Chemotherapy for malignant gliomas

1988 ◽  
Vol 68 (1) ◽  
pp. 1-17 ◽  
Author(s):  
Paul L. Kornblith ◽  
Michael Walker
Keyword(s):  
Clinical Management ◽  
Malignant Gliomas ◽  
New Agents ◽  
Specific Patient ◽  
Content Type ◽  
Number Of Patients ◽  
New Findings ◽  
The Impact ◽  
The Brain ◽  
Fine Print

✓ There continues to be an extensive effort to develop chemotherapeutic approaches to the treatment of malignant gliomas of the brain. In the past 5 years there have been literally hundreds of trials of new agents, combinations of old and new agents, and even new routes and approaches to the delivery of chemotherapy. In this review, the literature has been studied and the individual reports analyzed to evaluate the impact of the new findings on clinical management of the patient with malignant glioma of the brain. The major areas of progress include the addition of new drugs with varying modes of action, the use of combinations of drugs in a synergistic fashion, and the development of new routes of drug delivery. None of the advances has brought about the revolution in clinical care that is so eagerly sought, but clearly the amount of new knowledge gained by these studies helps in understanding how to use chemotherapy more effectively. Furthermore, the remarkable degree of interest and involvement in the use of chemotherapy promises that an even greater number of patients with malignant gliomas will be considered for vigorous and enthusiastic clinical management programs even if chemotherapy itself is not the key modality in the treatment of a specific patient.

Survival following surgery and prognostic factors for recently diagnosed malignant glioma: data from the Glioma Outcomes Project

2003 ◽  
Vol 99 (3) ◽  
pp. 467-473 ◽  
Author(s):  
Edward R. Laws ◽  
Ian F. Parney ◽  
Wei Huang ◽  
Fred Anderson ◽  
Angel M. Morris ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Survival Data ◽  
Performance Status ◽  
Malignant Gliomas ◽  
Karnofsky Performance Scale ◽  
Median Length ◽  
Content Type ◽  
The Impact ◽  
Grade Iii ◽  
Fine Print

Object. The Glioma Outcomes Project represents a contemporary analysis of the management of malignant (Grade III and Grade IV/GBM) gliomas in North America. This observational database was used to evaluate the influence of resection, as opposed to biopsy, on patient outcome as measured by the length of survival. Attempts were made to reduce the impact of selection bias by repeating the data analysis after omitting patients with major negative prognostic factors. Methods. Outcome data from 788 patients accrued from multiple sites over a 4-year period (1997–2001) were analyzed with the primary outcome measure being length of survival. Of these, 565 patients with recent diagnoses formed the basis of the present analysis. Patients were systematically followed up until death or up to 24 months after enrollment in the study, and survival data were correlated with the histopathological grade and location of the tumor, the extent of surgery, the patient's performance status, and demographic factors. The median length of survival was 40.9 weeks for patients with recently diagnosed GBMs. The true median length of survival for patients with Grade III gliomas was not reached, although there was a 58% survival rate at 104 weeks. In multivariate analysis, resection rather than biopsy (p < 0.0001), age 60 years or younger (p < 0.0001), and a Karnofsky Performance Scale (KPS) score of 70 or greater (p = 0.0004) were associated with a prolonged survival time for patients with Grade III or IV gliomas. The prognostic value of resection compared with biopsy was maintained (p < 0.0001), even after eliminating patients considered to be “poor risk” (those with age > 60 years, KPS score < 70, or presence of multifocal tumors), who may have been overrepresented in the biopsy group. Survival “tails” at 24 months were 58% for Grade III gliomas and 11% for GBMs. Conclusions. These data provide Class II evidence to support tumor grade, patient's age, and patient's functional status as prognostic factors for survival in individuals with recently diagnosed malignant gliomas. Resection (compared with biopsy) is also a strong prognostic factor; however, no quantitative attempt was made to assess the true extent of the resection.

Uptake of tritiated methotrexate by mouse brain tumors after intravenous or intrathecal administration

1974 ◽  
Vol 40 (6) ◽  
pp. 706-716 ◽  
Author(s):  
Yukitaka Ushio ◽  
Toru Hayakawa ◽  
Heitaro Mogami
Keyword(s):  
Brain Tumors ◽  
Brain Tissue ◽  
Intravenous Injection ◽  
Malignant Gliomas ◽  
Intrathecal Administration ◽  
Drug Dosage ◽  
Content Type ◽  
Radioactive Assay ◽  
The Brain ◽  
Fine Print

✓ Malignant gliomas were induced in strain ddN mice by intracerebral implantation of a 20-methylcholanthrene pellet. The uptake and distribution of tritiated methotrexate (MTX-3H) in the tumor were investigated by radioactive assay and radioautography after single intravenous or intrathecal injections. By either route, a large amount of MTX-3H was taken up by gliomas, and a significantly higher concentration was observed in tumor than in the brain tissue. At 24 hours after intrathecal administration, the uptake of MTX-3H by gliomas exceeded that achieved after intravenous injection, although the drug dosage in the latter was 10 times that in the former.

