Re-irradiation spine stereotactic body radiotherapy following high-dose conventional radiotherapy for metastatic epidural spinal cord compression: a retrospective study.

PURPOSE:  We aimed to evaluate the efficacy and safety of re-irradiation stereotactic body radiation therapy (SBRT) in patients with metastatic epidural spinal cord compression (MESCC) following high-dose conventional radiotherapy. MATERIALS AND METHODS:  Twenty-one patients met the following eligibility criteria: with an irradiation history of 50 Gy2 equivalent dose in 2-Gy fractions (EQD2) or more, diagnosed MESCC in the cervical or thoracic spines, and treated with re-irradiation SBRT of 24 Gy in 2 fractions between April 2018 and March 2023. Prior treatment was radiotherapy alone, not including surgery. The primary endpoint was a 1-year local failure rate. Overall survival (OS) and treatment-related adverse events were assessed as the secondary endpoints. Since our cohort includes one treatment-related death (TRD) of esophageal perforation, the cumulative esophageal dose was evaluated to find the dose constraints related to severe toxicities. RESULTS:  The median age was 68, and 14 males were included. The primary tumor sites (esophagus/lung/head and neck/others) were 6/6/7/2, and the median initial radiotherapy dose was 60 Gy2 EQD2 (range: 50-105 Gy2, 60-70/ > 70 Gy2 were 11/4). Ten patients underwent surgery followed by SBRT and 11 SBRT alone. At the median follow-up time of 10.4 months, 17 patients died of systemic disease progression including one TRD. No radiation-induced myelopathy or nerve root injuries occurred. Local failure occurred in six patients, with a 1-year local failure rate of 29.3% and a 1-year OS of 55.0%. Other toxicities included five cases of vertebral compression fractures (23.8%) and one radiation pneumonitis. The cumulative esophageal dose was recommended as follows: Dmax < 203, D0.035 cc < 187, and D1cc < 167 (Gy3 in biological effective dose). CONCLUSION:  Re-irradiation spine SBRT may be effective for selected patients with cervical or thoracic MESCC, even with high-dose irradiation histories. The cumulative dose assessment across the original and re-irradiated esophagus was recommended to decrease the risk of severe esophageal toxicities.

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.

[Acute spinal cord compression under systemic therapy - radiotherapy or surgery?] / Akuter Querschnitt unter Systemtherapie ­ Radiotherapie oder OP?

Vertebral bodies are one of the most common metastasis sites found in advanced prostate cancer and have a significant impact on patients' quality of life. Spinal metastases frequently cause severe back pain and in some occasions can lead to secondary complications, with serious neurological deficits and loss of function. The main treatment goals include adequate pain management, controlling tumour growth and restoring spinal stability. Publications on the role of surgery - both conventional and stereotactic radiotherapy, and either as an individual modality or in combination - have been inconclusive. The NOMS score has proven to be useful in making treatment decisions. Existing data show better outcomes in patients with surgical therapy, both when performed in isolation and also combined with radiotherapy, in which some of the cohorts studied including patients with primary cancer other than prostate cancer. Comparative studies that specifically investigate the superiority of specific therapy modalities for metastatic prostate carcinoma are scarce. Similarly, there are limited data on microsurgical interventions for spinal metastases. Radiotherapy alone is crucial in the setting of palliation, especially for pain relief, and its effectiveness has been shown in many studies. The patient's life expectancy plays a crucial role in deciding the most appropriate treatment approach. Given the complexity of the patient population, a multimodal therapy approach is necessary. Current trends in therapy favour greater use of surgical interventions, particularly in the early detection of spinal metastases.

Interim analysis of patient-reported outcome compliance and dosimetry in a phase 3 randomized clinical trial of oesophagus-sparing spinal radiotherapy.

