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Michele R. Aizenberg, Benjamin D. Fox, Dima Suki, Ian E. McCutcheon, Ganesh Rao and Laurence D. Rhines

Object

Patients presenting with spinal metastases from unknown primary tumors (UPTs) are rare. The authors reviewed their surgical experience to evaluate outcomes and identify predictors of survival in these patients.

Methods

This study is a retrospective analysis of patients undergoing surgery for metastatic spine disease from UPTs between June 1993 and February 2007 at The University of Texas M. D. Anderson Cancer Center.

Results

Fifty-one patients undergoing 52 surgical procedures were identified. The median age at spine surgery was 60 years. The median survival from time of diagnosis was 15.8 months (95% CI 8.1–23.6) and it was 8.1 months (95% CI 1.6–14.7) from time of spine surgery. Postoperative neurological function (Frankel score) was the same or improved in 94% of patients. At presentation, 77% had extraspinal disease, which was associated with poorer survival (6.4 vs 18.1 months; p = 0.041). Multiple sites (vs a single site) of spine disease did not impact survival (12.7 vs 8.7 months; p = 0.50). Patients with noncervical spinal disease survived longer than those with cervical disease (11.8 vs 6.4 months, respectively; p = 0.029). Complete versus incomplete resection at index surgery had no impact on survival duration (p > 0.5) or local recurrence (p = 1.0). Identification of a primary cancer was achieved in 31% of patients.

Conclusions

This is the first reported surgical series of patients with an unknown source of spinal metastases. The authors found that multiple sites of spinal disease did not influence survival; however, the presence of extraspinal disease had a negative impact. The extent of resection had no effect on survival duration or local recurrence. With an overall median survival of 8.1 months following surgery, aggressive evaluation and treatment of patients with metastatic disease of the spine from an unknown primary source is warranted.

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Frederick F. Lang, Raymond Sawaya, Dima Suki, Ian E. McCutcheon and Kenneth R. Hess

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Christopher M. McPherson, Dima Suki, Ian E. McCutcheon, Ziya L. Gokaslan, Laurence D. Rhines and Ehud Mendel

Object.

Metastastic lesions have been reported in 5 to 40% of patients with spinal and sacrococcygeal chordoma, but few contemporary series of chordoma metastastic disease exist in the literature. Additionally, the outcome in patients with chordoma-induced metastastic neoplasms remains unclear. The authors performed a retrospective review of the neurosurgery database at the University of Texas M. D. Anderson Cancer Center in Houston to determine the incidence of metastatic disease in a contemporary series of spinal and sacrococcygeal chordoma as well as to determine the outcomes.

Methods.

Thirty-seven patients underwent surgery for spinal and sacrococcygeal chordoma between June 1, 1993, and March 31, 2004. All records were reviewed, and appropriate statistical analyses were used to compare patient data for preoperative characteristics, treatments, and outcomes.

The authors identified seven patients (19%) in whom metastatic disease developed; in three the disease had metastasized to the lungs only, in two to the lungs and liver, and in two to distant locations in the spine. There were no significant differences in age, sex, tumor location, or history of radiation treatments between patients with and those without metastases. In cases with local recurrent tumors, metastastic disease was more likely to develop than in those without recurrence (28 compared with 0%, respectively; p = 0.07). In two (12%) of 17 patients who underwent en bloc resection, metastatic disease developed, whereas it developed in five (25%) of 20 patients treated by curettage (p = 0.42). The median time from first surgery to the appearance of metastatic disease, as calculated using the Kaplan–Meier method, was 143.4 months (95% confidence interval [CI] 66.8–219.9). The median survival duration of patients with metastatic disease after the first surgery was 106 months (95% CI 55.7–155.7), and this did not differ significantly from that in patients in whom no metastases developed (p = 0.93).

Conclusions.

Spinal chordoma metastasized to other locations in 19% of the patients in this series. In patients with local disease recurrence, metastatic lesions are more likely to develop. Metastatic lesions were shown to be aggressive in some cases. Surgery and chemotherapy can play a role in controlling metastatic disease.

