Case records of the Massachusetts General Hospital. Case 21-2006. A 61-year-old man with left-sided facial pain.
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Brain↗
Biomedical subjects
Fred G Barker
Publications and source records attributed to Fred G Barker.
Proton beam radiation therapy for skull base adenoid cystic carcinoma.
OBJECTIVE: To determine the treatment outcome and prognostic factors in patients with adenoid cystic carcinoma of the skull base treated with proton beam radiation therapy. DESIGN: Retrospective analysis. SETTING: Massachusetts General Hospital, Massachusetts Eye and Ear Infirmary, and Harvard Medical School, Boston. PATIENTS: From 1991 to 2002, 23 patients with newly diagnosed adenoid cystic carcinoma with skull base extension were treated with combined proton and photon radiotherapy. There was tumor involvement of the sphenoid sinus in 61% of patients (14), nasopharynx in 61% (14), clivus in 48% (11), and cavernous sinus in 74% (17). The extent of surgery was biopsy alone in 48% (11), partial resection in 39% (9), and gross total resection with positive margins in 13% (3). The median total dose to the primary site was 75.9 cobalt-gray equivalent. The median follow-up of all surviving patients was 64 months. MAIN OUTCOME MEASURES: Locoregional control and disease-free survival and overall survival rates. RESULTS: Tumors recurred locally in 2 patients at 33 and 68 months, respectively. No patients developed neck recurrence. Eight patients had distant metastasis as the first site of recurrence. The local control rate at 5 years was 93%. The rate of freedom from distant metastasis at 5 years was 62%. The disease-free and overall survival rates at 5 years were 56% and 77%, respectively. In multivariate analysis, significant adverse factors predictive for overall survival were change in vision at presentation (P = .02) and involvement of sphenoid sinus and clivus (P = .01). CONCLUSIONS: High-dose conformal proton beam radiation therapy results in a very encouraging local control rate in patients with adenoid cystic carcinoma of the skull base. Changes in vision at presentation and tumor involvement of the sphenoid sinus and clivus are important prognostic factors.
Adult↗
Clinical results: Radiosurgery and radiotherapy of cranial nerve schwannomas.
Stereotactic radiosurgery and fractionated radiotherapy are two attractive low-morbidity alternatives to surgical resection for managing cranial nerve schwannomas. Treatment outcomes from these radiation treatment approaches are well documented with long-term outcome studies from multiple institutions. Differences in outcome between these two modalities are difficult to define clearly. The low morbidity and high long-term tumor control rates with radiation treatment have made it the choice of many patients who opt for active initial management for small- or medium-sized cranial nerve schwannomas.
Combined Modality Therapy↗
Improving resection of malignant glioma.
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Adult↗
Unilateral vestibular schwannoma with other neurofibromatosis type 2-related tumors: clinical and molecular study of a unique phenotype.
OBJECT: Although the manifestations of neurofibromatosis Type 2 (NF2) vary, the hallmark is bilateral vestibular schwannomas (VSs). The authors studied the clinical course and genetic basis of unilateral VSs associated with other NF2-related tumors. METHODS: Forty-four adults presenting with unilateral VSs and other NF2-related tumors were identified. A comprehensive review of patient records and cranial imaging was conducted. Molecular analysis of the NF2 locus was performed in available tumors and paired blood specimens. Patient age at symptomatic onset ranged from 11 to 63 years (mean 32 years). Twenty-two patients (50%) presented with eighth cranial nerve dysfunction. Twenty-six presented with multiple lesions. Thirty-eight harbored other intracranial tumors and 27 had spinal tumors, with most lesions situated ipsilateral to the VS. No patient had a relative with NF2, although two of 63 offspring had isolated NF2-related findings. A contralateral VS developed in four patients 3 to 46 years after the symptomatic onset of a unilateral VS, and two of these patients experienced rapid progression to total deafness. Results of a Kaplan-Meier analysis identified actuarial chances of developing contralateral VS: 2.9% (3-17 years after the VS symptomatic onset of unilateral VS), 11% (18-24 years), and 28.8% (25-40 years). Mosaicism for the NF2 gene mutation was proven in eight patients. CONCLUSIONS: The authors describe the clinical features of this unique phenotype--unilateral VS with other NF2-related tumors. Persons with this phenotype should undergo evaluation and monitoring similar to that conducted in patients with NF2, and the possibility of aggressive contralateral VS formation should be considered in their treatment. Molecular genetic analysis is best performed using resected tumor specimens and will enable future studies to determine the genetic risks of individuals with mosaicism.
