Faculty Bibliography

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.

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.

Patients with metastatic disease including polymetastatic, oligometastatic, and oligorecurrent spinal lesions have extended life expectancy secondary to improvements in systemic agents, and thus require durable local control of spine metastases. Stereotactic body radiotherapy (SBRT), which uses highly conformal treatment planning techniques coupled with image-guided technology, has enabled the safe delivery of tumor-ablative doses of radiotherapy. The NOMS decision framework has been developed as a tool to aid in the determination of the optimal treatment of spinal metastases, incorporating radiosurgery, separation surgery, stabilization techniques, and conventional radiation. Tumor radiosensitivity is critical in determining appropriateness of radiosurgery. In general, higher radiation doses provide significant, more durable tumor control, whether single-fraction or hypofractionated regimens are used. Spine SBRT can provide a high likelihood of durable tumor control with very low rates of serious toxicity, and careful attention should be given to dose constraints of organs at risk. Here, we review the indications for spine SBRT via the NOMS decision framework and provide practical information to the radiation oncologist regarding spine radiosurgery.

OBJECTIVE Spine radiosurgery is increasingly being used to treat spinal metastases. As patients are living longer because of the increasing efficacy of systemic agents, appropriate follow-up and posttreatment management for these patients is critical. Tumor progression after spine radiosurgery is rare; however, vertebral compression fractures are recognized as a more common posttreatment effect. The use of radiographic imaging alone posttreatment may makeit difficult to distinguish tumor progression from postradiation changes such as fibrosis. This is the largest series from a prospective database in which the authors examine histopathology of samples obtained from patients who underwent surgical intervention for presumed tumor progression or mechanical pain secondary to compression fracture. The majority of patients had tumor ablation and resulting fibrosis rather than tumor progression. The aim of this study was to evaluate tumor histopathology and characteristics of patients who underwent pathological sampling because of radiographic tumor progression, fibrosis, or collapsed vertebrae after receiving high-dose single-fraction stereotactic radiosurgery. METHODS Between January 2005 and January 2014, a total of 582 patients were treated with linear accelerator-based single-fraction (18-24 Gy) stereotactic radiosurgery. The authors retrospectively identified 30 patients (5.1%) who underwent surgical intervention for 32 lesions with vertebral cement augmentation for either mechanical pain or instability secondary to vertebral compression fracture (n = 17) or instrumentation (n = 15) for radiographic tumor progression. Radiation and surgical treatment, histopathology, and long-term outcomes were reviewed. Survival and time to recurrence were calculated using the Kaplan-Meier method. RESULTS The mean age at the time of radiosurgery was 59 years (range 36-80 years). The initial pathological diagnoses were obtained for all patients and primarily included radioresistant tumor types, including renal cell carcinoma in 7 (22%), melanoma in 6 (19%), lung carcinoma in 4 (12%), and sarcoma in 3 (9%). The median time to surgical intervention was 24.7 months (range 1.6-50.8 months). The median follow-up and overall survival for all patients were 42.5 months and 41 months (overall survival range 7-86 months), respectively. The majority of assessed lesions showed no evidence of tumor on pathological review (25 of 32, 78%), while a minority of lesions revealed residual tumor (7 of 32, 22%). The median survival for patients after tumor recurrence was 5 months (range 2-70 months). CONCLUSIONS High-dose single-fraction radiosurgery is tumor ablative in the majority of instances. In a minority of cases, tumor persists and salvage treatments should be considered.

