Richard P. Williams

Factors influencing wound healing after surgery for metastatic disease of the spine.

Study Design. The study group consisted of 53 patients who underwent 75 operations for spine metastases. Patient and tumor demographic factors, preoperative nutritional status, and perioperative adjunctive therapy were retrospectively reviewed. Objective. To determine the risk factors for wound breakdown and infection in patients undergoing surgery for spinal metastases. Summary of Background Data. Spinal fusion using spine implants may be associated with an infection rate of 5% or more. Surgery for spine metastases is associated with an infection rate of more than 10%. Factors other than the type of surgery performed may account for the greater infection rate. Methods. Data were obtained by reviewing patient records. Age, sex, and neurologic status of the patient; tumor type and site; and surgical details were noted. Adjunctive treatment with corticosteroids and radiotherapy was recorded. Nutritional status was evaluated by determining serum protein and serum albumin concentrations and by total lymphocyte count. Results. Wound breakdown and infection occurred in 15 of 75 wounds. No patient or tumor demographic factors other than intraoperative blood loss (P < 0.1) were statistically associated with infection. The correlation between preoperative protein deficiency (P < 0.01) or perioperative corticosteroid administration (P < 0.10) and wound infection was significant. There was no statistical correlation between lymphocyte count or perioperative radiotherapy and wound infection. Conclusions. The results indicate that preoperative protein depletion and perioperative administration of corticosteroids are risk factors for wound infection in patients undergoing surgery for spine metastases. Perioperative correction of nutritional depletion and cessation of steroid therapy may reduce wound complications

Mobile spine chordoma: results of 166 patients from the AOSpine Knowledge Forum Tumor database

OBJECT A chordoma is an indolent primary spinal tumor that has devastating effects on the patients life. These lesions are chemoresistant, resistant to conventional radiotherapy, and moderately sensitive to proton therapy; however, en bloc resection remains the preferred treatment for optimizing patient outcomes. While multiple small and largely retrospective studies have investigated the outcomes following en bloc resection of chordomas in the sacrum, there have been few large-scale studies on patients with chordomas of the mobile spine. The goal of this study was to review the outcomes of surgically treated patients with mobile spine chordomas at multiple international centers with respect to local recurrence and survival. This multiinstitutional retrospective study collected data between 1988 and 2012 about prognosis-predicting factors, including various clinical characteristics and surgical techniques for mobile spine chordoma. Tumors were classified according to the Enneking principles and analyzed in 2 treatment cohorts: Enneking-appropriate (EA) and Enneking-inappropriate (EI) cohorts. Patients were categorized as EA when the final pathological assessment of the margin matched the Enneking recommendation; otherwise, they were categorized as EI. METHODS Descriptive statistics were used to summarize the data (Student t-test, chi-square, and Fisher exact tests). Recurrence and survival data were analyzed using Kaplan-Meier survival curves, log-rank tests, and multivariate Cox proportional hazard modeling. RESULTS A total of 166 patients (55 female and 111 male patients) with mobile spine chordoma were included. The median patient follow-up was 2.6 years (range 1 day to 22.5 years). Fifty-eight (41%) patients were EA and 84 (59%) patients were EI. The type of biopsy (p < 0.001), spinal location (p = 0.018), and if the patient received adjuvant therapy (p < 0.001) were significantly different between the 2 cohorts. Overall, 58 (35%) patients developed local recurrence and 57 (34%) patients died. Median survival was 7.0 years postoperative: 8.4 years postoperative for EA patients and 6.4 years postoperative for EI patients (p = 0.023). The multivariate analysis showed that the EI cohort was significantly associated with an increased risk of local recurrence in comparison with the EA cohort (HR 7.02; 95% CI 2.96-16.6; p < 0.001), although no significant difference in survival was observed. CONCLUSIONS EA resection plays a major role in decreasing the risk for local recurrence in patients with chordoma of the mobile spine.

