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Kaisorn L. Chaichana, Matthew J. McGirt, John Laterra, Alessandro Olivi and Alfredo Quiñones-Hinojosa

Object

Unlike their malignant counterparts, low-grade gliomas are associated with prolonged survival. However, these tumors have a propensity to progress after resection and ultimately undergo malignant degeneration. The factors associated with recurrence and malignant degeneration remain relatively unknown. The authors set out to determine factors that were independently associated with recurrence and malignant degeneration in patients who underwent resection of a hemispheric low-grade glioma.

Methods

Adult patients who underwent craniotomy and resection of a hemispheric low-grade glioma (WHO Grade II) at the Johns Hopkins Medical Institution's academic tertiary-care institution between 1996 and 2006 were retrospectively reviewed. Multivariate proportional hazards regression analyses were used to identify associations with tumor recurrence and malignant degeneration.

Results

Of the 191 consecutive patients with low-grade gliomas in this series (89 fibrillary astrocytomas, 89 oligodendrogliomas, and 13 mixed gliomas), 83 (43%) and 44 (23%) experienced tumor recurrence and malignant degeneration at last follow-up, respectively. The 5-year progression-free and malignancy-free survival rates were 44 and 74%, respectively. Independent predictors of recurrence were duration of longest lasting symptom (relative risk [RR] 0.978, 95% CI 0.954–0.996, p = 0.01), tumor size (RR 1.328, 95% CI 1.109–1.602, p = 0.002), and preoperative contrast enhancement (RR 2.558, 95% CI 1.241–5.021, p = 0.01). Independent factors associated with malignant degeneration were fibrillary astrocytoma pathology (RR 1.800, 95% CI 1.008–4.928, p = 0.04), tumor size (RR 1.086, 95% CI 1.044–1.358, p = 0.04), and gross-total resection (RR 0.526, 95% CI 0.221–1.007, p = 0.05).

Conclusions

The identification and consideration of factors associated with recurrence and malignant progression may help guide treatment strategies aimed at delaying recurrence and preventing malignant degeneration for patients with hemispheric low-grade gliomas.

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Matthew J. McGirt, Khoi D. Than, Jon D. Weingart, Kaisorn L. Chaichana, Frank J. Attenello, Alessandro Olivi, John Laterra, Lawrence R. Kleinberg, Stuart A. Grossman, Henry Brem and Alfredo Quiñones-Hinojosa

Object

Gliadel (BCNU) wafer and concomitant temozolomide (TMZ) therapy, when used individually as adjuvant therapies, extend survival from that achieved by resection and radiation therapy (XRT) for glioblastoma multiforme (GBM). It remains unstudied whether combining Gliadel and TMZ therapy is safe or further improves survival in patients with newly diagnosed GBM. The authors reviewed their initial experience utilizing combined Gliadel, TMZ, and radiation therapy for the treatment of GBM.

Methods

All cases involving patients undergoing primary resection of GBM with or without Gliadel wafer (3.85% BCNU) implantation and adjuvant XRT over a 10-year period (1997–2006) were retrospectively reviewed. Beginning in 2004, concomitant TMZ became the standard of care at the authors' institution and all patients with Gliadel implantation also received concomitant TMZ (Stupp protocol). Overall survival and treatment-related morbidity were assessed for all patients treated with Gliadel plus concomitant TMZ (XRT + Gliadel + TMZ). Age-matched (≤ 70 years) comparison of survival and morbidity was performed between the XRT + Gliadel + TMZ (post-2003) and XRT + Gliadel (pre-2004) cohorts.

