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Ann Liu, Elizabeth N. Kuhn, John T. Lucas Jr., Adrian W. Laxton, Stephen B. Tatter and Michael D. Chan

OBJECT

Neurofibromatosis Type 2 (NF2) is a rare autosomal dominant disorder predisposing patients to meningiomatosis. The role of stereotactic radiosurgery (SRS) is poorly defined in NF2, and although the procedure has excellent control rates in the non-NF2 population, its utility has been questioned because radiation has been hypothesized to predispose patients to malignant transformation of benign tumors. To the authors' knowledge, this is the first study to examine the use of SRS specifically for meningiomas in patients with NF2.

METHODS

The authors searched a tumor registry for all patients with NF2 who had undergone Gamma Knife radiosurgery (GKRS) for meningioma in the period from January 1, 1999, to September 19, 2013, at a single tertiary care cancer center. Medical records were retrospectively reviewed for patient and tumor characteristics and outcomes.

Results

Among the 12 patients who met the search criteria, 125 meningiomas were identified, 87 (70%) of which were symptomatic or progressive and thus treated with GKRS. The median age at the first GKRS was 31 years (interquartile range [IQR] 27–37 years). Five patients (42%) had multiple treatments with a median of 27 months (IQR 14–50 months) until the subsequent GKRS. The median follow-up in surviving patients was 43 months (IQR 34–110 months). The 5-year local tumor control and distant treatment failure rates were 92% and 77%, respectively. Toxicities occurred in 25% of the GKRS treatments, although the majority were Grade 1 or 2. At the last follow-up, 4 patients (33%) had died a neurological death at a median age of 39 years (IQR 37–46 years), and their cases accounted for 45% of all tumors, 55% of all treated tumors, and 58% of all GKRSs. Univariate analysis revealed several predictive variables for distant failure, including male sex (HR 0.28, 95% CI 0.086–0.92, p = 0.036), age at distant failure (HR 0.92, 95% CI 0.90–0.95, p < 0.0001), and prior number of GKRS treatments (HR 1.2, 95% CI 1.1–1.4, p = 0.0049). Local failure, maximum size of the treated tumor, delivered tumor margin dose, and WHO grade were not significant. On multivariate analysis, age at distant failure (HR 0.91, 95% CI 0.88–0.95, p < 0.0001) and prior number of GKRSs (HR 1.3, 95% CI 1.1–1.5, p = 0.004) remained significant. No malignant transformation events among treated tumors were observed.

CONCLUSIONS

Radiosurgery represents a feasible modality with minimal toxicity for NF2-associated meningiomas. Increasing patient age was associated with a decreased rate of distant failure, whereas an increasing number of prior GKRS treatments predicted distant failure. Further studies are necessary to determine the long-term patterns of treatment failure in these patients.

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James L. West, Michael H. Soike, Jaclyn J. Renfrow, Michael D. Chan, Adrian W. Laxton and Stephen B. Tatter

OBJECTIVE

Rathke’s cleft cysts (RCCs) are benign lesions of the sella turcica that usually come to neurosurgical attention due to compression of the optic apparatus (OA) and headaches. Treatment options for these lesions include observation, aspiration of cyst contents, or open resection of the cyst with the cyst wall. All of these options involve the potential for cyst recurrence or enlargement. In this study the authors report on a potential new therapeutic option for RCCs, i.e., stereotactic radiosurgery (SRS).

METHODS

A retrospective review was conducted of 5 patients with histologically confirmed, multiply recurrent RCCs who were treated with single-fraction SRS at a tertiary referral academic medical center.

RESULTS

The total cohort consisted of 5 female patients with an average age of 31.8 years. The most common presenting symptom was headache followed by blurry vision. The symptoms were present on average for 7 months before intervention. The median number of surgeries prior to radiosurgery was 2. The average volume of lesion treated was 0.34 cm3. The median SRS dose was 12.5 Gy prescribed to the 50% isodose line with an average prescription coverage of 96.6%. The median dose to the OA was 5 Gy. At last follow-up, 3 of 5 cysts had completely regressed, 1 had regressed by more than 50% but was still present, and 1 was stable, with an overall mean follow-up duration of 34.2 months. There were no neurological, endocrinological, or visual complications attributable to SRS during the follow-up period.

