Emergency radiation therapy in modern-day practice: Now or never, or never again ?

Radiation therapy plays a fundamental role in oncological emergencies such as superior vena cava syndrome (SVCS) and metastatic epidural spinal cord compression (MESCC). These are two examples of critical complications of metastatic cancer in terms of pain and functional impact (respiratory and/or neurological). The aim of this review is to explore the current indications, treatment options and outcomes for emergency radiotherapy regarding to these complications.Regarding SVCS, studies are mostly retrospective and unanimously demonstrated a beneficial effect of radiotherapy on symptom relief. Spinal cord compression remains an indication for urgent radiotherapy, and should be combined with surgery when possible. The innovative stereotactic body radiotherapy (SBRT) showed promising results, however this technique requires small volumes and more time preparation and therefore is often unsuitable for SVCS and MESCC emergencies.This review concluded that radiotherapy has a central role to play within a multimodal approach for SVCS and MESCC treatment. Further prospective studies are needed to confirm the effectiveness of radiation and establish the criteria for selecting patients to benefit from this treatment option.

A deep learning-based technique for the diagnosis of epidural spinal cord compression on thoracolumbar CT.

PURPOSE: To develop a deep learning (DL) model for epidural spinal cord compression (ESCC) on CT, which will aid earlier ESCC diagnosis for less experienced clinicians. METHODS: We retrospectively collected CT and MRI data from adult patients with suspected ESCC at a tertiary referral institute from 2007 till 2020. A total of 183 patients were used for training/validation of the DL model. A separate test set of 40 patients was used for DL model evaluation and comprised 60 staging CT and matched MRI scans performed with an interval of up to 2 months. DL model performance was compared to eight readers: one musculoskeletal radiologist, two body radiologists, one spine surgeon, and four trainee spine surgeons. Diagnostic performance was evaluated using inter-rater agreement, sensitivity, specificity and AUC. RESULTS: Overall, 3115 axial CT slices were assessed. The DL model showed high kappa of 0.872 for normal, low and high-grade ESCC (trichotomous), which was superior compared to a body radiologist (R4, κ = 0.667) and all four trainee spine surgeons (κ range = 0.625-0.838)(all p < 0.001). In addition, for dichotomous normal versus any grade of ESCC detection, the DL model showed high kappa (κ = 0.879), sensitivity (91.82), specificity (92.01) and AUC (0.919), with the latter AUC superior to all readers (AUC range = 0.732-0.859, all p < 0.001). CONCLUSION: A deep learning model for the objective assessment of ESCC on CT had comparable or superior performance to radiologists and spine surgeons. Earlier diagnosis of ESCC on CT could reduce treatment delays, which are associated with poor outcomes, increased costs, and reduced survival.

Patient outcomes following implementation of an enhanced recovery after surgery pathway for patients with metastatic spine tumors.

BACKGROUND: Metastatic spine tumor surgery consists of palliative operations performed on frail patients with multiple medical comorbidities. Enhanced recovery after surgery (ERAS) programs involve an evidence-based, multidisciplinary approach to improve perioperative outcomes. This study presents clinical outcomes of a metastatic spine tumor ERAS pathway implemented at a tertiary cancer center. METHODS: The metastatic spine tumor ERAS program launched in April 2019, and data from January 2018 to May 2020 were reviewed. Measured outcomes included the following: hospital length of stay (LOS), time to ambulation, urinary catheter duration, time to resumption of diet, intraoperative fluid intake, estimated blood loss (EBL), and intraoperative and postoperative day 0-5 cumulative opioid use (morphine milligram equivalent [MME]). RESULTS: A total of 390 patients were included in the final analysis: 177 consecutive patients undergoing metastatic spine tumor surgery enrolled in the ERAS program and 213 consecutive pre-ERAS patients. Although the mean case durations were similar in the ERAS and pre-ERAS cohorts (265 vs. 274 min; p = .22), the ERAS cohort had decreased EBL (157 vs. 215 ml; p = .003), decreased postoperative day 0-5 cumulative mean opioid use (178 vs. 396 MME; p < .0001), earlier ambulation (mean, 34 vs. 57 h; p = .0001), earlier discontinuation of urinary catheters (mean, 36 vs. 56 h; p < .001), and shorter LOS (5.4 vs. 7.5 days; p < .0001). CONCLUSIONS: The implementation of a multidisciplinary ERAS program designed for metastatic spine tumor surgery led to improved clinical quality metrics, including shorter hospitalizations and significant reductions in opioid consumption.