Changes in extracellular potassium concentration in cortex and brain stem during the acute phase of experimental closed head injury

1981 ◽  
Vol 55 (5) ◽  
pp. 708-717 ◽  
Author(s):  
Hiroshi Takahashi ◽  
Shinya Manaka ◽  
Keiji Sano
Keyword(s):  
Blood Pressure ◽  
Brain Stem ◽  
Low Voltage ◽  
Potassium Concentration ◽  
Control Level ◽  
Extracellular Potassium ◽  
Content Type ◽  
The Impact ◽  
The Brain ◽  
Fine Print

✓ A high potassium concentration ([K+]o) in brain tissue impedes neuronal activity, as observed in spreading cortical depression. Experimental studies were performed on mice and rats to determine the role of changes of [K+]o in cerebral concussion. In the first experiment, a 600 gm-cm impact was delivered to the vertex of the mouse skull. This impact induced arrest of spontaneous movement for 465 ± 55.9 seconds (mean ± SD), accompanied by apnea, bradycardia, and low-voltage electroencephalographic recordings (EEG). The injury was also frequently followed immediately by epilepsy. This impact induced an increase of cortical [K+]o from the control level of 4.1 ± 1.8 mM to 20–30 mM, with gradual recovery within 30 minutes to the control level. In the second experiment, an impact of 9000 gm-cm was delivered to the midline parieto-occipital area of the rat and produced concussion-like phenomena similar to those elicited in mice. This level of trauma induced a significant increase of cortical [K+]o from the control level of 4.2 ± 0.8 mM to 20–50 mM in all of the rats, and also a significant increase of brain-stem [K+]o from 3.9 ± 0.6 to 20–30 mM in 73% of the rats. In these latter rats, the impact also induced apnea and a transient elevation of blood pressure, and resulted in low-voltage EEG recordings. In 23% of the rats in which [K+]o changes in the brain stem were not significant, the impact caused a transient reduction of blood pressure. The present study disclosed that an increase of [K+]o in the cerebral cortex and also in the brain stem is an important element in the phenomenon of concussion.

Role of dural fenestrations in acute subdural hematoma

2001 ◽  
Vol 95 (2) ◽  
pp. 263-267 ◽  
Author(s):  
Joseph N. Guilburd ◽  
Gil E. Sviri
Keyword(s):  
Brain Tissue ◽  
Surgical Decompression ◽  
Acute Subdural Hematoma ◽  
Intensive Care Treatment ◽  
Content Type ◽  
Poor Outcomes ◽  
Dural Opening ◽  
The Impact ◽  
The Brain ◽  
Fine Print

Object. Patients with acute subdural hematomas (ASDHs) have higher mortality and lower functional recovery rates compared with those of other head-injured patients. Early surgical decompression and active intensive care treatment represent, so far, the best way to assist these patients. Paradoxically, one of the factors contributing to poor outcomes in cases of ASDHs could be rapid surgical decompression, owing to the severe extrusion of the brain through the craniotomy defect in response to acute brain swelling. To avoid the deleterious consequences of abrupt decompression of the subdural space with disruption of brain tissue, the authors have adopted a new surgical technique for evacuation of ASDHs. This procedure consists of creating multiple fenestrations of the dura (MFD) in a meshlike fashion and removing clots through the small dural openings that are left open, avoiding the creation of a wide dural opening and the disruption of and additional damage to brain tissue. Methods. Thirty-one patients (26 male and five female patients with a mean age of 32.5 years) harboring ASDHs were treated using this method. On admission there were 16 patients (51.5%) with Glasgow Coma Scale (GCS) scores of 3 to 5, 11 patients (35.5%) with GCS scores of 6 to 8, and four patients (12.9%) with GCS scores of 9 to 12. Postoperative computerized tomography scans of the brain revealed evacuation of more than 80% of the hematoma in 29 of 31 patients. The overall mortality rate in this group was 51.6%. Conclusions. This preliminary report of a new surgical approach for patients who have sustained ASDHs should be considered to avoid abrupt disruption of the brain and to allow the gradual and gentle release of subdural clots. This is especially important in cases in which there are severe midline shifts and a tight brain. Further clinical studies should be conducted in a more selected series to estimate the impact of this new procedure on morbidity and mortality rates.