CONCLUSIONS

RCCs can be a challenging clinical entity to treat, especially when they are multiply recurrent. In patients with an average of 2 previous surgeries for resection, a single SRS session prevented recurrence universally, with an average follow-up of almost 3 years. These results indicate that further investigation of the treatment of RCCs with SRS is indicated.

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Michael W. Chan, Isabelle Thibault, Eshetu G. Atenafu, Eugene Yu, B. C. John Cho, Daniel Letourneau, Young Lee, Albert Yee, Michael G. Fehlings and Arjun Sahgal

OBJECT

The authors performed a pattern-of-failure analysis, with a focus on epidural disease progression, in patients treated with postoperative spine stereotactic body radiotherapy (SBRT).

METHODS

Of the 70 patients with 75 spinal metastases (cases) treated with postoperative spine SBRT, there were 26 cases of local disease recurrence and 25 cases with a component of epidural disease progression. Twenty-four of the 25 cases had preoperative epidural disease with subsequent epidural disease progression, and this cohort was the focus of this epidural-specific pattern-of-failure investigation. Preoperative, postoperative, and follow-up MRI scans were reviewed, and epidural disease was characterized based on location according to a system in which the vertebral anatomy is divided into 6 sectors, with the anterior compartment comprising Sectors 1, 2, and 6, and the posterior compartment comprising Sectors 3, 4, and 5.

RESULTS

Patterns of epidural progression are reported specifically for the 24 cases with preoperative epidural disease and subsequent epidural progression. Epidural disease progression within the posterior compartment was observed to be significantly lower in those with preoperative epidural disease confined to the anterior compartment than in those with preoperative epidural disease involving both anterior and posterior compartments (56% vs 93%, respectively; p = 0.047). In a high proportion of patients with epidural disease progression, treatment failure was found in the anterior compartment, including both those with preoperative epidural disease confined to the anterior compartment and those with preoperative epidural disease involving both anterior and posterior compartments (100% vs. 73%, respectively). When epidural disease was confined to the anterior compartment on the preoperative and postoperative MRIs, no epidural disease progression was observed in Sector 4, which is the most posterior sector. Postoperative epidural disease characteristics alone were not predictive of the pattern of epidural treatment failure.

CONCLUSIONS

Reviewing the extent of epidural disease on preoperative MRI is imperative when planning postoperative SBRT. When epidural disease is confined to the anterior epidural sectors pre- and postoperatively, covering the entire epidural space circumferentially with a prophylactic “donut” distribution may not be needed.

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Antoinette A. Chan, Aubrey Lau, Andrea Pirzkall, Susan M. Chang, Lynn J. Verhey, David Larson, Michael W. McDermott, William P. Dillon and Sarah J. Nelson

Object. The purpose of this study was to assess the differences in spatial extent and metabolic activity in a comparison of a radiosurgical target defined by conventional strategies that utilize the enhancing lesion and a metabolic lesion defined by proton magnetic resonance spectroscopy (MRS) imaging. The authors evaluated whether these differences manifest themselves in the clinical outcome of patients and assessed the value of incorporating 1H-MRS imaging—derived spatial information into the treatment planning process for gamma knife surgery (GKS).

Methods. Twenty-six patients harboring Grade IV gliomas who had previously been treated with external-beam radiation therapy were evaluated by comparing the radiosurgically treated lesion volume with the volume of metabolically active tumor defined on 1H-MRS imaging. The cohort was evenly divided into two groups based on the percentage of overlap between the radiosurgical target and the metabolic lesion volumes. Patients with a percentage of overlap greater than 50% with respect to the metabolic lesion volume were classified as low risk and those with an overlap less than 50% were classified as high risk.

