Perilesional Resection of Glioblastoma Is Independently Associated With Improved Outcomes.

BACKGROUND: Resection is a critical component in the initial treatment of glioblastoma (GBM). Often GBMs are resected using an intralesional method. Circumferential perilesional resection of GBMs has been described, but with limited data. OBJECTIVE: To conduct an observational retrospective analysis to test whether perilesional resection produced a greater extent of resection. METHODS: We identified all patients with newly diagnosed GBM who underwent resection at our institution from June 1, 1993 to December 31, 2015. Demographics, presenting symptoms, intraoperative data, method of resection (perilesional or intralesional), volumetric imaging data, and postoperative outcomes were obtained. Complete resection (CR) was defined as 100% resection of all contrast-enhancing disease. Univariate analyses employed analysis of variance (ANOVA) and Fisher's exact test. Multivariate analyses used propensity score-weighted multivariate logistic regression. RESULTS: Newly diagnosed GBMs were resected in 1204 patients, 436 tumors (36%) perilesionally and 766 (64%) intralesionally. Radiographic CR was achieved in 69% of cases. Multivariate analysis demonstrated that perilesional tumor resection was associated with a significantly higher rate of CR than intralesional resection (81% vs 62%, multivariate odds ratio = 2.5, 95% confidence interval: 1.8-3.4, P < .001). Among tumors in eloquent cortex, multivariate analysis showed that patients who underwent perilesional resection had a higher rate of CR (79% vs 58%, respectively, P < .001) and a lower rate of neurological complications (11% vs 20%, respectively, P = .018) than those who underwent intralesional resection. CONCLUSION: Circumferential perilesional resection of GBM is associated with significantly higher rates of CR and lower rates of neurological complications than intralesional resection, even for tumors arising in eloquent locations. Perilesional resection, when feasible, should be considered as a preferred option.

A Time-Tested Information System in Neurosurgical Oncology.

The Brain and Spine Center at The University of Texas MD Anderson Cancer Center is a leading multidisciplinary referral center for patients with nervous system (NS) tumors. It has a wealth of clinical experience and an internationally recognized leadership role in the management of NS cancers. In that context, an informatics infrastructure that allows the archiving of both the prospective and retrospective characterization of patients, diseases, treatments, and outcomes is invaluable. We describe our experience with the Neurosurgical Oncology Database, a database that has provided valuable, extensive, and readily searchable data on multifaceted patient, tumor, and treatment characteristics for many years, successfully serving as an administrative and operational resource and as a resource for retrospective and prospective research endeavors.

The role of surgical resection in patients with brain metastases.

Brain metastasis is a devastating complication of systemic malignancy that affects a considerable number of cancer patients. The appearance of brain metastases is often considered to be a sign of poor prognosis; in patients with brain metastases poor survival time has been reported in the literature. Therefore, treatment of these brain lesions in cancer patients is important for quality of life, providing local tumour control, preventing death from neurological causes, and improving survival, although potentially only in a minority of patients. Surgical resection of brain metastases has been the cornerstone treatment in select patients. Careful patient selection, the use of appropriate surgical techniques, and surgical adjuncts are the major determinants of favourable outcome in patients undergoing resection of brain metastases. In this review, we explain the role of surgical resection in the treatment of patients with brain metastases with consideration of patient selection, surgical techniques and the use of intraoperative adjuncts.

Radiation-induced osteosarcomas of the calvarium and skull base.

BACKGROUND: Although a rare complication of ionizing radiation, radiation-induced osteosarcoma is now more frequently recognized as radiation therapy has become common and cancer survival has increased. To date, publications on radiation-induced osteosarcoma of the cranium are limited to a few small series and case reports. METHODS: Data from 175 patients with a history of sarcoma of the head at The University of Texas M. D. Anderson Cancer Center from 1975 to 2007 were reviewed to identify patients with radiation-induced osteosarcoma. The diagnostic criteria were: 1) osteosarcoma arose within the previously irradiated field; 2) new sarcoma was histologically distinct from the original neoplasm; 3) no evidence of new sarcoma at the time of radiation; and 4) distinct latency period could be recognized. Frequencies and descriptive statistics were obtained for the various characteristics under study. RESULTS: The authors identified 16 patients with radiation-induced osteosarcoma of the cranium at their institution. The average age at diagnosis was 35 years. The median latency period was 12.5 years. Nine patients had skull base tumors, and 7 had calvarial tumors. Of the 14 patients treated surgically, 86% developed local recurrence. The median survival time was 29 months, and the 5-year survival rate was 29.6%. CONCLUSIONS: The authors report the largest series of cranial radiation-induced osteosarcoma. Although radiation-induced osteosarcoma is an uncommon but dire complication of radiotherapy, its incidence will probably increase in the future as the frequency of radiation treatment and cancer survival increase. These tumors are locally aggressive, and despite aggressive surgical and medical management, they have a high rate of local recurrence and mortality.