Adolescent↗
Is there a "July phenomenon" in pediatric neurosurgery at teaching hospitals?
OBJECT: Concern for patient safety, among other reasons, recently prompted sweeping changes in resident work policies in the US. Some have speculated that the arrival of new interns and residents at teaching hospitals each July might cause an annual transient increase in poor patient outcomes and inefficient care. METHODS: Data were analyzed for 4323 craniotomies for tumor resection and 22,072 shunt operations performed in pediatric patients between 1988 and 2000 in US nonfederal hospitals (Nationwide Inpatient Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality, Rockville, MD). In-hospital mortality rates, discharge outcome, complications, and efficiency measures (length of stay [LOS] and hospital charges) for patients treated in July and August were compared with similar data for patients in other months. There were no significant increases in any adverse end point for either tumor or shunt operations in July and August. Odds ratios (95% confidence interval [CI]) for outcome of tumor craniotomies performed in July and August compared with outcome for tumor craniotomies performed in other months were as follows: for mortality rate, 0.43 (0.14-1.32); for adverse discharge disposition, 1.03 (0.71-1.51); for neurological complications, 1.00 (0.63-1.59); for transfusion, 0.70 (0.41-1.19). Hospital charges were 0.5% lower (range -6 to 5%) in July and August, and LOS was 3% shorter (range -8 to 3%). Odds ratios (95% CI) for July or August shunt surgery compared with shunt surgery performed in other months were as follows: for mortality rate, 0.96 (0.58-1.60); for adverse discharge disposition, 0.85 (0.66-1.11); for neurological complications, 1.27 (0.75-2.16); for transfusion, 0.81 (0.48-1.37). Hospital charges were 0.2% higher in July and August (range -3 to 3%), and LOS was 3% shorter (range -5 to 0.5%). CONCLUSIONS: Although moderate increases in some adverse end points could not be excluded, there was no evidence that brain tumor or shunt surgery performed in pediatric patients at US teaching hospitals during July and August is associated with more frequent adverse patient outcome or inefficient care than similar surgery performed during other months.
Brain Neoplasms↗
Magnetic resonance imaging characteristics predict epidermal growth factor receptor amplification status in glioblastoma.
PURPOSE: Two clinical-molecular glioblastoma subtypes have been described: "primary" glioblastomas arise de novo in older patients and often overexpress epidermal growth factor receptor (EGFR); "secondary" glioblastomas progress from lower-grade tumors in younger patients and commonly have TP53 mutations. EGFR overexpression correlates in experimental gliomas with increased angiogenesis, edema, and invasion. No radiographic predictors of molecular glioblastoma subtype are known. EXPERIMENTAL DESIGN: We retrospectively reviewed 75 glioblastomas, classified as TP53-mutated (n=11), EGFR-amplified (n=31), or neither (non-TP53/non-EGFR; n=33). Four variables were derived from preoperative magnetic resonance imaging: (a) T2/T1, the ratio of T2-bright volume to enclosed T1-enhancing volume; (b) percentage of tumor volume that was necrosis; and (c and d) T1 and T2 border sharpness coefficients (BSC), the rates of change in grayscale intensity of adjacent 0.02-cm2 voxels traversing the anterior, posterior, and lateral borders on T1-enhanced and T2 images. RESULTS AND CONCLUSIONS: Mean T2/T1 was 4.7 for EGFR-amplified glioblastomas, greater than that of TP53-mutated glioblastomas (2.3) or non-TP53/non-EGFR glioblastomas (2.6; P<0.00005). All four tumors with T2/T1>7.2 were EGFR-amplified; 0 of 15 with T2/T1<4.7 underwent gross total resection. The mean T2 BSC of EGFR-amplified glioblastomas was 33.7, less sharp (P<0.0000005) than TP53-mutated (72.2) and non-TP53/non-EGFR glioblastomas (81.2). All 15 glioblastomas with T2 BSC<30.8 were EGFR-amplified. Percentage necrosis and T1 BSC did not differ between glioblastoma subtypes. The increased T2/T1 ratio and decreased T2 BSC in EGFR-overexpressing tumors are the first radiographic distinctions described between glioblastoma molecular subtypes. These findings may reflect increased angiogenesis, edema, and/or invasion in EGFR-overexpressing tumors.
