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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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Atom Sarkar and E. Antonio Chiocca

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

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Akash J. Patel, Dima Suki, Mustafa Aziz Hatiboglu, Vikas Y. Rao, Benjamin D. Fox and Raymond Sawaya

OBJECT

Brain metastases are the most common intracranial neoplasms and are on the increase. As radiation side effects are increasingly better understood, more patients are being treated with surgery alone with varying outcomes. The authors previously reported that en bloc resection of a single brain metastasis was associated with decreased incidences of leptomeningeal disease and local recurrence compared with piecemeal resection. However, en bloc resection is often feared to cause an increased incidence of postoperative complications. This study aimed to answer this question.

METHODS

The authors reviewed data from patients with a previously untreated single brain metastasis, who were treated with resection at The University of Texas M.D. Anderson Cancer Center (1993–2012). Data related to the patient, tumor, and methods of resection were obtained. Discharge Karnofsky Performance Scale (KPS) scores and 30-day postoperative complications were noted. Complications were considered major when they persisted for longer than 30 days, resulted in hospitalization or prolongation of hospital stay, required aggressive treatment, and/or were life threatening.

RESULTS

During the study period, 1033 eligible patients were identified. The median age was 58 years, 83% had a KPS score greater than 70, and 81% were symptomatic at surgery. Sixty-two percent of the patients underwent en bloc resection of their tumor, and 38% underwent piecemeal resection. There were significant differences between the 2 groups in terms of preoperative tumor volume, tumor functional grade, and symptoms at presentation, among others. The overall complication rates were 13% for patients undergoing en bloc resection and 19% for patients undergoing piecemeal resection (p = 0.007). The incidences of major complications and neurological complications were also significantly different. There was a trend in the same direction for major neurological complications, although it was not significant. Among patients undergoing piecemeal resection of tumors in eloquent cortex, 24% had complications (13% had major, 18% had neurological, 9% had major neurological, and 13% had select neurological complications; 4% died within 1 month of surgery). Among those undergoing en bloc resection of such tumors, 11% had complications (6% had major, 8% had neurological, 4% had major neurological, and 4% had select neurological; 2% died within 1 month of surgery). The differences in overall, major, neurological, and select neurological complications were statistically significant, but 1-month mortality and major neurological complications were not. In addition, within subcategories of tumor volume, the incidence of various complications was generally higher for patients undergoing piecemeal resection than for those undergoing en bloc resection.

CONCLUSIONS

The authors' results indicate that postoperative complication rates are not increased by en bloc resection, including for lesions in eloquent brain regions or for large tumors. This gives credence to the idea that en bloc resection of brain metastases, when feasible, is at least as safe as piecemeal resection.

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Dima Suki, Hiba Abouassi, Akash J. Patel, Raymond Sawaya, Jeffrey S. Weinberg and Morris D. Groves

Object

The authors tested the hypothesis that patients with metastatic posterior fossa lesions (MPFLs) treated with resection have a higher risk of leptomeningeal disease (LMD) than those with MPFLs treated with stereotactic radiosurgery (SRS).

Methods

Between 1993 and 2004, 379 patients with MPFLs were treated with resection or SRS at The University of Texas M. D. Anderson Cancer Center. The authors' primary study outcome was the incidence of LMD, as diagnosed with cerebrospinal fluid cytological analysis and/or neuroimaging.

Results

Resection was performed in 260 patients, whereas 119 patients underwent SRS. The median patient age was 56 years, 51% of patients were male, and 93% had a Karnofsky Performance Scale score $ 70. The most common primary cancers were those of the lung, breast, and kidney, as well as melanoma. Leptomeningeal dissemination of cancer occurred in 33 patients: 26 in the resection group and 7 in the SRS group (resection group: rate ratio [RR] 2.06, 95% confidence interval [CI] 0.89–4.75, p = 0.09). Piecemeal tumor resection (137 cases) was associated with a significantly higher risk of LMD than en bloc resection (123 cases; RR 3.4, 95% CI 1.43–8.12, p = 0.006) or SRS (RR 3.37, 95% CI 1.41–8.04, p = 0.006), and there was no significant difference in the risk for LMD between en bloc resection and SRS (en bloc resection: RR 0.98, 95% CI 0.34–2.81, p = 0.98). The multivariate RR and significance associated with piecemeal resection, however, were consistent, with a strong effect (RR 2.45, 95% CI 1.19–5.02, p = 0.02) and no indication of biases associated with tumor size, location, or cystic/necrotic appearance.