BACKGROUND: The randomized clinical trial ESO-SPARE investigates if oesophagus-sparing radiotherapy (RT) can reduce dysphagia in patients with metastatic spinal cord compression (MSCC). Patient-reported outcome (PRO) is the only follow-up measure. Due to the fragile patient population, low respondent compliance was anticipated. We performed a planned interim analysis of dosimetry and respondent compliance, to ensure that the protocol requirements were met. METHODS: Patients >18 years referred for cervical/thoracic MSCC radiotherapy in 1-10 fractions were included from two centres. Patients were randomized (1:1) to standard RT or oesophagus-sparing RT, where predefined oesophageal dose constraints were prioritized over target coverage. Patients completed a trial diary with daily reports of dysphagia for 5 weeks (PRO-CTC-AE) and weekly quality of life reports for 9 weeks (QLQ-C30, EQ-5D-5L). According to power calculation, 124 patients are needed for primary endpoint analysis. The sample size was inflated to 200 patients to account for the fragile patient population. The co-primary endpoints, peak patient-reported dysphagia, and preserved ability to walk (EQ-5D-5L), are analysed at 5 and 9 weeks, respectively. The interim analysis was conducted 90 days after the inclusion of patient no 100. Respondent compliance was assessed at 5 and 9 weeks. In all RT plans, oesophagus and target doses were evaluated regarding adherence to protocol constraints. RESULTS: From May 2021 to November 2022, 100 patients were included. Fifty-two were randomized to oesophagus-sparing RT. In 23% of these plans, oesophagus constraints were violated. Overall, the dose to both target and oesophagus was significantly lower in the oesophagus-sparing plans. Only 51% and 41% of the patients were evaluable for co-primary endpoint analysis at five and nine weeks, respectively. Mortality and hospitalization rates were significantly larger in patients who completed <4 days PRO questionnaires. CONCLUSION: Compliance was lower than anticipated and interventions to maintain study power are needed.

Neurologic Outcomes After Radiation Therapy for Severe Spinal Cord Compression in Multiple Myeloma: A Study of 162 Patients.

BACKGROUND: Bone destruction is the most frequent disease-defining clinical feature of multiple myeloma (MM), resulting in skeletal-related events such as back pain, pathological fractures, or neurologic compromise including epidural spinal cord compression (ESCC). Up to 24% of patients with MM will be affected by ESCC. Radiation therapy has been proven to be highly effective in pain relief in patients with MM. However, a critical knowledge gap remains with regard to neurologic outcomes in patients with high-grade ESCC treated with radiation. METHODS: We retrospectively included 162 patients with MM and high-grade ESCC (grade 2 or 3) who underwent radiation therapy of the spine between January 2010 and July 2021. The primary outcome was the American Spinal Injury Association (ASIA) score after 12 to 24 months, or the last known ASIA score if the patient had had a repeat treatment or died. Multivariable logistic regression was used to assess factors associated with poor neurologic outcomes after radiation, defined as neurologic deterioration or lack of improvement. RESULTS: After radiation therapy, 34 patients (21%) had no improvement in their impaired neurologic function and 27 (17%) deteriorated neurologically. Thirty-six patients (22%) underwent either surgery or repeat irradiation after the initial radiation therapy. There were 100 patients who were neurologically intact at baseline (ASIA score of E), of whom 16 (16%) had neurologic deterioration. Four variables were independently associated with poor neurologic outcomes: baseline ASIA (odds ratio [OR] = 6.50; 95% confidence interval [CI] = 2.70 to 17.38; p < 0.001), Eastern Cooperative Oncology Group (ECOG) performance status (OR = 6.19; 95% CI = 1.49 to 29.49; p = 0.015), number of levels affected by ESCC (OR = 4.02; 95% CI = 1.19 to 14.18; p = 0.026), and receiving steroids prior to radiation (OR = 4.42; 95% CI = 1.41 to 16.10; p = 0.015). CONCLUSIONS: Our study showed that 38% of patients deteriorated or did not improve neurologically after radiation therapy for high-grade ESCC. The results highlight the need for multidisciplinary input and efforts in the treatment of high-grade ESCC in patients with MM. Future studies will help to improve patient selection for specific and standardized treatments and to clearly delineate which patients are likely to benefit from radiation therapy. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Does surgery for metastatic spinal tumors improve functional outcomes in patients without spinal cord compression but with potentially unstable spines (SINS 7-12)?