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Sherise D. Ferguson, Nicholas B. Levine, Dima Suki, Andrew J. Tsung, Fredrick F. Lang, Raymond Sawaya, Jeffrey S. Weinberg and Ian E. McCutcheon

OBJECTIVE

Fourth ventricle tumors are rare, and surgical series are typically small, comprising a single pathology, or focused exclusively on pediatric populations. This study investigated surgical outcome and complications following fourth ventricle tumor resection in a diverse patient population. This is the largest cohort of fourth ventricle tumors described in the literature to date.

METHODS

This is an 18-year (1993–2010) retrospective review of 55 cases involving patients undergoing surgery for tumors of the fourth ventricle. Data included patient demographic characteristics, pathological and radiographic tumor characteristics, and surgical factors (approach, surgical adjuncts, extent of resection, etc.). The neurological and medical complications following resection were collected and outcomes at 30 days, 90 days, 6 months, and 1 year were reviewed to determine patient recovery. Patient, tumor, and surgical factors were analyzed to determine factors associated with the frequently encountered postoperative neurological complications.

RESULTS

There were no postoperative deaths. Gross-total resection was achieved in 75% of cases. Forty-five percent of patients experienced at least 1 major neurological complication, while 31% had minor complications only. New or worsening gait/focal motor disturbance (56%), speech/swallowing deficits (38%), and cranial nerve deficits (31%) were the most common neurological deficits in the immediate postoperative period. Of these, cranial nerve deficits were the least likely to resolve at follow-up. Multivariate analysis showed that patients undergoing a transvermian approach had a higher incidence of postoperative cranial nerve deficits, gait disturbance, and speech/swallowing deficits than those treated with a telovelar approach. The use of surgical adjuncts (intraoperative navigation, neurophysiological monitoring) did not significantly affect neurological outcome. Twenty-two percent of patients required postoperative CSF diversion following tumor resection. Patients who required intraoperative ventriculostomy, those undergoing a transvermian approach, and pediatric patients (< 18 years old) were all more likely to require postoperative CSF diversion. Twenty percent of patients suffered at least 1 medical complication following tumor resection. Most complications were respiratory, with the most common being postoperative respiratory failure (14%), followed by pneumonia (13%).

CONCLUSIONS

The occurrence of complications after fourth ventricle tumor surgery is not rare. Postoperative neurological sequelae were frequent, but a substantial number of patients had neurological improvement at long-term followup. Of the neurological complications analyzed, postoperative cranial nerve deficits were the least likely to completely resolve at follow-up. Of all the patient, tumor, and surgical variables included in the analysis, surgical approach had the most significant impact on neurological morbidity, with the telovelar approach being associated with less morbidity.

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Claudio E. Tatsui, Dima Suki, Ganesh Rao, Stefan S. Kim, Abhijit Salaskar, Mustafa Aziz Hatiboglu, Ziya L. Gokaslan, Ian E. McCutcheon and Laurence D. Rhines

Object

Renal cell carcinoma (RCC) frequently metastasizes to the spine, and the prognosis can be quite variable. Surgical removal of the tumor with spinal reconstruction has been a mainstay of palliative treatment. The ability to predict prognosis is valuable when determining the role and magnitude of surgical intervention in cancer patients. To better identify factors affecting survival in patients undergoing surgery for spinal metastasis from RCC, the authors undertook a retrospective analysis of a large patient cohort at a tertiary care cancer center.

Methods

Relevant clinical data on a consecutive series of patients who had undergone surgery for spinal metastasis of RCC between 1993 and 2007 at The University of Texas MD Anderson Cancer Center were retrospectively reviewed. Demographic data, histopathological grade of primary tumor, timing of spinal surgery relative to diagnosis, treatment history prior to surgery, neurological status, and systemic disease burden were analyzed to determine the impact of these factors on survival outcome.