Factors affecting the prognosis of recovery of motor power and ambulatory function after surgery for metastatic epidural spinal cord compression.

OBJECTIVE: Metastatic epidural spinal cord compression (MESCC) causes neurological deficits that may hinder ambulation. Understanding the prognostic factors associated with increased neurological recovery and regaining ambulatory functions is important for surgical planning in MESCC patients with neurological deficits. The present study was conducted to elucidate prognostic factors of neurological recovery in MESCC patients. METHODS: A total of 192 patients who had surgery for MESCC due to preoperative neurological deficits were reviewed. A motor recovery rate ≥ 50% and ambulatory function restoration were defined as the primary favorable endpoints. Factors associated with a motor recovery rate ≥ 50%, regaining ambulatory function, and patient survival were analyzed. RESULTS: About one-half (48.4%) of the patients had a motor recovery rate ≥ 50%, and 24.4% of patients who were not able to walk due to MESCC before the surgery were able to walk after the operation. The factors "involvement of the thoracic spine" (p = 0.015) and "delayed operation" (p = 0.041) were associated with poor neurological recovery. Low preoperative muscle function grade was associated with a low likelihood of regaining ambulatory functions (p = 0.002). Furthermore, performing the operation ≥ 72 hours after the onset of the neurological deficit significantly decreased the likelihood of regaining ambulatory functions (p = 0.020). Postoperative ambulatory function significantly improved patient survival (p = 0.048). CONCLUSIONS: Delayed operation and the involvement of the thoracic spine were poor prognostic factors for neurological recovery after MESCC surgery. Furthermore, a more severe preoperative neurological deficit was associated with a lesser likelihood of regaining ambulatory functions postoperatively. Earlier detection of motor weaknesses and expeditious surgical interventions are necessary, not only to improve patient functional status and quality of life but also to enhance survival.

Evaluation of open and minimally invasive spinal surgery for the treatment of thoracolumbar metastatic epidural spinal cord compression: a systematic review.

BACKGROUND: Metastatic epidural spinal cord compression (MESCC) is a debilitating sequela of cancer that results in pain, disability, and neurologic deficits. Surgical techniques have included open surgical (OS) techniques with anterior and/or posterior decompression and fusion procedures. Further technical evolution has led to minimally invasive spinal (MIS) decompression and fusion. The objective of this study is to compare MIS to OS techniques in the treatment of thoracolumbar MESCC. METHODS: A review of the literature was performed using PubMed database. Inclusion criteria included patients 18 years or older, thoracolumbar MESCC, and surgeries with instrumented fusion. A total of 451 articles met the inclusion criteria and further analysis narrowed them down to 81 articles. Variables collected included blood loss, length of stay, operative time, pre- and postoperative Frankel grade, and complications. RESULTS: A total of 5726 papers were collected, with a total of 81 papers meeting final inclusion criteria: 26 papers with MIS technique and 55 with OS. A total of 2267 patients were evaluated. They were split into three surgical subtypes of MIS and OS: posterior decompression and fusion, partial corpectomy, and complete corpectomy. Overall, MIS had lower operative time, blood loss, and complications compared to OS. A timeline analysis showed reduction of complication rates in MIS surgery between papers published over a 28-year period. CONCLUSION: MESCC carries significant morbidity and mortality. Surgical approaches for palliative treatment should account for this fact. We conclude that MIS techniques offer a viable alternative to traditional OS approaches with lower overall morbidity and complications.

Factors associated with adjacent-level tumor progression in patients receiving surgery followed by radiosurgery for metastatic epidural spinal cord compression.

OBJECTIVE: Separation surgery followed by spine stereotactic radiosurgery (SSRS) has been shown to achieve favorable rates of local tumor control and patient-reported outcomes in patients with metastatic epidural spinal cord compression (MESCC). However, rates and factors associated with adjacent-level tumor progression (ALTP) in this population have not yet been characterized. The present study aimed to identify factors associated with ALTP and examine its association with overall survival (OS) in patients receiving surgery followed by radiosurgery for MESCC. METHODS: Thirty-nine patients who underwent separation surgery followed by SSRS for MESCC were identified using a prospectively collected database and were retrospectively reviewed. Radiological measurements were collected from preoperative, postoperative, and post-SSRS MRI. Statistical analysis was conducted using the Kaplan-Meier product-limit method and Cox proportional hazards test. Subgroup analysis was conducted for patients who experienced ALTP into the epidural space (ALTP-E). RESULTS: The authors' cohort included 39 patients with a median OS of 14.7 months (range 2.07-96.3 months). ALTP was observed in 16 patients (41.0%) at a mean of 6.1 ± 5.4 months postradiosurgery, of whom 4 patients (10.3%) experienced ALTP-E. Patients with ALTP had shorter OS (13.0 vs 17.1 months, p = 0.047) compared with those without ALTP. Factors associated with an increased likelihood of ALTP included the amount of bone marrow infiltrated by tumor at the index level, amount of residual epidural disease following separation surgery, and prior receipt of radiotherapy at the index level (p < 0.05). Subgroup analysis revealed that primary tumor type, amount of preoperative epidural disease, time elapsed between surgery and radiosurgery, and prior receipt of radiotherapy at the index level were significantly associated with ALTP-E (p < 0.05). CONCLUSIONS: To the authors' knowledge, this study is the first to identify possible risk factors for ALTP, and they suggest that it may be associated with shorter OS in patients receiving surgery followed by radiosurgery for MESCC. Future studies with higher power should be conducted to further characterize factors associated with ALTP in this population.