OBJECTIVE: In the absence of spinal cord compression, it is unclear if surgery is more effective than radiation treatment for improving functional outcomes in metastatic spinal tumor patients with potentially unstable spines. The authors compared functional status outcomes assessed with Karnofsky Performance Status (KPS) and Eastern Cooperative Oncology Group (ECOG) scores after surgery or radiation in patients without spinal cord compression with Spine Instability Neoplastic Score (SINS) values of 7-12 indicating possible instability (SINS 7-12). METHODS: A retrospective review was performed of patients with metastatic spinal tumor SINS values of 7-12 at a single institution between 2004 and 2014. Patients were divided into two different groups: 1) those treated with surgery and 2) those treated with radiation. Baseline clinical characteristics were measured, and KPS and ECOG scores were obtained pre- and postradiation or postsurgery. The paired, nonparametric Wilcoxon signed-rank test and ordinal logistic regression analysis were used for statistical analysis. RESULTS: A total of 162 patients met inclusion criteria; 63 patients were treated operatively and 99 patients were treated with radiation. The mean follow-up was 1.9 years, with a median of 1.1 years for the surgical cohort (ranging from 2.5 months to 13.8 years) and a mean of 2 years with a median of 0.8 years for the radiation cohort (ranging from 2 months to 9.3 years). After covariates were accounted for, the average posttreatment changes in KPS scores in the surgical cohort were 7.46 ± 17.3 and in the radiation cohort were -2 ± 13.6 (p = 0.045). No significant difference was observed in ECOG scores. KPS scores improved postoperatively in 60.3% of patients in the surgical group and postradiation in 32.3% of patients in the radiation cohort (p < 0.001). Subanalysis within the radiation cohort revealed no differences in fracture rates or local control between patients treated with external-beam radiation therapy versus stereotactic body radiation therapy. In patients initially treated with radiation, 21.2% eventually developed compression fractures at a treated level. Five of the 99 patients in the radiation cohort-all of whom had a fracture-eventually underwent either methyl methacrylate augmentation or instrumented fusion. CONCLUSIONS: Patients with SINS values of 7-12 who underwent surgery had greater improvement in KPS scores-but not in ECOG scores-than patients undergoing radiation alone. In patients treated with radiation, treatment was converted to a procedural intervention such as surgery only in patients who sustained fractures. Of the patients with fractures after radiation (21 of 99), 5 patients underwent an invasive procedure and 16 did not.

Electrochemotherapy in radiotherapy-resistant epidural spinal cord compression in metastatic cancer patients.

OBJECTIVE: To report efficacy and safety of percutaneous electrochemotherapy (ECT) in patients with radiotherapy-resistant metastatic epidural spinal cord compression (MESCC). MATERIAL/ METHODS: This retrospective study analyzed all consecutive patients treated with bleomycin-based ECT between February-2020 and September-2022 in a single tertiary referral cancer center. Changes in pain were evaluated with the Numerical Rating Score (NRS), in neurological deficit with the Neurological Deficit Scale, and changes in epidural spinal cord compression were evaluated with the epidural spinal cord compression scale (ESCCS) using an MRI. RESULTS: Forty consecutive solid tumour patients with previously radiated MESCC and no effective systemic treatment options were eligible. With a median follow-up of 5.1 months [1-19.1], toxicities were temporary acute radicular pain (25%), prolonged radicular hypoesthesia (10%), and paraplegia (7.5%). At 1 month, pain was significantly improved over baseline (median NRS: 1.0 [0-8] versus 7.0 [1.0-10], P < .001) and neurological benefits were considered as marked (28%), moderate (28%), stable (38%), or worse (8%). Three-month follow-up (21 patients) confirmed improved over baseline (median NRS: 2.0 [0-8] versus 6.0 [1.0-10], P < .001) and neurological benefits were considered as marked (38%), moderate (19%), stable (33.5%), and worse (9.5%). One-month post-treatment MRI (35 patients) demonstrated complete response in 46% of patients by ESCCS, partial response in 31%, stable disease in 23%, and no patients with progressive disease. Three-month post-treatment MRI (21 patients) demonstrated complete response in 28.5%, partial response in 38%, stable disease in 24%, and progressive disease in 9.5%. CONCLUSIONS: This study provides the first evidence that ECT can rescue radiotherapy-resistant MESCC.

