Induction of glioblastoma multiforme in nonhuman primates after therapeutic doses of fractionated whole-brain radiation therapy

2002 ◽  
Vol 97 (6) ◽  
pp. 1378-1389 ◽  
Author(s):  
Russell R. Lonser ◽  
Stuart Walbridge ◽  
Alexander O. Vortmeyer ◽  
Svetlana D. Pack ◽  
Tung T. Nguyen ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Glioblastoma Multiforme ◽  
Mr Imaging ◽  
Nonhuman Primates ◽  
Molecular Analyses ◽  
Content Type ◽  
Whole Brain Radiation ◽  
Brain Radiation ◽  
Fine Print

Object. To determine the acute and long-term effects of a therapeutic dose of brain radiation in a primate model, the authors studied the clinical, laboratory, neuroimaging, molecular, and histological outcomes in rhesus monkeys that had received fractionated whole-brain radiation therapy (WBRT). Methods. Twelve 3-year-old male primates (Macaca mulatta) underwent fractionated WBRT (350 cGy for 5 days/week for 2 weeks, total dose 3500 cGy). Animals were followed clinically and with laboratory studies and serial magnetic resonance (MR) imaging. They were killed when they developed medical problems or neurological symptoms, lesions appeared on MR imaging, or at study completion. Gross, histological, and molecular analyses were then performed. Nine (82%) of 11 animals that underwent long-term follow up (> 2.5 years) developed neurological symptoms and/or enhancing lesions on MR imaging, which were defined as glioblastoma multiforme (GBM), 2.9 to 8.3 years after radiation therapy. The GBMs were categorized as either unifocal (three) or multifocal (six), and were located in the supratentorial (six), infratentorial (two), or both (one) cranial regions. Histological examination revealed distant, noncontiguous tumor invasion within the white matter of all nine animals harboring GBMs. Novel interspecies comparative genomic hybridization (three animals) uniformly showed deletions in the GBMs that corresponded to chromosome 9 in humans. Conclusions. The high rate of GBM formation (82%) following a therapeutic dose of WBRT in nonhuman primates indicates that radioinduction of these neoplasms as a late complication of this therapy may occur more frequently than is currently recognized in human patients. The development of these tumors while monitoring the monkeys' conditions with clinical and serial MR imaging studies, and access to the tumor and the entire brain for histological and molecular analyses offers an opportunity to gather unique insights into the nature and development of GBMs.

Gamma knife treatment for multiple metastatic brain tumors compared with whole-brain radiation therapy

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 32-36 ◽  
Author(s):  
Toru Serizawa ◽  
Toshihiko Iuchi ◽  
Junichi Ono ◽  
Naokatsu Saeki ◽  
Katsunobu Osato ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Gamma Knife ◽  
Gamma Knife Radiosurgery ◽  
Cerebral Metastases ◽  
Whole Brain Radiation Therapy ◽  
Whole Brain ◽  
Content Type ◽  
Whole Brain Radiation ◽  
Brain Radiation ◽  
Fine Print

Object. The purpose of this retrospective study was to compare the effectiveness of gamma knife radiosurgery (GKS) for multiple cerebral metastases with that of whole-brain radiation therapy (WBRT). Methods. Ninety-six consecutive patients with cerebral metastases from nonsmall cell lung cancer were treated between 1990 and 1999. The entry criteria were the presence of between one and 10 multiple brain lesions at initial diagnosis, no surgically inaccessible tumors with more than a 30-mm diameter, no carcinomatous meningitis, and more than 2 months of life expectancy. The patients were divided into two groups: the GKS group (62 patients) and the WBRT group (34 patients). In the GKS group, large lesions (> 30 mm) were removed surgically and all other small lesions (≤ 30 mm) were treated by GKS. New distant lesions were treated by repeated GKS without prophylactic WBRT. In the WBRT group, the patients were treated by the traditional combined therapy of WBRT and surgery. In both groups, chemotherapy was administered according to the primary physician's protocol. The two groups did not differ in terms of age, sex, initial Karnofsky Performance Scale (KPS) score, type, lesion number, and size of lesion, systemic control, and chemotherapy. Neurological survival and qualitative survival of the GKS group were longer than those of the WBRT group. In multivariate analysis, significant poor prognostic factors were systemically uncontrolled patients, WBRT group, and poor initial KPS score. Conclusions. Gamma knife radiosurgery without prophylactic WBRT could be a primary choice of treatment for patients with as many as 10 cerebral metastases from nonsmall cell cancer.