[Analysis of the effect of percutaneous vertebroplasty combined with (125)I seed implantation in the treatment of spinal metastatic epidural spinal cord compression].

Objective: To investigate the clinical efficacy of percutaneous vertebroplasty (PVP) combined with iodine-125 ((125)I) seed brachytherapy in the treatment of spinal metastatic epidural spinal cord compression (MESCC) and toassess the changes inthe grade of epidural spinal cord compression (ESCC) by magnetic resonance imaging (MRI). Methods: A total of 37 MESCC patients treated with PVP combined with (125)I seed brachytherapy in the interventional and vascular surgery department of Zhongda Hospital affiliated to Southeast University from January 2014 to June 2019 were retrospectively analyzed, including 23 cases of bilateral lower limbs paralysis. Total diseased vertebrae are 39 segments. Visual analogue scale (VAS) and paralysis of lower extremities were evaluated regularly before and after treatment, and VAS values at different follow-up time points were compared. At the same time, MRI was used to evaluate the changes of ESCC grade in the spinal canal and calculate the local lesion efficiency after operation. The postoperative local lesion efficiency at different follow-up times was compared. Results: PVP combined with (125)I seed implantation in all diseased vertebral bodies was successful. The average injection volume of polymethylmethacrylate (PMMA) was (3.2±1.3) ml/segment, the average number of (125)I seed implanted was (25.0±8.6) seeds/segment and the average radiation dose was (15.0±5.1) mCi/segment. The VAS before operation was 8.5, and postoperative VAS were respectively 3.6±1.3, 3.8±1.5, 3.4±1.4, 5.5±1.0, 5.9±1.4 at 5 days, 1 month, 3 months, 6 months, and 1 year after operation. The differences between all follow-up time points and preoperative VAS values were statistically significant (all P<0.001). Compared with 5 days, 1 month and 3 months after operation, VAS increased significantly at 6 months and 1 year after operation, and the difference was statistically significant (all P<0.001); there was no significant difference between the VAS value at 6 months after operation and 1 year after operation (P=0.405). At a follow-up of 3 months, 22 of 23 patients with paralysis of bilateral lower limbs regained the functions of autonomous walking and voiding; the effective rates of MESCC local lesions evaluated by MRI at 1 month, 3 months, 6 months, and>1 year were 89.7%, 91.9%, 90.6%, and 94.7%, respectively, and there was no statistically significant differences among those follow-up time points (all P>0.05). Conclusions: PVP combined with (125)I seed brachytherapy in the treatment of MESCC has significant improvement in immediate pain relief and spinal cord function. After combined treatment, MRI showed that the tumors around the spinal cord regressed dramatically, which could considerably reduce the MESCC grade and remain stable for a long time.

Predictive factors of survival in a surgical series of metastatic epidural spinal cord compression and complete external validation of 8 multivariate models of survival in a prospective North American multicenter study.