Surgical Management of Spinal Chondrosarcomas

Study Design. An ambispective cohort study. Objective. The aim of this study was to determine whether the application of the Enneking classification in the management of spinal chondrosarcomas influences local recurrence and survival. Summary of Background Data. Primary spinal chondrosarcomas are rare. Best available evidence is based on small case series, thus making it difficult to determine optimal management and risk factors for local recurrence and survival. Methods. The AOSpine Knowledge Forum Tumor developed a multicenter ambispective database of surgically treated patients with spinal chondrosarcoma. Patient data pertaining to demographics, diagnosis, treatment, cross-sectional survival, and local recurrence were collected. Tumors were classified according to the Enneking classification. Patients were divided into two cohorts: Enneking appropriate (EA) and Enneking inappropriate (EI). They were categorized as EA when the final pathological assessment of the margin matched the Enneking recommendation, and otherwise, they were categorized as EI. Results. Between 1987 and 2011, 111 patients (37 female; 74 male) received surgical treatment for a primary spinal chondrosarcoma at a mean age of 47.4 ± 15.8 years. Patients were followed for a median period of 3.1 years (range = 203 d–18.7 yrs). Median survival for the entire cohort was 8.4 years postoperative. After 10 years postoperative, 36 (32%) patients died and 37 (35%) patients suffered a local recurrence. Twenty-three of these 37 patients who suffered a local recurrence died. Sixty (58%) patients received an EA procedure while 44 (42%) received an EI procedure. EI patients had a higher hazard ratio for local recurrence than those who received an EA procedure (P = 0.052). Local recurrence was strongly associated with chondrosarcoma-related death (risk ratio = 3.6, P < 0.010). Conclusion. This is the largest multicenter cohort of spinal chondrosarcomas. EA surgical management appeared to correlate with a decreased risk of local recurrence, yet no relationship with survival was found. Where possible, surgeons should strive to achieve EA margins to minimize the risk of local recurrence. Level of Evidence: 4

An evidence-based medicine model for rare and often neglected neoplastic conditions

OBJECT The National Institutes of Health recommends strategies to obtain evidence for the treatment of rare conditions such as primary tumors of the spine (PTSs). These tumors have a low incidence and are pathologically heterogeneous, and treatment approaches are diverse. Appropriate evidence-based care is imperative. Failure to follow validated oncological principles may lead to unnecessary mortality and profound morbidity. This paper outlines a scientific model that provides significant evidence guiding the treatment of PTSs. METHODS A four-stage approach was used: 1) planning: data from large-volume centers were reviewed to provide insight; 2) recruitment: centers were enrolled and provided the necessary infrastructure; 3) retrospective stage: existing medical records were reviewed and completed with survival data; and 4) prospective stage: prospective data collection has been implemented. The AOSpine Knowledge Forum Tumor designed six modules: demographic, clinical, diagnostic, therapeutic, local recurrence, survival, and perioperative morbidity data fields and provided funding. RESULTS It took 18 months to implement Stages 1-3, while Stage 4 is ongoing. A total of 1495 tumor cases were captured and diagnosed as one of 18 PTS histotypes. In addition, a PTS biobank network has been created to link clinical data with tumor pathology and molecular analysis. CONCLUSIONS This scientific model has not only aggregated a large amount of PTS data, but has also established an international collaborative network of spine oncology centers. Access to large volumes of data will generate further research to guide and enhance PTS clinical management. This model could be applied to other rare neoplastic conditions. Clinical trial registration no.: NCT01643174 (ClinicalTrials.gov).

Spinal hemangiomas: results of surgical management for local recurrence and mortality in a multicenter study.

