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Ziya L. Gokaslan, Julie E. York, Garrett L. Walsh, Ian E. McCutcheon, Frederick F. Lang, Joe B. Putnam Jr., David M. Wildrick, Stephen G. Swisher, Dima Abi-Said and Raymond Sawaya

Anterior approaches to the spine for the treatment of spinal tumors have gained acceptance; however, in most published reports, patients with primary, metastatic, or chest wall tumors involving cervical, thoracic, or lumbar regions of the spine are combined. The purpose of this study was to provide a clear perspective of results that can be expected in patients who undergo anterior vertebral body resection, reconstruction, and stabilization for spinal metastases that are limited to the thoracic region.

Outcome is presented for 72 patients with metastatic spinal tumors who were treated by transthoracic vertebrectomy at The University of Texas M. D. Anderson Cancer Center. The predominant primary tumors included renal cancer in 19 patients, breast cancer in 10, melanoma or sarcoma in 10, and lung cancer in nine patients. The most common presenting symptoms were back pain, which occurred in 90% of patients, and lower-extremity weakness, which occurred in 64% of patients. All patients underwent transthoracic vertebrectomy, decompression, reconstruction with methylmethacrylate, and anterior fixation with locking plate and screw constructs. Supplemental posterior instrumentation was required in seven patients with disease involving the cervicothoracic or thoracolumbar junction, which was causing severe kyphosis. After surgery, pain improved in 60 of 65 patients. This improvement was found to be statistically significant (p < 0.001) based on visual analog scales and narcotic analgesic medication use. Thirty-five of the 46 patients who presented with neurological dysfunction improved significantly (p < 0.001) following the procedure. Thirty-three patients had weakness but could ambulate preoperatively. Seventeen of these 33 regained normal strength, 15 patients continued to have weakness, and one patient was neurologically worse postoperatively. Of the 13 preoperatively nonambulatory patients, 10 could walk after surgery and three were still unable to walk but showed improved motor function. Twenty-one patients had complications ranging from minor atelectasis to pulmonary embolism. The 30-day mortality rate was 3%. The 1-year survival rate for the entire study population was 62%.

These results suggest that transthoracic vertebrectomy and spinal stabilization can improve the quality of life considerably in cancer patients with spinal metastasis by restoring or preserving ambulation and by controlling intractable spinal pain with acceptable rates of morbidity and mortality.

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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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Ziya L. Gokaslan, Julie E. York, Garrett L. Walsh, Ian E. McCutcheon, Frederick F. Lang, Joe B. Putnam Jr., David M. Wildrick, Stephen G. Swisher, Dima Abi-Said and Raymond Sawaya

Object. Anterior approaches to the spine for the treatment of spinal tumors have gained acceptance; however, in most published reports, patients with primary, metastatic, or chest wall tumors involving cervical, thoracic, or lumbar regions of the spine are combined. The purpose of this study was to provide a clear perspective of results that can be expected in patients who undergo anterior vertebral body resection, reconstruction, and stabilization for spinal metastases that are limited to the thoracic region.

Methods. Outcome is presented for 72 patients with metastatic spinal tumors who were treated by transthoracic vertebrectomy at The University of Texas M. D. Anderson Cancer Center. The predominant primary tumors included renal cancer in 19 patients, breast cancer in 10, melanoma or sarcoma in 10, and lung cancer in nine patients. The most common presenting symptoms were back pain, which occurred in 90% of patients, and lower-extremity weakness, which occurred in 64% of patients. All patients underwent transthoracic vertebrectomy, decompression, reconstruction with methylmethacrylate, and anterior fixation with locking plate and screw constructs. Supplemental posterior instrumentation was required in seven patients with disease involving the cervicothoracic or thoracolumbar junction, which was causing severe kyphosis. After surgery, pain improved in 60 of 65 patients. This improvement was found to be statistically significant (p < 0.001) based on visual analog scales and narcotic analgesic medication use. Thirty-five of the 46 patients who presented with neurological dysfunction improved significantly (p < 0.001) following the procedure. Thirty-three patients had weakness but could ambulate preoperatively. Seventeen of these 33 regained normal strength, 15 patients continued to have weakness, and one patient was neurologically worse postoperatively. Of the 13 preoperatively nonambulatory patients, 10 could walk after surgery and three were still unable to walk but showed improved motor function. Twenty-one patients had complications ranging from minor atelectasis to pulmonary embolism. The 30-day mortality rate was 3%. The 1-year survival rate for the entire study population was 62%.

Conclusions. These results suggest that transthoracic vertebrectomy and spinal stabilization can improve the quality of life considerably in cancer patients with spinal metastasis by restoring or preserving ambulation and by controlling intractable spinal pain with acceptable rates of morbidity and mortality.

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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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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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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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Eric D. Young, Davis Ingram, William Metcalf-Doetsch, Dilshad Khan, Ghadah Al Sannaa, Francois Le Loarer, Alexander J. F. Lazar, John Slopis, Keila E. Torres, Dina Lev, Raphael E. Pollock and Ian E. McCutcheon

OBJECTIVE

While sporadic peripheral schwannomas (SPSs) are generally well treated with surgery, their biology is not well understood. Consequently, treatment options are limited. The aim of this study was to provide a comprehensive description of SPS. The authors describe clinicopathological features and treatment outcomes of patients harboring these tumors, and they assess expression of biomarkers using a clinically annotated tissue microarray. Together, these data give new insight into the biology and management of SPS.