BACKGROUND: This study was designed to identify preoperative predictors of survival in surgically treated patients with metastatic epidural spinal cord compression (MESCC), to examine how these predictors are related to 8 prognostic models, and to perform the first full external validation of these models in accordance with the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) statement. METHODS: One hundred forty-two surgically treated patients with MESCC were enrolled in a prospective, multicenter North American cohort study and were followed for 12 months or until death. Cox regression was used. Noncollinear predictors with < 10% missing data, with ≥ 10 events per stratum, and with P < .05 in a univariate analysis were tested through a backward stepwise selection. For the original and revised Tokuhashi prognostic scoring systems (PSSs), Tomita PSS, modified Bauer PSS, van der Linden PSS, Bartels model, Oswestry Spinal Risk Index, and Bollen PSS, this study examined calibration graphically, discrimination with Harrell c-statistics, and survival stratified by risk groups with the Kaplan-Meier method and log-rank test. RESULTS: The following were significant in the univariate analysis: type of primary tumor, sex, organ metastasis, body mass index, preoperative radiotherapy to MESCC, physical component (PC) of the 36-Item Short Form Health Survey, version 2 (SF-36v2), and EuroQol 5-Dimension (EQ-5D) Questionnaire. Breast, prostate and thyroid primary tumor (HR: 2.9; P =.0005), presence of organ metastasis (hazard ratio (HR): 2.0; P = .005) and SF-36v2 PC (HR: 0.95; P < .0001) were associated with survival in multivariable analysis. Predicted prognoses poorly matched observed values on calibration plots; Bartels model calibration slope was 0.45. Bollen PSS (0.61; 95% CI: 0.58-0.64) and Bartels model (0.68; 95% CI: 0.65-0.71) had the lowest and highest c-statistics, respectively. CONCLUSIONS: The primary tumor type (breast, prostate, or thyroid), an absence of organ metastasis, and a lower degree of physical disability are preoperative predictors of longer survival for surgical MESCC patients. These results are in keeping with current models. This full external validation of 8 prognostic PSSs or model of survival in surgical MESCC patients has revealed that calibration is poor, especially for long-term survivors, whereas discrimination is possibly helpful.

Metastatic epidural spinal cord compression: does timing of surgery influence the chance of neurological recovery? An observational case-control study.

PURPOSE: Metastatic epidural spinal cord compression (MESCC) is radiologically defined as an epidural metastatic lesion causing the displacement of the spinal cord from its normal position in the vertebral canal. The purpose of this paper is the evaluation of the influence of timing of surgery on the chance of neurological recovery. METHODS: This is a retrospective observational case-control study performed on patients with MESCC from solid tumors surgically treated at our institute from January 2010 to December 2016. Patients included were divided in two groups depending on surgery that was performed within or after 24 h the admission to the hospital. Neurological status was assessed with American Spine Injury Association (ASIA) Impairment Scale. RESULTS: No statistically significant difference was observed in the variation of ASIA if surgery is performed within or after 24 h from the admission to the hospital. A statistically significant difference was observed after surgery in each group in the improvement of neurological status. A statistically significant difference was reported in the early post-operative complications in patients surgically treated within 24 h. CONCLUSION: MESCC management is challenge for spine surgeons and may represent an oncologic emergency and if not promptly diagnosed can lead to a permanent neurological damage. According to this study, there is no difference in the chance of neurological recovery if surgery is performed within or after 24 h the admission to hospital, but there is a greater rate of early post-operative complications when surgery is performed within 24 h from the admission to the hospital.

Reducing kyphotic deformity by posterior vertebral column resection with 360° osteosynthesis in metastatic epidural spinal cord compression (MESCC).

PURPOSE: Metastatic epidural spinal cord compression (MESCC) often requires anterior-posterior decompression and stabilization. To reduce approach-related complications, single-stage posterolateral vertebrectomy and 360° fusion is often performed. However, a sufficient reduction of kyphotic deformity through this approach has not been reported. The purpose of this study is to investigate the efficacy of kyphotic deformity reduction by this approach in MESCC. METHODS: A retrospective analysis and chart review was performed for 14 consecutive patients who underwent a vertebrectomy and decompression from a posterolateral approach. Anterior mesh stabilization of the ventral column is used as hypomochlion for the posterior compression manoeuvre, which leads to reduction of the kyphotic deformity. RESULTS: Pre-operative back pain was 7.2 on a visual analogue scale. Back pain was reduced to 4.4 at discharge and 2.0 at the latest follow-up with a mean follow-up of 12 months (p < 0.001). The Frankel score remains constant or improved from D to E. Radiological segmental kyphosis was corrected from a mean of 16° to 4° (p < 0.001) post-operatively with a loss of 3° at the final follow-up, but still with significant corrections compared with the pre-operative measurements (p < 0.003). CONCLUSION: Single-stage posterolateral vertebrectomy and reconstruction is a safe and less invasive approach that allows a sufficient reduction of hyperkyphosis and preservation of neurological function in patients with MESCC. This approach is an efficient alternative to anterior-posterior fusion with good pain reduction and improved sagittal profile.

The 100 most cited articles in metastatic spine disease.

