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Andrew E. Sloan

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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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Editorial

Metastatic spinal cord tumors

Mark N. Hadley

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Kaisorn L. Chaichana, Courtney Pendleton, Daniel M. Sciubba, Jean-Paul Wolinsky and Ziya L. Gokaslan

Object

Metastatic epidural spinal cord compression (MESCC) is a relatively common and debilitating complication of metastatic disease that often results in neurological deficits. Recent studies have supported decompressive surgery over radiation therapy for patients who present with MESCC. These studies, however, have grouped all patients with different histological types of metastatic disease into the same study population. The differential outcomes for patients with different histological types of metastatic disease therefore remain unknown.

Methods

An institutional database of patients undergoing decompressive surgery for MESCC at an academic tertiary-care institution between 1996 and 2006 was retrospectively reviewed. Patients with primary lung, breast, prostate, kidney, or gastrointestinal (GI) cancer or melanoma were identified. Fisher exact and log-rank analyses were used to compare pre-, peri-, and postoperative variables and survival for patients with these different types of primary cancers.

Results

Twenty-seven patients with primary lung cancer, 26 with breast cancer, 20 with prostate cancer, 21 with kidney cancer, 13 with GI cancer, and 7 with melanoma were identified and categorized. All of these patients were followed up for a mean ± SD of 10.8 ± 3.8 months following surgery. Patients with primary lung and prostate cancers were typically older than patients with other types of primary cancers. Patients with prostate cancer had the shortest duration of symptoms and more commonly presented with motor deficits, while patients with breast cancer more commonly had cervical spine involvement and compression fractures. For all histological types, > 90% of patients retained the ability to ambulate following surgery. However, the group with the highest percentage of patients who regained ambulatory function after decompressive surgery was the lung cancer group. Patients with breast or kidney cancer and those with melanoma had the highest median duration of survival following decompressive surgery.

Conclusions

The present study identifies differences in presenting symptoms, operative course, perioperative complications, long-term ambulatory outcomes, and duration of survival for patients with lung, breast, prostate, kidney, and GI cancers and melanoma. This understanding may allow better risk stratification for patients with MESCC.

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Ammar Shaikhouni and E. Antonio Chiocca

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Debraj Mukherjee, Kaisorn L. Chaichana, Ziya L. Gokaslan, Oran Aaronson, Joseph S. Cheng and Matthew J. McGirt

Object

Malignant primary osseous spinal neoplasms are aggressive tumors that remain associated with poor outcomes despite aggressive multidisciplinary treatment measures. To date, prognosis for patients with these tumors is based on results from small single-center patient series and controlled trials. Large population-based observational studies are lacking. To assess national trends in histology-specific survival, the authors reviewed patient survival data spanning 30 years (1973–2003) from the Surveillance, Epidemiology, and End Results (SEER) registry, a US population-based cancer registry.

Methods

The SEER registry was queried to identify cases of histologically confirmed primary spinal chordoma, chondrosarcoma, osteosarcoma, or Ewing sarcoma using coding from the International Classification of Disease for Oncology, Third Edition. Association of survival with histology, metastasis status, tumor site, and year of diagnosis was assessed using Cox proportional-hazards regression analysis.

Results

A total of 1892 patients were identified with primary osseous spinal neoplasms (414 with chordomas, 579 with chondrosarcomas, 430 with osteosarcomas, and 469 with Ewing sarcomas). Chordomas presented in older patients (60 ± 17 years; p < 0.01) whereas Ewing sarcoma presented in younger patients (19 ± 11 years; p < 0.01) compared with patients with all other tumors. The relative incidence of each tumor type remained similar per decade from 1973 to 2003. African Americans comprised a significantly greater proportion of patients with osteosarcomas than other tumors (9.6% vs 3.5%, respectively; p < 0.01). Compared with the sacrum, the mobile spine was more likely to be the site of tumor location for chordomas than for all other tumors (47% vs 23%, respectively; p < 0.05). Osteosarcoma and Ewing sarcoma were 3 times more likely than chondrosarcoma and chordoma to present with metastasis (31% vs 8%, respectively). Resection was performed more frequently for chordoma (88%) and chondrosarcoma (89%) than for osteosarcoma (61%) and Ewing sarcoma (53%). Overall median survival was histology-specific (osteosarcoma, 11 months; Ewing sarcoma, 26 months; chondrosarcoma, 37 months; chordoma, 50 months) and significantly worse in patients with metastasis at presentation for all tumor types. Survival did not significantly differ as a function of site (mobile spine vs sacrum/pelvis) for any tumor type, but more recent year of diagnosis was associated with improved survival for isolated spinal Ewing sarcoma (hazard ration [HR] 0.95; p = 0.001), chondrosarcoma (HR 0.98; p = 0.009), and chordoma (HR 0.98; p = 0.10), but not osteosarcoma.

Conclusions

In this analysis of a 30-year, US population-based cancer registry (SEER), the authors provide nationally representative prognosis and survival data for patients with malignant primary spinal osseous neoplasms. Overall patient survival has improved for isolated spine tumors with advancements in care over the past 4 decades. These results may be helpful in providing historical controls for understanding the efficacy of new treatment paradigms, patient education, and guiding level of aggressiveness in treatment strategies.

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Matthew J. McGirt, Kaisorn L. Chaichana, April Atiba, Frank Attenello, Kevin C. Yao and George I. Jallo

Object

With modern surgical advances, radical resection of pediatric intramedullary spinal cord tumors (IMSCTs) can be expected to preserve long-term neurological function. Nevertheless, postoperative neurological decline is not uncommon after surgery, and many patients continue to experience long-term dysesthetic symptoms. Preoperative predictors of postoperative neurological decline and sensory syndromes have not been investigated and may serve as a guide for surgical risk stratification.

