not with chemotherapy. MATERIAL AND METHOD: In this retrospective study, 48 patients with glioblastoma were treated between 1997 and 2007. All patients wereclassified according the recursive partitioning analysis (RPA) criteria.RESULTS: The majority of patients were female, with 50 years of age or above. Performance status of 70 or greater were found in 70.8% of cases, and RPA classes V and VI prevailed. Seventy-two percent of patients were submitted to partial resection and 27.1% to total or subtotal resection. Chemotherapy wasadministered in 47.9% of patients and doses between 50 and 60 Gy were delivered in 72.9%. The median overall survival was 52 weeks. CONCLUSION: Our data show an overall survival that approaches the related in others reports and were dependent of factors such as chemotherapy, dose of radiation and Karnofsky performance status.

Evidence-based adjuvant therapy for gliomas: current concepts and newer developments.

The incidence of gliomas is increasing worldwide, including India. Of the 18,820 new cases of primary central nervous system (CNS) tumors diagnosed annually in the United States, gliomas account for over 60% with 30-40% of them being glioblastoma multiforme (GBM), 10% being anaplastic astrocytoma (AA), and 10% being low grade gliomas (LGGs). This is in contrast to one study from West Bengal, India, in which only 7.9% of the brain tumors were GBMs, while 46.8% were astrocytomas. Of all adult primary CNS tumors, GBM is the most common and the most malignant with about 7,000 to 8,000 new cases annually in the United States. Given poor outcomes, a number of treatment approaches have been investigated. Common to these approaches is the use of adjuvant radiation therapy, even as surgery alone, with or without chemotherapy, may be the mainstay for some lower grade and low-risk gliomas. Today, treatment typically involves external beam radiation, with concurrent and adjuvant chemotherapy for more aggressive histologies. Although gliomas are relatively uncommon, active research is ongoing. Results of landmark trials along with some of the recently published trials are presented. These trials and management strategies as well as evolving concepts are found by reviewing over 200 articles in the National Library Medical (NLM) database, PubMed, more than 60 of which are refrenced. Specifically, the database is searched using the following keywords, with various combinations: glioma, low-grade, anaplastic, astrocytoma, oligodendroglioma, oligoastrocytoma, glioblastoma multiforme, chemotherapy, radiation, new concepts, phase III, MGMT, CDX-110 (Celldex), temozolomide, 1p/19q deletion, and bevacizumab.

Gliosarcoma: an audit from a single institution in India of 24 post-irradiated cases over 15 years.

BACKGROUND: Gliosarcomas (GS) are biphasic brain tumors composed of glioblastoma multiforme (GBM) and sarcomatous component. Therapeutic approaches include maximum surgical decompression with postoperative radiotherapy. Outcomes in gliosarcoma are poor despite multimodality management. AIMS: To analyze the outcome in patients of GS treated in our institute over a period of 15 years and compare it with GBM treated during the same period. SETTINGS AND DESIGN: Clinical records of the post-irradiated GS patients and GBM patients seen between 1990 and 2004 were retrieved. MATERIALS AND METHODS: Demographic and treatment variables were evaluated for their influence on overall survival (OS). The survival outcomes of GBM and GS treated during the same period were also compared. STATISTICAL ANALYSIS: Univariate analysis was carried out using the Kaplan-Meier method and tested using log-rank test for significance. RESULTS: During these 15 years, 24 evaluable GS patients were treated as compared to 251 evaluable patients of GBM. There was a slight male preponderance in GS (14 males vs.10 females) with a median age of 50 years. All patients underwent surgery followed by post-operative radiotherapy (median dose of 60 Gy). None of the patient or treatment related factors were found to be significantly influencing their OS. Median OS in GS was 7.3 months compared to 7.5 months in GBM patients (P = 0.790). CONCLUSIONS: The OS appears to be similar for GS and GBM. None of the demographic variables appeared to prognosticate the survivals of GS.

Concurrent temozolomide [TMZ] and irradiation for the management of high grade malignant glioma

This pilot study was conducted on 18 newly diagnosed patients with malignant glioma [11 patients with glioblastoma multiforme [GBM] and 7 patients with anaplastic astrocytoma [AA]] to assess the safety, tolerability and efficacy of concurrent administration of temozolomide [TMZ] and radiation. The eligible patients received 40 Gy [1.8 Gy/fraction, 1 fraction/day, 5 days/week] to the computed tomography [CT] or magnetic resonance imaging [MRI] enhancing lesion and surrounding edema with a 3 cm margin, then 20 Gy to a smaller volume including the contrast enhancing lesion plus 1-2 cm margin. Starting from the first day of radiation, the patients received oral TMZ [150 mg/m2] daily for 5 days and repeated every 28 days for two cycles. The study demonstrated the safety and efficacy of concurrent TMZ with radiation in newly diagnosed high grade gliomas and supported a further continued investigation of low daily dose TMZ with concurrent radiation, preferably with some cycles of TMZ as an adjuvant to radiation, in a multicenter phase III randomized trial containing a large number of patients and comparing this regimen with radiotherapy alone in newly diagnosed high-grade astrocytomas

Análisis estadístico de los astrocitomas cerebrales / Statistical analysis of the cerebral astrocytomas

