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Ori Barzilai, Lily McLaughlin, Eric Lis, Yoshiya Yamada, Mark H. Bilsky and Ilya Laufer

OBJECTIVE

As patients with metastatic cancer live longer, an increased emphasis is placed on long-term therapeutic outcomes. The current study evaluates outcomes of long-term cancer survivors following surgery for spinal metastases.

METHODS

The study population included patients surgically treated at a tertiary cancer center between January 2010 and December 2015 who survived at least 24 months postoperatively. A retrospective chart and imaging review was performed to collect data regarding patient demographics; tumor histology; type and extent of spinal intervention; radiation data, including treatment dose and field; long-term sequelae, including local tumor control; and reoperations, repeat irradiation, or postoperative kyphoplasty at a previously treated level.

RESULTS

Eighty-eight patients were identified, of whom 44 were male, with a mean age of 61 years. The mean clinical follow-up for the cohort was 44.6 months (range 24.2–88.3 months). Open posterolateral decompression and stabilization was performed in 67 patients and percutaneous minimally invasive surgery in 21. In the total cohort, 84% received postoperative adjuvant radiation and 27% were operated on for progression following radiation. Posttreatment local tumor progression was identified in 10 patients (11%) at the index treatment level and 5 additional patients had a marginal failure; all of these patients were treated with repeat irradiation with 5 patients requiring a reoperation. In total, at least 1 additional surgical intervention was performed at the index level in 20 (23%) of the 88 patients: 11 for hardware failure, 5 for progression of disease, 3 for wound complications, and 1 for postoperative hematoma. Most reoperations (85%) were delayed at more than 3 months from the index surgery. Wound infections or dehiscence requiring additional surgical intervention occurred in 3 patients, all of which occurred more than a year postoperatively. Kyphoplasty at a previously operated level was performed in 3 cases due to progressive fractures.

CONCLUSIONS

Durable tumor control can be achieved in long-term cancer survivors surgically treated for symptomatic spinal metastases with limited complications. Complications observed after long-term follow-up include local tumor recurrence/progression, marginal tumor control failures, early or late hardware complications, late wound complications, and progressive spinal instability or deformity.

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Ilya Laufer and Mark H. Bilsky

An improved understanding of tumor biology, the ability to target tumor drivers, and the ability to harness the immune system have dramatically improved the expected survival of patients diagnosed with cancer. However, many patients continue to develop spine metastases that require local treatment with radiotherapy and surgery. Fortunately, the evolution of radiation delivery and operative techniques permits durable tumor control with a decreased risk of treatment-related toxicity and a greater emphasis on restoration of quality of life and daily function. Stereotactic body radiotherapy allows delivery of ablative radiation doses to the majority of spine tumors, reducing the need for surgery. Among patients who still require surgery for decompression of the spinal cord or spinal column stabilization, minimal access approaches and targeted tumor excision and ablation techniques minimize the surgical risk and facilitate postoperative recovery. Growing interdisciplinary collaboration among scientists and clinicians will further elucidate the synergistic possibilities among systemic, radiation, and surgical interventions for patients with spinal tumors and will bring many closer to curative therapies.

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Ibrahim Hussain, Ori Barzilai, Anne S. Reiner, Lily McLaughlin, Natalie M. DiStefano, Shahiba Ogilvie, Anne L. Versteeg, Charles G. Fisher, Mark H. Bilsky and Ilya Laufer

OBJECTIVE

The Spinal Instability Neoplastic Score (SINS) correlates with preoperative disability and response to stabilization, with patients with higher scores experiencing greater relief after surgery. However, there is a paucity of data demonstrating the extent to which each component contributes to preoperative clinical status and response to stabilization surgery. The objectives of this study were 2-fold. First, to determine how SINS components correlate with pre- and postoperative patient-reported outcomes (PROs). Second, to determine whether patients with higher SINS (10–12) in the “indeterminate” group respond differently to surgery compared to patients with lower SINS (7–9).

METHODS

SINS and PROs were prospectively collected in 131 patients undergoing stabilization surgery for metastatic spinal disease. Association of SINS components and their individual scores with preoperative symptom burden and PRO symptom change after surgery was analyzed using the Spearman rank correlation coefficient (rho) and the Kruskal-Wallis test. SINS and association with preoperative PRO scores and mean differences in post- and preoperative PRO scores were compared for 2 SINS categories within the indeterminate group (7–9 vs 10–12) using the Wilcoxon 2-sample test and Wilcoxon signed-rank test.

