Musculoskeletal misdiagnoses in pediatric patients with spinal tumors.

OBJECTIVE: Childhood spinal tumors often present with musculoskeletal symptoms, potentially causing a misdiagnosis and delays in diagnosis and treatment. This study aims to identify, characterize, and compare children with spinal tumors who had prior musculoskeletal misdiagnoses to those without, analyzing clinical presentation, diagnostic interval, and outcome. STUDY DESIGN: This retrospective cohort study evaluated all children aged 0-14 years diagnosed with a spinal tumor in Denmark from 1996 to 2018. The cohort was identified through the Danish Childhood Cancer Registry, and the registry data were supplemented with data from medical records. The survival was compared using the Kaplan-Meier method. RESULTS: Among 58 patients, 57% (33/58) received musculoskeletal misdiagnoses before the spinal tumor diagnosis. Misdiagnoses were mostly nonspecific (64%, 21/33), involving pain and accidental lesions, while 36% (12/33) were rheumatologic diagnoses. The patients with prior misdiagnosis had less aggressive tumors, fewer neurological/general symptoms, and 5.5 months median diagnostic interval versus 3 months for those without a misdiagnosis. Those with prior misdiagnoses tended to have a higher 5-year survival of 83% (95% confidence interval [CI]: 63%-92%) compared to 66% (95% CI: 44%-82%) for those without (p = .15). CONCLUSION: Less aggressive spinal tumors may manifest as gradual skeletal abnormalities and musculoskeletal symptoms without neurological/general symptoms, leading to misdiagnoses and delays.

Prognostic Scoring System Development for Malignant Spinal Cord Compression.

OBJECTIVE: Although many prognostic scoring systems have been used to predict survival of malignant spinal cord compression (MSCC) patients, some previous data have shown that the accuracy of the scoring system remains problematic. Current advanced cancer therapies may influence the altered survival predictions. The aim of this study was to develop a new prognostic scoring system for higher accuracy of survival prediction in patients with malignant spinal cord compression (MSCC). METHODS: Data were collected from 89 patients diagnosed with MSCC in 2018-2020. Potential clinical factors were analyzed using univariate and multivariate Cox's regression analysis. The selected logistic coefficients were transformed into a prognostic predictive scoring system. Internal validation was performed using the bootstrapping procedure. RESULTS: According to multivariate Cox's regression analysis, 9 potential prognostic factors were obtained, i.e. Neutrophil-to-Lymphocyte ratio >3.6, breast cancer, lung cancer, other types of cancer (except prostate cancer), male, complete paralysis, spinal metastases in three levels, hypercalcemia, and no further systemic treatment. The data was developed into a Buddhasothorn Hospital Malignant Spinal Cord Compression (BSH-MSCC) score with an interval of 0-52 points (AUC = 0.77; AUC to predict short-term survival = 0.93). When using the cut-off point > 18 to predict short-term survival, AUC = 0.84, sensitivity = 81.5%, specificity = 85.7%, PPV = 89.8%, and NPV = 75.0%. Internal validation with 1,000 bootstrap resampling showed good discrimination. CONCLUSION: BSH-MSCC score had a simplified score and high accuracy. The new tool is more accurate and can help decision-making for better treatment using a multidisciplinary approach.

Sacral Chordoma: A Population-based Analysis of Epidemiology and Survival Outcomes.

BACKGROUND/AIM: Sacral chordoma is a rare primary bone neoplasm associated with high morbidity. The aim of this study is to identify demographic and clinicopathological characteristics of this tumor and evaluate their impact on survival outcomes. PATIENTS AND METHODS: The Surveillance, Epidemiology and End Results (SEER) database collecting data between 2000 and 2018 was searched for all cases of sacral chordoma. We analyzed demographic aspects, cancer stage and treatment patterns. Overall survival was calculated using the Kaplan-Meier method and compared between subgroups using the log-rank test. A multivariate Cox hazard regression analysis was conducted to identify independent predictors of overall survival. RESULTS: Four hundred and forty-two patients were identified with a mean age of 62.7 years. Most tumors presented regional invasion at diagnosis (43.2%). Mean overall survival was 124.7 months. No significant difference in terms of overall survival was found between surgery alone and surgery associated with radiotherapy. Both options provided a significantly increased survival than radiotherapy alone. Age of less than 50 years or between 50 and 69 correlated significantly with improved survival. CONCLUSION: Age and stage at diagnosis impact significantly survival outcomes. Surgery remains the mainstay treatment with the highest overall survival. Its association with radiotherapy is currently questionable and needs further research.