Personalization of Radiation Therapy in the Primary Treatment of Malignant Epidural Spinal Cord Compression (MESCC).

"True" malignant epidural spinal cord compression (MESCC) is used here to describe a lesion compressing of infiltrating the spinal cord associated with neurologic deficits. Radiotherapy alone is the most common treatment, for which several dose-fractionation regimens are available including single-fraction, short-course and longer-course regimens. Since these regimens are similarly effective regarding functional outcomes, patients with poor survival are optimally treated with short-course or even single-fraction radiotherapy. Longer-course radiotherapy results in better local control of malignant epidural spinal cord compression. Since most in-field recurrences occur 6 months or later, local control is particularly important for longer-term survivors who, therefore, should receive longer-course radiotherapy. It is important to estimate survival prior to treatment, which is facilitated by scoring tools. Radiotherapy should be supplemented by corticosteroids, if safely possible. Bisphosphonates and RANK-ligand inhibitors may improve local control. Selected patients can benefit from upfront decompressive surgery. Identification of these patients is facilitated by prognostic instruments considering degree of compression, myelopathy, radio-sensitivity, spinal stability, post-treatment ambulatory status, and patients' performance status and survival prognoses. Many factors including patients' preferences must be considered when designing personalized treatment regimens.

Long-Term Clinical Outcomes of Patients with Colorectal Cancer with Metastatic Epidural Spinal Cord Compression Treated with Hybrid Therapy (Surgery Followed by Stereotactic Body Radiation Therapy).

BACKGROUND: Hybrid therapy, consisting of separation surgery followed by stereotactic body radiation therapy, has become the mainstay treatment for radioresistant spinal metastases. Histology-specific outcomes for hybrid therapy are scarce. In clinical practice, colorectal cancer (CRC) is particularly thought to have poor outcomes regarding spinal metastases. The goal of this study was to evaluate clinical outcomes for patients treated with hybrid therapy for spinal metastases from CRC. METHODS: This retrospective study was performed at a tertiary cancer center. Adult patients with CRC spinal metastasis who were treated with hybrid therapy for high-grade epidural spinal cord or nerve root compression from 2005 to 2020 were included. Outcome variables evaluated included patient demographics, overall survival and progression-free survival, surgical and radiation complications, and clinical-genomic correlations. RESULTS: Inclusion criteria were met by 50 patients. Progression of disease occurred in 7 (14%) patients at the index level, requiring reoperation and/or reirradiation at a mean of 400 days after surgery. Postoperative complications occurred in 16% of patients, with 3 (6%) requiring intervention. APC exon 14 and 16 mutations were found in 15 of 17 patients tested and in all 3 of 7 local failures tested. Twenty patients (40%) underwent further radiation due to disease progression at other spinal levels. CONCLUSIONS: Hybrid therapy in patients with CRC resulted in 86.7% local control at 2 years after surgery, with limited complications. APC mutations are commonly present in CRC patients with spine metastases and may suggest worse prognosis. Patients with CRC spinal metastases commonly progress outside the index treatment level.

Efficacy and toxicity of primary re-irradiation for malignant spinal cord compression based on radiobiological modelling: a phase II clinical trial.

