Analysis of homozygous deletion of the p16 gene and correlation with survival in patients with glioblastoma multiforme

2002 ◽  
Vol 96 (5) ◽  
pp. 815-822 ◽  
Author(s):  
Takanori Kamiryo ◽  
Kenji Tada ◽  
Shoji Shiraishi ◽  
Naoki Shinojima ◽  
Hideo Nakamura ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Suppressor Gene ◽  
Homozygous Deletion ◽  
Karnofsky Performance Scale ◽  
Content Type ◽  
Male Patients ◽  
Cox Proportional Hazard Regression ◽  
Fine Print

Object. One of the most frequent genetic abnormalities found in patients with glioblastoma multiforme (GBM) is homozygous deletion of the p16 tumor suppressor gene. The authors investigated whether this deletion is associated with prognosis in patients with GBM. Methods. In 46 adult patients with supratentorial GBM, homozygous deletion of the p16 gene in tumor DNA was examined using the multiplex polymerase chain reaction assay. The deletion was confirmed in 14 (30.4%) of 46 patients, eight (30.8%) of 26 men and six (30.0%) of 20 women. Cox proportional hazard regression analysis, adjusted for age at surgery, the Karnofsky Performance Scale score, extent of resection, and the MIB-1 labeling index, revealed that homozygous deletion of the p16 gene was significantly associated with overall survival and progression-free survival in men, but not in women. Conclusions. The results of this study suggest that p16 homozygous deletion is a significant unfavorable prognostic factor in male patients with GBM.

A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival

2001 ◽  
Vol 95 (2) ◽  
pp. 190-198 ◽  
Author(s):  
Michel Lacroix ◽  
Dima Abi-Said ◽  
Daryl R. Fourney ◽  
Ziya L. Gokaslan ◽  
Weiming Shi ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Mr Imaging ◽  
Tumor Resection ◽  
Extent Of Resection ◽  
Karnofsky Performance Scale ◽  
Content Type ◽  
Predictive Variables ◽  
Significant Survival ◽  
Performance Scale ◽  
Fine Print

Object. The extent of tumor resection that should be undertaken in patients with glioblastoma multiforme (GBM) remains controversial. The purpose of this study was to identify significant independent predictors of survival in these patients and to determine whether the extent of resection was associated with increased survival time. Methods. The authors retrospectively analyzed 416 consecutive patients with histologically proven GBM who underwent tumor resection at the authors' institution between June 1993 and June 1999. Volumetric data and other tumor characteristics identified on magnetic resonance (MR) imaging were collected prospectively. Conclusions. Five independent predictors of survival were identified: age, Karnofsky Performance Scale (KPS) score, extent of resection, and the degree of necrosis and enhancement on preoperative MR imaging studies. A significant survival advantage was associated with resection of 98% or more of the tumor volume (median survival 13 months, 95% confidence interval [CI] 11.4–14.6 months), compared with 8.8 months (95% CI 7.4–10.2 months; p < 0.0001) for resections of less than 98%. Using an outcome scale ranging from 0 to 5 based on age, KPS score, and tumor necrosis on MR imaging, we observed significantly longer survival in patients with lower scores (1–3) who underwent aggressive resections, and a trend toward slightly longer survival was found in patients with higher scores (4–5). Gross-total tumor resection is associated with longer survival in patients with GBM, especially when other predictive variables are favorable.

Current neurosurgical management and the impact of the extent of resection in the treatment of malignant gliomas of childhood: a report of the Children's Cancer Group Trial No. CCG-945

1998 ◽  
Vol 89 (1) ◽  
pp. 52-59 ◽  
Author(s):  
Jeffrey H. Wisoff ◽  
James M. Boyett ◽  
Mitchel S. Berger ◽  
Catherine Brant ◽  
Hao Li ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Posterior Fossa ◽  
Anaplastic Astrocytoma ◽  
Tumor Resection ◽  
Radical Resection ◽  
Extent Of Resection ◽  
Total Resection ◽  
Content Type ◽  
Cancer Group ◽  
Fine Print