Results

The authors identified 267 patients who met the study criteria. Five-year overall survival (OS) after spine tumor resection was 7.8%, with a median OS of 11.3 months (95% CI 9.5–13.0 months). Patients with Fuhrman Grade 4 RCC had a median OS of 6.1 months (95% CI 3.5–8.7 months), which was significantly lower than the 14.3 months (95% CI 9.1–19.4 months) observed in patients with Fuhrman Grade 3 or less RCC (p < 0.001). Patients with preoperative neurological deficits had a median survival of 5.9 months (95% CI 4.1–7.7 months), which was significantly lower than the 13.5 months (95% CI 10.4–16.6 months) observed in patients with a normal neurological examination (p < 0.001). Patients whose spine was the only site of metastasis had a median OS of 19 months (95% CI 9.8–28.2 months) after surgery, significantly longer than the 9.7 months (95% CI 8.1–11.3 months) observed in patients with additional extraspinal metastasis sites (p < 0.001). Patients with nonprogressing extraspinal metastasis (no metastasis, stable, or concurrent) had a median survival of 20.6 months (95% CI 15.1–26.1 months), compared with 5.6 months (95% CI 4.4–6.8 months) in patients with progressing metastasis (p < 0.001).

Conclusions

The authors identified several factors influencing survival after spine surgery for metastatic spinal RCC, including grade of the original nephrectomy specimen, activity of the systemic disease, and neurological status at the time of surgery. These clinical features may help to identify patients who may benefit from aggressive surgical intervention.

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Jonathan N. Sellin, Dima Suki, Viraat Harsh, Benjamin D. Elder, Daniel K. Fahim, Ian E. McCutcheon, Ganesh Rao, Laurence D. Rhines and Claudio E. Tatsui

OBJECT

Spinal metastases account for the majority of bone metastases from thyroid cancer. The objective of the current study was to analyze a series of consecutive patients undergoing spinal surgery for thyroid cancer metastases in order to identify factors that influence overall survival.

METHODS

The authors retrospectively reviewed the records of all patients who underwent surgery for spinal metastases from thyroid cancer between 1993 and 2010 at the University of Texas MD Anderson Cancer Center.

RESULTS

Forty-three patients met the study criteria. Median overall survival was 15.4 months (95% CI 2.8–27.9 months) based on the Kaplan-Meier method. The median follow-up duration for the 4 patients who were alive at the end of the study was 39.4 months (range 1.7–62.6 months). On the multivariate Cox analysis, progressive systemic disease at spine surgery and postoperative complications were associated with worse overall survival (HR 8.98 [95% CI 3.46–23.30], p < 0.001; and HR 2.86 [95% CI 1.30–6.31], p = 0.009, respectively). Additionally, preoperative neurological deficit was significantly associated with worse overall survival on the multivariate analysis (HR 3.01 [95% CI 1.34–6.79], p = 0.008). Conversely, preoperative embolization was significantly associated with improved overall survival on the multivariate analysis (HR 0.43 [95% CI 0.20–0.94], p = 0.04). Preoperative embolization and longer posterior construct length were significantly associated with fewer and greater complications, respectively, on the univariate analysis (OR 0.24 [95% CI 0.06–0.93] p = 0.04; and OR 1.24 [95% CI 1.02–1.52], p = 0.03), but not the multivariate analysis.

CONCLUSIONS

Progressive systemic disease, postoperative complications, and preoperative neurological deficits were significantly associated with worse overall survival, while preoperative spinal embolization was associated with improved overall survival. These factors should be taken into consideration when considering such patients for surgery. Preoperative embolization and posterior construct length significantly influenced the incidence of postoperative complications only on the univariate analysis.

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Ganesh Rao, Dima Suki, Indro Chakrabarti, Iman Feiz-Erfan, Milan G. Mody, Ian E. McCutcheon, Ziya Gokaslan, Shreyaskumar Patel and Laurence D. Rhines

Object

Sarcomas of the spine are a challenging problem due to their frequent and extensive involvement of multiple spinal segments and high recurrence rates. Gross-total resection to negative margins, with preservation of neurological function and palliation of pain, is the surgical goal and may be achieved using either intralesional resection or en bloc excision. The authors report outcomes of surgery for primary and metastatic sarcomas of the mobile spine in a large patient series.