BACKGROUND: The efficacy and safety of primary re-irradiation for MSCC are not known. Our aim was to establish the efficacy and safety of biologically effective dose-based re-irradiation. METHODS: Patients presenting with MSCC at a previously irradiated spine segment, and not proceeding with surgical decompression, were eligible. A 3 Gray per fraction experimental schedule (minimum 18 Gy/6 fractions, maximum 30 Gy/10 fractions) was used, delivering a maximum cumulative spinal dose of 100 Gy2 if the interval since the last radiotherapy was within 6 months, or 130 Gy2 if longer. The primary outcome was a change in mobility from week 1 to week 5 post-treatment, as assessed by the Tomita score. The RTOG SOMA score was used to screen for spinal toxicity, and an MRI performed to assess for radiation-induced myelopathy (RIM). RESULTS: Twenty-two patients were enroled, of whom eleven were evaluable for the primary outcome. Nine of eleven (81.8%) had stable or improved Tomita scores at 5 weeks. One of eight (12.5%) evaluable for late toxicity developed RIM. CONCLUSIONS: Re-irradiation is an efficacious treatment for MSCC. There is a risk of RIM with a cumulative dose of 120 Gy2. CLINICAL TRIAL REGISTRATION: Cancer Trials Ireland (ICORG 07-11); NCT00974168.

The Impact of Targetable Mutations on Clinical Outcomes of Metastatic Epidural Spinal Cord Compression in Patients With Non-Small-Cell Lung Cancer Treated With Hybrid Therapy (Surgery Followed by Stereotactic Body Radiation Therapy).

BACKGROUND: In treatment of metastatic epidural spinal cord compression (MESCC), hybrid therapy, consisting of separation surgery, followed by stereotactic body radiation therapy, has become the mainstay of treatment for radioresistant pathologies, such as non-small-cell lung cancer (NSCLC). OBJECTIVE: To evaluate clinical outcomes of MESCC secondary to NSCLC treated with hybrid therapy and to identify clinical and molecular prognostic predictors. METHODS: This is a single-center, retrospective study. Adult patients (≥18 years old) with pathologically confirmed NSCLC and spinal metastasis who were treated with hybrid therapy for high-grade MESCC or nerve root compression from 2012 to 2019 are included. Outcome variables evaluated included overall survival (OS) and progression-free survival, local tumor control in the competing risks setting, surgical and radiation complications, and clinical-genomic correlations. RESULTS: One hundred and three patients met inclusion criteria. The median OS for this cohort was 6.5 months, with progression of disease noted in 5 (5%) patients at the index tumor level requiring reoperation and/or reirradiation at a mean of 802 days after postoperative stereotactic body radiation therapy. The 2-year local control rate was 94.6% (95% CI: 89.8-99.3). Epidermal growth factor receptor (EGFR) treatment-naïve patients who initiated EGFR-targeted therapy after hybrid therapy had significantly longer OS (hazard ratio 0.47, 95% CI 0.23-0.95, P = .04) even after adjusting for smoking status. The presence of EGFR exon 21 mutation was predictive of improved progression-free survival. CONCLUSION: Hybrid therapy in NSCLC resulted in 95% local control at 2 years after surgery. EGFR treatment-naïve patients initiating therapy after hybrid therapy had significantly improved survival advantage. EGFR-targeted therapy initiated before hybrid therapy did not confer survival benefit.

Role Of Palliative Radiotherapy In Improving Performance Status And Quality Of Life In Patients With Metastatic Spinal Cord Compression.