Outcomes and prognostic factors for patients with brainstem metastases undergoing stereotactic radiosurgery.

BACKGROUND: Treatment of tumors metastatic to the brainstem with stereotactic radiosurgery (SRS) has not been widely studied. OBJECTIVE: To identify the effects of SRS on patients with brainstem metastases by assessing duration of local progression-free survival (LPFS) and overall survival. METHODS: We retrospectively reviewed clinical data collected from 60 patients undergoing linear accelerator-based SRS for tumors metastatic to the brainstem between August 1994 and December 2007. The LPFS and overall survival were calculated with the Kaplan-Meier method. Prognostic factors were evaluated with the log-rank test and Cox proportional hazards model. RESULTS: The median age of patients was 61 years (range, 39-85 years); the median treated lesion volume was 1.0 mL (range, 0.1-8.7 mL); and the median SRS dose was 15 Gy (range, 8-18 Gy). The median overall survival interval after SRS was 4 months (95% confidence interval, 3.4-4.9 months); crude local tumor control was 76%; and median LPFS was 5.7 months (95% confidence interval, 3.0-8.4 months). Shorter overall survival was associated with a pretreatment tumor volume ≥4 mL (P < .001) and male sex (P = .03). Shorter LPFS was associated with a pretreatment tumor volume ≥4 mL (P = .008), a melanoma primary tumor (P = .002), and the presence of necrosis in pre-SRS magnetic resonance imaging (P = .04). A Basic Score for Brain Metastases of 2 to 3 vs 1 (P = .007) and a Score Index for Radiosurgery >5 (P = .003) were significantly associated with longer survival. Twelve patients (20%) developed SRS-related complications. CONCLUSION: Stereotactic radiosurgery provides noninvasive treatment and favorable local tumor control for patients with brainstem metastases.

Multiple craniotomies in the management of multifocal and multicentric glioblastoma. Clinical article.

OBJECT: Multiple craniotomies have been performed for resection of multiple brain metastases in the same surgical session with satisfactory outcomes, but the role of this procedure in the management of multifocal and multicentric glioblastomas is undetermined, although it is not the standard approach at most centers. METHODS: The authors performed a retrospective analysis of data prospectively collected between 1993 and 2008 in 20 patients with multifocal or multicentric glioblastomas (Group A) who underwent resection of all lesions via multiple craniotomies during a single surgical session. Twenty patients who underwent resection of solitary glioblastoma (Group B) were selected to match Group A with respect to the preoperative Karnofsky Performance Scale (KPS) score, tumor functional grade, extent of resection, age at time of surgery, and year of surgery. Clinical and neurosurgical outcomes were evaluated. RESULTS: In Group A, the median age was 52 years (range 32-78 years); 70% of patients were male; the median preoperative KPS score was 80 (range 50-100); and 9 patients had multicentric glioblastomas and 11 had multifocal glioblastomas. Aggressive resection of all lesions in Group A was achieved via multiple craniotomies in the same session, with a median extent of resection of 100%. Groups A and B were comparable with respect to all the matching variables as well as the amount of tumor necrosis, number of cysts, and the use of intraoperative navigation. The overall median survival duration was 9.7 months in Group A and 10.5 months in Group B (p = 0.34). Group A and Group B (single craniotomy) had complication rates of 30% and 35% and 30-day mortality rates of 5% (1 patient) and 0%, respectively. CONCLUSIONS: Aggressive resection of all lesions in selected patients with multifocal or multicentric glioblastomas resulted in a survival duration comparable with that of patients undergoing surgery for a single lesion, without an associated increase in postoperative morbidity. This finding may indicate that conventional wisdom of a minimal role for surgical treatment in glioblastoma should at least be questioned.

Immediate morbidity and mortality associated with transcallosal resection of tumors of the third ventricle.