RESULTS

The presence of mechanical pain, followed by metastatic location, correlated most strongly with preoperative functional disability measures and lower disability PRO scores following surgical stabilization. Blastic rather than lytic bone lesions demonstrated stronger association with pain reduction following stabilization. Following surgery, patients with SINS 10–12 demonstrated markedly greater improvement in pain and disability PRO scores nearly across the board compared to patients with SINS 7–9.

CONCLUSIONS

The presence of mechanical pain has the strongest correlation with preoperative disability and improvement in pain and disability PRO scores after surgery. Radiographic components of SINS also correlate with preoperative symptom severity and postoperative PRO, supporting their utilization in evaluation of spinal instability. Among patients with indeterminate SINS, patients with higher scores experience greater reduction in pain and disability PRO scores following surgical stabilization, suggesting that the indeterminate-SINS group includes distinct populations.

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Eric Lis, Ilya Laufer, Ori Barzilai, Yoshiya Yamada, Sasan Karimi, Lily McLaughlin, George Krol and Mark H. Bilsky

OBJECTIVE

Percutaneous vertebral augmentation procedures such as vertebroplasty and kyphoplasty are often performed in cancer patients to relieve mechanical axial-load pain due to pathological collapse deformities. The collapsed vertebrae in these patients can be associated with varying degrees of spinal canal compromise that can be worsened by kyphoplasty. In this study the authors evaluated changes to the spinal canal, in particular the cross-sectional area of the thecal sac, following balloon kyphoplasty (BKP) prior to stereotactic radiosurgery (SRS).

METHODS

The authors retrospectively reviewed the records of all patients with symptomatic vertebral compression fractures caused by metastatic disease who underwent kyphoplasty prior to single-fraction SRS. The pre-BKP cross-sectional image, usually MRI, was compared to the post-BKP CT myelogram required for radiation treatment planning. The cross-sectional area of the thecal sac was calculated pre- and postkyphoplasty, and intraprocedural CT imaging was reviewed for epidural displacement of bone fragments, tumor, or polymethylmethacrylate (PMMA) extravasation. The postkyphoplasty imaging was also evaluated for evidence of fracture progression or fracture reduction.

RESULTS

Among 30 consecutive patients, 41 vertebral levels were treated with kyphoplasty, and 24% (10/41) of the augmented levels showed a decreased cross-sectional area of the thecal sac. All 10 of these vertebral levels had preexisting epidural disease and destruction of the posterior vertebral body cortex. No bone fragments were displaced posteriorly. Minor epidural PMMA extravasation occurred in 20% (8/41) of the augmented levels but was present in only 1 of the 10 vertebral segments that showed a decreased cross-sectional area of the thecal sac postkyphoplasty.

CONCLUSIONS

In patients with preexisting epidural disease and destruction of the posterior vertebral body cortex who are undergoing BKP for pathological fractures, there is an increased risk of further mass effect upon the thecal sac and the potential to alter the SRS treatment planning.

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Nicolas Dea, Charles G. Fisher, Jeremy J. Reynolds, Joseph H. Schwab, Laurence D. Rhines, Ziya L. Gokaslan, Chetan Bettegowda, Arjun Sahgal, Áron Lazáry, Alessandro Luzzati, Stefano Boriani, Alessandro Gasbarrini, Ilya Laufer, Raphaële Charest-Morin, Feng Wei, William Teixeira, Niccole M. Germscheid, Francis J. Hornicek, Thomas F. DeLaney, John H. Shin and the AOSpine Knowledge Forum Tumor

OBJECTIVE

The purpose of this study was to investigate the spectrum of current treatment protocols for managing newly diagnosed chordoma of the mobile spine and sacrum.

METHODS

A survey on the treatment of spinal chordoma was distributed electronically to members of the AOSpine Knowledge Forum Tumor, including neurosurgeons, orthopedic surgeons, and radiation oncologists from North America, South America, Europe, Asia, and Australia. Survey participants were pre-identified clinicians from centers with expertise in the treatment of spinal tumors. The suvey responses were analyzed using descriptive statistics.

RESULTS

Thirty-nine of 43 (91%) participants completed the survey. Most (80%) indicated that they favor en bloc resection without preoperative neoadjuvant radiation therapy (RT) when en bloc resection is feasible with acceptable morbidity. The main area of disagreement was with the role of postoperative RT, where 41% preferred giving RT only if positive margins were achieved and 38% preferred giving RT irrespective of margin status. When en bloc resection would result in significant morbidity, 33% preferred planned intralesional resection followed by RT, and 33% preferred giving neoadjuvant RT prior to surgery. In total, 8 treatment protocols were identified: 3 in which en bloc resection is feasible with acceptable morbidity and 5 in which en bloc resection would result in significant morbidity.

