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Jill S. Barnholtz-Sloan, Andrew E. Sloan and Ann G. Schwartz

Object. The purpose of this study was to examine patterns of diagnosis and relative survival rates in individuals in whom a primary malignant brain tumor was diagnosed between 1973 and 1997; follow-up review of these patients continued through the end of 1999.

Methods. The study population was composed of 21,493 patients with primary malignant brain tumors that were diagnosed between 1973 and 1997. Data on these patients were obtained from the population-based Surveillance, Epidemiology, and End Results Program. The study population was divided into three cohorts based on the year of diagnosis, and these groups were compared with respect to variables of interest by performing chi-square tests and relative survival analysis with the life table method.

Over time, there were consistently more men, more Caucasians, more patients undergoing surgery, and more individuals 70 years and older who received the diagnosis of primary malignant brain tumor. An examination of proportions of individuals with astrocytoma, other; oligodendroglioma, other; and oligodendroglioma Grade III showed significant temporal changes with frontal and temporal lobe tumors occurring most often. The diagnosis was obtained at an earlier age in African-American than in Caucasian patients. Caucasians had higher proportions of glioblastoma multiforme (GBM), which was associated with decreased survival times, and of oligodendroglioma, other, whereas African Americans had higher proportions of astrocytoma, other; ependymoma Grade II or III; and medulloblastoma, all of which were associated with increased survival times. The relative survival case demonstrated a continuous improvement over time, although older patients, those who underwent biopsy only, and those with GBMs continue to have the poorest survival times. The relative survival rates of African Americans consistently were similar or worse than those of Caucasians when the groups were stratified by prognostic factors.

Conclusions. Over time, the relative survival rate of individuals with primary malignant brain tumor has improved and differences in survival are seen by examining the race of the patients.

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Gene H. Barnett, Andrew E. Sloan and Claudio E. Tatsui

Laser ablation (also known as laser interstitial thermal therapy [LITT]) has emerged as an important new technology for treating various disorders of the brain and spine. As with any new or emerging technology, there is a learning curve for its optimal use, and video tutorials can be important learning tools to help bridge gaps in knowledge for those who wish to become more familiar with laser ablation. In this special supplement to Neurosurgical Focus, videos illustrate laser ablation’s use in the treatment of epilepsy and failed radiosurgery, as well as technical aspects of performing these procedures in eloquent brain and in the spine. We hope that these videos will enable you to enhance your understanding of the evolving use of laser ablation for disorders of the brain or spine. It is the editors’ sincere hope that this will be helpful either in your own practice or in determining whether to refer to a neurosurgical colleague experienced in this field.

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Andrew E. Sloan

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Gene H. Barnett, Clark C. Chen, Robert E. Gross and Andrew E. Sloan

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Steven Hsu, Marisa Quattrone, Quinn Ostrom, Timothy C. Ryken, Andrew E. Sloan and Jill S. Barnholtz-Sloan

Object

Primary malignant spinal glioma represents a significant clinical challenge due to the devastating effect on clinical outcomes in the majority of cases. As they are infrequently encountered in any one center, there has been limited population-based data analysis on the incidence patterns of these aggressive tumors. The objective of this study was to use publically available Surveillance, Epidemiology and End Results (SEER) program data to examine the overall incidence and incidence patterns over time with regard to age at diagnosis, sex, race, primary site of tumor, and histological subtype in patients in whom primary malignant spinal cord gliomas were diagnosed between 1973 and 2006.

Methods

The study population of interest was limited to primary, malignant, pathologically confirmed spinal cord gliomas based on data drawn from the SEER 9 standard registries for patients diagnosed between 1973 and 2006. Variables of interest included age at diagnosis, sex, race, primary site of tumor, and histological subtype of tumor. The SEER*Stat 6.5.2 program was used to calculate frequencies, age-adjusted incidence rates with 95% CIs, and annual percentage change (APC) statistics with a 2-sided p value. In addition, linear correlation coefficients (R2) were calculated for the time association stratified by variables of interest.

Results

The overall age-adjusted incidence rate for primary malignant spinal gliomas was 0.12 per 100,000, which increased significantly over the study period (APC = 1.74; p = 0.0004; R2 = 0.36). The incidence was highest in patients diagnosed at ages 35–49 (0.17 per 100,000), males (0.14 per 100,000), whites (0.13 per 100,000), and those with ependymomas (0.07 per 100,000). Over the study period, the incidence of ependymomas increased significantly (APC = 3.17; p < 0.0001; R2 = 0.58) as did the incidence of these tumors in whites (APC = 2.13; p = 0.0001) and for both males (APC = 1.90, p value < 0.0001) and females (APC = 1.60, p < 0.0001). The authors found no significant changes in the incidence over time by age of diagnosis.

Conclusions

This study demonstrates an increasing overall incidence of primary, malignant spinal cord glioma over the past 3 decades. Notably, for ependymoma the incidence has increased, whereas the incidence of most other glioma subtypes remained stable. This may be due to improved diagnostic and surgical techniques, changes in histological classification criteria, and changes in neuropathology diagnostic criteria. Although primary, malignant spinal cord gliomas are rare, an improved understanding of the incidence will assist investigators and clinicians in planning potential studies and preparing for allocation of resources to care for these challenging patients.