Radiosurgery for patients with recurrent small cell lung carcinoma metastatic to the brain: outcomes and prognostic factors

2005 ◽  
Vol 102 (Special_Supplement) ◽  
pp. 247-254 ◽  
Author(s):  
Jason Sheehan ◽  
Douglas Kondziolka ◽  
John Flickinger ◽  
L. Dade Lunsford
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Content Type ◽  
The Brain ◽  
Fine Print

Object. Lung carcinoma is the leading cause of death from cancer. More than 50% of those with small cell lung cancer develop a brain metastasis. Corticosteroid agents, radiotherapy, and resection have been the mainstays of treatment. Nonetheless, median survival for patients with small cell lung carcinoma metastasis is approximately 4 to 5 months after cranial irradiation. In this study the authors examine the efficacy of gamma knife surgery for treating recurrent small cell lung carcinoma metastases to the brain following tumor growth in patients who have previously undergone radiation therapy, and they evaluate factors affecting survival. Methods. A retrospective review of 27 patients (47 recurrent small cell lung cancer brain metastases) undergoing radiosurgery was performed. Clinical and radiographic data obtained during a 14-year treatment period were collected. Multivariate analysis was utilized to determine significant prognostic factors influencing survival. The overall median survival was 18 months after the diagnosis of brain metastases. In multivariate analysis, factors significantly affecting survival included: 1) tumor volume (p = 0.0042); 2) preoperative Karnofsky Performance Scale score (p = 0.0035); and 3) time between initial lung cancer diagnosis and development of brain metastasis (p = 0.0127). Postradiosurgical imaging of the brain metastases revealed that 62% decreased, 19% remained stable, and 19% eventually increased in size. One patient later underwent a craniotomy and tumor resection for a tumor refractory to radiosurgery and radiation therapy. In three patients new brain metastases were demonstrating on follow-up imaging. Conclusions. Stereotactic radiosurgery for recurrent small cell lung carcinoma metastases provided effective local tumor control in the majority of patients. Early detection of brain metastases, aggressive treatment of systemic disease, and a therapeutic strategy including radiosurgery can extend survival.

Relief of facial pain after combined removal of precentral and postcentral cortex

1971 ◽  
Vol 34 (4) ◽  
pp. 537-543 ◽  
Author(s):  
Richard A. Lende ◽  
Wolff M. Kirsch ◽  
Ralph Druckman
Keyword(s):  
Facial Pain ◽  
The Other ◽  
Precentral Gyrus ◽  
Nerve Section ◽  
Content Type ◽  
Burning Pain ◽  
Cortical Localization ◽  
The Brain ◽  
Fine Print ◽  
Frontal Lobotomy

✓ Cortical removals which included precentral and postcentral facial representations resulted in relief of facial pain in two patients. Because of known failures following only postcentral (SmI) ablations, these operations were designed to eliminate also the cutaneous afferent projection to the precentral gyrus (MsI) and the second somatic sensory area (SmII). In one case burning pain developed after a stroke involving the brain stem and was not improved by total fifth nerve section; prompt relief followed corticectomy and lasted until death from heart disease 20 months later. In the other case persistent steady pain that developed after fifth rhizotomy for trigeminal neuralgia proved refractory to frontal lobotomy; relief after corticectomy was immediate and has lasted 14 months. Cortical localization was established by stimulation under local anesthesia. Each removal extended up to the border of the arm representation and down to the upper border of the insula. Such a resection necessarily included SmII, and in one case responses presumably from SmII were obtained before removal. The suggestions of Biemond (1956) and Poggio and Mountcastle (1960) that SmII might be concerned with pain sensibility may be pertinent in these cases.

Hyperthermia catheter implantation and therapy in the brain

1990 ◽  
Vol 72 (6) ◽  
pp. 975-979 ◽  
Author(s):  
J. Alexander Marchosky ◽  
Christopher J. Moran ◽  
Neal E. Fearnot ◽  
Charles F. Babbs
Keyword(s):  
Computerized Tomography ◽  
Malignant Gliomas ◽  
Twist Drill ◽  
Ct Scanner ◽  
Tumor Blood Flow ◽  
Content Type ◽  
Catheter Implantation ◽  
Computer Controlled ◽  
Drill Holes ◽  
The Brain

✓ For the treatment of malignant gliomas, a technique for implanting hyperthermia catheters was developed that utilized a stereotactic template and head-stabilization frame mounted on a computerized tomography (CT) scanner. Computerized tomography scans were used to measure tumor dimensions and to determine the number, implantation depths, and active heating lengths of the catheters, which were implanted through twist-drill holes while the patient was in the CT room. Heat was subsequently delivered via implanted catheters using a computer-controlled hyperthermia system, which partially compensates for heterogeneous and time-varying tumor blood flow.