Presentamos los resultados del tratamiento quirúrgico de 120 casos de astrocitomas supratentoriales operados en el Instituto de Enfermedades Neoplásicas entre 1984 - 1994. El objetivo del presente estudio fue determinar si existen factores pronósticos relacionados con los parámetros clínico y tratamiento. La población de estudio estuvo conformada por 61 mujeres y 59 hombres; 23 fueron niños y 97 adultos; con una edad media de 39, 4 años; los síntomas y signos más frecuentes fueron: cefalea 90,8 por ciento, déficit motor 42,5 por ciento, convulsiones 41,6 por ciento, papiledema 70,8 por ciento, diversos grados de hemiparesia 58,3 por ciento. Localización: lóbulo parietal y frontal (24 y 18 casos); compromiso de dos o más lóbulos en 31 pacientes (25,8 por ciento); en cuerpo calloso y ganglios basases (14 en cada uno); región quiasmática y pineal en cinco y uno respectivamente. Se realizó biopsia en 36 (30 por ciento) casos, resección subtotal en 69 (58 por ciento) y total en 15 casos (13 por ciento). Recibieron radioterapia 85 pacientes. La histopatología de Kernohan confirmó: grado I y II en 29 (24 por ciento) casos, grado III en 42 (35 por ciento) pacientes y grado IV en 49 (14 por ciento) pacientes. La mortalidad operatoria fue 10,8 por ciento. a media de sobrevida en 23 niños fue 24 meses y en 84 adultos fue 10 meses, con diferencias estadísticamente significativas (p menor 0,008). Las mejores condiciones clínicas de karnofski en el preoperatorio, dieron los mejores resultados en el postoperatorio. La media de sobrevida en pacientes con astrocitomas grado I-II fue 43 meses, en el grado III, 16 meses y en el grado IV fue 7 meses, con diferencias estadísticamente significativas entre grado I-II con el grado III (p menor 0,001) y grado IV (p menor 0,0001). En 29 casos con astrocitoma grado I-II, la media de sobrevida en resección total (S casos), subtotal (14 pacientes) y biopsia (10 casos) fue 571 45 y 28 meses respectivamente, con diferencias estadísticamente significativas entre resección total y biopsia (p menor 000,1). En 37 casos con astrocitoma grado III, la media de sobrevida en resección total (S casos), subtotal (18 pacientes) y biopsia (14 casos) fue 72, 17 y ocho meses, con diferencias estadísticamente significativas entre resección total con resección subtotal y biopsia (p menor 0,001)...

Hypofractionanted radiotherapy as a convenient treatment in high grade astrocytomas

In the present study 61 patients with grade III and IV malignant astrocytoma and glioblastoma multiform were randomized into two groups of radiation treatment schedules. Conventional treatment [6000 cGy/30 tt/6 weeks] and hypofractionation treatment [3000 cGy/6tt /3weeks] i.e. 500 cGy per fraction twice weekly by Cobalt 60 machine. Overall response 3 months after treatment were 48.1% in hypofractionation group and 40.7% in conventional group. After 6 months responders were 35.4% versus 36.6% respectively. Early treatment reactions were moderate more in hypofractionation group. Mean time of progression were 10.1 months in hypofractionation versus 9.8 months in conventional treatment. Median survival time were 12 months in hypofractionation versus 9 months in conventional group. Cost of treatment including hospitalization were 690 EP for hypofractionation arm and 1560 E.P for conventional arm. It was concluded that hypofractionation is a simple palliative treatment with comparable results to conventional radiation treatment, save more time [work load], less cost. So, it is a convenient treatment in high grade glioma, where palliation is considered, for patients and physicians as well as treatment place

outcome of treatment in patients with glioblastoma multiforme treated by hypofractionation radiotherapy in NEMROCK

This is a prospective non-randomized trial which included 62 patients suffering from glioblastoma multiforme [GBM] who attended Kasr El-Aini Center of Radiation Oncology and Nuclear Medicine [NEMROCK] from January 1991 to December 1995. All patients were operated upon by biopsy or partial surgical excision and received hypofractionation radiation therapy through a wide field technique. They all received a dose of 500 Gy twice weekly for three successive weeks on the Telecobalt machine. The percentage of overall response was assessed in 50 evaluable patients after 3, 6, 12 and 18 months and was found to be 30, 24, 12 and 0 successively. No severe acute reactions or late toxicity was observed. The median survival was 13 months. Those patients with KPS [Karnofsky performance status] 80-70 had longer survival than those KPS [less than 70] but the difference was not statistically significant. Patients who were initially treated by partial excision had longer survival than those who had undergone biopsy, the results were not statistically significant

Preliminary experiences with intraoperative radiation therapy (IORT) for the treatment of brain tumors

Ten brain tumor patients underwent wide resection of the tumor followed by Intraoperative Radiation Therapy (IORT) at the first surgery or at the second salvage surgery after failure of conventional external beam irradiation. Two patients(1 meningioma, 1 glioblastoma multiforme) were treated at the first surgery and 8 patients(3 anaplastic astrocytoma, 3 glioblastoma multiforme, 1 meningioma, 1 gliosarcoma) were treated after salvage surgery. The IORT doses were ranged from 15-25 Gy depending on the tumor volume and previous radiation therapy. The neurological status(Karnofsky performance status) was improved in 4 cases, not changed in 6 cases after IORT. There were several complications after IORT; radiation necrosis, communicating hydrocephalus, wound infection, and abnormal CT findings such as diffuse low density area in an around operation site. The radiation necrosis was confirmed by operation in a recurrent meningioma patient 12 months after IORT. At follow-up, ranging from 1 to 16 months, there was no deaths. Based on our limited experiences, the IORT might be one of the adjuvant therapeutic modalities especially for the malignant brain tumors and unresectable huge meningioma.