OBJECTIVE Despite the growing neurosurgical literature, a subset of pioneering studies have significantly impacted the field of metastatic spine disease. The purpose of this study was to identify and analyze the 100 most frequently cited articles in the field. METHODS A keyword search using the Thomson Reuters Web of Science was conducted to identify articles relevant to the field of metastatic spine disease. The results were filtered based on title and abstract analysis to identify the 100 most cited articles. Statistical analysis was used to characterize journal frequency, past and current citations, citation distribution over time, and author frequency. RESULTS The total number of citations for the final 100 articles ranged from 74 to 1169. Articles selected for the final list were published between 1940 and 2009. The years in which the greatest numbers of top-100 studies were published were 1990 and 2005, and the greatest number of citations occurred in 2012. The majority of articles were published in the journals Spine (15), Cancer (11), and the Journal of Neurosurgery (9). Forty-four individuals were listed as authors on 2 articles, 9 were listed as authors on 3 articles, and 2 were listed as authors on 4 articles in the top 100 list. The most cited article was the work by Batson (1169 citations) that was published in 1940 and described the role of the vertebral veins in the spread of metastases. The second most cited article was Patchell's 2005 study (594 citations) discussing decompressive resection of spinal cord metastases. The third most cited article was the 1978 study by Gilbert that evaluated treatment of epidural spinal cord compression due to metastatic tumor (560 citations). CONCLUSIONS The field of metastatic spine disease has witnessed numerous milestones and so it is increasingly important to recognize studies that have influenced the field. In this bibliographic study the authors identified and analyzed the most influential articles in the field of metastatic spine disease.

Decompression surgery for spinal metastases: a systematic review.

OBJECTIVE The aim of this study was to systematically review the literature on reported outcomes following decompression surgery for spinal metastases. METHODS The authors conducted MEDLINE, Scopus, and Web of Science database searches for studies reporting clinical outcomes and complications associated with decompression surgery for metastatic spinal tumors. Both retrospective and prospective studies were included. After meeting inclusion criteria, articles were categorized based on the following reported outcomes: survival, ambulation, surgical technique, neurological function, primary tumor histology, and miscellaneous outcomes. RESULTS Of the 4148 articles retrieved from databases, 36 met inclusion criteria. Of those included, 8 were prospective studies and 28 were retrospective studies. The year of publication ranged from 1992 to 2015. Study size ranged from 21 to 711 patients. Three studies found that good preoperative Karnofsky Performance Status (KPS ≥ 80%) was a significant predictor of survival. No study reported a significant effect of time-to-surgery following the onset of spinal cord compression symptoms on survival. Three studies reported improvement in neurological function following surgery. The most commonly cited complication was wound infection or dehiscence (22 studies). Eight studies reported that preoperative ambulatory or preoperative motor status was a significant predictor of postoperative ambulatory status. A wide variety of surgical techniques were reported: posterior decompression and stabilization, posterior decompression without stabilization, and posterior decompression with total or subtotal tumor resection. Although a wide range of functional scales were used to assess neurological outcomes, four studies used the American Spinal Injury Association (ASIA) Impairment Scale to assess neurological function. Four studies reported the effects of radiation therapy and local disease control for spinal metastases. Two studies reported that the type of treatment was not significantly associated with the rate of local control. The most commonly reported primary tumor types included lung cancer, prostate cancer, breast cancer, renal cancer, and gastrointestinal cancer. CONCLUSIONS This study reports a systematic review of the literature on decompression surgery for spinal metastases. The results of this study can help educate surgeons on the previously published predictors of outcomes following decompression surgery for metastatic spinal disease. However, the authors also identify significant gaps in the literature and the need for future studies investigating the optimal practice with regard to decompression surgery for spinal metastases.

Skeletal complications in cancer patients with bone metastases.

As a result of significant improvements in current therapies, the life expectancy of cancer patients with bone metastases has dramatically improved. Unfortunately, these patients often experience skeletal complications that significantly impair their quality of life. The major skeletal complications associated with bone metastases include: cancer-induced bone pain, hypercalcemia, pathological bone fractures, metastatic epidural spinal cord compression and cancer cachexia. Once cancer cells invade the bone, they perturb the normal physiology of the marrow microenvironment, resulting in bone destruction, which is believed to be a direct cause of skeletal complications. However, full understanding of the mechanisms responsible for these complications remains unknown. In the present review, we discuss the complications associated with bone metastases along with matched conventional therapeutic strategies. A better understanding of this topic is crucial, as targeting skeletal complications can improve both the morbidity and mortality of patients suffering from bone metastases.

