Local disease control for spinal metastases following "separation surgery" and adjuvant hypofractionated or high-dose single-fraction stereotactic radiosurgery: outcome analysis in 186 patients.
TL;DR: Postoperative adjuvant SRS following epidural spinal cord decompression and instrumentation is a safe and effective strategy for establishing durable local tumor control regardless of tumor histology-specific radiosensitivity.
Abstract: Object Decompression surgery followed by adjuvant radiotherapy is an effective therapy for preservation or recovery of neurological function and achieving durable local disease control in patients suffering from metastatic epidural spinal cord compression (ESCC). The authors examine the outcomes of postoperative image-guided intensity-modulated radiation therapy delivered as single-fraction or hypofractionated stereotactic radiosurgery (SRS) for achieving long-term local tumor control. Methods A retrospective chart review identified 186 patients with ESCC from spinal metastases who were treated with surgical decompression, instrumentation, and postoperative radiation delivered as either single-fraction SRS (24 Gy) in 40 patients (21.5%), high-dose hypofractionated SRS (24–30 Gy in 3 fractions) in 37 patients (19.9%), or low-dose hypofractionated SRS (18–36 Gy in 5 or 6 fractions) in 109 patients (58.6%). The relationships between postoperative adjuvant SRS dosing and fractionation, patient characteristics...
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TL;DR: Surgical intervention provides immediate and sustained improvement in pain, neurologic, functional, and HRQoL outcomes, with acceptable risks in patients with a focal symptomatic MESCC lesion who have at least a 3 month survival prognosis.
Abstract: PurposeAlthough surgery is used increasingly as a strategy to complement treatment with radiation and chemotherapy in patients with metastatic epidural spinal cord compression (MESCC), the impact of surgery on health-related quality of life (HRQoL) is not well established. We aimed to prospectively evaluate survival, neurologic, functional, and HRQoL outcomes in patients with MESCC who underwent surgical management.Patients and MethodsOne hundred forty-two patients with a single symptomatic MESCC lesion who were treated surgically were enrolled onto a prospective North American multicenter study and were observed at least up to 12 months. Clinical data, including Brief Pain Inventory, ASIA (American Spinal Injury Association) impairment scale, SF-36 Short Form Health Survey, Oswestry Disability Index, and EuroQol 5 dimensions (EQ-5D) scores, were obtained preoperatively, and at 6 weeks and 3, 6, 9, and 12 months postoperatively.ResultsMedian survival time was 7.7 months. The 30-day and 12-month mortality ...
159 citations
TL;DR: Postoperative SBRT with high total doses ranging from 18 to 26 Gy delivered in 1-2 fractions predicted superior LC, as did postoperative epidural grade, and systemic therapy post-SBRT as the only significant predictor of OS.
Abstract: Although surgery plays a major role in the management of patients with symptomatic single level malignant epidural spinal cord compression,1 one of the major questions that remains is the optimal degree of epidural disease resection and whether there is an association with local control (LC). With respect to adjuvant therapy, radiation has been the standard in reducing the risk for local recurrence,2,3 although the rates of LC following the current standard of conventional low-dose external beam radiotherapy (CRT) ranges widely from 40% to 80% at 1 year.2–4
With modern radiation technology, the technique of stereotactic body radiotherapy (SBRT) has emerged and is being applied to various disease sites, including the spine.5–7 The Canadian Association of Radiation Oncology recently defined SBRT as “the precise delivery of highly conformal and image-guided hypo-fractionated external beam radiotherapy, delivered in a single or few fraction(s), to an extra-cranial body target with doses at least biologically equivalent to a radical course when given over a conventionally fractionated (1.8–3.0 Gy/fraction) schedule.”7 This definition translates to treating metastatic patients with locally “curative” intent, as opposed to locally “palliative” intent. In the postoperative spine metastases patient, spine SBRT makes even more philosophical sense because after exposing patients to the risks of a major spinal surgery,8 it is only logical to offer an aggressive local treatment to consolidate the therapeutic intent. The aim of our study was to report the University of Toronto postoperative spine SBRT experience and specifically analyze the impact of epidural disease extension on LC.