Study Design. Multicenter, ambispective observational study. Objective. To quantify local recurrence and mortality rates after surgical treatment of symptomatic spinal hemangiomas and identify prognostic variables for local disease control. Summary of Background Data. Spinal hemangiomas are the most common primary tumors of the spine and are generally benign and usually asymptomatic. Because of the rarity of symptomatic spinal hemangiomas, optimal surgical treatment remains unclear. Methods. AOSpine Knowledge Forum Tumor Investigators created a multicenter database of primary spinal tumors including demographics, presentation, diagnosis, treatment, survival, and recurrence data. Tumors were classified according to Enneking and Weinstein-Boriani-Biagini. Descriptive statistics were summarized and time to mortality and recurrence was determined. Results. Between 1996 and 2012, 68 patients (mean age = 51 yr, SD = 16) underwent surgical treatment of a spinal hemangioma. Epidural disease was present in 55% of patients (n = 33). Pain and neurological compromise were presenting symptoms in 82% (n = 54) and 37% (n = 24) of patients, respectively. Preoperative embolization was performed in 35% of patients (n = 23), 10% (n = 7) had adjuvant radiotherapy, and 81% (n = 55) underwent posterior-alone surgery. The local recurrence rate was 3% (n = 2). Mortality secondary to spinal hemangioma was not observed (mean follow-up = 3.9 yr, SD = 3.8). Conclusion. This is the largest multicenter surgical cohort of spinal hemangiomas. Symptomatic spinal hemangiomas are a benign tumor despite frequently presenting with epidural disease and neurological compromise. Thus, formal en bloc resection is not required, and excellent rates of local control and long-term survival can result from aggressive intralesional resection during index surgery. Level of Evidence: 3

Osteosarcoma of the spine: prognostic variables for local recurrence and overall survival, a multicenter ambispective study.

OBJECTIVE Primary spinal osteosarcomas are rare and aggressive neoplasms. Poor outcomes can occur, as obtaining marginal margins is technically demanding; further Enneking-appropriate en bloc resection can have significant morbidity. The goal of this study is to identify prognostic variables for local recurrence and mortality in surgically treated patients diagnosed with a primary osteosarcoma of the spine. METHODS A multicenter ambispective database of surgically treated patients with primary spine osteosarcomas was developed by AOSpine Knowledge Forum Tumor. Patient demographic, diagnosis, treatment, perioperative morbidity, local recurrence, and cross-sectional survival data were collected. Tumors were classified in 2 cohorts: Enneking appropriate (EA) and Enneking inappropriate (EI), as defined by pathology margin matching Enneking-recommended surgical margins. Prognostic variables were analyzed in reference to local recurrence and survival. RESULTS Between 1987 and 2012, 58 patients (32 female patients) underwent surgical treatment for primary spinal osteosarcoma. Patients were followed for a mean period of 3.5 ± 3.5 years (range 0.5 days to 14.3 years). The median survival for the entire cohort was 6.7 years postoperative. Twenty-four (41%) patients died, and 17 (30%) patients suffered a local recurrence, 10 (59%) of whom died. Twenty-nine (53%) patients underwent EA resection while 26 (47%) patients underwent EI resection with a postoperative median survival of 6.8 and 3.7 years, respectively (p = 0.048). EI patients had a higher rate of local recurrence than EA patients (p = 0.001). Patient age, previous surgery, biopsy type, tumor size, spine level, and chemotherapy timing did not significantly influence recurrence and survival. CONCLUSIONS Osteosarcoma of the spine presents a significant challenge, and most patients die in spite of aggressive surgery. There is a significant decrease in recurrence and an increase in survival with en bloc resection (EA) when compared with intralesional resection (EI). The effect of adjuvant and neoadjuvant chemotherapeutics, as well as method of biopsy, requires further exploration.

Spinal column chordoma: prognostic significance of clinical variables and T (brachyury) gene SNP rs2305089 for local recurrence and overall survival.