OBJECTIVE An analysis of factors contributing to durable radiographic control of spinal metastases was undertaken, drawing from a large single-institution database in an attempt to elucidate indications and dose requirements for successful treatment. METHODS All patients treated at a single institution with stereotactic radiosurgery (SRS) of the spine as first-line therapy were assessed for local progression of the treated site, defined as radiographic enlargement of the treated tumor and/or biopsy-proven evidence of active tumor cells. All patients were followed with CT, PET, or MR imaging every 3-6 months until death. Treatment decisions were made by a multidisciplinary team of radiation oncologists, neurosurgeons, and neuroradiologists. Target volumes were defined according to the international consensus guidelines and were reviewed in a multidisciplinary conference. Image-guided techniques and intensity modulation were used for every case. The tumor's histological type, gross tumor volume (GTV), dose that covers 95% of the GTV (GTV D95), percentage of GTV covered by 95% of the prescribed dose (GTV V95), planning target volume (PTV), dose that covers 95% of the PTV (PTV D95), and percentage of PTV covered by 95% of the prescribed dose (PTV V95) were analyzed for significance in relation to local control, based on time to local progression. RESULTS A total of 811 lesions were treated in 657 patients between 2003 and 2015 at a single institution. The mean follow-up and overall survival for the entire cohort was 26.9 months (range 2-141 months). A total of 28 lesions progressed and the mean time to failure was 26 months (range 9.7-57 months). The median prescribed dose was 2400 cGy (range 1600-2600 cGy). Both GTV D95 and PTV D95 were highly significantly associated with local failure in univariate analysis, but GTV and PTV and histological type did not reach statistical significance. The median GTV D95 for the cohort equal to or above the GTV D95 1830 cGy cut point (high dose) was 2356 cGy, and it was 1709 cGy for the cohort of patients who received less than 1830 cGy (low dose). In terms of PTV D95, the median dose for those equal to or above the cut point of 1740 cGy (high dose) was 2233 cGy, versus 1644 cGy for those lesions below the PTV D95 cut point of 1740 cGy (low dose). CONCLUSIONS High-dose single-session SRS provides durable long-term control, regardless of the histological findings or tumor size. In this analysis, the only significant factors predictive of local control were related to the actual dose of radiation given. Although the target volumes were well treated with the intended dose, those lesions irradiated to higher doses (median GTV D95 2356 cGy, minimum 1830 cGy) had a significantly higher probability of durable local control than those treated with lower doses (median PTV D95 2232 cGy, minimum of 1740 cGy) (p < 0.001). Patients in the high-dose cohort had a 2% cumulative rate of local failure. Histological findings were not associated with local failure, suggesting that radioresistant histological types benefit in particular from radiosurgery. For patients with a favorable prognosis, a higher dose of SRS is important for long-term outcomes.

OBJECTIVE The purpose of this study was to determine the rate of symptomatic vertebral body compression fractures (VCFs) requiring kyphoplasty or surgery in patients treated with 24-Gy single-fraction stereotactic radiosurgery (SRS). METHODS This retrospective analysis included all patients who had been treated with 24-Gy, single-fraction, image-guided intensity-modulated radiation therapy for histologically confirmed solid tumor metastases over an 8-year period (2005-2013) at Memorial Sloan Kettering Cancer Center. Charts and imaging studies were reviewed for post-SRS kyphoplasty or surgery for mechanical instability. A Spinal Instability Neoplastic Score (SINS) was calculated for each patient both at the time of SRS and at the time of intervention for VCF. RESULTS Three hundred twenty-three patients who had undergone single-fraction SRS between C-1 and L-5 were included in this analysis. The cumulative incidence of VCF 5 years after SRS was 7.2% (95% CI 4.1-10.2), whereas that of death following SRS at the same time point was 82.5% (95% CI 77.5-87.4). Twenty-six patients with 36 SRS-treated levels progressed to symptomatic VCF requiring treatment with kyphoplasty (6 patients), surgery (10 patients), or both (10 patients). The median time to symptomatic VCF was 13 months. Seven patients developed VCF at 11 levels adjacent to the SRS-treated level. Fractured levels had no evidence of tumor progression. The median SINS changed from 6.5 at SRS (interquartile range [IQR] 4.3-8.8) to 11.5 at stabilization (IQR 9-13). In patients without prior stabilization at the level of SRS, there was an association between the SINS and the time to fracture. CONCLUSIONS Five years after ablative single-fraction SRS to spinal lesions, the cumulative incidence of symptomatic VCF at the treated level without tumor recurrence was 7.2%. Higher SINSs at the time of SRS correlated with earlier fractures.

OBJECTIVE The object of this study was to determine the percentage of high-dose (1800-2600 cGy) single-fraction stereotactic radiosurgery (SF-SRS) treatments to the spine that result in peripheral nervous system (PNS) injury. METHODS All patients treated with SF-SRS for primary or metastatic spine tumors between January 2004 and May 2013 and referred to the Rehabilitation Medicine Service for evaluation and treatment of neuromuscular, musculoskeletal, or functional impairments or pain were retrospectively identified. RESULTS Five hundred fifty-seven SF-SRS treatments in 447 patients resulted in 14 PNS injuries in 13 patients. All injures resulted from SF-SRS delivered to the cervical or lumbosacral spine at 2400 cGy. The overall percentage of SF-SRS treatments resulting in PNS injury was 2.5%, increasing to 4.5% when the thoracic spine was excluded from analysis. The median time to symptom onset following SF-SRS was 10 months (range 4-32 months). The plexus (cervical, brachial, and/or lumbosacral) was affected clinically and/or electrophysiologically in 12 (86%) of 14 cases, the nerve root in 2 (14%) of 14, and both in 6 (43%) of 14 cases. All patients experienced pain and most (93%) developed weakness. Peripheral nervous system injuries were CTCAE Grade 1 in 14% of cases, 2 in 64%, and 3 in 21%. No dose relationship between SF-SRS dose and PNS injury was detected. CONCLUSIONS Single-fraction SRS to the spine can result in PNS injury with major implications for function and quality of life.