Predicting the survival probability of gastric cancer patients developing metastatic epidural spinal cord compression (MESCC).

To create a tool for estimating the survival of gastric cancer patients developing MESCC, clinical factors were evaluated in 29 patients. Factors were age, gender, performance status, affected vertebrae, ambulatory status, further bone metastases, visceral metastases, time from gastric cancer diagnosis until MESCC and rapidity of developing weakness of legs. On multivariate analyses, visceral metastases (risk ratio: 6.80; p = 0.003) and rapidity of weakening of legs (risk ratio: 2.73; p = 0.023) had a significant effect on survival and were included in the tool. Scoring points for each of the two factors were either 0 or 1, depending on the 6-month survival rates. According to the sum of the points, three groups were built: 0 points (n = 12), 1 point (n = 10) and 2 points (n = 7). Six-month survival rates were 0, 20 and 100 % (p < 0.001). This tool for patients with MESCC from gastric cancer estimates survival probabilities, which is important for tailoring treatment to patients' needs.

AB078. Patterns of treatment delay in patients with symptomatic metastatic epidural spinal cord compression.

BACKGROUND: Delayed treatment in symptomatic metastatic epidural spinal cord compression (MESCC) is significantly associated with poorer functional outcomes. In this study, we aim to identify the patterns of treatment delay in patients and factors predictive of postoperative ambulatory function. METHODS: Retrospective review of patients with symptomatic MESCC treated surgically between January 2015 and January 2022. MESCC symptoms were categorized into symptoms suggesting cord compression requiring immediate referral and symptoms suggestive of spinal metastases. Multivariate analysis was performed to identify factors predictive of postoperative ambulatory function. Delays in treatment were identified and categorized into patient delay (onset of symptoms till initial medical consultation), diagnostic delay (medical consultation till radiological diagnosis of MESCC), referral delay (from diagnosis till spine surgeon review) and surgical delay (from spine surgeon review till surgery) and compared between patients. RESULTS: One hundred and seventy-eight patients were identified. In this cohort 92 (52.0%) patients were able to ambulate independently, and 86 (48.3%) patients were non independent. One hundred and thirty-nine (78.1%) of patients had symptoms of cord compression and 93 (52.3%) had neurological deficits on presentation. On multivariate analysis, pre-operative neurological deficits (P=0.01) and symptoms of cord compression (P=0.01) were significantly associated with post-operative ambulatory function. Mean total delay was 66 days, patient delay was 41 days, diagnostic delay was 16 days, referral delay was 3 days and surgical delay was 6 days. In patients with neurological deficits, there was a significant decrease in all forms of treatment delay (P<0.05). There was no significant decrease in patient delay, diagnostic delay and referral delay in patients with symptoms of cord compression. CONCLUSIONS: Both patients and physicians understand the need for urgent surgical treatment of MESCC with neurological deficits, however there is still a need for increased education and recognition of the symptoms of MESCC.

Reirradiation of metastases of the central nervous system: part 2-metastatic epidural spinal cord compression.

An increasing number of patients irradiated for metastatic epidural spinal cord compression (MESCC) experience an in-field recurrence and require a second course of radiotherapy. Reirradiation can be performed with conventional radiotherapy or highly-conformal techniques such as intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), and stereotactic body radiation therapy (SBRT). When using conventional radiotherapy, a cumulative biologically effective dose (BED) ≤120 calculated with an α/ß value of 2 Gy (Gy2) was not associated with radiation myelopathy in a retrospective study of 124 patients and is considered safe. In that study, conventional reirradiation led to improvements of motor deficits in 36% of patients and stopped further symptomatic progression in another 50% (overall response 86%). In four other studies, overall response rates were 82-89%. In addition to the cumulative BED or equivalent dose in 2 Gy fractions (EQD2), the interval between both radiotherapy courses <6 months and a BED per course ≥102 Gy2 (corresponding to an EQD2 ≥51 Gy2) were identified as risk factors for radiation myelopathy. Without these risk factors, a BED >120 Gy2 may be possible. Scoring tools have been developed that can assist physicians in estimating the risk of radiation myelopathy and selecting the appropriate dose-fractionation regimen of re-treatment. Reirradiation of MESCC may also be performed with highly-conformal radiotherapy. With IMRT or VMAT, rates of pain relief and improvement of neurologic symptoms of 60-93.5% and 42-73%, respectively, were achieved. One-year local control rates ranged between 55% and 88%. Rates of myelopathy or radiculopathy and vertebral compression fractures were 0% and 0-9.3%, respectively. With SBRT, rates of pain relief were 65-86%. Two studies reported improvements in neurologic symptoms of 0% and 82%, respectively. One-year local control rates were 74-83%. Rates of myelopathy or radiculopathy and vertebral compression fractures were 0-4.5% and 4.5-13.8%, respectively. For SBRT, a cumulative maximum EQD2 to thecal sac ≤70 Gy2, a maximum EQD2 of SBRT ≤25 Gy2, a ratio ≤0.5 of thecal sac maximum EQD2 of SBRT to maximum cumulative EQD2, and an interval between both courses ≥5 months were associated with a lower risk of myelopathy. Additional prospective trials are required to better define the options of reirradiation of MESCC.