Kaplan—Meier estimators were calculated using time to progression and survival as dependent variables. The metabolite levels within the metabolic lesion were significantly greater than those within the radiosurgical target (p ≤ 0.001). The median survival was 15.7 months for patients in the low-risk group and 10.4 months for those in the highrisk group. This difference was statistically significant (p < 0.01).

Conclusions. Analysis of the results of this study indicates that patients undergoing GKS may benefit from the inclusion of 1H-MRS imaging in the treatment planning process.

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Elizabeth N. Kuhn, Glen B. Taksler, Orrin Dayton, Amritraj G. Loganathan, Tamara Z. Vern-Gross, J. Daniel Bourland, Adrian W. Laxton, Michael D. Chan and Stephen B. Tatter

Object

The purpose of this study was to evaluate patterns of failure after stereotactic radiosurgery (SRS) for meningiomas and factors that may influence these outcomes.

Methods

Based on a retrospective chart review, 279 patients were treated with SRS for meningiomas between January 1999 and March 2011 at Wake Forest Baptist Health. Disease progression was determined using serial imaging, with a minimum follow-up of 6 months (median 34.2 months).

Results

The median margin dose was 12.0 Gy (range 8.8–20 Gy). Local control rates for WHO Grade I tumors were 96.6%, 84.4%, and 75.7% at 1, 3, and 5 years, respectively. WHO Grade II and III tumors had local control rates of 72.3%, 57.7%, and 52.9% at 1, 3, and 5 years, respectively. Tumors without pathological grading had local control rates of 98.7%, 97.6%, and 94.2% at 1, 3, and 5 years, respectively. Of the local recurrences, 63.1% were classified as marginal (within 2 cm of treatment field). The 1-, 3-, and 5-year rates of distant failure were 6.5%, 10.3%, and 16.6%, respectively, for Grade I tumors and 11.4%, 17.2%, and 22.4%, respectively, for Grade II/III tumors. Tumors without pathological grading had distant failure rates of 0.7%, 3.2%, and 6.5% at 1, 3, and 5 years, respectively. Wilcoxon analysis revealed that multifocal disease (p < 0.001) and high-grade histology (WHO Grade II or III; p < 0.001) were significant predictors of local recurrence. Additionally, male sex was a significant predictor of distant recurrence (p = 0.04). Multivariate analysis also showed that doses greater than or equal to 12 Gy were associated with improved local control (p = 0.015).

Conclusions

In this patient series, 12 Gy was the minimum sufficient margin dose for the treatment of meningiomas. Male sex is a risk factor for distant failure, whereas high-grade histology and multifocal disease are risk factors for local failure.

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Will H. McKay, Emory R. McTyre, Catherine Okoukoni, Natalie K. Alphonse-Sullivan, Jimmy Ruiz, Michael T. Munley, Shadi Qasem, Hui-Wen Lo, Fei Xing, Adrian W. Laxton, Stephen B. Tatter, Kounosuke Watabe and Michael D. Chan

OBJECTIVE

There are a variety of salvage options available for patients with brain metastases who experience local failure after stereotactic radiosurgery (SRS). These options include resection, whole-brain radiation therapy, laser thermoablation, and repeat SRS. There is little data on the safety and efficacy of repeat SRS following local failure of a prior radiosurgical procedure. This study evaluates the clinical outcomes and dosimetric characteristics of patients who experienced tumor recurrence and were subsequently treated with repeat SRS.

METHODS

Between 2002 and 2015, 32 patients were treated with repeat SRS for local recurrence of ≥ 1 brain metastasis following initial SRS treatment. The Kaplan-Meier method was used to estimate time-to-event outcomes including overall survival (OS), local failure, and radiation necrosis. Cox proportional hazards analysis was performed for predictor variables of interest for each outcome. Composite dose-volume histograms were constructed for each reirradiated lesion, and these were then used to develop a predictive dosimetric model for radiation necrosis.