CONCLUSIONS

The results confirm that there is treatment variability across centers worldwide for managing newly diagnosed chordoma of the mobile spine and sacrum. This information will be used to design an international prospective cohort study to determine the most appropriate treatment strategy for patients with spinal chordoma.

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Dennis T. Lockney, Angela Y. Jia, Eric Lis, Natalie A. Lockney, Chengbao Liu, Benjamin Hopkins, Daniel S. Higginson, Yoshiya Yamada, Ilya Laufer, Mark Bilsky and Adam M. Schmitt

OBJECTIVE

Spinal stereotactic body radiation therapy (SBRT) has emerged as an attractive method to deliver high doses of radiation to oligometastatic spinal tumors with radioresistant histology. Because SBRT is a palliative therapy, attention to potential radiation toxicities is paramount when counseling patients. The objective of this study was to report radiation-induced myositis after SBRT, a previously undescribed complication.

METHODS

A total of 667 patients received 891 spine SBRT treatments (either 24 Gy in 1 fraction or 27 Gy in 3 fractions) from 2011 to 2016 and underwent retrospective review. Eleven patients were identified as having radiographic evidence of myositis following SBRT. Clinical and pathologic results were collected, including receipt of anti–vascular endothelial growth factor (VEGF) therapy, radiation dose, equivalent dose in 2-Gy fractions (EQD2), biologically effective dose (BED), and volume of muscle treated. Treatment toxicities were classified according to the Common Terminology Criteria for Adverse Events (CTCAE; version 4.03). Univariate statistical analyses were performed to evaluate the relationships between radiation fractionation schedule and myositis and between anti-VEGF therapy and myositis.

RESULTS

The cumulative incidence of myositis was 1.9% at 1 year. The median of the mean dose administered to muscle with myositis was 17.5 Gy. The median EQD2 was 55.1 Gy, and the median BED was 82.7 Gy. The median time to the development of clinical symptoms was 1.4 months, while the median time to imaging evidence was 4.7 months. Two patients (18.2%) had CTCAE grade 3 complications. Single-fraction spine SBRT (HR 4.5, 95% CI 1.2–16.9; p = 0.027) was associated with increased risk of developing myositis whereas receipt of anti-VEGF therapy was not (HR 2.2, 95% CI 0.6–7.1; p = 0.2).

CONCLUSIONS

Radiation myositis following spinal radiosurgery is a rare but important complication. Single-fraction treatment schedules may be associated with increased risk of myositis but should be validated in a larger series.

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Theresa Kraetzig, Lily McLaughlin, Mark H. Bilsky and Ilya Laufer

OBJECTIVE

Myxopapillary ependymoma is a benign WHO Grade I tumor most commonly located in the conus–cauda equina region of the spine. Although this tumor is defined by an overall excellent survival, dissemination throughout the whole neuraxis occurs frequently. The current study evaluated the clinical characteristics and significance of myxopapillary ependymoma metastases.

METHODS

Patients who underwent surgery from 2005 to 2015 for treatment of spinal myxopapillary ependymoma were included in the study. Charts were reviewed for primary tumor symptoms and initial treatment, local recurrence, response to salvage therapy, and presence and behavior of distant metastases.

RESULTS

Nineteen patients with spinal myxopapillary ependymoma were included in the study (52.6% female). The median age at first diagnosis was 32 years old (range 9–58 years old), and 26.3% were ≤ 18 years old. The median follow-up of all included patients was 48 months (range 6–456 months). Of the primary tumors, 84.2% were located in the lower thoracic or upper lumbar spine, spanning 1–3 levels in 94.7%. All patients underwent surgery for initial treatment: in 78.9% a gross-total resection (GTR) was achieved, with adjuvant radiation therapy (RT) in 20%. Of the 21.2% who underwent a subtotal resection (STR), 75% underwent postoperative RT. Tumor progression was noted in 26.3% of patients after a median 36-month follow-up (range 12–240 months). In 57.9% of patients, distant metastases were found, of which 36.4% were present at initial diagnosis. Further metastases occurred within a median of 20 months (range 2–360 months). Following a diagnosis of metastatic tumor, 72.7% did not show progression and no symptoms were observed during a median follow-up of 36 months (range 6–216 months). Metastases occurred in all parts of the neuroaxis, but were principally localized in the thoracic and sacral spine in 38.9% and 33.3%, respectively; the brain was involved in 11.1%. In 54.5%, more than 1 level was affected. Overall survival was 100% with an excellent clinical and neurological outcome in 78.9% of cases.