Malignant astrocytomas: focal tumor recurrence after focal external beam radiation therapy

1991 ◽  
Vol 75 (4) ◽  
pp. 559-563 ◽  
Author(s):  
Bertrand C. Liang ◽  
Allan F. Thornton ◽  
Howard M. Sandler ◽  
Harry S. Greenberg
Keyword(s):  
Radiation Therapy ◽  
Tumor Recurrence ◽  
Treatment Protocol ◽  
External Beam Radiation ◽  
Beam Radiation ◽  
Content Type ◽  
Whole Brain Radiation ◽  
Malignant Astrocytomas ◽  
Brain Radiation ◽  
Fine Print

✓ Hochberg and Pruitt have reported glioblastomas recurring within 2 cm of the primary site in 90% of patients after whole-brain radiation therapy. They suggested that computerized tomography (CT) scan accuracy would permit smaller radiation fields. A treatment protocol with smaller-field focal brain irradiation following surgical resection is reported. The first 4500 cGy of radiation is focused to within a 3-cm margin around the tumor, with a 1500-cGy boost within a 1.5-cm margin. Forty-two patients with grade III or IV astrocytoma, treated with focal brain radiation therapy were reviewed retrospectively to assess patterns of tumor recurrence. Thirty patients received intra-arterial bromodeoxyuridine (BUdR) radiosensitization with focal brain radiation therapy, and 12 patients underwent conventional focal brain radiation therapy. Tumor margin was defined on preoperative and recurrence CT scans as the contrast-enhanced area; these were traced on acetate templates and compared with each other and with the actual scans. In all 42 patients, the lesion recurred within a 2-cm margin of the original tumor. Four patients had two recurrent areas: the second area was within the 2-cm margin in two, and outside this margin in two. These results are similar to those of Hochberg and Pruitt. It is suggested that focal irradiation is now the optimal treatment for malignant astrocytoma. Since recurrences continue to be within the irradiated volumes, it appears that higher focal doses of radiation are appropriate for clinical treatment trials of malignant astrocytomas.

Dual-isotope single-photon emission computerized tomography scanning in patients with glioblastoma multiforme: association with patient survival and histopathological characteristics of tumor after high-dose radiotherapy

1998 ◽  
Vol 89 (1) ◽  
pp. 60-68 ◽  
Author(s):  
Richard B. Schwartz ◽  
B. Leonard Holman ◽  
Joseph F. Polak ◽  
Basem M. Garada ◽  
Marc S. Schwartz ◽  
...  
Keyword(s):  
Survival Rate ◽  
Glioblastoma Multiforme ◽  
Single Photon ◽  
Photon Emission ◽  
High Dose ◽  
Term Survival ◽  
Content Type ◽  
Dual Isotope ◽  
Fine Print