Comparison of Oncologic Outcomes and Treatment-Related Toxicity of Carbon Ion Radiotherapy and En Bloc Resection for Sacral Chordoma.

Importance: Maximal resection is the preferred management for sacral chordomas but can be associated with unacceptable morbidity. Outcomes with radiotherapy are poor. Carbon ion radiotherapy (CIRT) is being explored as an alternative when surgery is not preferred. Objective: To compare oncologic outcomes and treatment-related toxicity of CIRT and en bloc resection for sacral chordoma. Design, Setting, and Participants: Univariable logistic regression was performed to evaluate the association between treatment type and oncologic and toxicity outcomes in this retrospective cohort study. Nearest-neighbor propensity score matching was used to match the CIRT cohort with the en bloc resection cohort and 10 National Cancer Database (NCDB) cohorts separately, with the objective of obtaining more homogeneous cohorts when comparing treatments. Patient- and tumor-related characteristics from 2 institutional cohorts were collected for patients diagnosed with sacral chordomas between April 1, 1994, and July 31, 2017. The NCDB was queried for data on patients with sacral chordoma from January 1, 2004, to December 31, 2016, as a comparator in overall survival (OS) analyses. Data analysis was conducted from February 24, 2020, to January 16, 2021. Exposures: En bloc resection, incomplete resection, photon radiotherapy, proton radiotherapy, and CIRT. Main Outcomes and Measures: Overall survival was estimated using the Kaplan-Meier method and compared using the Cox proportional hazards model. Peripheral motor nerve toxic effects were scored using Common Terminology Criteria for Adverse Events, version 4.03. Results: A total of 911 patients were included in the study (NCDB: n = 669; median age, 64 [IQR, 52-74] years; 410 [61.3%] men; CIRT: n = 188; median age, 66 [IQR, 58-71] years; 128 [68.1%] men; en bloc surgical resection: n = 54; median age, 53.5 [IQR 49-64] years, 36 [66.7%] men). Comparison of the propensity score-matched institutional en bloc resection and CIRT cohorts revealed no statistically significant difference in OS (CIRT: median OS, 68.1 [95% CI, 44.0-102.6] months; en bloc resection: median OS, 58.6 [95% CI, 25.6-123.5] months; P = .57; hazard ratio, 0.71 [95% CI, 0.25-2.06]; P = .53). The CIRT cohort experienced lower rates of peripheral motor neuropathy (odds ratio, 0.13 [95% CI, 0.04-0.40]; P < .001). On comparison of the propensity score-matched NCDB cohorts with the CIRT cohort, significantly higher OS was found for CIRT compared with margin-positive surgery without adjuvant radiotherapy (CIRT: median OS, 64.7 [95% CI, 57.8-69.7] months; margin-positive surgery without adjuvant radiotherapy: median OS, 60.6 [95% CI, 44.2-69.7] months, P = .03) and primary radiotherapy alone (CIRT: median OS, 64.9 [95% CI 57.0-70.5] months; primary radiotherapy alone: 31.8 [95% CI, 27.9-40.6] months; P < .001). Conclusions and Relevance: These findings suggest that CIRT can be used as treatment for older patients with high performance status and sacral chordoma in whom surgery is not preferred. CIRT might provide additional benefit for patients who undergo margin-positive resection or who are candidates for primary photon radiotherapy.

Long-term outcomes of spinal SBRT. Is it important to select the treatment time?

PURPOSE: SBRT (stereotactic body radiation therapy) is widely used as a curative treatment in tumoral lesions and has become a fundamental tool for the treatment of spine metastasis. In this study, we present survival and toxicity outcomes of spine SBRT after a 2-year follow-up. METHODS/PATIENTS: Data from spine SBRT treatments performed at our institution between March 2012 and February 2020 was collected. Medical records, including demographic, primary tumor, and treatment characteristics were reviewed. Patient follow-up included clinical evaluation, imaging, and blood tests. Toxicity was recorded according to CTCAE v4.0. RESULTS: We analyzed 73 consecutive spine SBRT treatments in 60 patients. 39.7% of the cases had primary breast cancer and 23.3% had prostate cancer. Most cases (87.7%) were treated with a single SBRT fraction of 16 Gy. Median follow-up was 26.1 months (range 1.7-78.6), and 1- and 2-year overall survival (OS) rates were 96.9% and 84.2%, respectively. Local control (LC) rates at 1- and 2-years were 76.3% and 70.6%, respectively. Multivariate analysis identified histology as a prognostic factor for both OS and LC. Patients who underwent spine SBRT 6 months after the spinal lesion diagnosis had LC at 2 years of 88%, vs 61.7% for those who underwent SBRT before this period. No grade III or higher toxicity was reported. The vertebral compression fracture (VCF) rate was 4.1%. CONCLUSION: Spine SBRT at our institution showed a 2-year LC of 70.6%, without G3 toxicities. Delaying SBRT at least 6 months to administer systemic treatment was related to an improvement in local control.

