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  • By Author: Nakaji, Peter x
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David G. Brachman, Emad Youssef, Christopher J. Dardis, Nader Sanai, Joseph M. Zabramski, Kris A. Smith, Andrew S. Little, Andrew G. Shetter, Theresa Thomas, Heyoung L. McBride, Stephen Sorensen, Robert F. Spetzler and Peter Nakaji

OBJECTIVE

Effective treatments for recurrent, previously irradiated intracranial meningiomas are limited, and resection alone is not usually curative. Thus, the authors studied the combination of maximum safe resection and adjuvant radiation using permanent intracranial brachytherapy (R+BT) in patients with recurrent, previously irradiated aggressive meningiomas.

METHODS

Patients with recurrent, previously irradiated meningiomas were treated between June 2013 and October 2016 in a prospective single-arm trial of R+BT. Cesium-131 (Cs-131) radiation sources were embedded in modular collagen carriers positioned in the operative bed on completion of resection. The Cox proportional hazards model with this treatment as a predictive term was used to model its effect on time to local tumor progression.

RESULTS

Nineteen patients (median age 64.5 years, range 50–78 years) with 20 recurrent, previously irradiated tumors were treated. The WHO grade at R+BT was I in 4 (20%), II in 14 (70%), and III in 2 (10%) cases. The median number of prior same-site radiation courses and same-site surgeries were 1 (range 1–3) and 2 (range 1–4), respectively; the median preoperative tumor volume was 11.3 cm3 (range 0.9–92.0 cm3). The median radiation dose from BT was 63 Gy (range 54–80 Gy). At a median radiographic follow-up of 15.4 months (range 0.03–47.5 months), local failure (within 1.5 cm of the implant bed) occurred in 2 cases (10%). The median treatment-site time to progression after R+BT has not been reached; that after the most recent prior therapy was 18.3 months (range 3.9–321.9 months; HR 0.17, p = 0.02, log-rank test). The median overall survival after R+BT was 26 months, with 9 patient deaths (47% of patients). Treatment was well tolerated; 2 patients required surgery for complications, and 2 experienced radiation necrosis, which was managed medically.

CONCLUSIONS

R+BT utilizing Cs-131 sources in modular carriers represents a potentially safe and effective treatment option for recurrent, previously irradiated aggressive meningiomas.

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Jason P. Sheehan, Robert M. Starke, Hideyuki Kano, Anthony M. Kaufmann, David Mathieu, Fred A. Zeiler, Michael West, Samuel T. Chao, Gandhi Varma, Veronica L. S. Chiang, James B. Yu, Heyoung L. McBride, Peter Nakaji, Emad Youssef, Norissa Honea, Stephen Rush, Douglas Kondziolka, John Y. K. Lee, Robert L. Bailey, Sandeep Kunwar, Paula Petti and L. Dade Lunsford

Object

Parasellar and sellar meningiomas are challenging tumors owing in part to their proximity to important neurovascular and endocrine structures. Complete resection can be associated with significant morbidity, and incomplete resections are common. In this study, the authors evaluated the outcomes of parasellar and sellar meningiomas managed with Gamma Knife radiosurgery (GKRS) both as an adjunct to microsurgical removal or conventional radiation therapy and as a primary treatment modality.

Methods

A multicenter study of patients with benign sellar and parasellar meningiomas was conducted through the North American Gamma Knife Consortium. For the period spanning 1988 to 2011 at 10 centers, the authors identified all patients with sellar and/or parasellar meningiomas treated with GKRS. Patients were also required to have a minimum of 6 months of imaging and clinical follow-up after GKRS. Factors predictive of new neurological deficits following GKRS were assessed via univariate and multivariate analyses. Kaplan-Meier analysis and Cox multivariate regression analysis were used to assess factors predictive of tumor progression.

Results

The authors identified 763 patients with sellar and/or parasellar meningiomas treated with GKRS. Patients were assessed clinically and with neuroimaging at routine intervals following GKRS. There were 567 females (74.3%) and 196 males (25.7%) with a median age of 56 years (range 8–90 years). Three hundred fifty-five patients (50.7%) had undergone at least one resection before GKRS, and 3.8% had undergone prior radiation therapy. The median follow-up after GKRS was 66.7 months (range 6–216 months). At the last follow-up, tumor volumes remained stable or decreased in 90.2% of patients. Actuarial progression-free survival rates at 3, 5, 8, and 10 years were 98%, 95%, 88%, and 82%, respectively. More than one prior surgery, prior radiation therapy, or a tumor margin dose < 13 Gy significantly increased the likelihood of tumor progression after GKRS.