Methods

A retrospective review of patients undergoing resection for sarcomas of the mobile spine between 1993 and 2005 was undertaken. Sarcomas were classified by histology study results and as either primary or metastatic. Details of the surgical approach, levels of involvement, and operative complications were recorded. Outcome measures included neurological function, palliation of pain, local recurrence, and overall survival.

Results

Eighty patients underwent 110 resections of either primary or metastatic sarcomas of the mobile spine. Twenty-nine lesions were primary sarcomas (36%) and 51 were metastatic sarcomas (64%). Intralesional resections were performed in 98 surgeries (89%) and en bloc resections were performed in 12 (11%). Median survival from surgery for all patients was 20.6 months. Median survival for patients with a primary sarcoma of the spine was 40.2 months and was 17.3 months for patients with a metastatic sarcoma. Predictors of improved survival included a chondrosarcoma histological type and a better preoperative functional status, whereas osteosarcoma and a high-grade tumor were negative influences on survival. Multivariate analysis showed that only a high-grade tumor was an independent predictor of shorter overall survival. American Spinal Injury Association scale grades were maintained or improved in 97% of patients postoperatively, and there was a significant decrease in pain scores postoperatively. No significant differences in survival or local recurrence rates between intralesional or en bloc resections for either primary or metastatic spine sarcomas were found.

Conclusions

Surgery for primary or metastatic sarcoma of the spine is associated with an improvement in neurological function and palliation of pain. The results of this study show a significant difference in patient survival for primary versus metastatic spine sarcomas. The results do not show a statistically significant benefit in survival or local recurrence rates for en bloc versus intralesional resections for either metastatic or primary sarcomas of the spine, but this may be due to the small number of patients undergoing en bloc resections.

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Anita Mahajan, Ian E. McCutcheon, Dima Suki, Eric L. Chang, Samuel J. Hassenbusch, Jeffrey S. Weinberg, Almon Shiu, Moshe H. Maor and Shiao Y. Woo

Object. The role of stereotactic radiosurgery (SRS) for recurrent glioblastoma multiforme (GBM) was evaluated in a case—control study.

Methods. All patients who underwent SRS for recurrent GBM before March 2003 formed the case group. A control group of patients who did not undergo SRS was created from an institutional database, and each case was matched for known prognostic factors in GBM. The medical and neuroimaging records of all the patients were reviewed, and survival and treatment outcomes were recorded.

The case and control groups were well matched with regard to demographics and pre-SRS interventions. In the control group, the date on which magnetic resonance imaging identified a recurrent lesion that would have been eligible for SRS was deemed the “SRS” date. The number of surgeries performed in the control group was statistically higher than that in the case group. The median duration of overall survival from diagnosis was 26 months in the case group and 23 months in the control group. From the date of SRS or “SRS”, the median duration of survival was 11 months in the case group and 10 months in the control group, a difference that was not statistically significant.

Conclusions. It appears that a subgroup of patients with GBMs has a higher than expected median survival duration despite the initial prognostic factors. In patients with localized recurrences, survival may be prolonged by applying aggressive local disease management by using either SRS or resection to equal advantage.

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Adam S. Wu, Victoria T. Trinh, Dima Suki, Susan Graham, Arthur Forman, Jeffrey S. Weinberg, Ian E. McCutcheon, Sujit S. Prabhu, Amy B. Heimberger, Raymond Sawaya, Xuemei Wang, Wei Qiao, Kenneth R. Hess and Frederick F. Lang

Object

Seizures are a potentially devastating complication of resection of brain tumors. Consequently, many neurosurgeons administer prophylactic antiepileptic drugs (AEDs) in the perioperative period. However, it is currently unclear whether perioperative AEDs should be routinely administered to patients with brain tumors who have never had a seizure. Therefore, the authors conducted a prospective, randomized trial examining the use of phenytoin for postoperative seizure prophylaxis in patients undergoing resection for supratentorial brain metastases or gliomas.