147 citations
Cites background from "Local disease control for spinal me..."
...The postoperative spine SBRT literature has been limited to preliminary experiences involving small cohorts(5,15); however, in 2013, the Memorial Sloan Kettering Cancer Center (MSKCC) reported its experience following postoperative SBRT in 186patients.(16) The researchers observed failures in34 patients (18....
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TL;DR: This multi-institutional cohort study reports high rates of efficacy with spine SBRT, and the optimal fractionation within high dose practice is unknown.
Abstract: Purpose: To evaluate patient selection criteria, methodology, safety and clinical outcomes of stereotactic body radiotherapy (SBRT) for treatment of vertebral metastases. Materials and methods: Eight centers from the United States (n = 5), Canada (n = 2) and Germany (n = 1) participated in the retrospective study and analyzed 301 patients with 387 vertebral metastases. No patient had been exposed to prior radiation at the treatment site. All patients were treated with linac-based SBRT using cone-beam CT image-guidance and online correction of set-up errors in six degrees of freedom. Results: 387 spinal metastases were treated and the median follow-up was 11.8 months. The median number of consecutive vertebrae treated in a single volume was one (range, 1-6), and the median total dose was 24 Gy (range 8-60 Gy) in 3 fractions (range 1-20). The median EQD210 was 38 Gy (range 12-81 Gy). Median overall survival (OS) was 19.5 months and local tumor control (LC) at two years was 83.9%. On multivariate analysis for OS, male sex (p 1 vertebra treated with SBRT (p = 0.04; HR = 0.62) were correlated with worse outcomes. For LC, an interval between primary diagnosis of cancer and SBRT of ≤30 months (p = 0.01; HR = 0.27) and histology of primary disease (NSCLC, renal cell cancer, melanoma, other) (p = 0.01; HR = 0.21) were correlated with worse LC. Vertebral compression fractures progressed and developed de novo in 4.1% and 3.6%, respectively. Other adverse events were rare and no radiation induced myelopathy reported. Conclusions: This multi-institutional cohort study reports high rates of efficacy with spine SBRT. At this time the optimal fractionation within high dose practice is unknown.
139 citations
Cites methods or result from "Local disease control for spinal me..."
...outcome after high-dose (median total dose 27 Gy in 3 fractions) compared to low dose SBRT (median total dose 30 Gy in 5 or 6 fractions) [33]....
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...This is in agreement with other reports of spine SBRT, where long-term local tumor control was achieved in >80% of the cases [28,31,33-37]....
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TL;DR: Stereotactic body radiation therapy for primary liver tumors provides high rates of durable local control, with no clear evidence for a dose-response relationship among commonly utilized schedules.
Abstract: Purpose To quantitatively evaluate published experiences with hepatic stereotactic body radiation therapy (SBRT), to determine local control rates after treatment of primary and metastatic liver tumors and to examine whether outcomes are affected by SBRT dosing regimen. Methods and Materials We identified published articles that reported local control rates after SBRT for primary or metastatic liver tumors. Biologically effective doses (BEDs) were calculated for each dosing regimen using the linear-quadratic equation. We excluded series in which a wide range of BEDs was used. Individual lesion data for local control were extracted from actuarial survival curves, and data were aggregated to form a single dataset. Actuarial local control curves were generated using the Kaplan-Meier method after grouping lesions by disease type and BED ( 100 Gy10). Comparisons were made using log–rank testing. Results Thirteen articles met all inclusion criteria and formed the dataset for this analysis. The 1-, 2-, and 3-year actuarial local control rates after SBRT for primary liver tumors (n = 431) were 93%, 89%, and 86%, respectively. Lower 1- (90%), 2- (79%), and 3-year (76%) actuarial local control rates were observed for liver metastases (n = 290, log–rank P = .011). Among patients treated with SBRT for primary liver tumors, there was no evidence that local control is influenced by BED within the range of schedules used. For liver metastases, on the other hand, outcomes were significantly better for lesions treated with BEDs exceeding 100 Gy10 (3-year local control 93%) than for those treated with BEDs of ≤100 Gy10 (3-year local control 65%, P Conclusions Stereotactic body radiation therapy for primary liver tumors provides high rates of durable local control, with no clear evidence for a dose–response relationship among commonly utilized schedules. Excellent local control rates are also seen after SBRT for liver metastases when BEDs of >100 Gy10 are utilized.