RESULTS

Forty-six lesions in 32 patients were re-treated with a second course of SRS after local failure. A median dose of 20 Gy (range 14–22 Gy) was delivered to the tumor margin at the time of repeat SRS. Local control at 1 year was 79% (95% CI 67%–94%). Estimated 1-year OS was 70% (95% CI 55%–88%). Twelve patients had died at the most recent follow-up, with 8/12 patients experiencing neurological death (as described in Patchell et al.). Eleven of 46 (24%) lesions in 11 separate patients treated with repeat SRS were associated with symptomatic radiation necrosis. Freedom from radiation necrosis at 1 year was 71% (95% CI 57%–88%). Analysis of dosimetric data revealed that the volume of a lesion receiving 40 Gy (V40Gy) was the most predictive factor for the development of radiation necrosis (p = 0.003). The following V40Gy thresholds were associated with 10%, 20%, and 50% probabilities of radiation necrosis, respectively: 0.28 cm3 (95% CI 3%–28%), 0.76 cm3 (95% CI 9%–39%), 1.60 cm3 (95% CI 26%–74%).

CONCLUSIONS

Repeat SRS appears to be an effective salvage option for patients with brain metastases experiencing local failure following initial SRS treatment. This series demonstrates durable local control and, although rates of radiation necrosis are significant, repeat SRS may be indicated for select cases of local disease recurrence. Because the V40Gy is predictive of radiation necrosis, limiting this value during treatment planning may allow for a reduction in radiation necrosis rates.

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Corbin A. Helis, Emory McTyre, Michael T. Munley, J. Daniel Bourland, John T. Lucas Jr., Christina K. Cramer, Stephen B. Tatter, Adrian W. Laxton and Michael D. Chan

OBJECTIVE

A small subset of patients with trigeminal neuralgia (TN) will experience bilateral symptoms. Treatment in these patients is controversial because the population is heterogeneous and patients may have nonvascular etiologies of their pain. This study reports treatment outcomes in the largest cohort of patients with bilateral TN who have undergone Gamma Knife radiosurgery (GKRS) to date.

METHODS

A retrospective chart review identified 51 individual nerves in 34 patients with bilateral TN who were treated with GKRS at the authors’ institution between 2001 and 2015, with 12 nerves in 11 patients undergoing repeat GKRS for recurrent or persistent symptoms. Long-term follow-up was obtained by telephone interview. Pain outcomes were measured using the Barrow Neurological Institute (BNI) pain scale, with BNI IIIb or better considered a successful treatment.

RESULTS

There was sufficient follow-up to determine treatment outcomes for 48 individual nerves in 33 patients. Of these nerves, 42 (88%) achieved at least BNI IIIb pain relief. The median duration of pain relief was 1.9 years, and 1-, 3-, and 5-year pain relief rates were 64%, 44%, and 44%, respectively. No patients experienced bothersome facial numbness, and 1 case of anesthesia dolorosa and 2 cases of corneal dryness were reported. Patients with a history of definite or possible multiple sclerosis were significantly more likely to experience BNI IV–V relapse. There was no statistically significant difference in treatment outcomes between patients in this series versus a large cohort of patients with unilateral TN treated at the authors’ institution. There was sufficient follow-up to determine treatment outcomes for 11 individual nerves in 10 patients treated with repeat GKRS. Ten nerves (91%) improved to at least BNI IIIb after treatment. The median duration of pain relief was 2.8 years, with 1-, 3-, and 5-year rates of pain relief of 79%, 53%, and 53%, respectively. There was no statistically significant difference in outcomes between initial and repeat GKRS. One case of bothersome facial numbness and 1 case of corneal dryness were reported, with no patients developing anesthesia dolorosa with retreatment.

CONCLUSIONS

GKRS is a safe, well-tolerated treatment for patients with medically refractory bilateral TN. Efficacy of treatment appears similar to that in patients with unilateral TN. GKRS can be safely repeated in this population if necessary.