Methods

Patients with brain tumors (metastases or gliomas) who did not have seizures and who were undergoing craniotomy for tumor resection were randomized to receive either phenytoin for 7 days after tumor resection (prophylaxis group) or no seizure prophylaxis (observation group). Phenytoin levels were monitored daily. Primary outcomes were seizures and adverse events. Using an estimated seizure incidence of 30% in the observation arm and 10% in the prophylaxis arm, a Type I error of 0.05 and a Type II error of 0.20, a target accrual of 142 patients (71 per arm) was planned.

Results

The trial was closed before completion of accrual because Bayesian predictive probability analyses performed by an independent data monitoring committee indicated a probability of 0.003 that at the end of the study prophylaxis would prove superior to observation and a probability of 0.997 that there would be insufficient evidence at the end of the trial to choose either arm as superior. At the time of trial closure, 123 patients (77 metastases and 46 gliomas) were randomized, with 62 receiving 7-day phenytoin (prophylaxis group) and 61 receiving no prophylaxis (observation group). The incidence of all seizures was 18% in the observation group and 24% in the prophylaxis group (p = 0.51). Importantly, the incidence of early seizures (< 30 days after surgery) was 8% in the observation group compared with 10% in the prophylaxis group (p = 1.0). Likewise, the incidence of clinically significant early seizures was 3% in the observation group and 2% in the prophylaxis group (p = 0.62). The prophylaxis group experienced significantly more adverse events (18% vs 0%, p < 0.01). Therapeutic phenytoin levels were maintained in 80% of patients.

Conclusions

The incidence of seizures after surgery for brain tumors is low (8% [95% CI 3%–18%]) even without prophylactic AEDs, and the incidence of clinically significant seizures is even lower (3%). In contrast, routine phenytoin administration is associated with significant drug-related morbidity. Although the lower-than-anticipated incidence of seizures in the control group significantly limited the power of the study, the low baseline rate of perioperative seizures in patients with brain tumors raises concerns about the routine use of prophylactic phenytoin in this patient population.

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Wael Hassaneen, Nicholas B. Levine, Dima Suki, Abhijit L. Salaskar, Alessandra de Moura Lima, Ian E. McCutcheon, Sujit S. Prabhu, Frederick F. Lang, Franco DeMonte, Ganesh Rao, Jeffrey S. Weinberg, David M. Wildrick, Kenneth D. Aldape and Raymond Sawaya

Object

Multiple craniotomies have been performed for resection of multiple brain metastases in the same surgical session with satisfactory outcomes, but the role of this procedure in the management of multifocal and multicentric glioblastomas is undetermined, although it is not the standard approach at most centers.

Methods

The authors performed a retrospective analysis of data prospectively collected between 1993 and 2008 in 20 patients with multifocal or multicentric glioblastomas (Group A) who underwent resection of all lesions via multiple craniotomies during a single surgical session. Twenty patients who underwent resection of solitary glioblastoma (Group B) were selected to match Group A with respect to the preoperative Karnofsky Performance Scale (KPS) score, tumor functional grade, extent of resection, age at time of surgery, and year of surgery. Clinical and neurosurgical outcomes were evaluated.

Results

In Group A, the median age was 52 years (range 32–78 years); 70% of patients were male; the median preoperative KPS score was 80 (range 50–100); and 9 patients had multicentric glioblastomas and 11 had multifocal glioblastomas. Aggressive resection of all lesions in Group A was achieved via multiple craniotomies in the same session, with a median extent of resection of 100%. Groups A and B were comparable with respect to all the matching variables as well as the amount of tumor necrosis, number of cysts, and the use of intraoperative navigation. The overall median survival duration was 9.7 months in Group A and 10.5 months in Group B (p = 0.34). Group A and Group B (single craniotomy) had complication rates of 30% and 35% and 30-day mortality rates of 5% (1 patient) and 0%, respectively.

Conclusions

Aggressive resection of all lesions in selected patients with multifocal or multicentric glioblastomas resulted in a survival duration comparable with that of patients undergoing surgery for a single lesion, without an associated increase in postoperative morbidity. This finding may indicate that conventional wisdom of a minimal role for surgical treatment in glioblastoma should at least be questioned.