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Yan Michael Li, Dima Suki, Kenneth Hess and Raymond Sawaya

OBJECT

Glioblastoma multiforme (GBM) is the most common and deadliest primary brain tumor. The value of extent of resection (EOR) in improving survival in patients with GBM has been repeatedly confirmed, with more extensive resections providing added advantages. The authors reviewed the survival of patients with significant EORs and assessed the relative benefit/risk of resecting 100% of the MRI region showing contrast-enhancement with or without additional resection of the surrounding FLAIR abnormality region, and they assessed the relative benefit/risk of performing this additional resection.

METHODS

The study cohort included 1229 patients with histologically verified GBM in whom ≥ 78% resection was achieved at The University of Texas MD Anderson Cancer Center between June 1993 and December 2012. Patients with > 1 tumor and those 80 years old or older were excluded. The survival of patients having 100% removal of the contrast-enhancing tumor, with or without additional resection of the surrounding FLAIR abnormality region, was compared with that of patients undergoing 78% to < 100% EOR of the enhancing mass. Within the first subgroup, the survival durations of patients with and without resection of the surrounding FLAIR abnormality were subsequently compared. The data on patients and their tumor characteristics were collected prospectively. The incidence of 30-day postoperative complications (overall and neurological) was noted.

RESULTS

Complete resection of the T1 contrast-enhancing tumor volume was achieved in 876 patients (71%). The median survival time for these patients (15.2 months) was significantly longer than that for patients undergoing less than complete resection (9.8 months; p < 0.001). This survival advantage was achieved without an increase in the risk of overall or neurological postoperative deficits and after correcting for established prognostic factors including age, Karnofsky Performance Scale score, preoperative contrast-enhancing tumor volume, presence of cyst, and prior treatment status (HR 1.53, 95% CI 1.33–1.77, p < 0.001). The effect remained essentially unchanged when data from previously treated and previously untreated groups of patients were analyzed separately. Additional analyses showed that the resection of ≥ 53.21% of the surrounding FLAIR abnormality beyond the 100% contrast-enhancing resection was associated with a significant prolongation of survival compared with that following less extensive resections (median survival times 20.7 and 15.5 months, respectively; p < 0.001). In the multivariate analysis, the previously treated group with < 53.21% resection had significantly shorter survival than the 3 other groups (that is, previously treated patients who underwent FLAIR resection ≥ 53.21%, previously untreated patients who underwent FLAIR resection < 53.21%, and previously untreated patients who underwent FLAIR resection ≥ 53.21%); the previously untreated group with ≥ 53.21% resection had the longest survival.

CONCLUSIONS

What is believed to be the largest single-center series of GBM patients with extensive tumor resections, this study supports the established association between EOR and survival and presents additional data that pushing the boundary of a conventional 100% resection by the additional removal of a significant portion of the FLAIR abnormality region, when safely feasible, may result in the prolongation of survival without significant increases in overall or neurological postoperative morbidity. Additional supportive evidence is warranted.

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Editorial

Neurosurgical “pearls” and neurosurgical evidence

E. Antonio Chiocca

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Benjamin D. Fox, Akash Patel, Dima Suki and Ganesh Rao

Object

Metastatic sarcoma to the brain is rare and represents a therapeutic challenge due to its relative resistance to radio- and chemotherapy. Resection has traditionally been the mainstay of treatment. The authors reviewed a series of patients with metastatic sarcoma to the brain treated surgically to determine outcomes and identify predictors of survival in these patients.

Methods

A retrospective review of prospectively collected data was undertaken on patients undergoing surgery between 1993 and 2005 for metastatic sarcoma to the brain at The University of Texas, M.D. Anderson Cancer Center.

Results

During the study period, 62 patients underwent 84 operations for metastatic sarcoma to the brain. The median postoperative overall and progression-free survival rates were 7.5 and 4.7 months, respectively. Fifty-nine (95%) of 62 patients had a gross-total resection. The 30-day mortality rate was 4.2%. The Karnofsky Performance Scale scores at discharge from the hospital and 3 months postoperatively were the same or improved in 50 (85%) of 59 and 26 (51%) of 51, respectively. Overall postcraniotomy survival was 62% at 6 months, 39% at 1 year, 21% at 2 years, and 8% at 5 years. In multivariate and univariate analysis, control of systemic disease, and sarcomas originating from bone, cartilage, or soft tissue were predictors of survival. Patients with control of systemic disease had survival advantage when compared with those who did not. In patients with alveolar soft-part sarcoma, there was a significantly increased survival advantage compared with all other histological subgroups.

Conclusions

The authors' results suggest that in selected patients, resection of metastatic sarcoma to the brain is associated with a relatively low risk of operative death and results in improvement in neurological function. Patients with systemic control of their primary disease and certain histological subtypes (specifically alveolar soft-part sarcoma) have improved overall and progression-free survival.