Methods

Neurological function (as determined using the modified McCormick Scale [mMS]) preoperatively, postoperatively, and 3 months after surgery was retrospectively recorded from patient charts in 164 consecutive patients undergoing resection of IMSCTs. A median 4 years (interquartile range [IQR] 1–8 years) after surgery, long-term motor and sensory symptoms were assessed by telephone interviews and corroborated by subsequent medical visits in 120 available patients. This long-term assessment was retrospectively reviewed for the purposes of this study. The authors reviewed this series to assess long-term motor, sensory, and urinary outcomes and to determine independent risk factors of postoperative neurological decline and long-term sensory dysfunction.

Results

Patients were 8.6 ± 5.7 years old and presented with a median mMS of 2 (IQR 2–4). Three months after surgery, 38 patients (23%) continued to experience decreased neurological function (1 mMS point) incurred perioperatively. Increasing age (p = 0.028), unilateral symptoms (p = 0.046), and urinary dysfunction at presentation (p = 0.004) independently predicted persistent 3-month perioperative decline. At long-term follow-up (median 4 years), 39 (33%) exhibited improvements in their mMS scores, 13 (30%) had improvement in their urinary dysfunction, and 27 (30%) had resolution of their dysesthesias. Seventy-eight patients (65%) experienced long-term dysesthetic symptoms. Increasing age (p = 0.024), preoperative symptom duration > 12 months (p = 0.027), and worsened postoperative mMS score at hospital discharge (p = 0.013) independently increased the risk of long-term dysesthesias.

Conclusions

In the authors' experience, nearly one third of patients may experience improvement in motor, sensory, and urinary dysfunction years after IMSCT resection, whereas the majority will continue to experience long-term dysesthetic symptoms. Improvement in motor deficits preceded improvement in sensory syndromes, and urinary dysfunction typically resolved much longer after surgery. The risk of persistent perioperative motor decline was increased with older age, unilateral symptoms, preoperative urinary symptoms, and less severe preoperative neurological deficit. The risk of long-term dysesthesias was increased with older age, increased duration of symptoms prior to resection, and greater postoperative neurological deficit.

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Matthew J. McGirt, Kaisorn L. Chaichana, April Atiba, Ali Bydon, Timothy F. Witham, Kevin C. Yao and George I. Jallo

Object

Gross-total resection of pediatric intramedullary spinal cord tumor (IMSCT) can be achieved in the majority of cases while preserving long-term neurological function. Nevertheless, postoperative progressive spinal deformity often complicates functional outcome years after surgery. The authors set out to determine whether laminoplasty in comparison with laminectomy has reduced the incidence of subsequent spinal deformity requiring fusion after IMSCT resection at their institution.

Methods

The first 144 consecutive patients undergoing resection of IMSCTs at a single institution underwent laminectomy with preservation of facet joints. The next 20 consecutive patients presenting for resection of IMSCTs underwent osteoplastic laminotomy regardless of patient or tumor characteristics. All patients were followed up with telephone interviews corroborated by medical records for the following outcomes: 1) neurological and functional status (modified McCormick Scale [MMS] score and Karnofsky Performance Scale [KPS] score); and 2) development of progressive spinal deformity requiring fusion. The incidence of progressive spinal deformity and the long-term neurological function were compared between the laminectomy and osteoplastic laminotomy cohorts. The means are expressed ± the standard deviation.

Results

Overall, the patients' mean age was 8.6 ± 5 years, and they presented with median MMS scores of 2 (interquartile range [IQR] 2–4). A > 95% resection was achieved in 125 cases (76%). There were no differences (p > 0.10) between patients treated with osteoplastic laminotomy and those treated with laminectomy in terms of the following characteristics: age; sex; duration of symptoms; location of tumor; incidence of preoperative scoliosis (Cobb angle > 10°: 7 [35%] with laminoplasty compared with 49 [34%] with laminectomy); involvement of the cervicothoracic junction (7 [35%] compared with 57 [40%]); thoracolumbar junction (4 [20%] compared with 36 [25%]); tumor size; extent of resection; radiation therapy; histopathological findings; or mean operative spinal levels (7.5 ± 2 compared with 7.5 ± 3). Nevertheless, patients who underwent osteoplastic laminotomy had better median preoperative MMS scores than those treated with laminectomy (2 [IQR 2–2] compared with 2 [IQR 2–4]; p = 0.04). A median of 3.5 years (IQR 1–7 years) after surgery, only 1 patient (5%) in the osteoplastic laminotomy cohort required fusion for progressive spinal deformity, compared with 43 (30%) in the laminectomy cohort (p = 0.027). Adjusting for the inter-cohort difference in preoperative MMS scores, osteoplastic laminotomy was associated with a 7-fold reduction in the odds of subsequent fusion for progressive spinal deformity (odds ratio 0.13, 95% confidence interval 0.02–1.00; p = 0.05). The median MMS and KPS scores were similar between patients who underwent osteoplastic laminotomy and those in whom laminectomy was performed (MMS Score 2 [IQR 2–3] for laminotomy compared with 2 [IQR 2–4] for laminectomy, p = 0.54; KPS Score 90 [IQR 70–100] for laminotomy compared with 90 [IQR 80–90] for laminectomy, p = 0.545) at a median of 3.5 years after surgery.

Conclusions

In the authors' experience, osteoplastic laminotomy for the resection of IMSCT in children was associated with a decreased incidence of progressive spinal deformity requiring fusion but did not affect long-term functional outcome. Laminoplasty used for pediatric IMSCT resection may decrease the incidence of progressive spinal deformity requiring subsequent spinal stabilization in some patients.

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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.