Object. The study was conducted to determine the association between dual-isotope single-photon emission computerized tomography (SPECT) scanning and histopathological findings of tumor recurrence and survival in patients treated with high-dose radiotherapy for glioblastoma multiforme. Methods. Studies in which SPECT with 201Tl and 99mTc-hexamethypropyleneamine oxime (HMPAO) were used were performed 1 day before reoperation in 47 patients with glioblastoma multiforme who had previously been treated by surgery and high-dose radiotherapy. Maximum uptake of 201Tl in the lesion was expressed as a ratio to that in the contralateral scalp, and uptake of 99mTc-HMPAO was expressed as a ratio to that in the cerebellar cortex. Patients were stratified into groups based on the maximum radioisotope uptake values in their tumor beds. The significance of differences in patient gender, histological characteristics of tissue at reoperation, and SPECT uptake group with respect to 1-year survival was elucidated by using the chi-square statistic. Comparisons of patient ages and time to tumor recurrence as functions of 1-year survival were made using the t-test. Survival data at 1 year were presented according to the Kaplan—Meier method, and the significance of potential differences was evaluated using the log-rank method. The effects of different variables (tumor type, time to recurrence, and SPECT grouping) on long-term survival were evaluated using Cox proportional models that controlled for age and gender. All patients in Group I (201Tl ratio < 2 and 99mTc-HMPAO ratio < 0.5) showed radiation changes in their biopsy specimens: they had an 83.3% 1-year survival rate. Group II patients (201T1 ratio < 2 and 99mTc-HMPAO ratio of ≥ 0.5 or 201Tl ratio between 2 and 3.5 regardless of 99mTc-HMPAO ratio) had predominantly infiltrating tumor (66.6%); they had a 29.2% 1-year survival rate. Almost all of the patients in Group III (201Tl ratio > 3.5 and 99mTc-HMPAO ratio ≥ 0.5) had solid tumor (88.2%) and they had a 6.7% 1-year survival rate. Histological data were associated with 1-year survival (p < 0.01); however, SPECT grouping was more closely associated with 1-year survival (p < 0.001) and was the only variable significantly associated with long-term survival (p < 0.005). Conclusions. Dual-isotope SPECT data correlate with histopathological findings made at reoperation and with survival in patients with malignant gliomas after surgical and high-dose radiation therapy.

The influence of sex and the presence of giant cells on postoperative long-term survival in adult patients with supratentorial glioblastoma multiforme

2004 ◽  
Vol 101 (2) ◽  
pp. 219-226 ◽  
Author(s):  
Naoki Shinojima ◽  
Masato Kochi ◽  
Jun-Ichiro Hamada ◽  
Hideo Nakamura ◽  
Shigetoshi Yano ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Giant Cell ◽  
Adult Patients ◽  
Term Survival ◽  
Long Term Survival ◽  
Content Type ◽  
Free Interval ◽  
Younger Age ◽  
Fine Print

Object. Glioblastoma multiforme (GBM) remains incurable by conventional treatments, although some patients experience long-term survival. A younger age, a higher Karnofsky Performance Scale (KPS) score, more aggressive treatment, and long progression-free intervals have been reported to be positively associated with long-term postoperative patient survival. The aim of this retrospective study was the identification of additional favorable prognostic factors affecting long-term survival in surgically treated adult patients with supratentorial GBM. Methods. Of 113 adult patients newly diagnosed with histologically verified supratentorial GBM who were enrolled in Phase III trials during the period between 1987 and 1998, six (5.3%) who survived for longer than 5 years were defined as long-term survivors, whereas the remaining 107 patients served as controls. All six were women and were compared with the controls; they were younger (mean age 44.2 years, range 31–60 years), and their preoperative KPS scores were higher (mean 85, range 60–100). Four of the six patients underwent gross-total resection. In five patients (83.3%) the progression-free interval was longer than 5 years and in three a histopathological diagnosis of giant cell GBM was made. This diagnosis was not made in the other 107 patients. Conclusions. Among adult patients with supratentorial GBM, female sex and histopathological characteristics consistent with giant cell GBM may be predictive of a better survival rate, as may traditional factors (that is, younger age, good KPS score, more aggressive resection, and a long progression-free interval).

Failure of third ventriculostomy in the treatment of aqueductal stenosis in children

1999 ◽  
Vol 90 (3) ◽  
pp. 448-454 ◽  
Author(s):  
Giuseppe Cinalli ◽  
Christian Sainte-Rose ◽  
Paul Chumas ◽  
Michel Zerah ◽  
Francis Brunelle ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Aqueductal Stenosis ◽  
Third Ventriculostomy ◽  
Content Type ◽  
Group I ◽  
Endoscopic Guidance ◽  
Group Ii ◽  
Fine Print