Object. One hundred seventy-two children with high-grade astrocytomas were treated by members of the Children's Cancer Group in a prospective randomized trial designed to evaluate the role of two chemotherapy regimens. Seventy-six percent of the patients (131 children) in whom a diagnosis of either anaplastic astrocytoma or glioblastoma multiforme was confirmed by central pathological review are the subject of this report. Methods. Patients were stratified according to the extent of tumor resection (biopsy [< 10%], partial resection [10–50%], subtotal resection [51–90%], near-total resection [> 90%], and total resection) as determined by surgical observation and postoperative computerized tomography scanning. Information on contemporary neurosurgical management was obtained from the patient's operative records and standardized neurosurgical report forms. The vast majority of tumors were supratentorial: 63% (83 tumors) in the superficial cerebral hemisphere, 28% (37 tumors) in the deep or midline cerebrum, and only 8% (11 tumors) in the posterior fossa. A significant association was detected between the primary tumor site and the extent of resection (p < 0.0001). A radical resection (> 90%) was performed in 37% of the children: 49% of the tumors in the superficial hemisphere and 45% of tumors in the posterior fossa compared with 8% of midline tumors. Tumor location could also be used to predict the need for both temporary and permanent cerebrospinal fluid (CSF) diversion. Half of the deep tumors and 8% of the hemispheric astrocytomas ultimately required a permanent CSF shunt. Improvement in preoperative neurological deficits and level of consciousness was seen in 36% and 34% of the children, respectively. New or increased deficits were present in 14% of the children, with 6% experiencing a diminished sensorium after surgery. Postoperative nonneurological complications were rare: infection, hematoma, and CSF fistula each occurred in 1.7% of the children. Univariate and multivariate analyses demonstrated that radical tumor resection (> 90%) was the only therapeutic variable that significantly improved progression-free survival (PFS) rates. For all patients with malignant astrocytomas, the distributions of PFS rates were significantly different (p = 0.006) following radical resection compared with less extensive (< 90%) resection. The 5-year PFS rates were 35 ± 7% and 17 ± 4%, respectively. The differences in the distribution of PFS rate were significant for the subsets of patients with anaplastic astrocytoma (p = 0.055) and glioblastoma multiforme (p = 0.046). The 5-year PFS rates for anaplastic astrocytoma were 44 ± 11% and 22 ± 6% for cases in which the tumor was radically resected and less than radically resected, respectively; whereas the 5-year PFS rates for glioblastoma multiforme were 26 ± 9% and 4 ± 3% for cases in which the tumor was radically resected and less than radically resected, respectively. Conclusions. The demonstration of a survival advantage provided by radical resection should prompt neurosurgeons to treat malignant pediatric astrocytomas with aggressive surgical resection prior to initiation of radiotherapy or adjuvant chemotherapy.

Surgical resection and radiation therapy versus biopsy and radiation therapy in the treatment of glioblastoma multiforme

1993 ◽  
Vol 78 (5) ◽  
pp. 762-766 ◽  
Author(s):  
Friedrich W. Kreth ◽  
Peter C. Warnke ◽  
Rudolf Scheremet ◽  
Christoph B. Ostertag
Keyword(s):  
Radiation Therapy ◽  
Glioblastoma Multiforme ◽  
Surgical Resection ◽  
Cytoreductive Surgery ◽  
Neurological Deficits ◽  
Karnofsky Performance Scale ◽  
Treatment Variable ◽  
Content Type ◽  
Resection Group ◽  
Fine Print

✓ There has been considerable controversy over the concept of treating glioblastoma multiforme with cytoreductive surgery. Therefore, a retrospective study of cases treated between 1986 and 1991 was conducted to analyze and compare the results of stereotactic biopsy followed by radiation therapy performed in 58 patients with those of surgical resection plus radiation therapy in 57 patients. In both groups, conventionally fractionated radiation (1.7 to 2.0 Gy/day) was delivered, with a total dose of 50 to 60 Gy. Biopsy was performed only in patients with tumors judged to be inoperable. These patients carried a higher surgical risk and were in worse neurological condition than the patients in the resection group. The median survival time for the resection group was 39.5 weeks, as compared with 32 weeks for the biopsy group. This difference was not significant. The most important prognostic factor was the patient's age. The treatment variable biopsy versus resection did not reach prognostic relevance. In patients with midline shift who underwent biopsy, the Karnofsky Performance Scale score decreased in more patients during radiation therapy. The clinical status 6 weeks after surgery, however, showed no significant differences between the two groups. The comparable survival times for the two groups place doubt on the concept of treating glioblastoma multiforme with cytoreductive surgery. Presently, radiation therapy is the most effective treatment for patients with glioblastoma. There is no question that decompressive surgery followed by radiation therapy should be performed whenever necessary for severe space-occupying lesions and when it will not cause new neurological deficits.

