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Eric W. Amundson, Matthew J. McGirt, and Alessandro Olivi

✓ The authors report on the technique and results of stereotactic biopsy for intrinsic lateral pontine and medial cerebellar lesions via a contralateral, transfrontal, extraventricular approach. Multiplanar stereotactic magnetic resonance imaging was used to plan an intraparenchymal approach, thus limiting the number of crossed pial surfaces to one and eliminating the need to cross ependymal surfaces. After the administration of a local anesthetic agent with light intravenous sedation, six patients harboring intrinsic lateral pontine lesions underwent biopsies via this intraparenchymal approach with 100% diagnostic yield and no operative morbidity. In comparison to the ipsilateral transfrontal approach, the contralateral approach laterally expands the infratentorial area accessible during biopsy to include the lateral pons and middle cerebellar peduncle. The contralateral, transfrontal, extraventricular approach is a useful, straight-forward and safe alternative to the suboccipital transcerebellar and ipsilateral, transfrontal, transtentorial routes for reaching lesions of the lateral pons and middle cerebellar peduncle.

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Kaisorn Chaichana, Scott Parker, Alessandro Olivi, and Alfredo Quiñones-Hinojosa

Object

Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor in adults. Although the average survival is ~ 12 months, individual survival is heterogeneous. The ability to predict short- and long-term survivors is limited. Therefore, the aims of this study were to ascertain preoperative risk factors associated with survival, develop a preoperative prognostic grading system, and evaluate the utility of this grading system in predicting survival for patients undergoing resection of a primary intracranial GBM.

Methods

Cases involving adult patients who underwent surgery for an intracranial primary (de novo) GBM between 1997 and 2007 at The Johns Hopkins Hospital, an academic tertiary-care institution, were retrospectively reviewed. Multivariate proportional hazards regression analysis was used to identify preoperative factors associated with survival, after controlling for extent of resection and adjuvant therapies. The identified associations with survival were then used to develop a grading system based on preoperative variables. Survival as a function of time was plotted using the Kaplan-Meier method, and survival rates were compared using Log-rank analysis. Associations with p < 0.05 were considered statistically significant.

Results

Of the 393 patients in this study, 310 (79%) had died as of most recent follow-up (median time from surgery to death 11.9 months). The preoperative factors, independent of extent of resection and adjuvant therapies (carmustine wafers, temozolomide, and radiation), found to be negatively associated with survival were: age > 60 years (p < 0.0001), Karnofsky performance status score ≤ 80 (p < 0.0001), motor deficit (p = 0.02), language deficit (p = 0.001), and periventricular tumor location (p = 0.04). Patients possessing 0–1, 2, 3, and 4–5 of these variables were assigned a preoperative grade of 1, 2, 3, and 4, respectively. Patients with a preoperative grade of 1, 2, 3, and 4 had a median survival of 16.6, 10.2, 6.8, and 6.1 months, respectively.

Conclusions

The present study found that older age, poor performance status, motor deficit, language deficit, and periventricular tumor location independently predicted poorer survival in patients undergoing GBM resection. A grading system based on these factors was able to identify 4 distinct groups of patients with different survival rates. This grading system, based only on preoperative variables, may provide patients and physicians with prognostic information that may guide medical and surgical therapy before any intervention is pursued.

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Kaisorn L. Chaichana, Scott L. Parker, Alessandro Olivi, and Alfredo Quiñones-Hinojosa

Object

Seizures are a common presenting symptom and cause of morbidity for patients with malignant astrocytomas. The authors set out to determine preoperative seizure characteristics, effects of surgery on seizure control, and factors associated with prolonged seizure control in patients with malignant astrocytomas.

Methods

Cases involving adult patients who underwent primary resection of a hemispheric anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM) at the Johns Hopkins Medical Institutions between 1996 and 2006 were retrospectively reviewed. Multivariate logistical regression analysis was used to identify associations with pre-operative seizures, and multivariate proportional hazards regression analyses were used to identify associations with prolonged seizure control following resection.

