Identification of incidental brain tumors in prostate cancer patients via PSMA PET/CT.

PURPOSE: Brain metastases are rare in patients with prostate cancer and portend poor outcome. Prostate-specific membrane antigen positron emission tomography (PSMA PET)/CT scans including the brain have identified incidental tumors. We sought to identify the incidental brain tumor detection rate of PSMA PET/CT performed at initial diagnosis or in the setting of biochemical recurrence. METHODS: An institutional database was queried for patients who underwent 68Ga-PSMA-11 or 18F-DCFPyL (18F-piflufolastat) PET/CT imaging at an NCI-designated Comprehensive Cancer Center from 1/2018 to 12/2022. Imaging reports and clinical courses were reviewed to identify brain lesions and describe clinical and pathologic features. RESULTS: Two-thousand seven hundred and sixty-three patients underwent 3363 PSMA PET/CT scans in the absence of neurologic symptoms. Forty-four brain lesions were identified, including 33 PSMA-avid lesions: 10 intraparenchymal metastases (30%), 4 dural-based metastases (12%), 16 meningiomas (48%), 2 pituitary macroadenomas (6%), and 1 epidermal inclusion cyst (3%) (incidences of 0.36, 0.14, 0.58, 0.07, and 0.04%). The mean parenchymal metastasis diameter and mean SUVmax were 1.99 cm (95%CI:1.25-2.73) and 4.49 (95%CI:2.41-6.57), respectively. At the time of parenchymal brain metastasis detection, 57% of patients had no concurrent extracranial disease, 14% had localized prostate disease only, and 29% had extracranial metastases. Seven of 8 patients with parenchymal brain metastases remain alive at a median 8.8 months follow-up. CONCLUSION: Prostate cancer brain metastases are rare, especially in the absence of widespread metastatic disease. Nevertheless, incidentally detected brain foci of PSMA uptake may represent previously unknown prostate cancer metastases, even in small lesions and in the absence of systemic disease.

The SORG nomogram accurately predicts 3- and 12-months survival for operable spine metastatic disease: External validation.

BACKGROUND AND OBJECTIVES: 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.

Frequency of symptomatic vertebral body compression fractures requiring intervention following single-fraction stereotactic radiosurgery for spinal metastases.

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.

The impact of histology and delivered dose on local control of spinal metastases treated with stereotactic radiosurgery.

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.

Surgery for Metastatic Spinal Disease in Octogenarians and Above: Analysis of 78 Patients.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVE: Octogenarians living with spinal metastases are a challenging population to treat. Our objective was to identify the rate, types, management, and predictors of complications and survival in octogenarians following surgery for spinal metastases. METHODS: A retrospective review of a prospectively collected cohort of patients aged 80 years or older who underwent surgery for metastatic spinal tumor treatment between 2008 and 2019 were included. Demographic, intraoperative, complications, and postoperative follow-up data was collected. Cox proportional hazards regression and logistic regression were used to associate variables with overall survival and postoperative complications, respectively. RESULTS: 78 patients (mean 83.6 years) met inclusion criteria. Average operative time and blood loss were 157 minutes and 615 mL, respectively. The median length of stay was 7 days. The overall complication rate was 31% (N = 24), with 21% considered major and 7% considered life-threatening or fatal. Blood loss was significantly associated with postoperative complications (OR = 1.002; P = 0.02) and mortality (HR = 1.0007; P = 0.04). Significant associations of increased risk of death were also noted with surgeries with decompression, and cervical/cervicothoracic index level of disease. For deceased patients, median time to death was 4.5 months. For living patients, median follow-up was 14.5 months. The Kaplan-Meier based median overall survival for the cohort was 11.6 months (95% CI: 6.2-19.1). CONCLUSIONS: In octogenarians undergoing surgery with instrumentation for spinal metastases, the median overall survival is 11.6 months. There is an increased complication rate, but only 7% are life-threatening or fatal. Patients are at increased risk for complications and mortality particularly when performing decompression with stabilization, with increasing intraoperative blood loss, and with cervical/cervicothoracic tumors.

The spinal distribution of metastatic renal cell carcinoma: Support for locoregional rather than arterial hematogenous mode of early bony dissemination.