Background: Palliative radiotherapy in patients with metastatic spinal cord compression is a well known treatment modality but little is known whether it improves quality of life and performance status. Our study focusses on analyzing the impact of palliative radiotherapy on these two parameters in patients with metastatic spinal cord compression. Methods: We performed a prospective observational study from August 2020 to April 2021 to assess consecutive patients presenting to emergency department with suspected MSCC. We enrolled 24 patients in the study, and they were evaluated for their performance status and quality of life using ECOG and FACIT PAL 14 scores respectively. Palliative radiotherapy was administered, and the patients were followed up four to six weeks later. Their ECOG and FACIT-PAL 14 scores before and after receiving palliative radiotherapy were analyzed. Results: The mean age of the patients was 48 (IQR 35-62), with 14 (58%) being male. 1 patient died soon after admission. Median dose fractionation was 2000 cGy. Median (IQR) of ECOG performance status score on admission and follow up was 2.5 (1.0-3.7) and 1.5 (1.0-3.7), p=0.719, respectively. Median (IQR) FACIT-PAL 14 score on admission and follow up were 35.5 (34.0-37.6) and 36.5 (30.2-44.7), p=0.277, respectively. Our results indicate that there was no statistically significant difference in the median ECOG performance status and FACIT PAL 14 scores before and after the administration of palliative radiotherapy. Conclusion: Our study indicates that palliative radiotherapy in patients with metastatic spinal cord compression had little benefit in objectively improving quality of life and performance status using the well-known and widely used scores. This lack of response could be due to delayed presentation of the patients. Earlier involvement of palliative care team could have improved both these parameters. Further research with larger population of patients over a longer period is needed to further assess these outcomes.

Acute Metastatic Spinal Cord Compression: Urgent Surgery versus Radiotherapy and Treatment Result Prediction versus Actual Results.

Background Context: The role of radiotherapy versus surgery in treating acute metastatic spinal cord compression (AMSCC) has changed over the years. Purpose: Our study evaluates neurological and functional outcomes following urgent surgery and radiotherapy (USFR) versus urgent radiotherapy alone in treating AMSCC. Study Design/Setting: A retrospective cohort of 54 patients with AMSCC with variable neurological deficits. Overall, 32 patients were treated with USFR, and 22 received urgent radiotherapy alone. Outcome Measures: Neurological status regarding the Asia and Frankel scores, continence and ambulation, and Kranofsky's functional score and patient life span comprised the outcome measures. Methods: This was a retrospective EMR study. Results: USFR and radiotherapy cohorts were similar in age, gender, tumor origin, and the number of spinal metastases. The most common cause of AMSCC was carcinoma of the breast (24.1%), followed by carcinoma of the lung (16.7%) and multiple myeloma (13%). Neurological status at AMSCC presentation was similar between cohorts regarding Asia and Frankel scores, continence and ambulation, and Kranofsky's functional score. Following USFR, 59.3% of the patients had a motor strength improvement, 31.3% regained sphincter function, and 34.4% regained ambulation, while 90% of the patients treated by radiotherapy did not show any improvement. One patient under radiotherapy lost sphincter function. The treatment received did not affect the patient's survival. A subanalysis of patients with a short life expectancy, by Tomita and Tokuhashi scores, showed missed prediction in 29.4% of cases. Conclusion: The study supports the beneficial effect of UFSR compared to urgent radiotherapy alone in treating AMSCC in all subgroups. Early surgery improved function, motor strength, sphincter control, and ambulation without affecting life span. Prognostic scores failed to predict life span in almost one-third of the patients, requiring further investigation.

Identifying patients with malignant spinal cord compression (MSCC) near end of life who can benefit from palliative radiotherapy.

BACKGROUND: A previous score predicted death ≤ 2 months following radiotherapy for MSCC. For patients with a high probability of early death, best supportive care was recommended. However, some of these patients may benefit from radiotherapy regarding preservation or improvement of motor function. To identify these patients, an additional score was developed. METHODS: Pre-treatment factors plus radiotherapy regimen were retrospectively evaluated for successful treatment (improved motor function or remaining ambulatory without aid) and post-treatment ambulatory status in 545 patients who died ≤ 2 months. Factors included age, interval from tumor diagnosis until MSCC, visceral metastases, further bone metastases, primary tumor type, sex, time developing motor deficits, pre-treatment ambulatory status, and number of affected vertebrae. Factors significant on both multivariable analyses were included in the score (worse outcomes 0 points, better outcomes 1 point). RESULTS: On multivariable analyses, myeloma/lymphoma, time developing motor deficits > 14 days, and pre-treatment ambulatory status were significantly associated with both successful treatment and ambulatory status, affection of 1-2 vertebrae with successful treatment only. On univariable analyses, 1 × 8 and 5 × 4 Gy were not inferior to 5 × 5 Gy and longer-course regimens. Considering the three factors significant for both endpoints, three groups were designed (0, 1, 2-3 points) with treatment success rates of 4%, 15% and 39%, respectively (p < 0.0001), and post-treatment ambulatory rates of 4%, 43% and 86%, respectively (p < 0.0001). CONCLUSION: This score helps identify patients with MSCC who appear to benefit from palliative radiotherapy in terms of improved motor function or remaining ambulatory in spite of being near end of life.