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.

Gamma knife radiosurgery for intracranial metastatic melanoma: a 6-year experience

2002 ◽  
Vol 97 ◽  
pp. 494-498 ◽  
Author(s):  
Jorge Gonzalez-martinez ◽  
Laura Hernandez ◽  
Lucia Zamorano ◽  
Andrew Sloan ◽  
Kenneth Levin ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Brain Metastases ◽  
Metastatic Melanoma ◽  
Gamma Knife Radiosurgery ◽  
Tumor Control ◽  
Karnofsky Performance Scale ◽  
Content Type ◽  
Significant Difference ◽  
The Mean ◽  
Fine Print

Object. The purpose of this study was to evaluate retrospectively the effectiveness of stereotactic radiosurgery for intracranial metastatic melanoma and to identify prognostic factors related to tumor control and survival that might be helpful in determining appropriate therapy. Methods. Twenty-four patients with intracranial metastases (115 lesions) metastatic from melanoma underwent radiosurgery. In 14 patients (58.3%) whole-brain radiotherapy (WBRT) was performed, and in 12 (50%) chemotherapy was conducted before radiosurgery. The median tumor volume was 4 cm3 (range 1–15 cm3). The mean dose was 16.4 Gy (range 13–20 Gy) prescribed to the 50% isodose at the tumor margin. All cases were categorized according to the Recursive Partitioning Analysis classification for brain metastases. Univariate and multivariate analyses of survival were performed to determine significant prognostic factors affecting survival. The mean survival was 5.5 months after radiosurgery. The analyses revealed no difference in terms of survival between patients who underwent WBRT or chemotherapy and those who did not. A significant difference (p < 0.05) in mean survival was observed between patients receiving immunotherapy or those with a Karnofsky Performance Scale (KPS) score of greater than 90. Conclusions. The treatment with systemic immunotherapy and a KPS score greater than 90 were factors associated with a better prognosis. Radiosurgery for melanoma-related brain metastases appears to be an effective treatment associated with few complications.

Glioblastoma multiforme at the site of metal splinter injury: a coincidence?

1999 ◽  
Vol 91 (6) ◽  
pp. 1041-1044 ◽  
Author(s):  
Michael Sabel ◽  
Jörg Felsberg ◽  
Martina Messing-Jünger ◽  
Eva Neuen-Jacob ◽  
Jürgen Piek
Keyword(s):  
Brain Tumor ◽  
Glioblastoma Multiforme ◽  
Malignant Glioma ◽  
Causal Relationship ◽  
Propionibacterium Acnes ◽  
Glioma Tissue ◽  
Left Frontal Lobe ◽  
Content Type ◽  
Chronic Abscess ◽  
Fine Print

✓ The authors report the case of a man who had suffered a penetrating metal splinter injury to the left frontal lobe at 18 years of age. Thirty-seven years later the patient developed a left-sided frontal tumor at the precise site of the meningocerebral scar and posttraumatic defect. Histological examination confirmed a glioblastoma multiforme adjacent to the dural scar and metal splinters. In addition, a chronic abscess from which Propionibacterium acnes was isolated was found within the glioma tissue. The temporal and local association of metal splinter injury with chronic abscess, scar formation, and malignant glioma is highly suggestive of a causal relationship between trauma and the development of a malignant brain tumor.

Teratomas of the central nervous system: treatment considerations based on 34 cases

1998 ◽  
Vol 89 (5) ◽  
pp. 728-737 ◽  
Author(s):  
Yutaka Sawamura ◽  
Tsutomu Kato ◽  
Jun Ikeda ◽  
Jun-ichi Murata ◽  
Mitsuhiro Tada ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Radiation Therapy ◽  
Adjuvant Therapy ◽  
Karnofsky Performance Scale ◽  
Content Type ◽  
Treatment Considerations ◽  
Low Incidence ◽  
A Prospective Study ◽  
Fine Print