Spine-specific skeletal related events and mortality in non-small cell lung cancer patients: a single-institution analysis.

OBJECTIVE: The population prevalence of non-small cell lung cancer (NSCLC) continues to increase; however, data are limited regarding the incidence rate of skeletal related events (SREs) (i.e., surgery to the spinal column, radiation to the spinal column, radiofrequency ablation, kyphoplasty/vertebroplasty, spinal cord compression, or pathological vertebral body fractures) and their impact on overall mortality. In this study, the authors sought to estimate the incidence rates of SREs in NSCLC patients and to quantify their impact on overall mortality. METHODS: This was a single-institution retrospective study of patients diagnosed with NSCLC between 2002 and 2014. The incidence rates for bone metastasis and subsequent SREs (per 1000 person-years) by time since lung cancer diagnosis were calculated and analyses were stratified separately for each histological type. Incidence rates for mortality at 1, 2, and 3 years from diagnosis stratified by the presence of SREs were also calculated. Kaplan-Meier survival curves were constructed to describe crude survival ratios in patients with spine metastasis and SREs and those with spine metastasis but without SREs. These curves were used to estimate the 1- and 2-year survival rates for each cohort. RESULTS: We identified 320 patients with incident NSCLC (median follow-up 9.5 months). The mean ± SD age was 60.65 ± 11.26 years; 94.48% of patients were smokers and 60.12% had a family history of cancer. The majority of first-time SREs were pathological vertebral body compression fractures (77.00%), followed by radiation (35%), surgery (14%), and spinal cord compression (13.04%). Mortality rates were highest in NSCLC patients with spine metastasis who had at least 1 SRE. Stratifying by histological subtype, the incidence rate of mortality in patients with SRE was highest in the large cell cohort, 7.42 per 1000 person-years (95% CI 3.09-17.84 per 1000 person-years); followed by the squamous cell cohort, 2.49 per 1000 person-years (95% CI 1.87-3.32 per 1000 person-years); and lowest in the adenocarcinoma cohort, 1.68 per 1000 person-years (95% CI 1.46-1.94 per 1000 person-years). Surgery for decompression of neural structures and stabilization of the spinal column was required in 6% of patients. CONCLUSIONS: SREs in NSCLC patients with bone metastasis are associated with an increased incidence rate of mortality.

Impact of preoperative sarcopenia in patients undergoing sacral tumor resection.

INTRODUCTION: Sacral tumor resection is known for a high rate of complications. Sarcopenia has been found to be associated with wound complications; however, there is a paucity of data examining the impact of sarcopenia on the outcome of sacral tumor resection. METHODS: Forty-eight patients (31 primary sarcomas, 17 locally recurrent carcinomas) undergoing sacrectomy were reviewed. Central sarcopenia was assessed by measuring the psoas:lumbar vertebra index (PLVI), with the 50th percentile (0.97) used to determine which patients were high (>0.97) versus low (<0.97). RESULTS: Twenty-four (50%) patients had a high PLVI and 24 (50%) had a low PLVI (sarcopenic). There was no difference (p > 0.05) in the demographics of patients with or without sarcopenia. There was no difference in the incidence of postoperative wound complications (odds ratio [OR] = 1.0, p = 1.0) or deep infection (OR = 0.83, p = 1.0). Sarcopenia was not associated with death due to disease (hazard ratio [HR] = 2.04, p = 0.20) or metastatic disease (HR = 2.47, p = 0.17), but was associated with local recurrence (HR = 6.60, p = 0.01). CONCLUSIONS: Central sarcopenia was not predictive of wound complications or infection following sacral tumor resection. Sarcopenia was, however, an independent risk factor for local tumor recurrence following sacrectomy and should be considered when counseling patients on the outcome of sacrectomy.

A Novel Nomogram for Predicting Cancer-Specific Survival in Patients With Spinal Chordoma: A Population-Based Analysis.