Treatment of ambulatory patients with metastatic epidural spinal cord compression: a systematic review and meta-analysis.

OBJECTIVE: Approximately 10% of patients with spinal metastases develop metastatic epidural spinal cord compression (MESCC), which left undiagnosed and untreated can lead to the loss of ambulation. Timely diagnosis and efficient multidisciplinary treatment are critically important to optimize neurological outcomes. This meta-analysis aimed to determine the most efficient treatment for ambulatory patients with MESCC. METHODS: The authors conducted a systematic review and meta-analysis of the treatment of mobile patients with MESCC in terms of outcomes described as local control (LC), ambulatory function, quality of life (QOL), morbidity, and overall survival (OS). RESULTS: Overall, 54 papers (4101 patients) were included. A trend toward improved LC with stereotactic body radiotherapy (SBRT) compared with conventional external beam radiotherapy (cEBRT) was demonstrated: random effects modeling 1-year LC rate 86% (95% CI 84%-88%) versus 81% (95% CI 74%-86%) (p > 0.05), respectively, and common effects modeling 1-year LC rate 85% (95% CI 82%-87%) versus 76% (95% CI 74%-78%) (p < 0.05). Surgery followed by adjuvant radiotherapy, either cEBRT or SBRT, showed no significant benefit in either LC (OR 0.88, 95% CI 0.65-1.19) or ambulatory function (OR 1.51, 95% CI 0.83-2.74) compared with radiotherapy without surgery. There was a significant benefit of surgery compared with cEBRT regarding QOL, and furthermore SBRT alone provided long-term improvement in QOL. The type of treatment was not a significant predictor of OS, but fully ambulatory status was significantly associated with improved OS (HR 0.46-0.52, relative risk 1.79-2.3). Radiation-induced myelopathy is a rare complication of SBRT (2 patients [0.1%] in the included papers). The morbidity rate associated with surgery was relatively high, with a 10% wound complication rate and 1.6% hardware-failure rate. CONCLUSIONS: SBRT is an extremely promising treatment modality being integrated into treatment algorithms and provides durable LC. In mobile patients with MESCC, surgery does not improve LC, survival, or ambulatory function; nonetheless, there is a significant benefit of surgery in terms of QOL. In patients with MESCC without neurological deficit, the role of surgery is still debatable as studies demonstrate good LC for patients who undergo SBRT without preceding surgery. However, surgery can provide safe margins for the administration of the ablative dose of SBRT to the entire tumor volume within the constraints of spinal cord tolerance. Further randomized controlled trials are needed on the benefit of surgery before SBRT in mobile patients with MESCC. With the excellent results of separation surgery and SBRT, the role of highly invasive vertebrectomy is diminishing given the complication rate and morbidity of these procedures.

Promoting postoperative recovery in patients with metastatic epidural spinal cord compression based on the concept of ERAS: a multicenter analysis of 304 patients.