Conclusions

There is an increased risk of LMD after piecemeal resection of an MPFL. This increase, although clinically and statistically significant, is not as alarming as previously reported and is absent when en bloc removal is achieved. Further assessment of the role of resection in a controlled prospective setting is warranted.

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Wael Hassaneen, Dima Suki, Abhijit L. Salaskar, David M. Wildrick, Frederick F. Lang, Gregory N. Fuller and Raymond Sawaya

Object

The aim of this study was to review the outcome of patients undergoing surgery for treatment of lateral-ventricle metastases.

Methods

Imaging information and chart reviews of operative reports were used to conduct a retrospective analysis in 29 patients who underwent resection of lateral-ventricle metastases at the authors' institution between 1993 and 2007. Clinical and neurosurgical outcomes and recurrence rates were studied.

Results

The mean patient age was 56 years (range 20–69 years); 66% of patients were male. Single intraventricular metastases occurred in 69% of patients, and 55% of them had systemic metastases. The 30-day postoperative mortality rate was 7%. There was intracerebral tumor recurrence in 41% of patients, with 1 patient undergoing a second operation for this. The median postoperative survival duration for 28 patients (excluding 1 patient with preoperative leptomeningeal disease) was 11.7 months; the 3- and 5-year survival rates were 17 and 11%, respectively. Univariate analysis identified factors significantly influencing survival, including the preoperative Karnofsky Performance Scale (KPS) score (p = 0.02), the number of cerebral metastases (p = 0.02), the presence of primary renal cell carcinoma (RCC) (p = 0.02), and the resection method (en bloc vs piecemeal; p = 0.05). The presence of extracranial metastases did not significantly influence survival. Multivariate analysis showed that the preoperative KPS score (p = 0.002), the presence of primary RCC (p = 0.039), and the resection method (en bloc vs piecemeal; p = 0.008) correlated significantly with survival time.

Conclusions

Surgery is an important component in the management of intraventricular metastases. To the authors' knowledge, this is the first study focusing totally on resection of lateral-ventricle metastases. The authors found that patients with primary RCC, those with a favorable preoperative KPS score, and those who underwent en bloc resection had a better outcome than others.

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Benjamin D. Fox, Hassan H. Amhaz, Akash J. Patel, Daniel H. Fulkerson, Dima Suki, Andrew Jea and Raymond E. Sawaya

Object

Medical student exposure to neurosurgery is limited. To improve the educational interactions between neurosurgeons and medical students as well as neurosurgical medical student rotations or clerkships (NSCs) we must first understand the current status.

Methods

Two questionnaires were sent, one to every neurosurgery course coordinator or director at each US neurosurgery residency program (99 questionnaires) and one to the associated parent medical school dean's office (91 questionnaires), to assess the current status of NSCs and the involvement of neurosurgeons at their respective institutions.

Results

We received responses from 86 (87%) of 99 neurosurgery course coordinators or directors and 64 (70%) of 91 medical school deans' offices. Most NSCs do not have didactic lectures (53 [62%] of 86 NSCs), provide their medical students with a syllabus or educational handouts (53 [62%] of 86), or have a recommended/required textbook (77 [90%] of 86). The most common method of evaluating students in NSCs is a subjective performance evaluation. Of 64 medical school deans, 38 (59%) felt that neurosurgery should not be a required rotation. Neurosurgical rotations or clerkships are primarily offered to students in their 4th year of medical school, which may be too late for appropriate timing of residency applications. Only 21 (33%) of 64 NSCs offer neurosurgery rotations to 3rd-year students.

Conclusions

There is significant room for improvement in the neurosurgeon-to–medical student interactions in both the NSCs and during the didactic years of medical school.