Brain Neoplasms↗
Marital status, treatment, and survival in patients with glioblastoma multiforme: a population based study.
BACKGROUND: Social factors influence cancer treatment choices, potentially affecting patient survival. In the current study, the authors studied the interrelations between marital status, treatment received, and survival in patients with glioblastoma multiforme (GM), using population-based data. METHODS: The data source was the Surveillance, Epidemiology, and End Results (SEER) Public Use Database, 1988-2001, 2004 release, all registries. Multivariate logistic, ordinal, and Cox regression analyses adjusted for demographic and clinical variables were used. RESULTS: Of 10,987 patients with GM, 67% were married, 31% were unmarried, and 2% were of unknown marital status. Tumors were slightly larger at the time of diagnosis in unmarried patients (49% of unmarried patients had tumors larger than 45 mm vs. 45% of married patients; P = 0.004, multivariate analysis). Unmarried patients were less likely to undergo surgical resection (vs. biopsy; 75% of unmarried patients vs. 78% of married patients) and were less likely to receive postoperative radiation therapy (RT) (70% of unmarried patients vs. 79% of married patients). On multivariate analysis, the odds ratio (OR) for resection (vs. biopsy) in unmarried patients was 0.88 (95% confidence interval [95% CI], 0.79-0.98; P = 0.02), and the OR for RT in unmarried patients was 0.69 (95% CI, 0.62-0.77; P < 0.001). Unmarried patients more often refused both surgical resection and RT. Unmarried patients who underwent surgical resection and RT were found to have a shorter survival than similarly treated married patients (hazard ratio for unmarried patients, 1.10; P = 0.003). CONCLUSIONS: Unmarried patients with GM presented with larger tumors, were less likely to undergo both surgical resection and postoperative RT, and had a shorter survival after diagnosis when compared with married patients, even after adjustment for treatment and other prognostic factors.
Aged↗
Synthesizing medical evidence: systematic reviews and metaanalyses.
Systematic reviews and metaanalyses have become increasingly popular ways of summarizing, and sometimes extending, existing medical knowledge. In this review the authors summarize current methods of performing metaanalyses, including the following: formulating a research question; performing a structured literature search and a search for trials not published in the formal medical literature; summarizing and, where appropriate, combining results from several trials; and reporting and presenting results. Topics such as cumulative and Bayesian metaanalysis and metaregression are also addressed. References to textbooks, articles, and Internet resources are also provided. The goal is to assist readers who wish to perform their own metaanalysis or to interpret critically a published example.
Bayes Theorem↗
Prizes, lectures, and awards of the American Association of Neurological Surgeons/Congress of Neurological Surgeons Section on Tumors.
An important goal of the Section on Tumors of the American Association of Neurological Surgeons (AANS) and Congress of Neurological Surgeons (CNS) since its founding in 1985 has been to foster both education and research in the field of brain tumor treatment. As one means of achieving this, the Section awards a number of prizes, research grants, and named lectures at the annual meetings of the AANS and CNS. After a brief examination of similar honors that were given in recognition of pioneering work by Knapp, Cushing, and other early brain tumor researchers, the authors describe the various awards given by the AANS/CNS Section on Tumors since its founding, their philanthropic donors, and the recipients of the awards. The subsequent career of the recipients is briefly examined, in terms of the rate of full publication of award-winning abstracts and achievement of grant funding by awardees.
Awards and Prizes↗
Surgical and radiosurgical management of brain metastases.
When should surgery be used? First, when there is a need to establish the diagnosis of metastatic cancer, particularly in patients who have no known primary lesion. Second, as an effective therapy in patients who have a single brain metastasis, symptomatic or recurrent metastases, or when a metastasis threatens hydrocephalus if treated with radiation alone. Surgery is probably more effective in relieving symptoms from metastases than other treatments,although formal proof of this is lacking. Stereotactic radiosurgery can replace resection when the metastases are smaller than 3 cm and symptoms can be controlled with an acceptable steroid dose. Location of larger lesions in the posterior fossa is a relative contraindication to radiosurgery. The best candidates for resection and radiosurgery are those who have good systemic control of the primary disease; older age is a relative contraindication to resection. Aggressive treatment of oligometastatic brain disease probably is underused in current U.S. practice.