BACKGROUND CONTEXT: Enhanced recovery after surgery (ERAS) has proven beneficial for patients undergoing orthopedic surgery. However, the application of ERAS in the context of metastatic epidural spinal cord compression (MESCC) remains undefined. PURPOSE: This study aims to establish a medical pathway rooted in the ERAS concept, with the ultimate goal of scrutinizing its efficacy in enhancing postoperative outcomes among patients suffering from MESCC. STUDY DESIGN/SETTING: An observational cohort study. PATIENT SAMPLE: A total of 304 patients with MESCC who underwent surgery were collected between January 2016 and January 2023 at two large tertiary hospitals. OUTCOME MEASURES: Surgery-related variables, patient quality of life, and pain outcomes. Surgery-related variables in the study included surgery time, surgery site, intraoperative blood loss, and complication. METHODS: From January 2020 onwards, ERAS therapies were implemented for MESCC patients in both institutions. Thus, the ERAS cohort included 138 patients with MESCC who underwent surgery from January 2020 to January 2023, whereas the traditional cohort consisted of 166 patients with MESCC who underwent surgery from January 2016 to December 2019. Clinical baseline characteristics, surgery-related features, and surgical outcomes were collected. Patient quality of life was evaluated using the Functional Assessment of Cancer Therapy-General Scale (FACT-G), and pain outcomes were assessed using the Visual Analogue Scale (VAS). RESULTS: Comparison of baseline characteristics revealed that the two cohorts were similar (all p>.050), indicating comparable distribution of clinical characteristics. In terms of surgical outcomes, patients in the ERAS cohort exhibited lower intraoperative blood loss (p<.001), shorter postoperative hospital stays (p<.001), lower perioperative complication rates (p=.020), as well as significantly shorter time to ambulation (P<0.001), resumption of regular diet (p<.001), removal of urinary catheter (p<.001), initiation of radiation therapy (p<.001), and initiation of systemic internal therapy (p<.001) compared with patients in the traditional cohort. Regarding pain outcomes and quality of life, patients undergoing the ERAS program demonstrated significantly lower VAS scores (p<.010) and higher scores for physical (p<.001), social (p<.001), emotional (p<.001), and functional (p<.001) well-being compared with patients in the traditional cohort. CONCLUSIONS: The ERAS program, renowned for its ability to expedite postoperative recuperation, emerges as a promising approach to ameliorate the recovery process in MESCC patients. Not only does it exhibit potential in enhancing pain management outcomes, but it also holds the promise of elevating the overall quality of life for these individuals. Future investigations should delve deeper into the intricate components of the ERAS program, aiming to unravel the precise mechanisms that underlie its remarkable impact on patient outcomes.

Spinal Metastases of the Vertebrae: Three Main Categories of Pain.

Oncologic back pain, infection, inflammation, and trauma are the only specific etiologies of chronic low back pain (CLBP) in contrast to most patients who have non-specific CLBP. In oncologic patients developing CLBP, it is critically important to perform further investigation to exclude spinal metastases (SM).The incidence of cancer is increasing, with 15.7-30% developing SM. In the case of symptomatic SM, we can distinguish three main categories: tumor pain; mechanical pain due to instability, with or without pathologic fractures; and metastatic epidural spinal cord compression (MESCC) or radicular compression. Treatment of SM-related pain is dependent on these categories and consists of symptomatic treatment, target therapy to the bone, radiotherapy, systemic oncologic treatment, and surgery. The care for SM is a multidisciplinary concern, with rapid evolutions in all specialties involved. It is of primordial importance to incorporate the knowledge of specialists in all participating disciplines, such as oncology, radiotherapy, and spinal surgery, to determine the adequate treatment to preserve ambulatory function and quality of life while limiting the burden of treatment if possible. Awareness of potential SM is the first and most important step in the treatment of SM-related pain. Early diagnosis and timely treatment could prevent further deterioration. In this review, we explore the pathophysiology and symptomatology of SM and the treatment options for SM-related pain: tumor pain; mechanical pain due to instability, with or without pathologic fractures; and MESCC or radicular compression.

Radiotherapy for Metastatic Epidural Spinal Cord Compression with Increased Doses: Final Results of the RAMSES-01 Trial.

Patients with metastatic epidural spinal cord compression (MESCC) and favorable survival prognoses may benefit from radiation doses exceeding 10 × 3.0 Gy. In a multi-center phase 2 trial, patients receiving 15 × 2.633 Gy (41.6 Gy10) or 18 × 2.333 Gy (43.2 Gy10) were evaluated for local progression-free survival (LPFS), motor/sensory functions, ambulatory status, pain, distress, toxicity, and overall survival (OS). They were compared (propensity score-adjusted Cox regression) to a historical control group (n = 266) receiving 10 × 3.0 Gy (32.5 Gy10). In the phase 2 cohort, 50 (of 62 planned) patients were evaluated for LPFS. Twelve-month rates of LPFS and OS were 96.8% and 69.9%, respectively. Motor and sensory functions improved in 56% and 57.1% of patients, and 94.0% were ambulatory following radiotherapy. Pain and distress decreased in 84.4% and 78.0% of patients. Ten and two patients experienced grade 2 and 3 toxicities, respectively. Phase 2 patients showed significantly better LPFS than the control group (p = 0.039) and a trend for improved motor function (p = 0.057). Ambulatory and OS rates were not significantly different. Radiotherapy with 15 × 2.633 Gy or 18 × 2.333 Gy was well tolerated and appeared superior to 10 × 3.0 Gy.