Introduction:Tumors invading the sacrum and/or ilium often represent incurable metastatic disease, and treatment is targeted toward palliation of symptoms and control of pain. As systemic opioid therapy is frequently inadequate and limited by side effects, a variety of interventional techniques are available to better optimize analgesia. Using six patients as a paradigm for interventional approaches to pain relief, we present a therapeutic algorithm for treating sacroiliac tumor-related pain in the oncologic population. Methods:We describe the use of ultrasound-guided proximal sacroiliac joint corticosteroid injection, sacroiliac lateral branch radiofrequency ablation, percutaneous sacroplasty, and implantable neuraxial drug delivery devices to treat malignant sacroiliac pain in six patients. Pre- and postprocedure numerical rating scale (NRS) pain scores, duration of pain relief, and postprocedure pain medication requirements were studied for each patient. Results:Each patient had marked improvement in their pain based on an average postprocedure NRS difference of six points. The average duration of pain relief was eight months. In all cases, opioid requirements decreased after the intervention. Discussion:Depending on tumor location, burden of disease, and patient preference, patients suffering from metastatic disease to the sacrum may find benefit from use of ultrasound-guided proximal sacroiliac joint corticosteroid injection, sacroiliac lateral branch radiofrequency ablation, percutaneous sacroplasty, dorsal column stimulator leads, and/or implantable neuraxial drug delivery devices. We provide a paradigm for treatment in this patient population.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Externally validate the SORG12 nomogram and SORG classic algorithm at estimating survival in patients with spine metastatic disease, and compare predictive accuracy with other survival algorithms. METHODS:We received data from 100 patients who had surgery for spine metastatic disease at an external institution. Algorithms were accurate if the Area Under Curve (AUC) was >0.70, and we used Receiver Operating Characteristic (ROC) analysis to compare predictive accuracy with other algorithms. RESULTS:The SORG nomogram accurately estimated 3-months (AUC = 0.74) and 12-months survival (AUC = 0.78); it did not accurately estimate 1-month survival (AUC = 0.65). There was no difference in 1-month survival accuracy between the SORG nomogram and SORG classic algorithm (P = 0.162). The SORG nomogram was best at predicting 3-months survival, compared with the Tokuhashi score and SORG classic algorithm (P = 0.009). The SORG nomogram was best at predicting 12-months survival, compared with the Tomita score, Ghori score, Bauer modified score, Tokuhashi score, and SORG classic algorithm (P = 0.033). CONCLUSIONS:The SORG nomogram accurately estimated 3- and 12-months survival for operable spine metastatic disease, and is therefore, useful in clinical practice.

BACKGROUND:Whether primary or metastatic, tumors of the craniovertebral junction (CVJ) are rare and challenging. OBJECTIVE:To examine the surgical indications, operative variables, and outcomes in patients with tumors of the CVJ undergoing occipitocervical (OC) stabilization. METHODS:A single-institution, retrospective case series was performed from a prospectively maintained spine database. Patients with primary or metastatic tumors of the CVJ who underwent OC stabilization were identified. Out of 46 patients who underwent OC fusion, 39 were for tumor. Paired t -tests and Wilcoxon rank-sum tests were performed to assess for postoperative changes. RESULTS:Ten patients (26%) harbored primary tumors, and the remaining 29 (74%) had metastatic disease. Of the metastatic patients, 14 had a neurological deficit, 10 had severe neck pain, and 5 were deemed mechanically unstable. Postoperative visual analog pain scores were significantly reduced at all 3 follow-up times ( P < .001, 95% confidence interval [CI; 3.2, 6.0]; P = .001, 95% CI [2.6, 7.7]; P = .020, 95% CI [0.6, 5.5]). The percentage of patients who were ambulatory and neurologically improved or intact remained stable postoperatively with no significant declines. There were 2 perioperative mortalities (5%), and 13 patients (33%) experienced a major complication. CONCLUSIONS:In patients with primary or metastatic tumor of the CVJ, OC stabilization using a cervical screw-rod system affixed to a midline-keel buttress plate, with or without posterior decompression, is a reliable method for CVJ stabilization in the oncologic setting. Improvement in pain and preservation of neurological function was seen.