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 ◽  
...  

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.

2000 ◽  
Vol 93 (6) ◽  
pp. 1003-1013 ◽  
Author(s):  
Walter Stummer ◽  
Alexander Novotny ◽  
Herbert Stepp ◽  
Claudia Goetz ◽  
Karl Bise ◽  
...  

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.


1998 ◽  
Vol 89 (1) ◽  
pp. 52-59 ◽  
Author(s):  
Jeffrey H. Wisoff ◽  
James M. Boyett ◽  
Mitchel S. Berger ◽  
Catherine Brant ◽  
Hao Li ◽  
...  

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.


2002 ◽  
Vol 96 (5) ◽  
pp. 815-822 ◽  
Author(s):  
Takanori Kamiryo ◽  
Kenji Tada ◽  
Shoji Shiraishi ◽  
Naoki Shinojima ◽  
Hideo Nakamura ◽  
...  

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.


2002 ◽  
Vol 97 (6) ◽  
pp. 1378-1389 ◽  
Author(s):  
Russell R. Lonser ◽  
Stuart Walbridge ◽  
Alexander O. Vortmeyer ◽  
Svetlana D. Pack ◽  
Tung T. Nguyen ◽  
...  

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.


2001 ◽  
Vol 95 (3) ◽  
pp. 381-390 ◽  
Author(s):  
Rudolf Fahlbusch ◽  
Oliver Ganslandt ◽  
Michael Buchfelder ◽  
Werner Schott ◽  
Christopher Nimsky

Object. The aim of this study was to evaluate whether intraoperative magnetic resonance (MR) imaging can increase the efficacy of transsphenoidal microsurgery, primarily in non—hormone-secreting intra- and suprasellar pituitary macroadenomas. Methods. Intraoperative imaging was performed using a 0.2-tesla MR imager, which was located in a specially designed operating room. The patient was placed supine on the sliding table of the MR imager, with the head placed near the 5-gauss line. A standard flexible coil was placed around the patient's forehead. Microsurgery was performed using MR-compatible instruments. Image acquisition was started after the sliding table had been moved into the center of the magnet. Coronal and sagittal T1-weighted images each required over 8 minutes to acquire, and T2-weighted images were obtained optionally. To assess the reliability of intraoperative evaluation of tumor resection, the intraoperative findings were compared with those on conventional postoperative 1.5-tesla MR images, which were obtained 2 to 3 months after surgery. Among 44 patients with large intra- and suprasellar pituitary adenomas that were mainly hormonally inactive, intraoperative MR imaging allowed an ultra-early evaluation of tumor resection in 73% of cases; such an evaluation is normally only possible 2 to 3 months after surgery. A second intraoperative examination of 24 patients for suspected tumor remnants led to additional resection in 15 patients (34%). Conclusions. Intraoperative MR imaging undoubtedly offers the option of a second look within the same surgical procedure, if incomplete tumor resection is suspected. Thus, the rate of procedures during which complete tumor removal is achieved can be improved. Furthermore, additional treatments for those patients in whom tumor removal was incomplete can be planned at an early stage, namely just after surgery.


2002 ◽  
Vol 97 (3) ◽  
pp. 709-713 ◽  
Author(s):  
Gerald A. Grant ◽  
Donald Farrell ◽  
Daniel L. Silbergeld

✓ The neurosurgical management of intrinsic brain tumors and brain metastases mandates maximum resection with preservation of functional cortex. There have been previous reports on the use of cortical somatosensory evoked potentials (SSEPs) for localization of functional cortex prior to resection. The identification of rolandic cortex with the use of intraoperative SSEP monitoring enables the neurosurgeon to tailor the surgery to achieve a greater extent of resection while minimizing the risk of morbidity. The use of continuous SSEP monitoring during resection to provide an ongoing functional assessment of somatosensory cortex has not been reported. This powerful technique is illustrated using four case examples.


Neurosurgery ◽  
2009 ◽  
Vol 65 (3) ◽  
pp. 463-470 ◽  
Author(s):  
Matthew J. McGirt ◽  
Debraj Mukherjee ◽  
Kaisorn L. Chaichana ◽  
Khoi D. Than ◽  
Jon D. Weingart ◽  
...  