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Giacomo G. Vecil, Dima Suki, Marcos V. C. Maldaun, Frederick F. Lang and Raymond SaWaya

Object. To date, no report has been published on outcomes of patients undergoing resection for brain metastases who were previously treated with stereotactic radiosurgery (SRS). Consequently, the authors reviewed their institutional experience with this clinical scenario to assess the efficacy of surgical intervention.

Methods. Sixty-one patients (each harboring three or fewer brain lesions), who were treated at a single institution between June 1993 and August 2002 were identified. Patient charts and their neuroimaging and pathological reports were retrospectively reviewed to determine overall survival rates, surgical complications, and recurrence rates.

A univariate analysis revealed that patient preoperative recursive partitioning analysis (RPA) classification, primary disease status, preoperative Karnofsky Performance Scale score, type of focal treatment undergone for nonindex lesions, and major postoperative surgical complications were factors that significantly affected survival (p ≤ 0.05). In contrast, only the RPA class and focal (conventional surgery or SRS) treatment of nonindex lesions significantly (or nearly significantly) affected survival in the multivariate analysis. Major neurological complications occurred in only 2% of patients. The median time to distant recurrence after resection was 8.4 months; that to local recurrence was not reached. The overall median survival time was 11.1 months, with 25% of patients surviving 2 or more years. Conventional surgery facilitated tapering of steroid administration.

Conclusions. The complication, morbidity, survival, and recurrence rates are consistent with those seen after conventional surgery for recurrent brain metastases. Our results indicate that in selected patients with a favorable RPA class in whom nonindex lesions are treated with focal modalities, surgery can provide long-term control of SRS-treated lesions and positively affect overall survival.

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Roukoz Chamoun, Dima Suki, Shankar P. Gopinath, J. Clay Goodman and Claudia Robertson

Object

Authors of several studies have implied a key role of glutamate, an excitatory amino acid, in the pathophysiology of traumatic brain injury (TBI). However, the place of glutamate measurement in clinical practice and its impact on the management of TBI has yet to be elucidated. The authors' objective in the present study was to evaluate glutamate levels in TBI, analyzing the factors affecting them and determining their prognostic value.

Methods

A prospective study of patients with severe TBI was conducted with an inclusion criterion of a Glasgow Coma Scale score ≤ 8 within 48 hours of injury. Invasive monitoring included intracranial pressure measurements, brain tissue PO2, jugular venous O2 saturation, and cerebral microdialysis. Patients received standard care including mass evacuation when indicated and treatment of elevated intracranial pressure values. Demographic data, CT findings, and outcome at 6 months of follow-up were recorded.

Results

One hundred sixty-five patients were included in the study. Initially high glutamate values were predictive of a poor outcome. The mortality rate was 30.3% among patients with glutamate levels > 20 μmol/L, compared with 18% among those with levels ≤ 20 μmol/L.

Two general patterns were recognized: Pattern 1, glutamate levels tended to normalize over the monitoring period (120 hours); and Pattern 2, glutamate levels tended to increase with time or remain abnormally elevated. Patients showing Pattern 1 had a lower mortality rate (17.1 vs 39.6%) and a better 6-month functional outcome among survivors (41.2 vs 20.7%).

Conclusions

Glutamate levels measured by microdialysis appear to have an important role in TBI. Data in this study suggest that glutamate levels are correlated with the mortality rate and 6-month functional outcome.

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Michele R. Aizenberg, Benjamin D. Fox, Dima Suki, Ian E. McCutcheon, Ganesh Rao and Laurence D. Rhines

Object

Patients presenting with spinal metastases from unknown primary tumors (UPTs) are rare. The authors reviewed their surgical experience to evaluate outcomes and identify predictors of survival in these patients.

Methods

This study is a retrospective analysis of patients undergoing surgery for metastatic spine disease from UPTs between June 1993 and February 2007 at The University of Texas M. D. Anderson Cancer Center.

Results

Fifty-one patients undergoing 52 surgical procedures were identified. The median age at spine surgery was 60 years. The median survival from time of diagnosis was 15.8 months (95% CI 8.1–23.6) and it was 8.1 months (95% CI 1.6–14.7) from time of spine surgery. Postoperative neurological function (Frankel score) was the same or improved in 94% of patients. At presentation, 77% had extraspinal disease, which was associated with poorer survival (6.4 vs 18.1 months; p = 0.041). Multiple sites (vs a single site) of spine disease did not impact survival (12.7 vs 8.7 months; p = 0.50). Patients with noncervical spinal disease survived longer than those with cervical disease (11.8 vs 6.4 months, respectively; p = 0.029). Complete versus incomplete resection at index surgery had no impact on survival duration (p > 0.5) or local recurrence (p = 1.0). Identification of a primary cancer was achieved in 31% of patients.