128 citations
TL;DR: This review recapitulates the current state‐of‐the‐art, evidence‐based data on the treatment of spinal metastases, integrating these data into a decision framework, NOMS, which integrates the 4 sentinel decision points in metastatic spine tumors.
Abstract: Treatment paradigms for patients with spine metastases have evolved significantly over the past decade. Incorporating stereotactic radiosurgery into these paradigms has been particularly transformative, offering precise delivery of tumoricidal radiation doses with sparing of adjacent tissues. Evidence supports the safety and efficacy of radiosurgery as it currently offers durable local tumor control with low complication rates even for tumors previously considered radioresistant to conventional radiation. The role for surgical intervention remains consistent, but a trend has been observed toward less aggressive, often minimally invasive, techniques. Using modern technologies and improved instrumentation, surgical outcomes continue to improve with reduced morbidity. Additionally, targeted agents such as biologics and checkpoint inhibitors have revolutionized cancer care, improving both local control and patient survivals. These advances have brought forth a need for new prognostication tools and a more critical review of long-term outcomes. The complex nature of current treatment schemes necessitates a multidisciplinary approach including surgeons, medical oncologists, radiation oncologists, interventionalists, and pain specialists. This review recapitulates the current state-of-the-art, evidence-based data on the treatment of spinal metastases, integrating these data into a decision framework, NOMS, which integrates the 4 sentinel decision points in metastatic spine tumors: Neurologic, Oncologic, Mechanical stability, and Systemic disease and medical co-morbidities.
115 citations
References
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TL;DR: Direct decompressive surgery plus postoperative radiotherapy is superior to treatment with radiotherapy alone for patients with spinal cord compression caused by metastatic cancer.
1,936 citations
TL;DR: Microvascular damage regulates tumor cell response to radiation at the clinically relevant dose range, indicating that endothelial apoptosis is a homeostatic factor regulating angiogenesis-dependent tumor growth.
Abstract: About 50% of cancer patients receive radiation therapy. Here we investigated the hypothesis that tumor response to radiation is determined not only by tumor cell phenotype but also by microvascular sensitivity. MCA/129 fibrosarcomas and B16F1 melanomas grown in apoptosis-resistant acid sphingomyelinase (asmase)-deficient or Bax-deficient mice displayed markedly reduced baseline microvascular endothelial apoptosis and grew 200 to 400% faster than tumors on wild-type microvasculature. Thus, endothelial apoptosis is a homeostatic factor regulating angiogenesis-dependent tumor growth. Moreover, these tumors exhibited reduced endothelial apoptosis upon irradiation and, unlike tumors in wild-type mice, they were resistant to single-dose radiation up to 20 grays (Gy). These studies indicate that microvascular damage regulates tumor cell response to radiation at the clinically relevant dose range.
1,487 citations
TL;DR: It is concluded that RT without decompressive laminectomy is as effective as decompressive Laminectomy in treating epidural spinal cord compression from systemic cancer.
Abstract: The clinical findings in 130 conseucutive cases of spinal cord compression by metastatic extradural tumors were analyzed. These 130 patients were combined with a previous survey of 105 patients to compare the effectiveness of radiation therapy (RT) alone with that of surgical decompression followed by RT. Ambulation after treatment was considered a successful outcome. The most common primary tumors producing spinal cord compression were (in order) breast, lung, prostate, and kidney. In 68% of these tumors the thoracic region was involved. Pain was the primary symptom of 96% of the patients, while motor or sensory deficits (or both) were found in 82% of them. Therapy consisted of surgery and RT in 65 patients and RT alone in 170 patients. There were no differences in outcome between those treated by surgery combined with RT and those managed by RT alone. Patients with radiosensitive tumors and those ambulatory at the onset of treatment benefited whether treated by surgery or by RT. Seventy-five percent of living patients who improved from treatment remained ambulatory at 6 months, and approximately 50% of living patients were ambulatory at 1 year. We conclude that RT without decompressive laminectomy is as effective as decompressive laminectomy in treating epidural spinal cord compression from systemic cancer.