Abstract OBJECTIVE Balancing the benefits of extensive tumor resection with the consequence of potential postoperative deficits remains a challenge in malignant astrocytoma surgery. Although studies have suggested that increasing extent of resection may benefit survival, the effect of new postoperative deficits on survival remains unclear. We set out to determine whether new-onset postoperative motor or speech deficits were associated with survival in our institutional experience with glioblastoma multiforme (GBM). METHODS We retrospectively reviewed records of all patients (age range, 18–70 years; Karnofsky Performance Scale score, 80–100) who had undergone GBM resection between 1996 and 2006 at a single institution. Survival was compared between patients who had experienced surgically acquired motor or language deficits versus those who did not experience these deficits. RESULTS Three hundred six consecutive patients (age, 54 ± 11 years; median Karnofsky Performance Scale score, 80) underwent primary GBM resection. Nineteen patients (6%) developed surgically acquired motor deficits and 15 (5%) developed surgically acquired language deficits. Median survival was decreased in patients who acquired language deficits (9.6 months; P &lt; 0.05) or motor deficits (9.0 months; P &lt; 0.05) versus patients without surgically acquired deficits (12.8 months). Two-year survival was 8% and 0% for patients with surgically acquired motor or language deficits, respectively, versus 23% for patients without new-onset deficits. CONCLUSION In our experience, the development of new perioperative motor or language deficits was associated with decreased overall survival despite similar extent of resection and adjuvant therapy. Although it is well known that surgically induced neurological deficits affect quality of life, our results suggest that these surgical morbidities may also affect survival. Care should be taken to avoid surgically induced deficits in the management of GBM.


2004 ◽  
Vol 100 (6) ◽  
pp. 1014-1024 ◽  
Author(s):  
Hischam Bassiouni ◽  
Anja Hunold ◽  
Siamak Asgari ◽  
Dietmar Stolke

Object. The aim of this study was to analyze a subgroup of patients harboring cerebellopontine angle meningiomas originating from the posterior petrous bone in regard to clinical presentation, surgical anatomy, complications, and long-term functional postoperative results. Methods. Data in a series of 51 patients with meningiomas of the posterior petrous bone who had undergone microsurgical treatment at the authors' institution between 1989 and 2002 were retrospectively reviewed. The patient population consisted of 46 women and five men with a mean age of 53 years (range 22–70 years). The main symptom on first admission was impaired hearing in 41%, dizziness in 20%, and tinnitus in 18% of the patients. Results of physical examination and audiological testing revealed hypacusis in 65% of patients, cerebellar ataxia in 31%, and impairment of the fifth cranial nerve in 26%. All patients underwent surgical treatment via a lateral suboccipital approach. Intraoperatively, the tumor was found to be attached to the postmeatal dura in 37%, the premeatal dura in 27.5%, the suprameatal dura in 19.6%, the inframeatal dura in 7.8%, and centered on the porus acusticus in 5.9% of cases. Tumor extension into the internal acoustic meatus was present in seven patients. Tumor resection was categorized as Grade I in 14 patients, Grade II in 29, Grade III in six, and Grade IV in two patients, according to the Simpson classification system. The site of displacement of the cranial nerves was predictable in up to 84% of patients, depending on the dural origin of the tumor as depicted on preoperative magnetic resonance (MR) imaging studies. Postoperatively, a new and permanent facial paresis was observed in five patients (9.8%). In 38 patients in whom both pre- and postoperative audiological data were available, hearing function deteriorated after surgery in 18.4% and improved in 7.9%. Clinical and MR imaging postsurgical data from a mean period of 5.8 years (range 13 months–13 years) were available in all patients. Forty-four patients (86%) resumed normal daily activity. Tumor recurrence was observed in two patients (3.9%), and both underwent a second surgery. Conclusions. Preoperative detailed analysis of MR imaging data gives the surgeon a clue about the dislocation of critical neurovascular structures, particularly the cranial nerves. Nonetheless, the exact relationship of the cranial nerves to the tumor (dislocation, adherence, infiltration, and splaying of nerves) can only be fully appreciated during surgery.


2011 ◽  
Vol 115 (2) ◽  
pp. 220-229 ◽  
Author(s):  
Ovidiu Marina ◽  
John H. Suh ◽  
Chandana A. Reddy ◽  
Gene H. Barnett ◽  
Michael A. Vogelbaum ◽  
...  