Results

Of the 648 patients (505 with GBM, 143 with AA) in this series, 153 (24%) presented with seizures. The factors more commonly associated with preoperative seizures were AA pathology (p = 0.03), temporal lobe involvement (p = 0.04), and cortical location (p = 0.04), while the factors less commonly associated with preoperative seizures were greater age (p = 0.03) and larger tumor size (p ≤ 0.001). Among those patients with a history of seizures, outcome 12 months after surgery was Engel Class I (seizure free) in 77%, Class II (rare seizures) in 12%, Class III (meaningful improvement) in 6%, and Class IV (no improvement) in 5%. Postoperative seizures were rare in patients without a history of preoperative seizures. The factor positively associated with prolonged seizure control was increased Karnofsky Performance Scale score (p = 0.002), while the factors negatively associated with seizure control were preoperative uncontrolled seizures (p = 0.03) and parietal lobe involvement (p = 0.005). Seizure recurrence in patients with postoperative seizure control was independently associated with tumor recurrence (p = 0.006).

Conclusions

The identification and consideration of factors associated with prolonged seizure control may help guide treatment strategies aimed at improving the quality of life for patients with malignant astrocytomas.

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Grazia Menna, Alessandro Olivi, and Giuseppe Maria Della Pepa

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Matthew A. Koenig, Romergryko G. Geocadin, Piotr Kulesza, Alessandro Olivi, and Henry Brem

✓ Rhabdoid meningioma (RM) is a recently described, aggressive variant of meningioma. The authors report a case of RM occurring in the resection cavity of an unrelated neurosurgical procedure, temporal lobectomy for intractable seizures. The patient presented with intractable headache 10 years after the temporal lobectomy. Imaging revealed a dura-based, uniformly enhancing lesion within the resection cavity. She underwent gross-total resection and the findings of the surgical pathological report were consistent with an RM, with a dramatically elevated MIB-1 index of approximately 50%. The patient's clinical course was complicated by severe pain and communicating hydrocephalus secondary to rapid dissemination of malignant cells throughout the CSF pathways. Despite aggressive measures, including tumor resection, ventriculoperitoneal shunt placement, and the initiation of conventional radiation therapy, the ensuing leptomeningeal carcinomatosis proved to be rapidly fatal.

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Francesco Dimeco, Richard E. Clatterbuck, Khan W. Li, Edward F. McCarthy, and Alessandro Olivi

✓ The synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a recently described, currently evolving clinical entity that groups together several idiopathic disorders of bone and skin formerly described under a variety of names. Among the spectrum of possible locations for the bone lesions, there is no previous report in the literature of primary involvement of the skull vault. A patient with primary involvement of the calvaria in the setting of SAPHO syndrome is described here, which, to the authors' knowledge, is the first report of such localization. The clinically and radiologically benign evolution of the different stages of the bone lesions is presented. The authors suggest that the SAPHO syndrome should be considered in the differential diagnosis of lytic, sclerotic, or hyperostotic lesions of the skull, particularly before considering invasive diagnostic procedures.

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Francesco DiMeco, Khan W. Li, Betty M. Tyler, Ariel S. Wolf, Henry Brem, and Alessandro Olivi

Object. Mitoxantrone is a drug with potent in vitro activity against malignant brain tumor cell lines; however, its effectiveness as a systemic agent has been hampered by poor central nervous system penetration and dose-limiting myelosuppression. To avoid these problems, we incorporated mitoxantrone into biodegradable polymeric wafers to be used for intracranial implantation, a strategy that has been shown to be safe and successful in the treatment of malignant gliomas. The authors investigated the release kinetics, toxicity, distribution, and efficacy of mitoxantrone delivered from intracranially implanted biodegradable wafers in the treatment of 9L gliosarcoma in Fischer 344 rats.

Methods. Mitoxantrone released from the biodegradable wafer matrix reached therapeutic drug concentrations in the brain for at least 35 days. Only animals with implanted wafers of the highest drug loading dose (20% mitoxantrone by weight) showed signs of significant toxicity. In three separate efficacy experiments, animals treated with mitoxantrone-loaded biodegradable wafers had significantly improved survival compared with control animals. The combined median survival for each treatment group was the following: 0% mitoxantrone wafers, 19 days; 1%, 30 days, p < 0.0001; 5%, 34 days, p < 0.0001; and 10%, 50 days, p < 0.0001.

Conclusions. These findings establish that mitoxantrone delivered from intracranially implanted biodegradable wafers is effective in the treatment of malignant gliomas in rodents and should be considered for future clinical application in humans.