Conclusions

This is the first reported surgical series of patients with an unknown source of spinal metastases. The authors found that multiple sites of spinal disease did not influence survival; however, the presence of extraspinal disease had a negative impact. The extent of resection had no effect on survival duration or local recurrence. With an overall median survival of 8.1 months following surgery, aggressive evaluation and treatment of patients with metastatic disease of the spine from an unknown primary source is warranted.

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Dima Suki, Rami Khoury Abdulla, Minming Ding, Soumen Khatua and Raymond Sawaya

Object

Metastasis to the brain is frequent in adult cancer patients but rare among children. Advances in primary tumor treatment and the associated prolonged survival are said to have increased the frequency of brain metastasis in children. The authors present a series of cases of brain metastases in children diagnosed with a solid primary cancer, evaluate brain metastasis trends, and describe tumor type, patterns of occurrence, and prognosis.

Methods

Patients with brain metastases whose primary cancer was diagnosed during childhood were identified in the 1990–2012 Tumor Registry at The University of Texas M.D. Anderson Cancer Center. A review of their hospital records provided demographic data, history, and clinical data, including primary cancer sites, number and location of brain metastases, sites of extracranial metastases, treatments, and outcomes.

Results

Fifty-four pediatric patients (1.4%) had a brain metastasis from a solid primary tumor. Sarcomas were the most common (54%), followed by melanoma (15%). The patients' median ages at diagnosis of the primary cancer and the brain metastasis were 11.37 years and 15.03 years, respectively. The primary cancer was localized at diagnosis in 48% of patients and disseminated regionally in only 14%. The primary tumor and brain metastasis presented synchronously in 15% of patients, and other extracranial metastases were present when the primary cancer was diagnosed. The remaining patients were diagnosed with brain metastasis after initiation of primary cancer treatment, with a median presentation interval of 17 months after primary cancer diagnosis (range 2–77 months). At the time of diagnosis, the brain metastasis was the first site of systemic metastasis in only 4 (8%) of the 51 patients for whom data were available. Up to 70% of patients had lung metastases when brain metastases were found. Symptoms led to the brain metastasis diagnosis in 65% of cases. Brain metastases were single in 60% of cases and multiple in 35%; 6% had only leptomeningeal disease. The median Kaplan-Meier estimates of survival after diagnoses of primary cancer and brain metastasis were 29 months (95% CI 24–34 months) and 9 months (95% CI 6–11 months), respectively. Untreated patients survived for a median of 0.9 months after brain metastasis diagnosis (95% CI 0.3–1.5 months). Those receiving treatment survived for a median of 8 months after initiation of therapy (95% CI 6–11 months).

Conclusions

The results of this study challenge the current notion of an increased incidence of brain metastases among children with a solid primary cancer. The earlier diagnosis of the primary cancer, prior to its dissemination to distant sites (especially the brain), and initiation of presumably more effective treatments may support such an observation. However, although the actual number of cases may not be increasing, the prognosis after the diagnosis of a brain metastasis remains poor regardless of the management strategy.

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Frederick F. Lang, Raymond Sawaya, Dima Suki, Ian E. McCutcheon and Kenneth R. Hess

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Paul J. Holman, Dima Suki, Ian McCutcheon, Jean-Paul Wolinsky, Laurence D. Rhines and Ziya L. Gokaslan

Object. The surgical treatment of metastatic spinal tumors is an essential component of the comprehensive care of cancer patients. In most large series investigators have focused on the treatment of thoracic lesions because 70% of cases involve this region. The lumbar spine is less frequently involved (20% cases), and it is unclear whether its unique anatomical and biomechanical features affect surgery-related outcomes. The authors present a retrospective study of a large series of patients with lumbar metastatic lesions, assessing neurological and pain outcomes, complications, and survival.

Methods. The authors retrospectively reviewed data obtained in 139 patients who underwent 166 surgical procedures for lumbar metastatic disease between August 1994 and April 2001. The impact of operative approach on outcomes was also analyzed.

Among the wide variety of metastatic lesions, pain was the most common presenting symptom (96%), including local pain, radicular pain, and axial pain due to instability. Patients underwent anterior, posterior, and combined approaches depending on the anatomical distribution of disease. One month after surgery, complete or partial improvement in pain was demonstrated in 94% of the cases. The median survival duration for the entire population was 14.8 months.

Conclusions. The surgical treatment of metastatic lesions in the lumbar spine improved neurological and ambulatory function, significantly reducing axial spinal pain; results were comparable with those for other spinal regions. Analysis of results obtained in the present study suggests that outcomes are similar when the operative approach mirrors the anatomical distribution of disease. When lumbar vertebrectomy is necessary, however, anterior approaches minimize blood loss and wound-related complications.