METHODS

Patients presenting with a primary SPS between 1993 and 2011 (n = 291) were selected from an institutional registry to construct a clinical database. All patients underwent follow-up, and short- and long-term outcomes were assessed. Expression of relevant biomarkers was assessed using a new tissue microarray (n = 121).

RESULTS

SPSs were generally large (mean 5.5 cm) and frequently painful at presentation (55%). Most patients were treated with surgery (80%), the majority of whom experienced complete resolution (52%) or improvement (18%) of their symptoms. Tumors that were completely resected (85%) did not recur. Some patients experienced short-term (16%) and long-term (4%) complications postoperatively. Schwannomas expressed higher levels of platelet-derived growth factor receptor–β (2.1) than malignant peripheral nerve sheath tumors (MPNSTs) (1.5, p = 0.004) and neurofibromas (1.33, p = 0.007). Expression of human epidermal growth factor receptor–2 was greater in SPSs (0.91) than in MPNSTs (0.33, p = 0.002) and neurofibromas (0.33, p = 0.026). Epidermal growth factor receptor was expressed in far fewer SPS cells (10%) than in MPNSTs (58%, p < 0.0001) or neurofibromas (37%, p = 0.007). SPSs more frequently expressed cytoplasmic survivin (66% of tumor cells) than normal nerve (46% of cells), but SPS expressed nuclear survivin in fewer tumor cells than in MPNSTs (24% and 50%, respectively; p = 0.018).

CONCLUSIONS

Complete resection is curative for SPS. Left untreated, however, these tumors can cause significant morbidity, and not all patients are candidates for resection. SPSs express a pattern of biomarkers consistent with the dysregulation of the tumor suppressor merlin observed in neurofibromatosis Type 2–associated schwannomas, suggesting a shared etiology. This SPS pattern is distinct from that of other tumors of the peripheral nerve sheath.

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Michel Lacroix, Dima Abi-Said, Daryl R. Fourney, Ziya L. Gokaslan, Weiming Shi, Franco DeMonte, Frederick F. Lang, Ian E. McCutcheon, Samuel J. Hassenbusch, Eric Holland, Kenneth Hess, Christopher Michael, Daniel Miller and Raymond Sawaya

Object. The extent of tumor resection that should be undertaken in patients with glioblastoma multiforme (GBM) remains controversial. The purpose of this study was to identify significant independent predictors of survival in these patients and to determine whether the extent of resection was associated with increased survival time.

Methods. The authors retrospectively analyzed 416 consecutive patients with histologically proven GBM who underwent tumor resection at the authors' institution between June 1993 and June 1999. Volumetric data and other tumor characteristics identified on magnetic resonance (MR) imaging were collected prospectively.

Conclusions. Five independent predictors of survival were identified: age, Karnofsky Performance Scale (KPS) score, extent of resection, and the degree of necrosis and enhancement on preoperative MR imaging studies. A significant survival advantage was associated with resection of 98% or more of the tumor volume (median survival 13 months, 95% confidence interval [CI] 11.4–14.6 months), compared with 8.8 months (95% CI 7.4–10.2 months; p < 0.0001) for resections of less than 98%. Using an outcome scale ranging from 0 to 5 based on age, KPS score, and tumor necrosis on MR imaging, we observed significantly longer survival in patients with lower scores (1–3) who underwent aggressive resections, and a trend toward slightly longer survival was found in patients with higher scores (4–5). Gross-total tumor resection is associated with longer survival in patients with GBM, especially when other predictive variables are favorable.

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Kelsey L. Watson, Ghadah A. Al Sannaa, Christine M. Kivlin, Davis R. Ingram, Sharon M. Landers, Christina L. Roland, Janice N. Cormier, Kelly K. Hunt, Barry W. Feig, B. Ashleigh Guadagnolo, Andrew J. Bishop, Wei-Lien Wang, John M. Slopis, Ian E. McCutcheon, Alexandar J. Lazar and Keila E. Torres

OBJECTIVE

Malignant peripheral nerve sheath tumors (MPNSTs) are an aggressive group of soft tissue sarcomas that can arise sporadically, in the context of neurofibromatosis Type 1 (NF1) or at a site of prior irradiation. Large series profiling the features and outcomes of sporadic, NF1-associated, and radiation-associated MPNSTs are limited. The goal of this study was to elucidate differences between MPNST etiologies in a large single-institution retrospective study.

METHODS

Patients (n = 317) were identified through the tumor registry of The University of Texas MD Anderson Cancer Center. Clinicopathological features were retrospectively collected. Features were compared among MPNST subtypes for patients who had sufficient clinical history (n = 289), and clinicopathological features were used to identify adverse predictors of recurrence and survival outcomes.

RESULTS

Five-year local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), and disease-specific survival (DSS) estimates were 56.6%, 49.6%, and 53.6%, respectively, for the high-grade MPNST cohort. Five-year DSS was lower in NF1-associated and radiation-associated MPNST than in sporadic MPNST (52%, 47%, and 67%, respectively, p = 0.140). Patients with radiation-associated MPNST had worse 5-year LRFS than those with the sporadic and NF1-associated subtypes (RT-associated vs sporadic, p = 0.010; RT-associated vs NF1-associated, p = 0.232). Truncally located tumors, positive surgical margins, local recurrence, and metastasis were predictors of adverse DSS in multivariate analysis.

CONCLUSIONS

Radiation-associated MPNSTs are associated with poorer local recurrence-free and disease-specific survival than sporadic and NF1-associated tumors. NF1-associated MPNSTs may have worse survival outcomes owing to large tumor size, compromising truncal location, and lower rate of negative resection margins compared with sporadic tumors.