Age Factors↗
Surgery for primary supratentorial brain tumors in the United States, 1988 to 2000: the effect of provider caseload and centralization of care.
Contemporary reports of patient outcomes after biopsy or resection of primary brain tumors typically reflect results at specialized centers. Such reports may not be representative of practices in nonspecialized settings. This analysis uses a nationwide hospital discharge database to examine trends in mortality and outcome at hospital discharge in 38,028 admissions for biopsy or resection of supratentorial primary brain tumors in adults between 1988 and 2000, particularly in relation to provider caseload. Multivariate analyses showed that large-volume centers had lower in-hospital postoperative mortality rates than centers with lighter caseloads, both for craniotomies (odds ratio [OR] 0.75 for a tenfold larger caseload) and for needle (closed) biopsies (OR 0.54). Adverse discharge disposition was also less likely at high-volume hospitals, both for craniotomies (OR 0.77) and for needle biopsies (OR 0.67). The annual number of surgical admissions increased by 53% during the 12-year study period, and in-hospital mortality rates decreased during this period, from 4.8% to 1.8%. Mortality rates decreased over time, both for craniotomies and for needle biopsies. Subgroup analyses showed larger relative mortality rate reductions at large-volume centers than at small-volume centers (73% vs. 43%, respectively). The number of US hospitals performing one or more craniotomies annually for primary brain tumors decreased slightly, and the number performing needle biopsies increased. There was little change in median hospital annual craniotomy caseloads, but the largest centers had disproportionate growth in volume. The 100 highest-caseload US hospitals accounted for an estimated 30% of the total US surgical primary brain tumor caseload in 1988 and 41% in 2000. Our findings do not establish minimum volume thresholds for acceptable surgical care of primary brain tumors. However, they do suggest a trend toward progressive centralization of craniotomies for primary brain tumor toward large-volume US centers during this interval.
Adult↗
Stereotactic radiotherapy for vestibular schwannomas: favorable outcome with minimal toxicity.
OBJECTIVE: To determine the outcome and toxicity in patients with vestibular schwannomas treated with conventionally fractionated stereotactic radiotherapy (SRT) and to identify prognostic factors that are predictive of outcome. METHODS: Between 1992 and 2001, 70 patients with vestibular schwannomas were treated with linear accelerator-based SRT in our institutions. Eleven patients had neurofibromatosis Type II (NF2). The median age was 53 years (range, 17-82 yrs). The median tumor volume was 2.4 cm3 (range, 0.05-21.1 cm3). The indications for SRT were distributed as follows: 47% newly diagnosed, 31% progressive tumors after watchful waiting, 3% adjuvant postoperative radiation, and 19% recurrent tumors after surgical resection. The median dose was 54 Gy in 1.8 Gy per fraction, prescribed to 95% of the isodose line. Relocatable stereotactic frames were used for daily treatments. The median follow-up was 45.3 months. RESULTS: Tumor recurrence was defined as progressive enlargement of tumor on follow-up magnetic resonance imaging studies. One patient had a tumor recurrence at 38 months after SRT. The actuarial tumor control rates were 100 and 98% at 3 and 5 years, respectively. Three patients with a median tumor volume of 16.2 cm3 required surgical resection for persistent or increasing symptoms at a median of 37 months. The actuarial freedom from resection rates were 98 and 92% at 3 and 5 years, respectively. In multivariate analysis, tumor volume at time of treatment was predictive for neurosurgical intervention (surgical resection or shunt placement) after SRT (P = 0.001). The 3- and 5-year actuarial rates of freedom from any neurosurgical intervention were 100 and 97% for patients with tumor volume less than 8 cm3 and 74 and 47% respectively for patients with tumor of at least 8 cm3 (P < 0.0001). The 3-year actuarial rates of facial and trigeminal nerve preservation were 99 and 96%, respectively. Surgery before SRT was predictive of posttreatment trigeminal neuropathy. The 3-year actuarial rates of freedom from trigeminal neuropathy were 86 and 98% for patients with and without previous resection, respectively (P = 0.04). There was no difference in tumor control and cranial nerve function preservation rates seen in NF2 patients compared with non-NF2 patients. No second primary cancer or malignant transformation was observed. CONCLUSION: SRT in the conventionally fractionated approach results in a very favorable outcome with minimal toxicity, with results comparable to those of the best of the radiosurgery series. Patients with large tumors are more likely to undergo neurosurgical interventions after SRT. Patients who have undergone previous surgery are at increased risk of developing trigeminal neuropathy.