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Michael R. Levitt, Randall J. Hlubek, Karam Moon, M. Yashar S. Kalani, Peter Nakaji, Kris A. Smith, Andrew S. Little, Kerry Knievel, Jane W. Chan, Cameron G. McDougall and Felipe C. Albuquerque

OBJECTIVE

Cerebral venous pressure gradient (CVPG) from dural venous sinus stenosis is implicated in headache syndromes such as idiopathic intracranial hypertension (IIH). The incidence of CVPG in headache patients has not been reported.

METHODS

The authors reviewed all cerebral venograms with manometry performed for headache between January 2008 and May 2015. Patient demographics, headache etiology, intracranial pressure (ICP) measurements, and radiographic and manometric results were recorded. CVPG was defined as a difference ≥ 8 mm Hg by venographic manometry.

RESULTS

One hundred sixty-four venograms were performed in 155 patients. There were no procedural complications. Ninety-six procedures (58.5%) were for patients with IIH. The overall incidence of CVPG was 25.6% (42 of 164 procedures): 35.4% (34 of 96 procedures) in IIH patients and 11.8% (8 of 68 procedures) in non-IIH patients. Sixty procedures (36.6%) were performed in patients with preexisting shunts. Seventy-seven patients (49.7%) had procedures preceded by an ICP measurement within 4 weeks of venography, and in 66 (85.7%) of these patients, the ICP had been found to be elevated. CVPG was seen in 8.3% (n = 5) of the procedures in the 60 patients with a preexisting shunt and in 0% (n = 0) of the 11 procedures in the 77 patients with normal ICP (p < 0.001 for both). Noninvasive imaging (MR venography, CT venography) was assessed prior to venography in 112 (68.3%) of 164 cases, and dural venous sinus abnormalities were demonstrated in 73 (65.2%) of these cases; there was a trend toward CVPG (p = 0.07). Multivariate analysis demonstrated an increased likelihood of CVPG in patients with IIH (OR 4.97, 95% CI 1.71–14.47) and a decreased likelihood in patients with a preexisting shunt (OR 0.09, 95% CI 0.02–0.44).

CONCLUSIONS

CVPG is uncommon in IIH patients, rare in those with preexisting shunts, and absent in those with normal ICP.

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Andrew K. Chan, Erica F. Bisson, Mohamad Bydon, Steven D. Glassman, Kevin T. Foley, Eric A. Potts, Christopher I. Shaffrey, Mark E. Shaffrey, Domagoj Coric, John J. Knightly, Paul Park, Kai-Ming Fu, Jonathan R. Slotkin, Anthony L. Asher, Michael S. Virk, Panagiotis Kerezoudis, Silky Chotai, Anthony M. DiGiorgio, Alvin Y. Chan, Regis W. Haid and Praveen V. Mummaneni

OBJECTIVE

The American Association of Neurological Surgeons launched the Quality Outcomes Database (QOD), a prospective longitudinal registry that includes demographic, clinical, and patient-reported outcome (PRO) data, to measure the safety and quality of neurosurgical procedures, including spinal surgery. Differing results from recent randomized controlled trials have established a need to clarify the groups that would most benefit from surgery for degenerative lumbar spondylolisthesis. In the present study, the authors compared patients who were the most and the least satisfied following surgery for degenerative lumbar spondylolisthesis.

METHODS

This was a retrospective analysis of a prospective, national longitudinal registry including patients who had undergone surgery for grade 1 degenerative lumbar spondylolisthesis. The most and least satisfied patients were identified based on an answer of “1” and “4,” respectively, on the North American Spine Society (NASS) Satisfaction Questionnaire 12 months postoperatively. Baseline demographics, clinical variables, surgical parameters, and outcomes were collected. Patient-reported outcome measures, including the Numeric Rating Scale (NRS) for back pain, NRS for leg pain, Oswestry Disability Index (ODI), and EQ-5D (the EuroQol health survey), were administered at baseline and 3 and 12 months after treatment.