Background Chordomas are rare, locally aggressive bony tumors associated with poor outcomes. Recently, the single nucleotide polymorphism (SNP) rs2305089 in the T (brachyury) gene was strongly associated with sporadic chordoma development, but its clinical utility is undetermined. Methods In 333 patients with spinal chordomas, we identified prognostic factors for local recurrence-free survival (LRFS) and overall survival and assessed the prognostic significance of the rs2305089 SNP. Results The median LRFS was 5.2 years from the time of surgery (95% CI: 3.8-6.0); greater tumor volume (≥100cm3) (hazard ratio [HR] = 1.99, 95% CI: 1.26-3.15, P = .003) and Enneking inappropriate resections (HR = 2.35, 95% CI: 1.37-4.03, P = .002) were independent predictors of LRFS. The median overall survival was 7.0 years (95% CI: 5.8-8.4), and was associated with older age at surgery (HR = 1.11 per 5-year increase, 95% CI: 1.02-1.21, P = .012) and previous surgical resection (HR = 1.73, 95% CI: 1.03-2.89, P = .038). One hundred two of 109 patients (93.6%) with available pathologic specimens harbored the A variant at rs2305089; these patients had significantly improved survival compared with those lacking the variant (P = .001), but there was no association between SNP status and LRFS (P = .876). Conclusions The ability to achieve a wide en bloc resection at the time of the primary surgery is a critical preoperative consideration, as subtotal resections likely complicate later management. This is the first time the rs2305089 SNP has been implicated in the prognosis of individuals with chordoma, suggesting that screening all patients may be instructive for risk stratification.

A novel scientific model for rare and often neglected neoplastic conditions.

Study Type Retrospective cohort. Introduction The treatment of rare neoplastic conditions is challenging, especially because studies providing high levels of evidence are often lacking. Such is the case with primary tumors of the spine (PTS), which have a low incidence, are pathologically heterogeneous, and have diverse treatment approaches.1 Despite these difficulties, appropriate evidence-based care of these complex patients is imperative. Failure to follow validated oncologic principles may lead to unnecessary mortality and profound morbidity. Objective With the aim of offering patients the most appropriate treatment based on the best available evidence, a novel scientific model was developed and employed. This article outlines this model, which has not only provided significant evidence guiding treatment of this rare condition, but we believe is readily transferrable to other similarly rare conditions. Methods A four-stage approach was employed. (1) Planning: Data from large volume centers were reviewed together with results from a feasibility questionnaire to provide insight into epidemiology, patient volumes, tumor pathology, treatment modalities, and outcomes. (2) Recruitment: Centers with sufficient volume and valid data were enrolled and provided with the necessary infrastructure. This included study coordinators and a secure, Web-based database (REDCap, Vanderbilt University, Nashville, Tennessee, United States) to capture international data from six modules comprising: demographic, clinical, diagnostic, therapeutic, local recurrence, perioperative morbidity fields, and a cross-sectional survey to update survival information. The AOSpine Knowledge Forum Tumor designed these modules and provided funding. Each center received institutional ethics approval. (3) Retrospective stage: Prospectively collected data from all recruited centers were reviewed and analyzed retrospectively. (4) Prospective stage: Following interim analysis, prospective data collection has been implemented. In addition, a PTS bio-bank network has been created to link clinical data with tumor pathology and molecular analysis. Results It took 18 months to implement stages 1 to 3 of this model and stage 4 is ongoing. A total of 1,495 tumor cases were captured and diagnosed as one of the 18 primary spine tumor subtypes listed (Fig. 1). The most prevalent diagnosis was chordoma (n = 344, 23%). There were 674 females and 821 males with a mean age of 43 ± 19 years at the time of surgery. Surgical treatment was performed between 1981 and 2012. The survival at 5 and 10 years postsurgery was 71.9 and 53.3%, respectively, with a median survival of 13 years postsurgery (Fig. 2). Conclusions To date, this is the largest international collection of PTS. This novel scientific model has not only aggregated a large amount of PTS data, but has also established an international collaborative network of spine oncology centers. The access to large volumes of clinical and bio-bank data will generate further research to guide and enhance the clinical management of PTS. This novel scientific model could be of similar tremendous value if applied to other rare neoplastic conditions.