BACKGROUND: Quantifying the degree to which spinal involvement of metastatic renal cell carcinoma (mRCC) is a locoregional phenomenon vs. a hematogenous, bone-specific affinity has implications for prognosis and antimetastatic therapy. OBJECTIVE: To investigate the distribution of spinal metastasis in mRCC and to explore relationships between clinical factors and patterns of spinal spread. METHODS: Patients with mRCC and spinal involvement from June 2005 to November 2018 were identified. Clinical and biologic features including primary tumor size and degree of spinal and nonbony metastatic involvement were collected. Spinal distributions were evaluated by the permutation test, with the null hypothesis that metastases are distributed uniformly across levels. RESULTS: One hundred patients with 685 spinal levels involved by mRCC were evaluated. A nonuniform spatial distribution was observed across the cohort (P < 0.001); a preponderance of thoracolumbar involvement was noted with the mode at L3. No significant deviation in metastatic distribution from uniform was observed in right- or left-sided tumors, subgroups of distant or local metastases, or histology. Patients with smaller tumors (<4 cm) and local spread had distribution of spinal metastases not significantly different from uniform (P = 0.292 and P = 0.126, respectively). CONCLUSIONS: These data support a dominant locoregional as opposed to arterial hematogenous mechanism for early spinal dissemination of mRCC. Characterizations of the biologic molecular features contributing to osseous tropism and aggressive tumor biology (as seen in the subset of outlier patients with small tumors who appear to have more uniform spread), have implications for surveillance and are an area of active investigation.

Utility of Cement Augmentation via Percutaneous Fenestrated Pedicle Screws for Stabilization of Cancer-Related Spinal Instability.

BACKGROUND: Cancer patients experience pathological fractures and the typical poor bone quality frequently complicates stabilization. Methods for overcoming screw failure include utilization of fenestrated screws that permit the injection of bone cement into the vertebral body to augment fixation. OBJECTIVE: To evaluate the safety and efficacy of cement augmentation via fenestrated screws. METHODS: A retrospective chart review of patients with neoplastic spinal instability who underwent percutaneous instrumented stabilization with cement augmentation using fenestrated pedicle screws. Patient demographic and treatment data and intraoperative and postoperative complications were evaluated by chart review and radiographic evaluation. Prospectively collected patient reported outcomes (PRO) were evaluated at short (2- <6 mo) and long term (6-12 mo). RESULTS: Cement augmentation was performed in 216 fenestrated pedicle screws in 53 patients. Three patients required reoperation. One patient had an asymptomatic screw fracture at 6 mo postoperatively that did not require intervention. No cases of lucency around the pedicle screws, rod fractures, or cement extravasation into the spinal canal were observed. Eight cases of asymptomatic, radiographically-detected venous extravasation were found. Systemic complications included a pulmonary cement embolism, a lower extremity deep vein thrombosis, and a postoperative mortality secondary to pulmonary failure from widespread metastatic pulmonary infiltration. Significant improvement in PRO measures was found in short- and long-term analysis. CONCLUSION: Cement augmentation of pedicle screws is an effective method to enhance the durability of spinal constructs in the cancer population. Risks include cement extravasation into draining blood vessels, but risk of clinically significant extravasation appears to be exceedingly low.

Outcome analysis of surgery for symptomatic spinal metastases in long-term cancer survivors.

OBJECTIVEAs 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.METHODSThe 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.RESULTSEighty-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.CONCLUSIONSDurable 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.

Spinal Instability Neoplastic Score component validation using patient-reported outcomes.

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.

Metastases of spinal myxopapillary ependymoma: unique characteristics and clinical management.

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.

Change in the cross-sectional area of the thecal sac following balloon kyphoplasty for pathological vertebral compression fractures prior to spine stereotactic radiosurgery.

OBJECTIVEPercutaneous 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).METHODSThe 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.RESULTSAmong 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.CONCLUSIONSIn 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.

Patient-reported outcomes after surgical stabilization of spinal tumors: symptom-based validation of the Spinal Instability Neoplastic Score (SINS) and surgery.