RESULTS

Four hundred seventy-seven patients underwent surgery for grade 1 degenerative lumbar spondylolisthesis in the period from July 2014 through December 2015. Two hundred fifty-five patients (53.5%) were the most satisfied and 26 (5.5%) were the least satisfied. Compared with the most satisfied patients, the least satisfied ones more often had coronary artery disease (CAD; 26.9% vs 12.2%, p = 0.04) and had higher body mass indices (32.9 ± 6.5 vs 30.0 ± 6.0 kg/m2, p = 0.02). In the multivariate analysis, female sex (OR 2.9, p = 0.02) was associated with the most satisfaction. Notably, the American Society of Anesthesiologists (ASA) class, smoking, psychiatric comorbidity, and employment status were not significantly associated with satisfaction. Although there were no significant differences at baseline, the most satisfied patients had significantly lower NRS back and leg pain and ODI scores and a greater EQ-5D score at 3 and 12 months postoperatively (p < 0.001 for all).

CONCLUSIONS

This study revealed that some patient factors differ between those who report the most and those who report the least satisfaction after surgery for degenerative lumbar spondylolisthesis. Patients reporting the least satisfaction tended to have CAD or were obese. Female sex was associated with the most satisfaction when adjusting for potential covariates. These findings highlight several key factors that could aid in setting expectations for outcomes following surgery for degenerative lumbar spondylolisthesis.

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Andrew K. Chan, Erica F. Bisson, Mohamad Bydon, Steven D. Glassman, Kevin T. Foley, Eric A. Potts, Christopher I. Shaffrey, Mark E. Shaffrey, Domagoj Coric, John J. Knightly, Paul Park, Michael Y. Wang, Kai-Ming Fu, Jonathan R. Slotkin, Anthony L. Asher, Michael S. Virk, Panagiotis Kerezoudis, Silky Chotai, Anthony M. DiGiorgio, Regis W. Haid and Praveen V. Mummaneni

OBJECTIVE

The AANS launched the Quality Outcomes Database (QOD), a prospective longitudinal registry that includes demographic, clinical, and patient-reported outcome (PRO) data to measure the safety and quality of spine surgery. Registry data offer “real-world” insights into the utility of spinal fusion and decompression surgery for lumbar spondylolisthesis. Using the QOD, the authors compared the initial 12-month outcome data for patients undergoing fusion and those undergoing laminectomy alone for grade 1 degenerative lumbar spondylolisthesis.

METHODS

Data from 12 top enrolling sites were analyzed and 426 patients undergoing elective single-level spine surgery for degenerative grade 1 lumbar spondylolisthesis were found. Baseline, 3-month, and 12-month follow-up data were collected and compared, including baseline clinical characteristics, readmission rates, reoperation rates, and PROs. The PROs included Oswestry Disability Index (ODI), back and leg pain numeric rating scale (NRS) scores, and EuroQol–5 Dimensions health survey (EQ-5D) results.

RESULTS

A total of 342 (80.3%) patients underwent fusion, with the remaining 84 (19.7%) undergoing decompression alone. The fusion cohort was younger (60.7 vs 69.9 years, p < 0.001), had a higher mean body mass index (31.0 vs 28.4, p < 0.001), and had a greater proportion of patients with back pain as a major component of their initial presentation (88.0% vs 60.7%, p < 0.001). There were no differences in 12-month reoperation rate (4.4% vs 6.0%, p = 0.93) and 3-month readmission rates (3.5% vs 1.2%, p = 0.45). At 12 months, both cohorts improved significantly with regard to ODI, NRS back and leg pain, and EQ-5D (p < 0.001, all comparisons). In adjusted analysis, fusion procedures were associated with superior 12-month ODI (β −4.79, 95% CI −9.28 to −0.31; p = 0.04).

CONCLUSIONS

Surgery for grade 1 lumbar spondylolisthesis—regardless of treatment strategy—was associated with significant improvements in disability, back and leg pain, and quality of life at 12 months. When adjusting for covariates, fusion surgery was associated with superior ODI at 12 months. Although fusion procedures were associated with a lower rate of reoperation, there was no statistically significant difference at 12 months. Further study must be undertaken to assess the durability of either surgical strategy in longer-term follow-up.