Fisher, Charles G.

BACKGROUNDThe Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ) was developed as the first spine oncology‐specific health‐related quality of life (HRQOL) measure. This study evaluated the psychometric properties and clinical validity of the SOSGOQ in a diverse cohort of patients with spinal metastases.METHODSAn international, multicenter, prospective observational cohort study including patients with spinal metastases who underwent surgery and/or radiotherapy was conducted by the AOSpine Knowledge Forum Tumor. Demographic, tumor, and treatment data were collected. HRQOL was evaluated using the SOSGOQ and Medical Outcomes Study Questionnaire Short Form 36 Health Survey (SF‐36) at baseline and fixed follow‐up times. Construct validity was assessed using multitrait scaling analyses, confirmatory factor analyses, and correlation with the SF‐36 and NRS pain score. Test‐retest reliability was assessed in a subgroup of patients between 12 weeks after treatment and the retest 4 to 9 days later.RESULTSA total of 238 patients were enrolled at 9 centers across North America; 153 of these patients had HRQOL data available at 12 weeks after treatment. Multitrait scaling analyses and confirmatory factor analyses resulted in a refined version of the SOSGOQ with 4 domains and 4 single items. The revised SOSGOQ (SOSGOQ2.0) demonstrated strong correlations with SF‐36 and the ability to discriminate between clinically distinct patient groups. Reliability of the SOSGOQ2.0 was demonstrated to be good, with an intraclass correlation coefficient ranging from 0.58 to 0.92 for the different domains.CONCLUSIONSThe SOSGOQ2.0 is a reliable and valid measure with which to evaluate HRQOL in patients with spinal metastases. It is recommended to use the SOSGOQ2.0 together with a generic HRQOL outcome measure to comprehensively assess HRQOL and increase sensitivity and specificity. Cancer 2018;124:1828‐38. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

Study Design: Systematic review. Objectives: The objective of this systematic review was to answer 2 key questions: (1) What is the clinical presentation and probability of symptomatic improvement following treatment for patients with renal cell carcinoma (RCC) of the spine? (2) What is the overall survival of patients diagnosed with spinal metastases from RCC? Methods: A literature review was performed to identify articles that reported on survival, clinical outcomes, and/or prognostic factors in the RCC population with spinal metastases from 1986 to 2016. Results: Forty-eight articles (807 patients) were included. The Fuhrman Nuclear Grade has been significantly associated with survival in previous studies but was underpowered in the current study. The Memorial Sloan-Kettering Cancer Center Score (MSKCC/Motzer) was also underpowered in the current study. From the time of spinal metastasis, the mean and median survival for patients with previously diagnosed primary RCC was 8.75 and 11.7 months, respectively, whereas synchronously diagnosed patients (primary RCC and spinal metastasis) had a mean and median survival of 6.75 and 11 months, respectively. Patients with a “low” (0-8), “intermediate” (9-11), or “high” (12-15) revised Tokuhashi score at initial presentation had a median survival of 5.4, 11.7, and 32.9 months, respectively. Conclusion: Patients with either a synchronous or latent diagnosis of RCC survived greater than 6 months from the time of presentation. Initial Furhman grade, Tokuhashi score, and MSKCC/Motzer can be useful tools in informing patient-specific prognosis for those with metastatic RCC of the spine.

Study Design: Systematic review. Objective: Surgical decompression and reconstruction of symptomatic spinal metastases has improved the quality of life in cancer patients. However, most data has been collected on cohorts of patients with mixed tumor histopathology. We systematically reviewed the literature for prognostic factors specific to the surgical treatment of prostate metastases to the spine. Methods: A systemic review of the literature was conducted to answer the following questions: Question 1. Describe the survival and functional outcomes of surgery or vertebral augmentation for prostate metastases to the spine. Question 2. Determine whether overall tumor burden, Gleason score, preoperative functional markers, and hormonal naivety favor operative intervention. Question 3. Establish whether clinical outcomes vary with the evolution of operative techniques. Results: A total of 16 studies met the preset inclusion criteria. All included studies were retrospective series with a level of evidence of IV. Included studies consistently showed a large effect of hormone-naivety on overall survival. Additionally, 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. Conclusions: There is a dearth of literature regarding the surgical treatment of prostate metastases to the spine, which represents an opportunity for future research. Based on 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.

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.

OBJECT Surgical procedures and/or adjuvant therapies are effective modalities for the treatment of symptomatic spinal metastases. However, clinical results specific to the skin cancer spinal metastasis cohort are generally lacking. The purpose of this study was to systematically review the literature for treatments, clinical outcomes, and survival following the diagnosis of a skin cancer spinal metastasis and evaluate prognostic factors in the context of spinal skin cancer metastases stratified by tumor subtype. METHODS The authors performed a literature review using PubMed, Embase, CINAHL, and Web of Science to identify articles since 1950 that reported survival, clinical outcomes, and/or prognostic factors for the skin cancer patient population with spinal metastases. The methodological quality of reviews was assessed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) tool. RESULTS Sixty-five studies met the preset criteria and were included in the analysis. Of these studies, a total of 25, 40, 25, and 12 studies included patients who underwent some form of surgery, radiotherapy, chemotherapy, or observation alone, respectively. Sixty-three of the 65 included studies were retrospective in nature (Class of Evidence [CoE] IV), and the 2 prospective studies were CoE II. Based on the studies analyzed, the median overall survival for a patient with a spinal metastasis from a primary skin malignancy is 4.0 months; survival by tumor subtype is 12.5 months for patients with basal cell carcinoma (BCC), 4.0 months for those with melanoma, 4.0 months for those with squamous cell carcinoma, 3.0 months for those with pilomatrix carcinoma, and 1.5 months for those with Merkel cell carcinoma (p < 0.0001). The overall percentage of known continued disease progression after spine metastasis diagnosis was 40.1% (n = 244/608, range 25.0%–88.9%), the rate of known recurrence of the primary skin cancer lesion was 3.5% (n = 21/608, range 0.2%–100.0%), and the rate of known spine metastasis recurrence despite treatment for all skin malignancies was 2.8% (n = 17/608, range 0.0%–33.3%). Age greater than 65 years, sacral spinal involvement, presence of a neurological deficit, and nonambulatory status were associated with decreased survival in patients diagnosed with a primary skin cancer spinal metastasis. All other clinical or prognostic parameters were of low or insufficient strength. CONCLUSIONS Patients diagnosed with a primary skin cancer metastasis to the spine have poor overall survival with the exception of those with BCC. The median duration of survival for patients who received surgical intervention alone, medical management (chemotherapy and/or radiation) alone, or the combination of therapies was similar across interventions. Age, spinal region, and neurological status may be associated with poor survival following surgery.