Resection of tumors of the third ventricle via the anterior interhemispheric transcallosal approach represents a surgical challenge. It carries a risk of postoperative complications, due to the role of surrounding structures in control of eloquent functions. We reviewed the immediate morbidity and mortality associated with this approach. Between June 1993 and July 2007, 38 patients underwent resection of tumors of the third ventricle via the anterior interhemispheric transcallosal approach at The University of Texas M. D. Anderson Cancer Center. Their 30-day postoperative morbidity and mortality rates were retrospectively analyzed relative to clinical variables possibly affecting these rates. Complications were categorized as neurological, regional, and systemic and were subclassified as major or minor. The overall complication rate was 50%. Major complications occurred in 37% of patients; 34% suffered neurological complications (16% being major complications). Surgical mortality was 8%. Univariate analysis demonstrated that tumor hemorrhage (p=0.04), preoperative Karnofsky Performance Scale (KPS) score (p=0.04), tumor status (recurrent versus [vs.] new or residual; p=0.01), and cauterization of any of the bridging veins (p=0.04) were associated with the incidence of postoperative complications. Multivariate analysis showed that increased age at surgery (p=0.04), tumor status (p=0.03), preoperative KPS score (p=0.02), and the extent of tumor resection (p=0.05) correlated significantly with the incidence of postoperative complications. Resection of tumors of the third ventricle via the interhemispheric transcallosal approach is associated with significant postoperative morbidity. Preserving the venous structures is of paramount importance in minimizing major neurological complications. Our results have practical risk-predictive value and can serve as the foundation for subsequent outcome studies.

Surgical management of lateral-ventricle metastases: report of 29 cases in a single-institution experience.

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.

Factors influencing the risk of local recurrence after resection of a single brain metastasis.

OBJECT: Local recurrence (LR) of a resected brain metastasis occurs in up to 46% of patients. Postoperative whole-brain radiation therapy (WBRT) reduces that incidence. To isolate factors associated with the risk of LR after resection, the authors only studied patients who did not receive adjuvant radiotherapy. METHODS: The authors reviewed data from 570 cases involving patients who had undergone resection of a previously untreated single brain metastasis at The University of Texas M. D. Anderson Cancer Center between 1993 and 2006 without receiving postoperative WBRT. All tumors were measured preoperatively on MR images. The resection method (en bloc resection [EBR] or piecemeal resection [PMR]) was noted at the time of surgery. Predictors of LR were assessed using the Cox proportional hazards model. RESULTS: The median patient age was 58 years, 55% were male, and 88% had a Karnofsky Performance Scale Score > or = 80. The most common primary cancers were those of the lung (28%), skin (melanoma, 21%), kidney (19%), and breast (11%). Piecemeal resection was performed in 201 patients (35%) and EBR in 369 (65%). Local recurrence developed in 84 patients (15%). The histological type of the primary cancer did not significantly predict LR; however, 7 of 22 patients with sarcoma developed LR (p = 0.16). The authors identified 2 variables that increased the risk of LR. Undergoing PMR carried a significantly higher LR risk than EBR (crude hazard ratio [HR] 1.7, 95% CI 1.1-2.6, p = 0.03). Tumors exceeding the median volume (9.7 cm(3)) had a significantly higher LR risk than those that were < 9.7 cm(3) (crude HR 1.7; 95% CI 1.1-2.6; p = 0.02). In the multivariate analysis, small tumors removed by EBR had a significantly lower LR risk. CONCLUSIONS: The LR risk of a single brain metastasis is influenced by biological factors (such as tumor volume) and treatments (such as the resection method). Early administration of postoperative WBRT may be particularly warranted when such negative tumor-related prognostic factors are noted or when treatment-related ones such as PMR are unavoidable.

Pineal cyst apoplexy: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Although most pineal cysts are clinically benign and asymptomatic, some can become symptomatic. Of the various symptomatic presentations, apoplexy is the rarest and most ill-defined. A comprehensive search of publications in the English language yielded 18 cases of pineal cyst apoplexy. We reviewed the literature to compare symptomatology and management strategies and their outcomes. CLINICAL PRESENTATION: A 29-year-old woman with a 1-month history of headaches presented with an acute worsening of her symptoms with a severe occipital headache and trouble focusing when reading. Her neurological examination was otherwise normal. Magnetic resonance imaging showed pineal cyst apoplexy and accompanying hydrocephalus. INTERVENTION: A left paramedian craniotomy with a transcallosal, transchoroidal approach using an intraoperative neuronavigation system was used to resect a pineal cyst. Postoperative imaging showed complete removal of the cyst and resolution of the hydrocephalus. Follow-up imaging at 12 months demonstrated no evidence of recurrence or any hydrocephalus. The patient has remained asymptomatic for 18 months. CONCLUSION: Pineal cyst apoplexy should always be considered when following a patient with a pineal cyst that becomes symptomatic. The most common symptom was severe headache of sudden onset or acute worsening. Other signs of hydrocephalus may or may not be present. Magnetic resonance imaging is essential to making a diagnosis. Although we believe that surgical resection is the most effective approach because it minimizes the risk for recurrence and complication, stereotactic aspiration has been used successfully to treat this condition.

Neurosurgical oncology at the university of Texas M. D. Anderson Cancer Center: its genesis and evolution.

