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Advances in the treatment of metastatic spine tumors: the future is not what it used to be

Laufer, Ilya; Bilsky, Mark H
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.
PMID: 30835704
ISSN: 1547-5646
CID: 4715812

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

Barzilai, Ori; McLaughlin, Lily; Lis, Eric; Yamada, Yoshiya; Bilsky, Mark H; Laufer, Ilya
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.
PMID: 31026814
ISSN: 1547-5646
CID: 4715822

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

Barzilai, Ori; McLaughlin, Lily; Lis, Eric; Reiner, Anne S; Bilsky, Mark H; Laufer, Ilya
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.
PMCID:7311793
PMID: 30508168
ISSN: 2332-4260
CID: 4715782

Survival, local control, and health-related quality of life in patients with oligometastatic and polymetastatic spinal tumors: A multicenter, international study

Barzilai, Ori; Versteeg, Anne L; Sahgal, Arjun; Rhines, Laurence D; Bilsky, Mark H; Sciubba, Daniel M; Schuster, James M; Weber, Michael H; Pal Varga, Peter; Boriani, Stefano; Bettegowda, Chetan; Fehlings, Michael G; Yamada, Yoshiya; Clarke, Michelle J; Arnold, Paul M; Gokaslan, Ziya L; Fisher, Charles G; Laufer, Ilya
BACKGROUND:The treatment of oligometastatic (≤5 metastases) spinal disease has trended toward ablative therapies, yet to the authors' knowledge little is known regarding the prognosis of patients presenting with oligometastatic spinal disease and the value of this approach. The objective of the current study was to compare the survival and clinical outcomes of patients with cancer with oligometastatic spinal disease with those of patients with polymetastatic (>5 metastases) disease. METHODS:The current study was an international, multicenter, prospective study. Patients who were admitted to a participating spine center with a diagnosis of spinal metastases and who underwent surgical intervention and/or radiotherapy between August 2013 and May 2017 were included. Data collected included demographics, overall survival, local control, and treatment information including surgical, radiotherapy, and systemic therapy details. Health-related quality of life (HRQOL) measures included the EuroQOL 5 dimensions 3-level questionnaire (EQ-5D-3L), the 36-Item Short Form Health Survey (SF-36v2), and the Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ). RESULTS:Of the 393 patients included in the current study, 215 presented with oligometastatic disease and 178 presented with polymetastatic disease. A significant survival advantage of 90.1% versus 77.3% at 3 months and 77.0% versus 65.1% at 6 months from the time of treatment was found for patients presenting with oligometastatic disease compared with those with polymetastatic disease. It is important to note that both groups experienced significant improvements in multiple HRQOL measures at 6 months after treatment, with no differences in these outcome measures noted between the 2 groups. CONCLUSIONS:The treatment of oligometastatic disease appears to offer a significant survival advantage compared with polymetastatic disease, regardless of treatment choice. HRQOL measures were found to improve in both groups, demonstrating a palliative benefit for all treated patients.
PMID: 30489634
ISSN: 1097-0142
CID: 4715752

Commentary: Steroid Use Associated With Increased Odds of 30-Day Mortality in Surgical Patients With Metastatic Spinal Tumors in the Setting of Disseminated Disease [Comment]

Laufer, Ilya
PMID: 30395274
ISSN: 1524-4040
CID: 4715742

Adjacent level fracture incidence in single fraction high dose spinal radiosurgery

Lockney, Dennis T; Hopkins, Benjamin; Lockney, Natalie A; Coleman, Christian Z; Rubin, Elena; Lis, Eric; Yamada, Yoshiya; Schmitt, Adam; Higginson, Daniel; Bilsky, Mark H; Laufer, Ilya
Background/UNASSIGNED:Vertebral body compression fracture (VCF) is a complication following spinal stereotactic radiosurgery (SRS). However, the incidence of VCF in vertebrae adjacent to the level of SRS is unknown. This study aimed to determine the incidence of adjacent level VCF (adjVCF) following spinal SRS. Methods/UNASSIGNED:A retrospective review of 239 lesions treated with single-fraction SRS from 2011-2014 was performed. Clinical and pathologic factors were collected including evaluation of VCFs in adjacent levels to SRS site. In patients with adjVCFs, dose-volume histograms for adjacent-level endplates were calculated. Cox regression analysis was performed to determine any association among clinical factors and adjVCF occurrence. Results/UNASSIGNED:Median follow-up was 14.7 months. Twenty-six adjVCFs occurred (10.8%). Of the adjVCFs, 19 had metastases following SRS, and seven did not (2.9% of total treatments). Median time to fracture post-SRS was 13.5 months. In adjVCFs, median of the mean dose to adjacent level fractured endplate was 23.3 Gy, and median of the mean dose of sixteen non-fractured endplates immediately adjacent to the SRS site was 19.1 Gy. Age, gender, and histology were not associated with adjVCF. Conclusions/UNASSIGNED:AdjVCF after spinal SRS occurs at a rate of 2.9%, when excluding metastatic sites of disease. Adjacent level endplates should be investigated as an organ at risk during SRS planning.
PMCID:6595213
PMID: 31297376
ISSN: 2305-5839
CID: 4715852

Association of neurologic deficits with surgical outcomes and health-related quality of life after treatment for metastatic epidural spinal cord compression

