Rhines, Laurence D.

OBJECTIVEPrimary osteosarcoma of the spine is a rare osseous neoplasm. While previously reported retrospective studies have demonstrated that overall patient survival is impacted mostly by en bloc resection and chemotherapy, the continued management of residual disease remains to be elucidated. This systematic review was designed to address the role of revision surgery and multimodal adjuvant therapy in cases in which en bloc excision is not initially achieved.METHODSA systematic literature search spanning the years 1966 to 2015 was performed on PubMed, Medline, EMBASE, and Web of Science to identify reports describing outcomes of patients who underwent biopsy alone, neurological decompression, or intralesional resection for osteosarcoma of the spine. Studies were reviewed qualitatively, and the clinical course of individual patients was aggregated for quantitative meta-analysis.RESULTSA total of 16 studies were identified for inclusion in the systematic review, of which 8 case reports were summarized qualitatively. These studies strongly support the role of chemotherapy for overall survival and moderately support adjuvant radiation therapy for local control. The meta-analysis revealed a statistically significant benefit in overall survival for performing revision tumor debulking (p = 0.01) and also for chemotherapy at relapse (p < 0.01). Adjuvant radiation therapy was associated with longer survival, although this did not reach statistical significance (p = 0.06).CONCLUSIONSWhile the initial therapeutic goal in the management of osteosarcoma of the spine is neoadjuvant chemotherapy followed by en bloc marginal resection, this objective is not always achievable given anatomical constraints and other limitations at the time of initial clinical presentation. This systematic review supports the continued aggressive use of revision surgery and multimodal adjuvant therapy when possible to improve outcomes in patients who initially undergo subtotal debulking of osteosarcoma. A limitation of this systematic review is that lesions amenable to subsequent resection or tumors inherently more sensitive to adjuvants would exaggerate a therapeutic effect of these interventions when studied in a retrospective fashion.

Introduction Primary tumors of the spine requiring enbloc resection are rare. Most published reports are small and focus on disease free survival and recurrence rates. Very few studies focus on the various anterior and posterior reconstructive options and subsequent outcomes with respect to fusion rates and need for revision due to hardware failure. The objective of this review was to (1) summarize the published literature and (2) report the failure rates of various anterior and posterior reconstructive techniques after enbloc resection of spinal tumors and (3) supplement the deficiencies in the available published literature with expert opinion for reconstructive options from a group of experienced international spine tumor surgeons. Material and Methods An electronic search of the literature was undertaken from January 1990 – December 2013 evaluating specific reconstructive techniques of the spine after primary tumor enbloc resection. Prospective/retrospective trials and case series were included in the final analysis when fusion rates or failure rates were reported. The data available for each reconstructive technique was then combined and construct survivorship was summarized. In addition, a questionnaire was administered to a group of 20 international spine tumor surgeons evaluating specific reconstructive preferences at different regions of the spine based on the number of vertebrae resected and whether post-operative radiation was planned. Results The initial search yielded 381 articles with 31 subsequently included for full text review. Fourteen articles were included in the final analysis. There were 146 patients included for final review. There were 2/9 (22%) patients revised from short to long segment constructs and 3 reports of broken pedicle screws with only one requiring revision in longer constructs. Rates of revision for anterior reconstruction were similar for autogenous strut grafts (10%), cages (7.7%) and allograft strut grafts (8.3%). No surgeons responding to the questionnaire recommended short segment posterior constructs. For anterior reconstruction, cages packed with morcellized allograft and autograft were preferred (75%, p < 0.05) while strut bone grafting was choosen more often at the cervicothoracic junction (65%, p < 0.05) and when more than one vertebrae was resected in the mid thoracic spine (75%, p < 0.05). Few surgeons changed their anterior reconstructive technique (15%) or posterior reconstructive technique (10%) when post-operative radiation was planned. Conclusion The literature and consensus opinion supports posterior reconstruction with at least two vertebral levels of support above and below. For anterior vertebral column reconstruction, structural allograft, autograft and cages packed with morcelized bone have shown similar rates of fusion and failure. Expert opinion, however, suggests that structural autograft or potentially vascularized strut grafts should be used when spanning a defect greater than 2 vertebral bodies especially at the cervicothoracic junction.