Results

Thirty-three patients were treated with XRT + Gliadel + TMZ. The median survival in this group was 20.7 months, with a 2-year survival rate of 36%. Six-month morbidity included surgical site infection in 1 case (3%), perioperative seizures in 2 cases (6%), deep-vein thrombus in 1 (3%), pulmonary embolism in 3 (9%), and cerebral edema requiring admission for intravenous dexamethasone in 1 case (3%). Myelosuppression required premature termination of TMZ in 7 patients (21%) (thrombocytopenia in 5, neutropenia in 2 cases). In patients ≤ 70 years of age, XRT + Gliadel + TMZ (30 patients, post-2003) was independently associated with improved median survival (21.3 vs 12.4 months, p = 0.005) versus XRT + Gliadel (78 patients, pre-2004), with 2-year survival of 39 versus 18%, respectively. In these patients, XRT + Gliadel + TMZ was not associated with an increase in perioperative morbidity in comparison with XRT + Gliadel.

Conclusions

In this experience, concomitant TMZ therapy in addition to Gliadel wafer implantation was associated with a median survival of nearly 21 months without increased perioperative morbidity. Temozolomide can be safely administered to patients receiving Gliadel wafers after resection of GBM.

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Matthew J. McGirt, Kaisorn L. Chaichana, Muraya Gathinji, Frank J. Attenello, Khoi Than, Alessandro Olivi, Jon D. Weingart, Henry Brem and Alf redo Quiñones-Hinojosa

Object

With recent advances in the adjuvant treatment of malignant brain astrocytomas, it is increasingly debated whether extent of resection affects survival. In this study, the authors investigate this issue after primary and revision resection of these lesions.

Methods

The authors retrospectively reviewed the cases of 1215 patients who underwent surgery for malignant brain astrocytomas (World Health Organization [WHO] Grade III or IV) at a single institution from 1996 to 2006. Patients with deep-seated or unresectable lesions were excluded. Based on MR imaging results obtained < 48 hours after surgery, gross-total resection (GTR) was defined as no residual enhancement, near-total resection (NTR) as having thin rim enhancement of the resection cavity only, and subtotal resection (STR) as having residual nodular enhancement. The independent association of extent of resection and subsequent survival was assessed via a multivariate proportional hazards regression analysis.

Results

Magnetic resonance imaging studies were available for review in 949 cases. The mean age and mean Karnofsky Performance Scale (KPS) score at time of surgery were 51 ± 16 years and 80 ± 10, respectively. Surgery consisted of primary resection in 549 patients (58%) and revision resection for tumor recurrence in 400 patients (42%). The lesion was WHO Grade IV in 700 patients (74%) and Grade III in 249 (26%); there were 167 astrocytomas and 82 mixed oligoastrocytoma. Among patients who underwent resection, GTR, NTR, and STR were achieved in 330 (35%), 388 (41%), and 231 cases (24%), respectively. Adjusting for factors associated with survival (for example, age, KPS score, Gliadel and/or temozolomide use, and subsequent resection), GTR versus NTR (p < 0.05) and NTR versus STR (p < 0.05) were independently associated with improved survival after both primary and revision resection of glioblastoma multiforme (GBM). For primary GBM resection, the median survival after GTR, NTR, and STR was 13, 11, and 8 months, respectively. After revision resection, the median survival after GTR, NTR, and STR was 11, 9, and 5 months, respectively. Adjusting for factors associated with survival for WHO Grade III astrocytoma (age, KPS score, and revision resection), GTR versus STR (p < 0.05) was associated with improved survival. Gross-total resection versus NTR was not associated with an independent survival benefit in patients with WHO Grade III astrocytomas. The median survival after primary resection of WHO Grade III (mixed oligoastrocytomas excluded) for GTR, NTR, and STR was 58, 46, and 34 months, respectively.

Conclusions

In the authors' experience with both primary and secondary resection of malignant brain astrocytomas, increasing extent of resection was associated with improved survival independent of age, degree of disability, WHO grade, or subsequent treatment modalities used. The maximum extent of resection should be safely attempted while minimizing the risk of surgically induced neurological injury.