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James Wright, Jessey Chugh, Christina Huang Wright, Fernando Alonso, Alia Hdeib, Haley Gittleman, Jill Barnholtz-Sloan and Andrew E. Sloan

OBJECTIVE

Laser interstitial thermal therapy (LITT), sometimes referred to as “stereotactic laser ablation,” has demonstrated utility in a subset of high-risk surgical patients with difficult to access (DTA) intracranial neoplasms. However, the treatment of tumors larger than 10 cm3 is associated with suboptimal outcomes and morbidity. This may limit the utility of LITT in dealing with precisely those large or deep tumors that are most difficult to treat with conventional approaches. Recently, several groups have reported on minimally invasive transsulcal approaches utilizing tubular retracting systems. However, these approaches have been primarily used for intraventricular or paraventricular lesions, and subtotal resections have been reported for intraparenchymal lesions. Here, the authors describe a combined approach of LITT followed by minimally invasive transsulcal resection for large and DTA tumors.

METHODS

The authors retrospectively reviewed the results of LITT immediately followed by minimally invasive, transsulcal, transportal resection in 10 consecutive patients with unilateral, DTA malignant tumors > 10 cm3. The patients, 5 males and 5 females, had a median age of 65 years. Eight patients had glioblastoma multiforme (GBM), 1 had a previously treated GBM with radiation necrosis, and 1 had a melanoma brain metastasis. The median tumor volume treated was 38.0 cm3.

RESULTS

The median tumor volume treated to the yellow thermal dose threshold (TDT) line was 83% (range 76%–92%), the median tumor volume treated to the blue TDT line was 73% (range 60%–87%), and the median extent of resection was 93% (range 84%–100%). Two patients suffered mild postoperative neurological deficits, one transiently. Four patients have died since this analysis and 6 remain alive. Median progression-free survival was 280 days, and median overall survival was 482 days.

CONCLUSIONS

Laser interstitial thermal therapy followed by minimally invasive transsulcal resection, reported here for the first time, is a novel option for patients with large, DTA, malignant brain neoplasms. There were no unexpected neurological complications in this series, and operative characteristics improved as surgeon experience increased. Further studies are needed to elucidate any differences in survival or quality of life metrics.

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Kenneth J. Levin, Emad F. Youssef, Andrew E. Sloan, Rajiv Patel, Rana K. Zabad and Lucia Zamorano

Object. Recent studies have suggested a high incidence of cognitive deficits in patients undergoing high-dose chemotherapy, which appears to be dose related. Whole-brain radiotherapy (WBRT) has previously been associated with cognitive impairment. The authors attempted to use gamma knife radiosurgery (GKS) to delay or avoid WBRT in patients with advanced breast cancer treated with high-dose chemotherapy and autologous bone marrow transplantation (HDC/ABMT) in whom brain metastases were diagnosed.

Methods. A retrospective review of our experience from 1996 to 2001 was performed to identify patients who underwent HDC/ABMT for advanced breast cancer and brain metastasis. They were able to conduct GKS as initial management to avoid or delay WBRT in 12 patients following HDC/ABMT. All patients were women. The median age was 48 years (range 30–58 years). The Karnofsky Performance Scale score was 70 (range 60–90). All lesions were treated with a median prescription dose of 17 Gy (range 15–18 Gy) prescribed to the 50% isodose.

Median survival was 11.5 months. Five patients (42%) had no evidence of central nervous system disease progression and no further treatment was given. Four patients were retreated with GKS and three of them eventually received WBRT as well. Two patients were treated with WBRT as the primary salvage therapy. The median time to retreatment with WBRT was 8 months after the initial GKS.

Conclusions. Gamma knife radiosurgery can be effectively used for the initial management of brain metastases to avoid or delay WBRT in patients treated previously with HDC, with acceptable survival and preserved cognitive function.

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Andrew E. Sloan

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Andrew E. Sloan, Roger Dansey, Lucia Zamorano, Geoffrey Barger, Caroline Hamm, Fernando Diaz, Roy Baynes and Gary Wood

Object

This trial was designed to determine the ability of autologous whole–tumor cell vaccines to induce cell-mediated immune responses in patients with recurrent malignant glioma, as well as to determine whether combining such vaccination with adoptive transfer of in vitro activated T lymphocytes prolongs patient survival.

Methods

Nineteen patients with recurrent malignant glioma, in whom previous external beam radiotherapy and at least one course of chemotherapy had failed were vaccinated twice with irradiated autologous whole tumor cells by using granulocyte-marcrophage colony–stimulating factor as an adjuvant. Patients then underwent leukapheresis followed by adoptive transfer of peripheral blood lymphocytes activated in vitro with anti-CD3 and interleukin-2. In vivo immune response, radiological response, clinical outcome, and survival were monitored.

Seventeen patients developed a delayed-type hypersensitivity (DTH) response to vaccination that appeared to be directed against the autologous tumor. In eight patients there was radiological evidence of a response and in five there was evidence of clinical improvement. Median survival was 12 months (range 6–28 months), and both the presence of a DTH response and the radiological response correlated with survival (p < 0.02 and p < 0.04, respectively).

Conclusions

These preliminary results suggest that autologous whole–tumor cell vaccines induce a cell-mediated immune response, which appears to be tumor specific in most patients. Furthermore, vaccination combined with adoptive immunotherapy with in vitro activated cells may induce a radiologically demonstrated tumor response and improved survival despite a condition of advanced disease and immunosuppression resulting from previous treatment or tumor burden. Further studies of immunotherapy are warranted.