Introduction Symptomatic Metastatic Epidural Spinal Cord Compression (MESCC) afflicts up to 10% of all cancer patients and is associated with shortened survival and worsened quality of life. This study aims to identify the key survival prognostic factors in MESCC patients who were surgically treated for a single symptomatic lesion. Material and Methods 142 MESCC patients were enrolled in a prospective North American multi-center study and followed postoperatively for 12 months. Using univariate analyses, Kaplan-Meier methods, and log-rank tests the prognostic value of various clinical predictors were assessed. Non-collinear predictors with p < 0.05 in univariate analyses were included in the final Cox proportional hazards model. Results The overall median survival was 7.7 months (range: 3 days – 35.6 months); breast cancer had the longest median survival (12.1 months). Ten patients (7%), whose primary cancer were lung (3), kidney (3), sarcoma (2), prostate (1), and breast (1), died within 30-days postoperatively and 88 had died at 12 months (62%). Univariate analyses yielded eight significant predictors for survival: the growth of primary tumor (Tomita Grade 1 vs Grade 2 and 3), BMI, gender, preoperative SF-36 physical component, EQ-5D, and ODI scores as well as the presence of either visceral or extraspinal bony metastasis. The multiple regression analysis revealed that the Tomita grade (Grade 1 vs Grade 2 and 3; HR: 2.81, p = 0.007), the absence of visceral metastasis (HR: 2.01; p = 0.0044), and higher score on SF-36 physical component (HR: 0.95, p < 0.0001) were independent predictors for longer survival regardless of the selection method used (backward, forward, or stepwise). Conclusion Slow growing tumor (Tomita Grade 1), absence of visceral metastasis, and lower degree of preoperative physical disability, as reflected by a higher score on the SF-36 physical component questionnaire, are good prognostic factors for survival in selected patients who underwent surgical treatment for a focal symptomatic MESCC lesion.

Introduction Although surgery is being increasingly used in patients with Metastatic Epidural Spinal Cord Compression (MESCC) as a complementary strategy to radiation and chemotherapy, the impact of surgery on quality of life (QoL) is not well established. This study aimed to prospectively evaluate survival, neurological, functional, and QoL outcomes in MESCC patients undergoing operative management. Material and Methods A total of 142 surgically treated patients with a single symptomatic MESCC lesion enrolled in a prospective North American multi-center study were followed for 12 months. Clinical data, such as Brief Pain Inventory (BPI), ASIA, SF-36, Oswestry Disability Index (ODI), and EQ-5D scores, were obtained both pre- and post-operatively. Results The median survival was 7.7 months. The 30-day and 12-month mortality rates were 9% and 62%, respectively. Six weeks post-operatively, ambulatory status ( p = 0.02) and bladder control ( p = 0.03) were significantly improved. Overall, 67.5% of ASIA B, C, or D patients gained at least 1 grade after surgery, 25% remained stable, and 7.5% deteriorated. ODI, EQ-5D, BPI scores were significantly improved at each follow-up (p ≤ 0.01). SF-36 scores were generally higher after surgery for mental and physical components, and for all domains except energy/fatigue. The incidence of wound complications was 10% and 2 patients required a second surgery (screw malposition and epidural hematoma). Conclusion Surgical intervention, as a complementary adjunct to radiation and chemotherapy, provides immediate and sustained improvement in pain, neurological, functional, and QoL outcomes with acceptable risks in patients with a focal symptomatic MESCC lesion.

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.

OBJECT A chordoma is an indolent primary spinal tumor that has devastating effects on the patient's 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.

Study Design Review of the literature. Objective Surgery and cement augmentation procedures are effective palliative treatment of symptomatic spinal metastases. Our objective is to systematically review the literature to describe the survival, prognostic factors, and clinical outcomes of surgery and cement augmentation procedures for breast cancer metastases to the spine. Methods We performed a literature review using PubMed to identify articles that reported outcomes and/or prognostic factors of the breast cancer patient population with spinal metastases treated with any surgical technique since 1990. Results The median postoperative survival for metastatic breast cancer was 21.7 months (8.2 to 36 months), the mean rate of any pain improvement was 92.9% (76 to 100%), the mean rate of neurologic improvement was 63.8% (53 to 100%), the mean rate of neurologic decline was 4.1% (0 to 8%), and the local tumor control rate was 92.6% (89 to 100%). Kyphoplasty studies reported a high rate of pain control in selected patients. Negative prognostic variables included hormonal (estrogen and progesterone) and human epidermal growth factor receptor 2 (HER2) receptor refractory tumor status, high degree of axillary lymph node involvement, and short disease-free interval (DFI). All other clinical or prognostic parameters were of low or insufficient strength. Conclusion With respect to clinical outcomes, surgery consistently yielded neurologic improvements in patients presenting with a deficit with a minimal risk of worsening; however, negative prognostic factors associated with shorter survival following surgery include estrogen receptor/progesterone receptor negativity, HER2 negativity, and a short DFI.

Introduction Treatment of symptomatic spinal metastases through surgical decompression and reconstruction is known to improve quality of life in patients with cancer. However, most studies have been performed on patients with mixed tumor histopathology. We systematically review the literature for prognostic factors specific to the surgical treatment of prostate metastases to the spine to determine the indications and outcomes of the surgical treatment. Material and Methods A systemic review of the literature was conducted to answer the following questions: Q1. Describe the survival and functional outcomes of surgery or vertebral augmentation for prostate metastases to the spine; Q2. Determine whether overall tumor burden, Gleason score, preoperative functional markers, and favorable hormonal naivety for operative intervention; Q3. Establish whether clinical outcomes vary with the evolution of operative techniques. Expert consensus was obtained using a modified Delphi process. Results A total of 16 studies met the preset inclusion criteria. These studies were all retrospective series with a level of evidence of IV. Included studies consistently showed a large effect of hormone naivety on overall survival. In addition, studies consistently demonstrated an improvement in motor function and the ability to maintain/regain ambulation following surgery resulting in moderate strength of recommendation. All other parameters were of insufficient or low strength. Conclusion There is scant literature on the surgical treatment of prostate metastases to the spine, which represents an opportunity for future research. On the basis of the existing evidence, it appears that the surgical treatment of prostate metastases to the spine has consistently favorable results. While no consistent preoperative indicators favor nonoperative treatment, hormone naivety and high Karnofsky Performance Scores have positive effects on survival and clinical outcomes.