BACKGROUND CONTEXT: Neoplastic spinal instability is movement-related pain or neurologic compromise under physiologic loads with the Spinal Instability Neoplastic Score (SINS) developed to facilitate diagnosis. There is a paucity of evidence that mechanical instability correlates with patient-reported symptoms and that surgical stabilization significantly improves these patient-reported outcomes (PROs). PURPOSE: The objective of this study was to determine if SINS correlates with patient-reported preoperative pain and disability, and if surgical stabilization significantly improves PRO. STUDY DESIGN: A single-institution prospective cohort study was carried out. PATIENT SAMPLE: A total of 131 patients who underwent stabilization for metastatic spinal tumor treatment between July 2014 and August 2016 were included. OUTCOMES MEASURES: Preoperative baseline and mean difference in perioperative PROs as assessed by the Brief Pain Inventory (BPI) and MD Anderson Symptom Inventory (MDASI) were the outcome measures. METHODS: The SINS was analyzed as a continuous, ordinal, and categorical variable (Stable: 0-6, Indeterminate: 7-12, Unstable: 13-18). Statistical analysis was performed using Spearman rank coefficient (rho), the Kruskal-Wallis test, and an extension of the Cochran-Armitage trend test. The SINS and association between the mean differences in post- and preoperative PRO scores was analyzed using the Wilcoxon signed-rank test. RESULTS: There was a statistically significant positive correlation between increasing SINS and severity of preoperative pain with BPI average pain (rho=0.20; p=.03) and MDASI pain (rho=0.19; p=.03). Increasing SINS correlated with severity of preoperative disability with BPI walking (rho=0.19; p=.04), MDASI activity (rho=0.24; p=.006), and MDASI walking (rho=0.20; p=.03). Similar associations were noted when SINS was analyzed as an ordinal categorical variable. Stabilization significantly improved nearly all PRO measures for patients with indeterminate and unstable SINS. Significant correlations persisted when controlling for neurologic status and were not affected based on the technique of surgical stabilization used. CONCLUSIONS: Patient-related outcome-based validation of SINS confirms this scoring system for diagnosing neoplastic spinal instability and provides surgeons with a tool to determine which patients will benefit from stabilization. Surgical stabilization of cancer patients with SINS consistent with mechanical instability provides significant reduction in pain and improves patient mobility independent of neurologic status and stabilization technique.

Corrigenda: Hybrid surgery-radiosurgery therapy for metastatic epidural spinal cord compression: A prospective evaluation using patient-reported outcomes.

[This corrects the article DOI: 10.1093/nop/npx017.][This corrects the article DOI: 10.1093/nop/npx017.].

Hybrid surgery-radiosurgery therapy for metastatic epidural spinal cord compression: A prospective evaluation using patient-reported outcomes.

BACKGROUND: Patient-reported outcomes (PRO) represent an important measure of cancer therapy effect. For patients with metastatic epidural spinal cord compression (MESCC), hybrid therapy using separation surgery and stereotactic radiosurgery preserves neurologic function and provides tumor control. There is currently a paucity of data reporting PRO after such combined modality therapy for MESCC. Delineation of hybrid surgery-radiosurgery therapy effect on PRO validates the hybrid approach as an effective therapy resulting in meaningful symptom relief. PATIENTS AND METHODS: Brief Pain Inventory (BPI) and MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP), PROs validated in the cancer population, were prospectively collected. Patients with MESCC who underwent separation surgery followed by stereotactic radiosurgery were included. Separation surgery included a posterolateral approach without extensive cytoreductive tumor excision. A median postoperative radiosurgery dose of 2700 cGy was delivered. The change in PRO 3 months after the hybrid therapy represented the primary study outcome. Preoperative and postoperative evaluations were analyzed using the Wilcoxon signed-rank test for matched pairs. RESULTS: One hundred eleven patients were included. Hybrid therapy resulted in a significant reduction in the BPI items "worst" and "right now" pain (P < .0001), and in all BPI constructs (severity, interference with daily activities, and pain experience, P < .001). The MDASI-SP demonstrated reduction in spine-specific pain severity and interference with general activity (P < .001), along with decreased symptom interference (P < .001). CONCLUSIONS: Validated PRO instruments showed that in patients with MESCC, hybrid therapy with separation surgery and radiosurgery results in a significant decrease in pain severity and symptom interference. These prospective data confirm the benefit of hybrid therapy for treatment of MESCC and should facilitate referral of patients with MESCC for surgical evaluation.

Predictors of quality of life improvement after surgery for metastatic tumors of the spine: prospective cohort study.