CONCLUSIONS

Metastatic dissemination within the CNS can be observed in many patients with myxopapillary ependymoma. GTR of the primary tumor should be the primary treatment goal, and additional RT is recommended after STR. For distant metastases of myxopapillary ependymoma without clinical manifestation, close clinical and MRI follow-up represents a sufficient strategy because most of the metastases remain asymptomatic and do not show progression over time. Additional resection or irradiation as salvage therapy would be recommended if metastases become symptomatic.

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Ori Barzilai, Natalie DiStefano, Eric Lis, Yoshiya Yamada, D. Michael Lovelock, Andrew N. Fontanella, Mark H. Bilsky and Ilya Laufer

OBJECTIVE

The aim of this study was to evaluate the safety and efficacy of kyphoplasty treatment prior to spine stereotactic radiosurgery (SRS) in patients with spine metastases.

METHODS

A retrospective review of charts, radiology reports, and images was performed for all patients who received SRS (single fraction; either standalone or post-kyphoplasty) at a large tertiary cancer center between January 2012 and July 2015. Patient and tumor variables were documented, as well as treatment planning data and dosimetry. To measure the photon scatter due to polymethyl methacrylate, megavolt photon beam attenuation was determined experimentally as it passed through a kyphoplasty cement phantom. Corrected electron density values were recalculated and compared with uncorrected values.

RESULTS

Of 192 treatment levels in 164 unique patients who underwent single-fraction SRS, 17 (8.8%) were treated with kyphoplasty prior to radiation delivery to the index level. The median time from kyphoplasty to SRS was 22 days. Four of 192 treatments (2%) demonstrated local tumor recurrence or progression at the time of analysis. Of the 4 local failures, 1 patient had kyphoplasty prior to SRS. This recurrence occurred 18 months after SRS in the setting of widespread systemic disease and spinal tumor progression. Dosimetric review demonstrated a lower than average treatment dose for this case compared with the rest of the cohort. There were no significant differences in dosimetry analysis between the group of patients who underwent kyphoplasty prior to SRS and the remaining patients in the cohort. A preliminary analysis of polymethyl methacrylate showed that dosimetric errors due to uncorrected electron density values were insignificant.

CONCLUSIONS

In cases without epidural spinal cord compression, stabilization with cement augmentation prior to SRS is safe and does not alter the efficacy of the radiation or preclude physicians from adhering to SRS planning and contouring guidelines.

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Brad E. Zacharia, Sweena Kahn, Evan D. Bander, Gustav Y. Cederquist, William P. Cope, Lily McLaughlin, Alexa Hijazi, Anne S. Reiner, Ilya Laufer and Mark Bilsky

OBJECTIVE

The authors of this study aimed to identify the incidence of and risk factors for preoperative deep venous thrombosis (DVT) in patients undergoing surgical treatment for spinal metastases.

METHODS

Univariate analysis of patient age, sex, ethnicity, laboratory values, comorbidities, preoperative ambulatory status, histopathological classification, spinal level, and surgical details was performed. Factors significantly associated with DVT univariately were entered into a multivariate logistic regression model.

RESULTS

The authors identified 314 patients, of whom 232 (73.9%) were screened preoperatively for a DVT. Of those screened, 22 (9.48%) were diagnosed with a DVT. The screened patients were older (median 62 vs 55 years, p = 0.0008), but otherwise similar in baseline characteristics. Nonambulatory status, previous history of DVT, lower partial thromboplastin time, and lower hemoglobin level were statistically significant and independent factors associated with positive results of screening for a DVT. Results of screening were positive in only 6.4% of ambulatory patients in contrast to 24.4% of nonambulatory patients, yielding an odds ratio of 4.73 (95% CI 1.88–11.90). All of the patients who had positive screening results underwent preoperative placement of an inferior vena cava filter.

CONCLUSIONS

Patients requiring surgery for spinal metastases represent a population with unique risks for venous thromboembolism. This study showed a 9.48% incidence of DVT in patients screened preoperatively. The highest rates of preoperative DVT were identified in nonambulatory patients, who were found to have a 4-fold increase in the likelihood of harboring a DVT. Understanding the preoperative thrombotic status may provide an opportunity for early intervention and risk stratification in this critically ill population.

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Ganesh M. Shankar, Michelle J. Clarke, Tamir Ailon, Laurence D. Rhines, Shreyaskumar R. Patel, Arjun Sahgal, Ilya Laufer, Dean Chou, Mark H. Bilsky, Daniel M. Sciubba, Michael G. Fehlings, Charles G. Fisher, Ziya L. Gokaslan and John H. Shin

OBJECTIVE

Primary 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.

METHODS

A 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.

RESULTS

A 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).

CONCLUSIONS

While 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.