At the last clinical follow-up, 86.2% of patients demonstrated no change or improvement in their neurological condition, whereas 13.8% of patients experienced symptom progression. New or worsening cranial nerve deficits were seen in 9.6% of patients, with cranial nerve (CN) V being the most adversely affected nerve. Functional improvements in CNs, especially in CNs V and VI, were observed in 34% of patients with preexisting deficits. New or worsened endocrinopathies were demonstrated in 1.6% of patients; hypothyroidism was the most frequent deficiency. Unfavorable outcome with tumor growth and accompanying neurological decline was statistically more likely in patients with larger tumor volumes (p = 0.022) and more than 1 prior surgery (p = 0.021).

Conclusions

Gamma Knife radiosurgery provides a high rate of tumor control for patients with parasellar or sellar meningiomas, and tumor control is accompanied by neurological preservation or improvement in most patients.

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Douglas A. Hardesty, Andrew B. Wolf, David G. Brachman, Heyoung L. McBride, Emad Youssef, Peter Nakaji, Randall W. Porter, Kris A. Smith, Robert F. Spetzler and Nader Sanai

Object

Patients with atypical meningioma often undergo gross-total resection (GTR) at initial presentation, but the role of adjuvant radiation therapy remains unclear. The increasing prevalence of stereotactic radiosurgery (SRS) in the modern neurosurgical era has led to the use of routine postoperative radiation therapy in the absence of evidence-based guidelines. This study sought to define the long-term recurrence rate of atypical meningiomas and identify the value of SRS in affecting outcome.

Methods

The authors identified 228 patients with microsurgically treated atypical meningiomas who underwent a total of 257 resections at the Barrow Neurological Institute over the last 20 years. Atypical meningiomas were diagnosed according to current WHO criteria. Clinical and radiographic data were collected retrospectively.

Results

Median clinical and radiographic follow-up was 52 months. Gross-total resection, defined as Simpson Grade I or II resection, was achieved in 149 patients (58%). The median proliferative index was 6.9% (range 0.4%–20.6%). Overall 51 patients (22%) demonstrated tumor recurrence at a median of 20.2 months postoperatively. Seventy-one patients (31%) underwent adjuvant radiation postoperatively, with 32 patients (14%) receiving adjuvant SRS and 39 patients (17%) receiving adjuvant intensity modulated radiation therapy (IMRT). The recurrence rate for patients receiving SRS was 25% (8/32) and for IMRT was 18% (7/39), which was not significantly different from the overall group. Gross-total resection was predictive of progression-free survival (PFS; relative risk 0.255, p < 0.0001), but postoperative SRS was not associated with improved PFS in all patients or in only those with subtotal resections.

Conclusions

Atypical meningiomas are increasingly irradiated, even after complete or near-complete microsurgical resection. This analysis of the largest patient series to date suggests that close observation remains reasonable in the setting of aggressive microsurgical resection. Although postoperative adjuvant SRS did not significantly affect tumor recurrence rates in this experience, a larger cohort study with longer follow-up may reveal a therapeutic benefit in the future.

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David A. Wilson, Al-Wala Awad, David Brachman, Stephen W. Coons, Heyoung McBride, Emad Youssef, Peter Nakaji, Andrew G. Shetter, Kris A. Smith, Robert F. Spetzler and Nader Sanai

Object

The optimal management of pineocytomas remains controversial. Although the value of complete microsurgical removal is well accepted, gross-total resection is not always feasible. Data regarding the role of postoperative adjuvant stereotactic radiosurgery (SRS) for residual disease is limited and conflicting. Here, the authors review the largest single-institution experience with multimodal pineocytoma management in an effort to quantify the utility of adjuvant radiosurgical treatment of residual disease.

Methods

The medical records and radiographic studies for all patients with histologically confirmed pineocytoma at the Barrow Neurological Institute between 1999 and 2011 were retrospectively reviewed. Clinical and radiographic data, including the volumetric extent of resection, were collected retrospectively, and Kaplan-Meier analysis was used to identify progression-free survival.

Results

Fourteen adults with newly diagnosed pineocytomas were surgically treated in the period from 1999 to 2011. The median clinical and radiographic follow-ups were 44 and 53 months, respectively. Twelve patients (86%) underwent microsurgical removal and 2 (14%) underwent endoscopic biopsy. Five patients (36%) had complete resections and 9 (64%) demonstrated residual disease. Three patients (21%) presented with radiographic recurrence at a median interval of 43 months after initial treatment (range 13–83 months). At the time of recurrence, the median preoperative tumor volume was 2.6 cm3. Adjuvant SRS was used to treat 3 subtotally resected tumors (33%) following initial presentation and 2 (66%) at the time of recurrence. Among patients with subtotally resected tumors, progression-free survival was significantly longer (p < 0.05) for those who did as compared with those who did not undergo adjuvant radiosurgery. To date, no patient who underwent adjuvant radiosurgery has demonstrated radiographic or clinical evidence of disease progression.

Conclusions

Microsurgical removal remains the definitive treatment for pineocytomas, yet residual disease can be effectively controlled using adjuvant SRS.