BACKGROUND CONTEXT: Surgical decompression and stabilization followed by radiosurgery represents an effective method for local tumor control and neurologic preservation for patients with metastatic epidural spinal cord compression (MESCC). We have previously demonstrated improvement in health-related quality of life (HrQOL) after this combined modality treatment ("hybrid therapy"). PURPOSE: The current analysis focuses on delineation of patient-specific prognostic factors predictive of HrQOL change after combined surgery-stereotactic radiosurgery (SRS) treatment of MESCC. STUDY DESIGN: This is a prospective, single-center, cohort study. PATIENT SAMPLE: One hundred and eleven patients with MESCC who underwent separation surgery followed by SRS were included. OUTCOME MEASURES: Prognostic factors associated with improved patient-reported outcome (PRO) measures. METHODS: Patient-reported outcome tools, that is, Brief Pain Inventory (BPI) and MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP), both validated in the cancer population, were prospectively collected. Numeric prognostic factors were correlated with PRO measures using the Spearman rank correlation coefficient. Categorical prognostic factors were correlated with PRO measures using the Wilcoxon two-sample test (for two categories) or the Kruskal-Wallis test (for three or more categories). All statistical tests were two-sided with a level of significance <.05 for correlation of prognostic factors with PRO constructs and a level of significance <.0014 for correlation of prognostic factors with PRO items. Statistical analyses were done in SAS (version 9.4, Cary, NC, USA). RESULTS: One hundred and eleven patients were included in this analysis. Patients with lower preoperative Medical Research Council (MRC) motor scores experienced a greater decrease in symptom interference (BPI interference construct (p=.03) and individual functional measures including general activity (p=.001), walking (p=.001), and normal work (p=.006)). Lumbar location was associated with better outcomes than cervical or thoracic as noted on the BPI pain experience construct (p=.03) and MDASI-SP interference (p=.01) and core symptom (p=.002) constructs. Patients with American Spinal Injury Association (ASIA) scores of C or D benefit more than those with ASIA E on BPI interference construct (p=.04). Patients with higher Eastern Cooperative Oncology Group (ECOG) scores at presentation benefit more than those with low ECOG scores on MDASI-SP interference construct (p=.03). Women benefit more than men on BPI interference (p=.03) and pain experience (p=.04) constructs. Patients with prior spinal surgery at the current level of interest benefit less than those who are naïve surgical patients in MDASI-SP interference construct (p=.04). CONCLUSIONS: Delineation of patient characteristics associated with HrQOL improvement provides crucial information for patient selection, patient education, and setting treatment expectations. For patients with MESCC treated with hybrid therapy using surgery and radiosurgery, the presence of neurologic deficits and diminished performance status, lumbar tumor level, and female gender were associated with greater PRO improvement.

Minimal Access Surgery for Spinal Metastases: Prospective Evaluation of a Treatment Algorithm Using Patient-Reported Outcomes.

BACKGROUND: Minimal access surgery (MAS) allows for an early return to systemic and radiation therapy in patients with cancer, leading to its increasing usage in the treatment of spinal metastases. Systematic examination of surgical indications resulted in the development of an algorithm for implementation of MAS in the treatment of spinal metastases. The objective of the present study was to evaluate a spine tumor MAS treatment algorithm using patient-reported outcomes for patients with cancer undergoing treatment of spinal metastases. METHODS: We performed a prospective cohort study of patients who had undergone spinal percutaneous instrumented stabilization with the addition of MAS spinal cord or nerve root decompression and/or kyphoplasty when indicated at a tertiary cancer center from December 2013 to August 2016. Validated patient-reported outcome measures, including the Brief Pain Inventory and the MD Anderson Symptom Inventory-spine module, were used. The patient-reported outcome measures were collected and compared at baseline, 3 months, and long-term follow-up (range, 4.5-12 months). RESULTS: A total of 51 patients were included. MAS resulted in a statistically significant decrease in the severity of pain and improved activity, ability to work, and enjoyment of life (P < 0.001). The improvement was reported at the short- and long-term follow-up points. CONCLUSIONS: We present our treatment algorithm for MAS implementation in the treatment of thoracolumbar spinal metastases. Prospectively collected data have demonstrated that using this algorithm, MAS surgery for the treatment of spinal metastases results in significant decreases in pain severity and symptom interference with daily activities.