Adolescent↗
Rapidly rising incidence of cerebrospinal fluid shunting procedures for idiopathic intracranial hypertension in the United States, 1988-2002.
OBJECTIVE: Obesity, a major risk factor for idiopathic intracranial hypertension (IIH), is rapidly increasing in all ages of the United States population. We studied trends in the incidence of cerebrospinal fluid (CSF) shunts for IIH in the United States between 1988 and 2002, using a national hospital discharge database. METHODS: This was a retrospective study using the Nationwide Inpatient Sample and robust weighted least-squares regression, adjusted for stratified survey methodology. RESULTS: There were 2779 admissions for CSF shunting procedures (new or revision) in IIH patients in the database. In-hospital mortality for new shunts was 0.5% (0.9% for ventricular shunts and 0.2% for lumbar shunts). The estimated total United States caseload of CSF shunting procedures for IIH increased 350% between 1988 and 2002 (P < 0.001). (The 2002 United States caseload was 1370 admissions). New shunt placements increased 320% during this interval (P < 0.001). In some subpopulations in which obesity is less important as a risk factor for IIH, caseload increases were less marked: pediatric IIH shunting (age < 13 yr) increased 52% and shunting in male IIH patients increased 38%, but shunting in older patients (age > 44 yr) increased 240% during the study period. Bariatric procedures (e.g., gastric bypass) increased very rapidly in incidence since 1998, with nearly 200 such procedures performed on IIH patients in 2002. CONCLUSION: The incidence of CSF shunting for IIH is increasing in the population of the United States at about the same relative rate as morbid obesity. Studies to establish the best shunting method in IIH and to explore alternative treatment strategies, such as optic nerve sheath fenestration and bariatric surgery, are urgently needed.
Adolescent↗
Craniotomy for meningioma in the United States between 1988 and 2000: decreasing rate of mortality and the effect of provider caseload.
OBJECT: The goal of this study was to determine the risk of adverse outcomes after contemporary surgical treatment of meningiomas in the US and trends in patient outcomes and patterns of care. METHODS: The authors performed a retrospective cohort study by using the Nationwide Inpatient Sample covering the period of 1988 to 2000. Multivariate regression models with disposition end points of death and hospital discharge were used to test patient, surgeon, and hospital characteristics, including volume of care, as outcome predictors. Multivariate analyses revealed that larger-volume centers had lower mortality rates for patients who underwent craniotomy for meningioma (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.59-0.93, p = 0.01). Adverse discharge disposition was also less likely at high-volume hospitals (OR 0.71, 95% CI 0.62-0.80, p < 0.001). With respect to the surgeon caseload, there was a trend toward a lower rate of mortality after surgery when higher-caseload providers were involved, and a significantly less frequent adverse discharge disposition (OR 0.71, 95% CI 0.62-0.80, p < 0.001). The annual meningioma caseload in the US increased 83% between 1988 and 2000, from 3900 patients/year to 7200 patients/year. In-hospital mortality rates decreased 61%, from 4.5% in 1988 to 1.8% in 2000. Reductions in the mortality rates were largest at high-volume centers (a 72% reduction in the relative mortality rate at largest-volume-quintile centers, compared with a 6% increase in the relative mortality rate at lowest-volume-quintile centers). The number of US hospitals where craniotomies were performed for meningiomas increased slightly. Fewer centers hosted one meningioma resection annually, whereas the largest centers had disproportionate increases in their caseloads, indicating a modest centralization of meningioma surgery in the US during this interval. CONCLUSIONS: The mortality and adverse hospital discharge disposition rates were lower when meningioma surgery was performed by high-volume providers. The annual US caseload increased, whereas the mortality rates decreased, especially at high-volume centers.