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Kaisorn L. Chaichana, Aditya N. Halthore, Scott L. Parker, Alessandro Olivi, Jon D. Weingart, Henry Brem, and Alfredo Quinones-Hinojosa

Object

The median survival duration for patients with glioblastoma is approximately 12 months. Maximizing quality of life (QOL) for patients with glioblastoma is a priority. An important, yet understudied, QOL component is functional independence. The aims of this study were to evaluate functional outcomes over time for patients with glioblastoma, as well as identify factors associated with prolonged functional independence.

Methods

All patients who underwent first-time resection of either a primary (de novo) or secondary (prior lower grade glioma) glioblastoma at a single institution from 1996 to 2006 were retrospectively reviewed. Patients with a Karnofsky Performance Scale (KPS) score ≥ 80 were included. Kaplan-Meier, log-rank, and multivariate proportional hazards regression analyses were used to identify associations (p < 0.05) with functional independence (KPS score ≥ 60) following glioblastoma resection.

Results

The median follow-up duration time was 10 months (interquartile range [IQR] 5.6–17.0 months). A patient's preoperative (p = 0.02) and immediate postoperative (within 2 months) functional status was associated with prolonged survival (p < 0.0001). Of the 544 patients in this series, 302 (56%) lost their functional independence at a median of 10 months (IQR 6–16 months). Factors independently associated with prolonged functional independence were: preoperative KPS score ≥ 90 (p = 0.004), preoperative seizures (p = 0.002), primary glioblastoma (p < 0.0001), gross-total resection (p < 0.0001), and temozolomide chemotherapy (p < 0.0001). Factors independently associated with decreased functional independence were: older age (p < 0.0001), coexistent coronary artery disease (p = 0.009), and incurring a new postoperative motor deficit (p = 0.009). Furthermore, a decline in functional status was independently associated with tumor recurrence (p = 0.01).

Conclusions

The identification and consideration of these factors associated with prolonged functional outcome (preoperative KPS score ≥ 90, seizures, primary glioblastoma, gross-total resection, temozolomide) and decreased functional outcome (older age, coronary artery disease, new postoperative motor deficit) may help guide treatment strategies aimed at improving QOL for patients with glioblastoma.

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Kaisorn L. Chaichana, Thomas Kosztowski, Ashwini Niranjan, Alessandro Olivi, Jon D. Weingart, John Laterra, Henry Brem, and Alfredo Quiñones-Hinojosa

Object

Patients harboring anaplastic astrocytomas (AAs) typically have a poor prognosis, with median survival times of approximately 3 years following resection. However, a significant variability in individual outcomes remains, with some patients surviving for a few months and others for several years. The ability to predict patient outcomes based on preoperative variables would help prognosticate survival and may also guide treatment strategies. The prognostic implications of a preoperative contrast-enhancing AA remain poorly understood.

Methods

The medical records of all patients who underwent a craniotomy for a hemispheric AA from 1996 to 2006 at a single institution were retrospectively reviewed. Multivariate proportional hazards regression analysis was used to identify independent associations with recurrence and survival. The Kaplan-Meier method and log-rank analysis were used to plot and compare outcomes for patients with and without preoperative contrast enhancement.

Results

One hundred sixty-five patients were available for analysis. The AAs were contrast enhancing in 102 patients (62%), and nonenhancing in 63 patients (38%). There were no significant differences in clinical and treatment-related variables between patients with and without contrast enhancement. After multivariate analysis, contrast enhancement was independently associated with decreased survival (p = 0.02) and increased recurrence (p = 0.04). The 5-year overall survival rates for patients with contrast-enhancing versus nonenhancing tumors were 31 and 38.5%, respectively. The 3-year rates of progression-free survival for patients with contrast-enhancing versus nonenhancing tumors were 32 and 56%, respectively. Interestingly, heterogeneously enhancing tumors appear to result in poorer outcomes as compared with other types of enhancement (such as ring enhancing, nodular, and others). Among patients with contrast-enhancing AAs, gross-total resection significantly delayed recurrence (p = 0.05) but did not significantly prolong survival (p = 0.52).

Conclusions

This study may provide insights into risk-stratifying patients with AAs, and most specifically those with AAs that enhance with contrast administration.