Incidence and risk factors for preoperative deep venous thrombosis in 314 consecutive patients undergoing surgery for spinal metastasis.

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.

Short-segment percutaneous pedicle screw fixation with cement augmentation for tumor-induced spinal instability.

BACKGROUND CONTEXT: Pathologic vertebral compression fractures (VCFs) represent a major source of morbidity and diminished quality of life in the spinal oncology population. Procedures with low morbidity that effectively treat patients with pathologic fractures are especially important in the cancer population where life expectancy is limited. Vertebroplasty and kyphoplasty are often not effective for mechanically unstable pathologic fractures extending into the pedicle and facet joints. Combination of cement augmentation and percutaneous instrumented stabilization represents a minimally invasive treatment option that does not delay radiation and systemic therapy. PURPOSE: The objective of the study was to evaluate the safety and efficacy of cement-augmented short-segment percutaneous posterolateral instrumentation for tumor-associated VCF with pedicle and joint involvement. METHODS: Forty-four consecutive patients underwent cement-augmented percutaneous spinal fixation for unstable tumors between 2011 and 2014. Retrospective analysis of prospectively collected data, including visual analog pain scale (VAS) response score and procedural complications, was performed. RESULTS: Patients with a median composite Spinal Instability Neoplastic Scale score of 10 (range=8-15) were treated with constructs spanning one to four disk spaces (median of two spaces, constituting 84% of all cases). The proportion of patients with severe pain decreased from 86% preoperatively to 0%; 65% of patients reported no referable instability pain postoperatively. There was one adjacent-level fracture responsive to kyphoplasty, and one case of asymptomatic screw pullout. Two patients subsequently required decompression in the setting of disease progression despite radiation; there was no perioperative morbidity. CONCLUSIONS: Percutaneous cement-augmented posterolateral spinal fixation is a safe and effective option for palliation of appropriately selected mechanically unstable VCF that extends into pedicle and/or joint.

Five-Year Outcomes of High-Dose Single-Fraction Spinal Stereotactic Radiosurgery.

PURPOSE: To characterize local tumor control and toxicity risk in very long-term survivors (>5 years) after high-dose spinal image guided, intensity modulated radiation therapy delivered as single-dose stereotactic radiosurgery (SRS). Previously published spinal SRS outcome analyses have included a heterogeneous population of cancer patients, mostly with short survival. This is the first study reporting the long-term tumor control and toxicity profiles after high-dose single-fraction spinal SRS. METHODS AND MATERIALS: The study population included all patients treated from June 2004 to July 2009 with single-fraction spinal SRS (dose 24 Gy) who had survived at least 5 years after treatment. The endpoints examined included disease progression, surgical or radiation retreatment, in-field fracture development, and radiation-associated toxicity, scored using the Radiation Therapy Oncology Group radiation morbidity scoring criteria and the Common Terminology Criteria for Adverse Events, version 4.0. Local control and fracture development were assessed using Kaplan-Meier analysis. RESULTS: Of 278 patients, 31 (11.1%), with 36 segments treated for spinal tumors, survived at least 5 years after treatment and were followed up radiographically and clinically for a median of 6.1 years (maximum 102 months). The histopathologic findings for the 5-year survivors included radiation-resistant metastases in 58%, radiation-sensitive metastases in 22%, and primary bone tumors in 19%. In this selected cohort, 3 treatment failures occurred at a median of 48.6 months, including 2 recurrences in the radiation field and 1 patient with demonstrated progression at the treatment margins. Ten lesions (27.8%) were associated with acute grade 1 cutaneous or gastrointestinal toxicity. Delayed toxicity ≥ 3 months after treatment included 8 cases (22.2%) of mild neuropathy, 2 (5.6%) of gastrointestinal discomfort, 8 (22.2%) of dermatitides, and 3 (8.3%) of myalgias/myositis. Thirteen treated levels (36.1%) in 12 patients demonstrated progressive vertebral body collapse or endplate fractures at a median of 25.7 months (range 11.6-76.0), of which 5 (14%) became symptomatic and subsequently required percutaneous cement augmentation or surgery. CONCLUSIONS: In the longest-term series to date, high-dose single-fraction spinal SRS retained an excellent safety profile among long-term survivors (>5 years).