Adult↗
Extracranial-intracranial bypass in the treatment of occlusive cerebrovascular disease and intracranial aneurysms in the United States between 1992 and 2001: a population-based study.
OBJECT: The authors assessed the results of extracranial-intracranial (EC-IC) bypass surgery in the treatment of occlusive cerebrovascular disease and intracranial aneurysms in the US between 1992 and 2001 by using population-based methods. METHODS: This is a retrospective cohort study based on data from the Nationwide Inpatient Sample (Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality, Rockville, MD). Five hundred fifty-eight operations were performed at 158 hospitals by 115 identified surgeons. The indications for surgery were cerebral ischemia in 74% of the operations (2.4% mortality rate), unruptured aneurysms in 19% of the operations (7.7% mortality rate), and ruptured aneurysms in 7% of the operations (21% mortality rate). Overall, 4.6% of the patients died and 4.7% of the patients were discharged to long-term facilities, 16.4% to short-term facilities, and 74.2% to their homes. The annual number of admissions in the US increased from 190 per year (1992-1996) to 360 per year (1997-2001), whereas the mortality rates increased from 2.8% (1992-1996) to 5.7% (1997-2001). The median annual number of procedures was three per hospital (range one-27 operations) or two per surgeon (range one-21 operations). For 29% of patients, their bypass procedure was the only one recorded at their particular hospital during that year; for these institutions the mean annual caseload was 0.4 admissions per year. For 42% of patients, their particular surgeon performed no other bypass procedure during that year. Older patient age (p < 0.001) and African-American race (p = 0.005) were risk factors for adverse outcome. In a multivariate analysis in which adjustments were made for age, sex, race, diagnosis, admission type, geographic region, medical comorbidity, and year of surgery, high-volume hospitals less frequently had an adverse discharge disposition (odds ratio 0.54, p = 0.03). CONCLUSIONS: Most EC-IC bypasses performed in the US during the last decade were performed for occlusive cerebrovascular disease. Community mortality rates for aneurysm treatment including bypass procedures currently exceed published values from specialized centers and, during the period under study, the mortality rates increased with time for all diagnostic subgroups. This technically demanding procedure has become a very low-volume operation at most US centers.
Adolescent↗
Craniotomy for the resection of metastatic brain tumors in the U.S., 1988-2000: decreasing mortality and the effect of provider caseload.
BACKGROUND: To assist in selecting treatment for patients with brain metastases, the current study assessed the risk of adverse outcomes after contemporary resection of metastatic brain tumors in relation to patient, surgeon, and hospital characteristics, with particular attention to the volume of care and trends in outcomes. METHODS: A retrospective cohort study of 13,685 admissions from the Nationwide Inpatient Sample between 1988-2000 was performed. Multivariate logistic, ordinal, and loglinear regression were used with endpoints of mortality, discharge disposition, length of stay, and total hospital charges. RESULTS: The overall in-hospital mortality rate was 3.1% and an additional 16.7% of patients were not discharged directly home. In multivariate analyses, larger-volume centers were found to have lower mortality rates for intracranial metastasis resection (odds ratio [OR], 0.79; 95% confidence interval [95% CI], 0.59-1.03 [P = 0.09]). An adverse discharge disposition also was less likely at higher-volume hospitals (OR, 0.75; 95% CI, 0.65-0.86 [P < 0.001]). For surgeon caseload, mortality was lower with higher-caseload providers (OR, 0.49; 95% CI, 0.30-0.80 [P = 0.004]) and an adverse discharge disposition occurred significantly less frequently (OR, 0.51; 95% CI, 0.40-0.64 [P < 0.001]). The annual number of resections increased by 79% during the study period, from 3900 (1988) to 7000 (2000). In-hospital mortality rates decreased from 4.6% (1988-1990) to 2.3% (1997-2000), a 49% relative decrease. Length of stay was reported to be significantly shorter with higher-volume providers. Hospital charges were not found to be associated significantly with hospital caseload and were found to be significantly lower after surgery that was performed by higher-caseload surgeons. CONCLUSIONS: The results of the current study found that higher-volume hospitals and surgeons provided superior short-term outcomes after resection of intracranial metastasis was performed, with shorter lengths of stay and a trend toward lower charges.
Adult↗