Thymidine kinase-mediated killing of rat brain tumors

1993 ◽  
Vol 79 (5) ◽  
pp. 729-735 ◽  
Author(s):  
David Barba ◽  
Joseph Hardin ◽  
Jasodhara Ray ◽  
Fred H. Gage
Keyword(s):  
Gene Therapy ◽  
Brain Tumors ◽  
Tumor Cells ◽  
Wild Type ◽  
Cns Disorders ◽  
Content Type ◽  
Potential Applications ◽  
Ganciclovir Treatment ◽  
The Brain ◽  
Fine Print

✓ Gene therapy has many potential applications in central nervous system (CNS) disorders, including the selective killing of tumor cells in the brain. A rat brain tumor model was used to test the herpes simplex virus (HSV)-thymidine kinase (TK) gene for its ability to selectively kill C6 and 9L tumor cells in the brain following systemic administration of the nucleoside analog ganciclovir. The HSV-TK gene was introduced in vitro into tumor cells (C6-TK and 9L-TK), then these modified tumor cells were evaluated for their sensitivity to cell killing by ganciclovir. In a dose-response assay, both C6-TK and 9L-TK cells were 100 times more sensitive to killing by ganciclovir (median lethal dose: C6-TK, 0.1 µg ganciclovir/ml; C6, 5.0 µg ganciclovir/ml) than unmodified wild-type tumor cells or cultured fibroblasts. In vivo studies confirmed the ability of intraperitoneal ganciclovir administration to kill established brain tumors in rats as quantified by both stereological assessment of brain tumor volumes and studies of animal survival over 90 days. Rats with brain tumors established by intracerebral injection of wild-type or HSV-TK modified tumor cells or by a combination of wild-type and HSV-TK-modified cells were studied with and without ganciclovir treatments. Stereological methods determined that ganciclovir treatment eliminated tumors composed of HSV-TK-modified cells while control tumors grew as expected (p < 0.001). In survival studies, all 10 rats with 9L-TK tumors treated with ganciclovir survived 90 days while all untreated rats died within 25 days. Curiously, tumors composed of combinations of 9L and 9L-TK cells could be eliminated by ganciclovir treatments even when only one-half of the tumor cells carried the HSV-TK gene. While not completely understood, this additional tumor cell killing appears to be both tumor selective and local in nature. It is concluded that HSV-TK gene therapy with ganciclovir treatment does selectively kill tumor cells in the brain and has many potential applications in CNS disorders, including the treatment of cancer.

Arteriovenous malformations in the posterior fossa

1977 ◽  
Vol 47 (1) ◽  
pp. 50-56 ◽  
Author(s):  
Hiroshi Matsumura ◽  
Yasumasa Makita ◽  
Kuniyuki Someda ◽  
Akinori Kondo
Keyword(s):  
Arteriovenous Malformation ◽  
Brain Stem ◽  
Posterior Fossa ◽  
Arteriovenous Malformations ◽  
Cerebellopontine Angle ◽  
Anterior Part ◽  
Content Type ◽  
The Brain ◽  
Fine Print

✓ We have operated on 12 of 14 cases of arteriovenous malformation (AVM) in the posterior fossa since 1968, with one death. The lesions were in the cerebellum in 10 cases (three anteromedial, one central, three lateral, and three posteromedial), and in the cerebellopontine angle in two; in two cases the lesions were directly related to the brain stem. The AVM's in the anterior part of the cerebellum were operated on through a transtentorial occipital approach.

Craniocerebral missile injuries in the monkey: an experimental physiological model

1972 ◽  
Vol 36 (1) ◽  
pp. 43-49 ◽  
Author(s):  
Arthur M. Gerber ◽  
Robert A. Moody
Keyword(s):  
Rhesus Monkeys ◽  
Common Factor ◽  
Blood Gases ◽  
Physiological Model ◽  
Content Type ◽  
Epidural Compression ◽  
The Brain ◽  
Strong Suspicion ◽  
Fine Print ◽  
Carotid Flow

✓ Experiments were carried out on rhesus monkeys to determine what physiological parameters were most closely correlated with death due to craniocerebral missile injuries. Observations of intracranial pressure, blood pressure, carotid flow, blood gases, respiratory rate, depth and volume, and electroencephalograms were made. These parameters were compared in survivors and nonsurvivors as were the pathological injuries. The most important single parameter that correlated with death was the drop in carotid flow. As this same correlation has been observed in epidural compression experiments in the monkey, there is a strong suspicion that reduced blood flow to the brain as measured by carotid flow is a common factor in craniocerebral missile injuries and epidural compression injuries.

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