Separation Surgery in the Treatment of Spinal Metastasis.

The life expectancy of patients with advanced cancer has been prolonged with the development of systemic treatment technology. Spinal metastasis is one of the common ways of metastasis of advanced tumors, leading to spinal cord compression and compression fractures, which often lead to a significant reduction in patients' quality of life and physical function. Therefore, surgical treatment is still needed for functional recovery and local control. Separation surgery has been known since 2014 when it was purposed. Combined with radiotherapy, it can achieve an ideal goal of local control. This paper gives a brief introduction to separation surgery, hoping to increase the reader's understanding and consider this method in the course of treatment.

ESTRO ACROP guidelines for external beam radiotherapy of patients with complicated bone metastases.

This is the second part of the guidelines on the management of bone metastases. In the first part, the diagnosis and management of uncomplicated bone metastases have been addressed. Bone metastases may significantly reduce quality of life due to related symptoms and possible complications. The most common symptoms include pain and neurologic deficits. The most serious complications of bone metastases are skeletal-related events (SRE), defined as pathologic fracture, spinal cord compression, pain, or other symptoms requiring an urgent intervention such as surgery or radiotherapy. Diffuse bone metastases may lead to hypercalcaemia that can be fatal if untreated. The growing access to modern diagnostic tools allows early detection of asymptomatic bone metastases that could be successfully managed with local treatment if oligometastatic or systemic treatment for diffuse bone metastases to try to avoid the development of SRE.

Prognostic factors for survival and ambulatory status at 8 weeks with metastatic spinal cord compression in the SCORAD randomised trial.

BACKGROUND: Metastatic spinal cord compression (MSCC) carries a poor prognosis and management is based on the likelihood of maintaining mobility and predicted survival. PATIENTS AND METHOD: SCORAD is a randomised trial of 686 patients comparing a single dose of 8 Gy radiotherapy with 20 Gy in 5 fractions. Data was split into a training set (412, 60%) and a validation set (274, 40%). A multivariable Cox regression for overall survival (OS) and a logistic regression for ambulatory status at 8 weeks were performed in the training set using baseline factors and a backward selection regression to identify a parsimonious model with p ≤ 0.10. Receiver Operating Characteristic (ROC) analysis evaluated model prognostic performance in the validation set. Validation of the final survival model was performed in a separate registry dataset (n = 348). RESULTS: The survival Cox model identified male gender, lung, gastrointestinal, and other types of cancer, compression at C1-T12, presence of non-skeletal metastases and poor ambulatory status all significantly associated with worse OS (all p < 0.05). The ROC AUC for the selected model was 75% (95%CI: 69-81) in the SCORAD validation set and 68% (95%CI: 62-74) in the external validation registry data. The logistic model for ambulatory outcome identified primary tumour breast or prostate, ambulatory status grade 1 or 2, bladder function normal and prior chemotherapy all significantly associated with increased odds of ambulation at 8 weeks (all p < 0.05). The ROC AUC for the selected model was 72.3% (95% CI 62.6-82.0) in the validation set. CONCLUSIONS: Primary breast or prostate cancer, and good ambulatory status at presentation, are favourable prognostic factors for both survival and ambulation after treatment.