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Graeme F. Woodworth, Matthew J. McGirt, Amer Samdani, Ira Garonzik, Alessandro Olivi and Jon D. Weingart

Object

The gold standard for stereotactic brain biopsy target localization has been frame-based stereotaxy. Recently, frameless stereotactic techniques have become increasingly utilized. Few authors have evaluated this procedure, analyzed preoperative predictors of diagnostic yield, or explored the differences in diagnostic yield and morbidity rate between the frameless and frame-based techniques.

Methods

A consecutive series of 110 frameless and 160 frame-based image-guided stereotactic biopsy procedures was reviewed. Associated variables for both techniques were reviewed and compared. All stereotactic biopsy procedures were included in a risk factor analysis of nondiagnostic biopsy sampling.

Frameless stereotaxy led to a diagnostic yield of 89%, with a total permanent morbidity rate of 6% and a mortality rate of 1%. Larger lesions were fivefold more likely to yield diagnostic tissues. Deep-seated lesions were 2.7-fold less likely to yield diagnostic tissues compared with cortical lesions. Frameless compared with frame-based stereotactic biopsy procedures showed no significant differences in diagnostic yield or transient or permanent morbidity. For cortical lesions, more than one needle trajectory was required more frequently to obtain diagnostic tissues with frame-based as opposed to frameless stereotaxy, although this factor was not associated with morbidity.

Conclusions

With regard to diagnostic yield and complication rate, the frameless stereotactic biopsy procedure was found to be comparable to or better than the frame-based method. Smaller and deep-seated lesions together were risk factors for a nondiagnostic tissue yield. Frameless stereotaxy may represent a more efficient means of obtaining biopsy specimens of cortical lesions but is otherwise similar to the frame-based technique.

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Matthew J. McGirt, Graeme F. Woodworth, Alex L. Coon, James M. Frazier, Eric Amundson, Ira Garonzik, Alessandro Olivi and Jon D. Weingart

Object. Image-guided stereotactic brain biopsy is associated with transient and permanent incidences of morbidity in 9 and 4.5% of patients, respectively. The goal of this study was to perform a critical analysis of risk factors predictive of an enhanced operative risk in frame-based and frameless stereotactic brain biopsy.

Methods. The authors reviewed the clinical and neuroimaging records of 270 patients who underwent consecutive frame-based and frameless image-guided stereotactic brain biopsies. The association between preoperative variables and biopsy-related morbidity was assessed by performing a multivariate logistic regression analysis.

Transient and permanent stereotactic biopsy-related morbidity was observed in 23 (9%) and 13 (5%) patients, respectively. A hematoma occurred at the biopsy site in 25 patients (9%); 10 patients (4%) were symptomatic. Diabetes mellitus (odds ratio [OR] 3.73, 95% confidence interval [CI] 1.37–10.17, p = 0.01), thalamic lesions (OR 4.06, 95% CI 1.63–10.11, p = 0.002), and basal ganglia lesions (OR 3.29, 95% CI 1.05–10.25, p = 0.04) were independent risk factors for morbidity. In diabetic patients, a serum level of glucose that was greater than 200 mg/dl on the day of biopsy had a 100% positive predictive value and a glucose level lower than 200 mg/dl on the same day had a 95% negative predictive value for biopsy-related morbidity. Pontine biopsy was not a risk factor for morbidity. Only two (4%) of 45 patients who had epilepsy before the biopsy experienced seizures postoperatively. The creation of more than one needle trajectory increased the incidence of neurological deficits from 17 to 44% when associated with the treatment of deep lesions (those in the basal ganglia or thalamus; p = 0.05), but was not associated with morbidity when associated with the treatment of cortex lesions.

Conclusions. Basal ganglia lesions, thalamic lesions, and patients with diabetes were independent risk factors for biopsy-associated morbidity. Hyperglycemia on the day of biopsy predicted morbidity in the diabetic population. Epilepsy did not predispose to biopsy-associated seizure. For deep-seated lesions, increasing the number of biopsy samples along an established track rather than performing a second trajectory may minimize the incidence of morbidity. Close perioperative observation of glucose levels may be warranted.

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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.