Object. The goal of this study was to analyze the types of failure and long-term efficacy of third ventriculostomy in children.Methods. The authors retrospectively analyzed clinical data obtained in 213 children affected by obstructive triventricular hydrocephalus who were treated by third ventriculostomy between 1973 and 1997. There were 120 boys and 93 girls. The causes of the hydrocephalus included: aqueductal stenosis in 126 cases; toxoplasmosis in 23 cases, pineal, mesencephalic, or tectal tumor in 42 cases; and other causes in 22 cases. In 94 cases, the procedure was performed using ventriculographic guidance (Group I) and in 119 cases by using endoscopic guidance (Group II). In 19 cases (12 in Group I and seven in Group II) failure was related to the surgical technique. Three deaths related to the technique were observed in Group I. For the remaining patients, Kaplan—Meier survival analysis showed a functioning third ventriculostomy rate of 72% at 6 years with a mean follow-up period of 45.5 months (range 4 days–17 years). No significant differences were found during long-term follow up between the two groups. In Group I, a significantly higher failure rate was seen in children younger than 6 months of age, but this difference was not observed in Group II. Thirty-eight patients required reoperation (21 in Group I and 17 in Group II) because of persistent or recurrent intracranial hypertension. In 29 patients shunt placement was necessary. In nine patients in whom there was radiologically confirmed obstruction of the stoma, the third ventriculostomy was repeated; this was successful in seven cases. Cine phase-contrast (PC) magnetic resonance (MR) imaging studies were performed in 15 patients in Group I at least 10 years after they had undergone third ventriculostomy (range 10–17 years, median 14.3 years); this confirmed long-term patency of the stoma in all cases.Conclusions. Third ventriculostomy effectively controls obstructive triventricular hydrocephalus in more than 70% of children and should be preferred to placement of extracranial cerebrospinal shunts in this group of patients. When performed using ventriculographic guidance, the technique has a higher mortality rate and a higher failure rate in children younger than 6 months of age and is, therefore, no longer preferred. When third ventriculostomy is performed using endoscopic guidance, the same long-term results are achieved in children younger than 6 months of age as in older children and, thus, patient age should no longer be considered as a contraindication to using the technique. Delayed failures are usually secondary to obstruction of the stoma and often can be managed by repeating the procedure. Midline sagittal T2-weighted MR imaging sequences combined with cine PC MR imaging flow measurements provide a reliable tool for diagnosis of aqueductal stenosis and for ascertaining the patency of the stoma during follow-up evaluation.

Brain metastasis from an adenoid cystic carcinoma of the Bartholin gland

2005 ◽  
Vol 102 (3) ◽  
pp. 543-546 ◽  
Author(s):  
Mustafa Aziz Hatiboglu ◽  
Murat Cosar ◽  
A. Celal Iplikcioglu ◽  
Deniz Ozcan
Keyword(s):  
Brain Metastasis ◽  
Adenoid Cystic Carcinoma ◽  
Review Of The Literature ◽  
Treatment Protocols ◽  
Content Type ◽  
Whole Brain Radiation ◽  
Adenoid Cystic ◽  
Gynecological Tumor ◽  
Brain Radiation ◽  
Fine Print

✓ Adenoid cystic carcinoma (ACC) of the Bartholin gland is an uncommon malignant gynecological tumor. Brain metastasis from a malignant gynecological lesion is encountered rarely and the prognosis for this type of metastasis is poor. Different treatment protocols, such as resection, stereotactic radiosurgery, whole-brain radiation therapy (WBRT), and chemotherapy, are available and should be considered on an individual basis. In this article, the authors report a case of brain metastasis from an ACC of the Bartholin gland that was treated by resection and WBRT. A review of the literature did not reveal any other such case.

Fluorescence-guided resection of glioblastoma multiforme utilizing 5-ALA-induced porphyrins: a prospective study in 52 consecutive patients

2000 ◽  
Vol 93 (6) ◽  
pp. 1003-1013 ◽  
Author(s):  
Walter Stummer ◽  
Alexander Novotny ◽  
Herbert Stepp ◽  
Claudia Goetz ◽  
Karl Bise ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Mr Imaging ◽  
Aminolevulinic Acid ◽  
Univariate Analysis ◽  
Tumor Resection ◽  
Mr Images ◽  
Content Type ◽  
Tissue Fluorescence ◽  
Solid Fluorescence ◽  
Fine Print