Object. The optimum clinical management of central nervous system (CNS) teratomas, particularly postsurgical adjuvant therapy, is still unclear, partly as a result of the tumors' low incidence. In this study the authors analyze 34 cases of CNS teratomas so that they may adequately indicate management of these lesions. Methods. The median age of the 34 patients was 13 years. Twenty-seven patients treated between 1970 and 1991 were retrospectively reviewed. Four of these 27 patients died as a result of radical surgery; each of them had a teratoma involving the hypothalamus. After initial treatment, which included radiation therapy, 20 patients (48%) had died. In all seven cases of mature teratomas there was no recurrence. In two cases of immature teratomas in which there was complete surgical resection there was recurrence; however, salvage therapies were effective. Seven of eight patients with highly malignant teratomas died; for these patients salvage therapies, including repeated radiation and chemotherapy, failed. Seven patients who presented with CNS teratomas between 1992 and 1996 received adjuvant chemotherapy and radiation therapy according to a prospective study protocol. All seven patients were free from recurrence with a 70 to 100% Karnofsky Performance Scale score at a median follow-up period of 41 months. Patients with CNS teratomas rarely responded completely to chemotherapy or radiation therapy; an effective adjuvant therapy produced a partial response at best. Conclusions. Because teratomas show various responses to adjuvant therapy, a misdiagnosis of their histological subtype will lead to inadequate therapy. A diverse therapeutic protocol based on histological diagnosis is necessary to plan appropriate management. Treatment recommendations are discussed in detail in the article.

Metastases of glioblastoma multiforme to cervical lymph nodes

1973 ◽  
Vol 38 (5) ◽  
pp. 631-634 ◽  
Author(s):  
Sayed El-Gindi ◽  
Mamdouh Salama ◽  
Mokhtar El-Henawy ◽  
Said Farag
Keyword(s):  
Brain Tumor ◽  
Glioblastoma Multiforme ◽  
Lymph Nodes ◽  
Metastatic Lesion ◽  
Cervical Lymph Nodes ◽  
Content Type ◽  
The Brain ◽  
Fine Print

✓ Two cases of occipital glioblastoma multiforme are reported in which a metastatic lesion involving the cervical lymph nodes on the side of the previous craniotomy was verified during life. This suggests to the authors that the brain tumor metastasized via lymphatic channels.

Isolation of immortalized, INK4a/ARF-deficient cells from the subventricular zone after in utero N-ethyl-N-nitrosourea exposure

2005 ◽  
Vol 102 (1) ◽  
pp. 98-108 ◽  
Author(s):  
Todd M. Savarese ◽  
Taichang Jang ◽  
Hoi Pang Low ◽  
Rebecca Salmonsen ◽  
N. Scott Litofsky ◽  
...  
Keyword(s):  
Cell Lines ◽  
Subventricular Zone ◽  
Defined Medium ◽  
In Utero ◽  
Homozygous Deletion ◽  
Content Type ◽  
Immortalized Cell Lines ◽  
Immortalized Cell ◽  
Fine Print

Object. Brain tumors, including gliomas, develop several months after rats are exposed in utero to N-ethyl-N-nitrosourea (ENU). Although pathological changes cannot be detected until these animals are several weeks old, the process that eventually leads to glioma formation must begin soon after exposure given the rapid clearance of the carcinogen and the observation that transformation of brain cells isolated soon after exposure occasionally occurs. This model can therefore potentially provide useful insights about the early events that precede overt glioma formation. The authors hypothesized that future glioma cells arise from stem/progenitor cells residing in or near the subventricular zone (SVZ) of the brain. Methods. Cells obtained from the SVZ or corpus striatum in ENU-exposed and control rats were cultured in an epidermal growth factor (EGF)-containing, chemically defined medium. Usually, rat SVZ cells cultured in this manner (neurospheres) are nestin-positive, undifferentiated, and EGF-dependent and undergo cell senescence. Consistent with these prior observations, control SVZ cells undergo senescence by the 12th to 15th doubling (20 of 20 cultures). In contrast, three of 15 cultures of cells derived from the SVZs of individual ENU-treated rats continue to proliferate for more than 60 cell passages. Each of these nestin-expressing immortalized cell lines harbored a common homozygous deletion spanning the INK4a/ARF locus and was unable to differentiate into neural lineages after exposure to specific in vitro stimuli. Nevertheless, unlike the rat C6 glioma cell line, these immortalized cell lines demonstrate EGF dependence and low clonogenicity in soft agar and did not form tumors after intracranial transplantation. Conclusions. Data in this study indicated that immortalized cells may represent glioma precursors that reside in the area of the SVZ after ENU exposure that may serve as a reservoir for further genetic and epigenetic hits that could eventually result in a full glioma phenotype.

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).

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