Introduction Symptomatic metastatic epidural spinal cord compression (MESCC) afflicts up to 10% of all cancer patients. MESCC is associated with shortened survival and worsened quality of life; thus, early diagnosis and management is crucial. In a multidisciplinary setting, life expectancy must be considered along with other factors, such as patient's symptoms and overall medical condition, to select the optimal patient-specific treatment plan. This study aims to identify and compare key survival prognostic factors in surgically treated symptomatic MESCC patients with a 12-month postoperative follow-up. Materials and Methods Over a 5-year period, 145 patients surgically treated for a single symptomatic MESCC lesion were enrolled in a prospective North American multicenter study. Univariate analyses, Kaplan–Meier methods, and log-rank tests were used to evaluate the prognostic value of various clinical predictors. Preoperative prognostic factors evaluated: age, gender, comorbidities, history of smoking, metastases outside the spine, site of primary tumor, previous systemic treatment for the primary tumor, MESCC location, number of vertebral body involved, previous MESCC treatment, ASIA score, motor deficits, bladder dysfunction, Oswestry Disability Index (ODI), EQ-5D, SF-36v2 mental and physical components, and ability to walk four steps. Predictors with p < 0.2 in univariate analyses were included into the final Cox proportional hazards model. Results The overall median survival was 7.7 months (235 days). Lung and breast cancer had the shortest and longest median survival, respectively (4.5 vs. 12.1 months). Nine patients (6%), whose primary cancer were lung (3), kidney (3), melanoma (1), prostate (1), and breast (1), died within 30 days after surgery; 46 (32%), 61 (42%), 74 (51%), and 86 (59%) patients died at 3, 6, 9, and 12 months, respectively. The site of primary tumor, number of vertebrae involved, ODI, EQ-5D, ASIA score, metastases outside the spine, bladder dysfunction, and ability to walk four steps were significant predictors on the univariate analyses. However, the multivariate Cox-regression analysis demonstrated that only spinal metastasis involving four or more vertebral bodies had a negative impact on survival ( p = 0.002, HR: 25). Conclusion The extent of spinal metastasis, which is regarded as an indicator of the severity of patient's metastasis burden, and the site of the primary tumor, although not statistically significant in our regression model but well recognized in the literature as an important clinical predictor, are considered as independent predictors of poor prognosis in patients with a single-level symptomatic MESCC lesion. MESCC patients are a challenging and vulnerable heterogenous population. It is essential to identify factors predicting survival, functional and clinical outcomes in this population to guide patient-centered management to optimize quality of life.

Introduction Surgical treatment and cement augmentation procedures are effective palliative techniques for the treatment of symptomatic spinal metastases. However, clinical results specific to a breast cancer cohort are generally lacking. We aim to systematically review the literature for clinical outcomes following operative interventions and prognostic factors for the treatment of breast metastases to the spine. Specifically, we describe the survival and clinical outcomes of surgery and cement augmentation procedures for breast metastases to the spine and to determine prognostic variables that may help recognize which patients will perform better or worse following surgery. Methods We performed a literature review using PubMed to identify articles that reported outcomes and/or prognostic factors of the breast cancer patient population with spinal metastases treated with any surgical technique since 1990. Results A total of 19 surgical studies, 4 cement augmentation studies, and 6 nonsurgical prognostic variable studies met the preset inclusion criteria. All but three studies (two surgical and one cement augmentation) were retrospective in nature, and all studies were of level of evidence IV. Median postoperative survival for metastatic breast cancer was 21.7 months (8.2–36 months), mean rate of pain improvement was 92.9% (76–100%), mean rate of neurological improvement was 63.8% (53–100%), mean rate neurological decline was 4.1% (0–8%), and mean rate LTC was 92.6% (89–100%). Kyphoplasty studies reported a high rate of pain control in selected patients. Negative prognostic variables included: hormonal (estrogen and progesterone) and HER2 receptor refractory tumor status, high degree of axillary lymph node involvement, and short disease-free interval (DFI). All other clinical or prognostic parameters were of low or insufficient strength. Conclusion With respect to clinical outcomes, studies consistently found that surgery resulted in neurological improvement for a majority of patients, with a minimal risk of worsening, and kyphoplasty studies reported a high rate of pain control. Increased postoperative survival 2002 onwards was likely due to FDA approval of new chemotherapies. However, specific factors associated with shorter survival following surgery involve hormone and HER2 receptor status and disease-free interval.