A New and Easy-to-Use Survival Score for Patients Irradiated for Metastatic Epidural Spinal Cord Compression.

PURPOSE: A survival score was created in 2008 to improve treatment personalization of patients irradiated for metastatic epidural spinal cord compression (MESCC). Since then, targeted therapies improved survival of patients with cancer, which may decrease this score's predictive value. A new score appears necessary. METHODS AND MATERIALS: Two hundred sixty-four patients receiving radiation therapy without surgery in prospective trials (2010-2021) were included. A dose-fractionation regimen plus 15 factors were analyzed: age, sex, tumor type, interval tumor diagnosis to MESCC, MESCC sites, affected vertebrae, additional bone lesions, other distant lesions (yes or no), number of organs involved by metastases, time developing motor deficits, ambulatory status, sensory function, sphincter dysfunction, pain, and distress. Six-month survival rates (%) of independent prognostic factors were divided by 10 and summed for each patient. The score was compared with the previous tool for predicting death ≤6 months and survival ≥6 months. RESULTS: In a multivariate analysis, tumor type (P = .001), other distant lesions (P < .001), and ambulatory status (P < .001) were significant. Based on 6-month survival rates, 4 groups (8-9, 10-13, 14-17, and 18 points) were created with 6-month survival rates of 12.8%, 34.7%, 62.8%, and 90.0%, respectively (version A). For version B, "other distant lesions" was replaced by "number of organs involved by metastases." Version B included 4 groups (8-10, 11-14, 15-16, and 17 points) with 6-month survival rates of 11.1%, 42.0%, 68.6%, and 91.7%, respectively. Positive predictive values to predict death ≤6 months were 87.2% (version A) and 88.9% (version B) versus 76.6% (3 groups) and 84.6% (5 groups) for the previous score. Positive predictive values to predict survival ≥6 months were 90.0% and 91.7% versus 59.0% and 64.3%. CONCLUSIONS: Both versions of the new score were more precise than the previous tool. Version B appears slightly superior to version A but requires more extensive diagnostic staging that may not be readily available when emergently treating.

Phase 2 Clinical Trial of Separation Surgery Followed by Stereotactic Body Radiation Therapy for Metastatic Epidural Spinal Cord Compression.

PURPOSE: Stereotactic body radiation therapy (SBRT) is a postoperative treatment option for spinal metastases. Because data on surgery with SBRT are limited to retrospective studies, this single-center, single-arm, phase 2 study aimed to prospectively evaluate the outcomes of separation surgery and SBRT for metastatic epidural spinal cord compression (MESCC). METHODS AND MATERIALS: Patients with symptomatic MESCC due to a solid carcinoma were enrolled. The protocol for treatments comprised preoperative embolization, separation surgery, and spine SBRT. Surgical procedures were performed via the posterior approach, with decompression and a fixation procedure. The prescribed dose for spine SBRT was 24 Gy in 2 fractions. The primary endpoint was the 12-month local failure rate. The secondary endpoints were ambulatory functions and adverse effects. RESULTS: A total of 33 patients were registered between November 2017 and October 2019. All patients met the inclusion criteria, and all but 1 completed the protocol treatment. Of the included patients, 23 (70%) had radioresistant lesions. The Bilsky grade at registration was 1c in 3 patients, 2 in 8 patients, and 3 in 21 patients. The median follow-up duration after registration was 15 months (range, 3-35 months). Three months after the administration of treatments according to the protocol, 90% of patients (26 of 29) had disease of Bilsky grade ≤1. The 12-month local failure rate was 13%. Twenty patients could walk normally or with a cane 12 months after registration. Radiation-induced myelopathy, radiculopathy, and vertebral compression fracture were observed in 0, 1, and 6 patients, respectively. CONCLUSIONS: Separation surgery with SBRT for MESCC was effective in decompression and long-term local control. These findings suggest that larger randomized controlled trials are warranted to compare SBRT with conventional radiation therapy.