Object The object of this study was to determine the benefit of surgery, radiation, and chemotherapy for patients with glioblastoma multiforme (GBM) and a low Karnofsky Performance Scale (KPS) score. Methods The authors retrospectively evaluated the records of patients who underwent primary treatment for pathologically confirmed GBM and with a KPS score ≤ 50 on initial evaluation for radiation therapy at a tertiary care institution between 1977 and 2006. Seventy-four patients with a median age of 69 years (range 19–88 years) and a median KPS score of 50 (range 20–50) were retrospectively grouped into the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) Classes IV (11 patients), V (15 patients), and VI (48 patients). Patients underwent biopsy (38 patients) or tumor resection (36 patients). Forty-seven patients received radiation. Nineteen patients also received chemotherapy (53% temozolomide), initiated concurrently (47%) or after radiotherapy. Results The median survival overall was 2.3 months (range 0.2–48 months). Median survival stratified by RPA Classes IV, V, and VI was 6.6, 6.6, and 1.8 months, respectively (p < 0.001, log-rank test). Median survival for patients receiving radiation (5.2 months) was greater than that for patients who declined radiation (1.6 months, p < 0.001). Patients in RPA Class VI appeared to benefit from radiotherapy only when tumor resection was also performed. The median survival from treatment initiation was greater for patients receiving chemotherapy concomitantly with radiotherapy (9.8 months) as compared with radiotherapy alone (1.7 months, p = 0.002). Of 20 patients seen for follow-up in the clinic at a median of 48 days (range 24–196 days) following radiotherapy, 70% were noted to have an improvement in the KPS score of between 10 and 30 points from the baseline score. On multivariate analysis, only RPA class (p = 0.01), resection (HR = 0.37, p = 0.001), and radiation therapy (HR = 0.39, p = 0.02) were significant predictors of a decreased mortality rate. Conclusions Patients with a KPS score ≤ 50 appear to have increased survival and functional status following tumor resection and radiation. The extent of benefit from concomitant chemotherapy is unclear. Future studies may benefit from reporting that utilizes a prognostic classification system such as the RTOG RPA class, which has been shown to be effective at separating outcomes even in patients with low performance status. Patients with GBMs and low KPS scores need to be evaluated in prospective studies to identify the extent to which different therapies improve outcomes.


2005 ◽  
Vol 102 (2) ◽  
pp. 267-275 ◽  
Author(s):  
Ian F. Parney ◽  
Sandeep Kunwar ◽  
Michael McDermott ◽  
Mitchel Berger ◽  
Michael Prados ◽  
...  

Object. Convection-enhanced delivery (CED) is a novel method for delivering therapeutic agents to infiltrative brain tumor cells. For agents administered by CED, changes on magnetic resonance (MR) imaging directly resulting from catheter placement, infusion, and the therapeutic compound may confound any interpretation of tumor progression. As part of an ongoing multiinstitutional Phase I study, 14 patients with recurrent malignant glioma underwent CED of interleukin (IL) 13—PE38QQR, a recombinant cytotoxin consisting of human IL-13 conjugated with a truncated Pseudomonas exotoxin. Serial neuroradiographic changes were assessed in this cohort of patients. Methods. Patients were treated in two groups: Group 1 patients received IL13—PE38QQR before and after tumor resection; Group 2 patients received infusion only after tumor resection. Preoperative and postinfusion MR images were obtained prospectively at specified regular intervals. Changes were noted along catheter tracks on postresection MR images obtained in all patients. A simple grading system was developed to describe these changes. When MR imaging changes appeared to be related to IL13—PE38QQR, patients were followed up without instituting new antitumor therapy. Conclusions. As CED of therapeutic agents becomes more common, clinicians and investigators must become aware of associated neuroimaging changes that should be incorporated into toxicity assessment. We have developed a simple grading system to facilitate communication about these changes among investigators. Biological imaging modalities that could possibly distinguish these changes from recurrent tumor should be evaluated. In this study the authors demonstrate the challenges in determining efficacy when surrogate end points such as time to tumor progression as defined by new or progressive contrast enhancement on MR imaging are used with this treatment modality.


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