The practice of neurosurgery at The University of Texas M. D. Anderson Cancer Center began in 1944 with one neurosurgeon among the 11 physicians present in a makeshift 16-room outpatient clinic at a temporary location. Neurosurgical oncology evolved as the hospital did, first as a neurosurgery service in 1951, then as the Section of Neurosurgery within the Department of Head and Neck Surgery in 1979, and finally, as the Department of Neurosurgery in 1990. Although M. D. Anderson is now one of the largest institutions in the world devoted exclusively to cancer patient care, research, education, and prevention, it has an unusual history, which is reviewed in terms of the institution's origin in 1941, its development under three presidents, and its fostering of neurosurgical oncology. We chronicle the growth and development of the department from 1990 to 2003 and describe the unique opportunities it presents for surgical innovation, for clinical and basic research, for training residents and fellows, and for multidisciplinary collaboration in neurosurgical oncology.

Cystic glioblastoma multiforme: survival outcomes in 22 cases.

OBJECT: The goal of this study was to determine whether the presence of a large tumor cyst was associated with improved outcome in patients undergoing surgery for newly diagnosed glioblastomas multiforme (GBMs) by comparing these patients with a matched cohort of patients with noncystic GBMs in clinical features, tumor imaging characteristics, survival, and time to tumor recurrence after surgery. METHODS: A retrospective analysis was conducted in 22 patients by using imaging information and chart reviews of operative reports of GBMs with large cysts (> or = 50% of tumor volume) at The University of Texas M. D. Anderson Cancer Center between 1993 and 2002. Clinical and neurosurgical outcomes and recurrence rates were studied. A statistical comparison was made with a matching cohort of 22 patients with noncystic GBMs. No significant differences in clinical variables were found between the cohort with cystic GBMs and the matched cohort with noncystic GBMs. To avoid bias in preoperative assessment of tumor volume, the tumor burden was compared in patients whose tumors had cysts (excluding the cystic mass) and in patients whose tumors did not contain cysts. There was no statistically significant difference between the two groups (p = 0.8). In patients with cystic GBMs the median survival time after surgery was 18.2 months (95% confidence interval [CI] 11.9-24.5 months) and at 2 years 43% of the patients were still alive. In comparison, in patients with noncystic GBMs, the median survival time was 14.3 months (95% CI 12.1-16.4 months) and only 16% of patients were alive at 2 years. The median time to tumor recurrence was 7.6 months (95% CI 0.01-18 months) in patients harboring cystic GBMs and 4.2 months (95% CI 1.8-6.6 months) in the matched cohort (log-rank test, p = 0.04). In the cystic GBM group, no recurrence was observed in 53% of patients at 6 months, 45% at 1 year, and 38% at 2 years after surgery, whereas the corresponding numbers for the noncystic group were 36, 14, and 9%, respectively. CONCLUSIONS: The results indicate that patients harboring a GBM that contains a large cyst survive longer and have a longer time to recurrence than those who lack such a cyst. This is the first such observation in the literature.

Necrosis and glioblastoma: a friend or a foe? A review and a hypothesis.

OBJECTIVE: Two main forms of cell death are encountered in biology: apoptosis (i.e., programmed cell death) and necrosis (i.e., accidental cell death). Because necrosis and apoptosis can lead to cell removal, one might intuit that they are both desirable in cancer treatment. However, in the setting of glioblastoma multiforme, a malignant brain tumor for which the presence of necrosis is an important diagnostic feature, clinical studies indicate that as the degree of necrosis advances, the patient's prognosis worsens. Despite the apparent importance of this form of cell death, the mechanism of development of necrosis in glioblastomas remains unelucidated. The purpose of this article is to try to resolve this dilemma by hypothesizing the mechanism of necrosis formation in these tumors. METHODS: On the basis of an extensive review of the literature, we present a hypothesis for the mechanism of necrosis formation in glioblastoma multiforme. RESULTS: One of the many possible pathways leading to necrosis formation may involve increased tumor cell secretion of tumor necrosis factor. Procoagulation and antiapoptotic mechanisms resulting from certain pathways could prevent the completion of tumor necrosis factor-induced apoptosis and could promote necrosis as the final mode of cell death. Such a hypothesis would explain the inverse correlation that exists between tumor necrosis and the survival of patients with glioblastomas, because the hypoxia that results from procoagulation selects for tumor cells that are more aggressive and more resistant to apoptosis-inducing therapies. CONCLUSION: A complete understanding of the series of events surrounding necrosis development in glioblastomas that is evidence-based is likely to provide targets for future therapies. On the basis of the potential mechanisms of development of necrosis described in this article, we postulate that effective therapies may have to be directed against the pathways that result in the formation of necrosis.