Object. It has been established that 5-aminolevulinic acid (5-ALA) induces the accumulation of fluorescent porphyrins in glioblastoma multiforme (GBM), a phenomenon potentially exploitable to guide tumor resection. In this study the authors analyze the influence of fluorescence-guided resection on postoperative magnetic resonance (MR) imaging and survival in a series of patients who underwent surgery in the authors' department.Methods. Fifty-two consecutive patients with GBM received oral doses of 5-ALA (20 mg/kg body weight) 3 hours before induction of anesthesia. Intraoperatively, tumor fluorescence was visualized using a modified operating microscope. Fluorescing tissue was removed whenever it was considered safely possible. Residual enhancement on early postoperative MR imaging was quantified and related to each patient's characteristics to determine which factors influenced resection. Survival was analyzed using the Kaplan—Meier method and multivariate analysis was performed in which the Karnofsky Performance Scale (KPS) score, residual fluorescence, patient age, and residual enhancement on MR images were considered.Intraoperatively, two fluorescence qualities were perceived: solid fluorescence generally reflected coalescent tumor, whereas vague fluorescence mostly corresponded to infiltrative tumor. Complete resection of contrast-enhancing tumor was accomplished in 33 patients (63%). Residual intraoperative tissue fluorescence left unresected for safety reasons predicted residual enhancement on MR images in 18 of the 19 remaining patients. Age, residual solid fluorescence, and absence of contrast enhancement in MR imaging were independent explanatory factors for survival, whereas the KPS score was significant only in univariate analysis. No perioperative deaths and one case of permanent morbidity were encountered.Conclusions. The observations in this study indicate the usefulness of 5-ALA—induced tumor fluorescence for guiding tumor resection. The completeness of resection, as determined intraoperatively from residual tissue fluorescence, was related to postoperative MR imaging findings and to survival in patients suffering from GBM.

The long-term side effects of radiation therapy for benign brain tumors in adults

1990 ◽  
Vol 73 (4) ◽  
pp. 502-512 ◽  
Author(s):  
Ossama Al-Mefty ◽  
Jane E. Kersh ◽  
Anupam Routh ◽  
Robert R. Smith
Keyword(s):  
Radiation Therapy ◽  
Side Effects ◽  
Brain Tumors ◽  
Adult Patients ◽  
Intracranial Tumors ◽  
Content Type ◽  
Pituitary Dysfunction ◽  
Fine Print

✓ Radiation therapy plays an integral part in managing intracranial tumors. While the risk:benefit ratio is considered acceptable for treating malignant tumors, risks of long-term complications of radiotherapy need thorough assessment in adults treated for benign tumors. Many previously reported delayed complications of radiotherapy can be attributed to inappropriate treatment or to the sensitivity of a developing child's brain to radiation. Medical records, radiological studies, autopsy findings, and follow-up information were reviewed for 58 adult patients (31 men and 27 women) treated between 1958 and 1987 with radiotherapy for benign intracranial tumors. Patient ages at the time of irradiation ranged from 21 to 87 years (mean 47.7 years). The pathology included 46 pituitary adenomas, five meningiomas, four glomus jugulare tumors, two pineal area tumors, and one craniopharyngioma. Average radiation dosage was 4984 cGy (range 3100 to 7012 cGy), given in an average of 27.2 fractions (range 15 to 45 fractions), over a period averaging 46.6 days. The follow-up period ranged from 3 to 31 years (mean 8.1 years). Findings related to tumor recurrence or surgery were excluded. Twenty-two patients had complications considered to be delayed side effects of radiotherapy. Two patients had visual deterioration developing 3 and 6 years after treatment; six had pituitary dysfunction; and 17 had varying degrees of parenchymal changes of the brain, occurring mostly in the temporal lobes and relating to the frequent presentation of pituitary tumors (two of these also had pituitary dysfunction). One clival tumor, with the radiographic appearance of a meningioma, developed 30 years post-irradiation for acromegaly. This study unveils considerable delayed sequelae of radiotherapy in a series of adult patients receiving what is considered “safe” treatment for benign brain tumors.

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