Barzilai, Ori; Versteeg, Anne L; Goodwin, C Rory; Sahgal, Arjun; Rhines, Laurence D; Sciubba, Daniel M; Schuster, James M; Weber, Michael H; Lazary, Aron; Fehlings, Michael G; Clarke, Michelle J; Arnold, Paul M; Boriani, Stefano; Bettegowda, Chetan; Gokaslan, Ziya L; Fisher, Charles G; Laufer, Ilya
BACKGROUND:A critical knowledge gap exists regarding the impact of neurologic deficits on surgical outcomes and health-related quality of life (HRQOL) for patients surgically treated for metastatic epidural spinal cord compression (MESCC). METHODS:This prospective, multicenter and international study analyzed the impact of the neurologic status on functional status, HRQOL, and postoperative survival. The collected data included the patient demographics, overall survival, American Spinal Injury Association (ASIA) impairment scale, Spinal Instability Neoplastic Score, treatment details and complications and HRQOL measures, including version 2 of the 36-Item Short Form Health Survey (SF-36v2) and version 2.0 of the Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ2.0). RESULTS:A total of 239 patients surgically treated for spinal metastases were included. Six weeks after treatment, 99 of the 108 patients with a preoperative ASIA grade of E remained stable, 8 deteriorated to ASIA D, and 1 deteriorated to ASIA A. Of 55 patients with ASIA D, 27 improved to ASIA E, 27 remained stable and 1 deteriorated to ASIA C. Of 11 patients with ASIA A to C, 2 improved to ASIA E, 4 improved to ASIA D, and 5 remained stable. At the 6- and 12-week follow-up, better ASIA scores were associated with better scores on multiple SF-36v2 and SOSGOQ items. Postoperatively, patients with ASIA grades of A to D were more likely to have urinary tract infections and wound complications. Patients with a baseline ASIA grade of E or D survived significantly longer. CONCLUSIONS:Patients with neurologic deficits due to MESCC have worse HRQOL and decreased overall survival. Nevertheless, surgery can result in stabilization or improvement of neurologic function which may translate into better HRQOL. Postoperative care and follow-up are challenging for patients with neurologic deficits because they experience more complications.
PMID: 31410854
ISSN: 1097-0142
CID: 4715882

Long-term outcomes of high-dose single-fraction radiosurgery for chordomas of the spine and sacrum

Jin, Chunzi Jenny; Berry-Candelario, John; Reiner, Anne S; Laufer, Ilya; Higginson, Daniel S; Schmitt, Adam M; Lis, Eric; Barzilai, Ori; Boland, Patrick; Yamada, Yoshiya; Bilsky, Mark H
OBJECTIVE:The current treatment of chordomas is associated with significant morbidity, high rates of local recurrence, and the potential for metastases. Stereotactic radiosurgery (SRS) as a primary treatment could reduce the need for en bloc resection to achieve wide or marginal margins. Spinal SRS outcomes support the exploration of SRS's role in the durable control of these conventionally radioresistant tumors. The goal of the study was to evaluate outcomes of patients with primary chordomas treated with spinal SRS alone or in combination with surgery. METHODS:Clinical records were reviewed for outcomes of patients with primary chordomas of the mobile spine and sacrum who underwent single-fraction SRS between 2006 and 2017. Radiographic local recurrence-free survival (LRFS), overall survival (OS), symptom response, and toxicity were assessed in relation to the extent of surgery. RESULTS:In total, 35 patients with de novo chordomas of the mobile spine (n = 17) and sacrum (n = 18) received SRS and had a median post-SRS follow-up duration of 38.8 months (range 2.0-122.9 months). The median planning target volume dose was a 24-Gy single fraction (range 18-24 Gy). Overall, 12 patients (34%) underwent definitive SRS and 23 patients (66%) underwent surgery and either neoadjuvant or postoperative adjuvant SRS. Definitive SRS was selectively used to treat both sacral (n = 7) and mobile spine (n = 5) chordomas. Surgical strategies for the mobile spine were either intralesional, gross-total resection (n = 5) or separation surgery (n = 7) and for the sacrum en bloc sacrectomy (n = 11). The 3- and 5-year LRFS rates were 86.2% and 80.5%, respectively. Among 32 patients (91%) receiving 24-Gy radiation doses, the 3- and 5-year LRFS rates were 96.3% and 89.9%, respectively. The 3- and 5-year OS rates were 90.0% and 84.3%, respectively. The symptom response rate to treatment was 88% for pain and radiculopathy. The extent or type of surgery was not associated with LRFS, OS, or symptom response rates (p > 0.05), but en bloc resection was associated with higher surgical toxicity, as measured using the Common Terminology Criteria for Adverse Events (version 5.0) classification tool, than epidural decompression and curettage/intralesional resection (p = 0.03). The long-term rate of toxicity ≥ grade 2 was 31%, including 20% grade 3 tissue necrosis, recurrent laryngeal nerve palsy, myelopathy, fracture, and secondary malignancy. CONCLUSIONS:High-dose spinal SRS offers the chance for durable radiological control and effective symptom relief with acceptable toxicity in patients with primary chordomas as either a definitive or adjuvant therapy.
PMID: 31628294
ISSN: 1547-5646
CID: 4715892

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

Barzilai, Ori; Amato, Mary-Kate; McLaughlin, Lily; Reiner, Anne S; Ogilvie, Shahiba Q; Lis, Eric; Yamada, Yoshiya; Bilsky, Mark H; Laufer, Ilya
Background/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED:< .001). Conclusions/UNASSIGNED: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.
PMID: 29770224
ISSN: 2054-2577
CID: 4715692

The Challenges of Renal Cell Carcinoma Metastatic to the Spine: A Systematic Review of Survival and Treatment

Goodwin, C Rory; Ahmed, A Karim; Boone, Christine; Abu-Bonsrah, Nancy; Xu, Risheng; Germscheid, Niccole; Fourney, Daryl R; Clarke, Michelle; Laufer, Ilya; Fisher, Charles G; Bettegowda, Chetan; Sciubba, Daniel M
Study Design/UNASSIGNED:Systematic review. Objectives/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED: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.
PMCID:6149047
PMID: 30258759
ISSN: 2192-5682
CID: 4715732