876 citations
University of British Columbia1, Allen Institute for Brain Science2, Memorial Sloan Kettering Cancer Center3, University of Virginia4, University of California, San Francisco5, Thomas Jefferson University6, University of Toronto7, University of Utah8, University of Minnesota9, Mayo Clinic10, Northwestern University11, University of Pittsburgh12, Johns Hopkins University13, Harvard University14, Ohio State University15, University of Texas Health Science Center at Houston16, University of Texas MD Anderson Cancer Center17, Icahn School of Medicine at Mount Sinai18, Kanazawa University19, Pontifícia Universidade Católica do Paraná20, University of South Florida21, University of Saskatchewan22
TL;DR: The Spine Instability Neoplastic Score is a comprehensive classification system with content validity that can guide clinicians in identifying when patients with neoplastic disease of the spine may benefit from surgical consultation and aid surgeons in assessing the key components of spinal instability due to neoplasia.
Abstract: Study design Systematic review and modified Delphi technique. Objective To use an evidence-based medicine process using the best available literature and expert opinion consensus to develop a comprehensive classification system to diagnose neoplastic spinal instability. Summary of background data Spinal instability is poorly defined in the literature and presently there is a lack of guidelines available to aid in defining the degree of spinal instability in the setting of neoplastic spinal disease. The concept of spinal instability remains important in the clinical decision-making process for patients with spine tumors. Methods We have integrated the evidence provided by systematic reviews through a modified Delphi technique to generate a consensus of best evidence and expert opinion to develop a classification system to define neoplastic spinal instability. Results A comprehensive classification system based on patient symptoms and radiographic criteria of the spine was developed to aid in predicting spine stability of neoplastic lesions. The classification system includes global spinal location of the tumor, type and presence of pain, bone lesion quality, spinal alignment, extent of vertebral body collapse, and posterolateral spinal element involvement. Qualitative scores were assigned based on relative importance of particular factors gleaned from the literature and refined by expert consensus. Conclusion The Spine Instability Neoplastic Score is a comprehensive classification system with content validity that can guide clinicians in identifying when patients with neoplastic disease of the spine may benefit from surgical consultation. It can also aid surgeons in assessing the key components of spinal instability due to neoplasia and may become a prognostic tool for surgical decision-making when put in context with other key elements such as neurologic symptoms, extent of disease, prognosis, patient health factors, oncologic subtype, and radiosensitivity of the tumor.
856 citations
TL;DR: The results indicate the potential of radiosurgery in the treatment of patients with spinal metastases, especially those with solitary sites of spine involvement, to improve long-term palliation.
Abstract: Study design A prospective nonrandomized, longitudinal cohort study. Objective To evaluate the clinical outcomes of single-fraction radiosurgery as part of the management of metastatic spine tumors. Summary of background data The role of stereotactic radiosurgery for the treatment of spinal lesions has previously been limited by the availability of effective target immobilization and target tracking devices. Large clinical experience with spinal radiosurgery to properly assess clinical experience has previously been limited. Methods A cohort of 500 cases of spinal metastases underwent radiosurgery. Ages ranged from 18 to 85 years (mean 56). Lesion location included 73 cervical, 212 thoracic, 112 lumbar, and 103 sacral. Results The maximum intratumoral dose ranged from 12.5 to 25 Gy (mean 20). Tumor volume ranged from 0.20 to 264 mL (mean 46). Long-term pain improvement occurred in 290 of 336 cases (86%). Long-term tumor control was demonstrated in 90% of lesions treated with radiosurgery as a primary treatment modality and in 88% of lesions treated for radiographic tumor progression. Twenty-seven of 32 cases (84%) with a progressive neurologic deficit before treatment experienced at least some clinical improvement. Conclusions The results indicate the potential of radiosurgery in the treatment of patients with spinal metastases, especially those with solitary sites of spine involvement, to improve long-term palliation.
681 citations