BACKGROUND: Chordoma is a rare malignant bone tumor, and the survival prediction for patients with chordoma is difficult. The objective of this study was to construct and validate a nomogram for predicting cancer-specific survival (CSS) in patients with spinal chordoma. METHODS: A total of 316 patients with spinal chordoma were identified from the SEER database between 1998 and 2015. The independent prognostic factors for patients with spinal chordoma were determined by univariate and multivariate Cox analyses. The prognostic nomogram was established for patients with spinal chordoma based on independent prognostic factors. Furthermore, we performed internal and external validations for this nomogram. RESULTS: Primary site, disease stage, histological type, surgery, and age were identified as independent prognostic factors for patients with spinal chordoma. A nomogram for predicting CSS in patients with spinal chordoma was constructed based on the above 5 variables. In the training cohort, the area under the curve for predicting 1-, 3-, and 5-year CSS were 0.821, 0.856, and 0.920, respectively. The corresponding area under the curve in the validation cohort were 0.728, 0.804, and 0.839, respectively. The calibration curves of the nomogram showed a high degree of agreement between the predicted and the actual results, and the decision curve analysis further demonstrated the satisfactory clinical utility of the nomogram. CONCLUSIONS: The prognostic nomogram provides a considerably more accurate prediction of prognosis for patients with spinal chordoma. Clinicians can use it to categorize patients into different risk groups and make personalized treatment methods.

Camrelizumab plus Zoledronic Acid Showed Sustained Efficacy in a Patient with Cranial and Spinal Metastases from Lung Adenocarcinoma.

The role of anti-programmed cell death protein-1 (PD-1) antibody camrelizumab in brain metastases (BMs) from lung adenocarcinoma is uncertain. Herein, for the first time, we report the efficacy of camrelizumab in a patient with chemotherapy-refractory BMs from lung adenocarcinoma. A 49-year-old male non-smoker was admitted with cough and back pain. Primary lung adenocarcinoma with brain and spinal metastases was diagnosed. The specimen from CT-guided lung biopsy showed a positive expression of PD-L1 (~20%).The BMs were enlarged after first-line intravenous pemetrexed/cisplatin and zoledronic acid; whereas second-line camrelizumab demonstrated impressive complete remission of the BMs. The intracranial progression-free survival and overall survival of the patients since the start of the immunotherapy plan prolonged to more than 12 months and 20 months, respectively. In addition, we searched PubMed for relevant studies from inception to May 2020, and a total of 23 reports enrolling 1187 patients also indicated the promising efficacy of immunotherapy for BMs from lung cancer. However, more and better evidence is still needed before a definite conclusion could be drawn.

Clinical features and prognostic factors in spinal meningioma surgery from a multicenter study.

Meningiomas are benign tumors that are treated surgically. Local recurrence is likely if the dura is preserved, and en bloc tumor and dura resection (Simpson grade I) is recommended. In some cases the dura is cauterized and preserved after tumor resection (Simpson grade II). The purpose of this study was performed to analyze clinical features and prognostic factors associated with spinal meningioma, and to identify the most effective surgical treatment. The subjects were 116 patients (22 males, 94 females) with spinal meningioma who underwent surgery at seven NSG centers between 1998 and 2018. Clinical data were collected from the NSG database. Pre- and postoperative neurological status was defined using the modified McCormick scale. The patients had a mean age of 61.2 ± 14.8 years (range 19-91 years) and mean symptom duration of 11.3 ± 14.7 months (range 1-93 months). Complete resection was achieved in 108 cases (94%), including 29 Simpson grade I and 79 Simpson grade II resections. The mean follow-up period was 84.8 ± 52.7 months. At the last follow-up, neurological function had improved in 73 patients (63%), was stable in 34 (29%), and had worsened in 9 (8%). Eight patients had recurrence, and recurrence rates did not differ significantly between Simpson grades I and II in initial surgery. Kaplan-Meier analysis of recurrence-free survival showed that Simpson grade III or IV, male, and dural tail sign were significant factors associated with recurrence (P < 0.05). In conclusion, Simpson I resection is anatomically favorable for spinal meningiomas. Younger male patients with a dural tail and a high-grade tumor require close follow-up. The tumor location and feasibility of surgery can affect the surgical morbidity in Simpson I or II resection. All patients should be carefully monitored for long-term outcomes, and we recommend lifelong surveillance after surgery.

Identification of Hub Genes to Regulate Breast Cancer Spinal Metastases by Bioinformatics Analyses.

Breast cancer (BC) had been one of the deadliest types of cancers in women worldwide. More than 65% of advanced-stage BC patients were identified to have bone metastasis. However, the molecular mechanisms involved in the BC spinal metastases remained largely unclear. This study screened dysregulated genes in the progression of BC spinal metastases by analyzing GSE22358. Moreover, we constructed PPI networks to identify key regulators in this progression. Bioinformatics analysis showed that these key regulators were involved in regulating the metabolic process, cell proliferation, Toll-like receptor and RIG-I-like receptor signaling, and mRNA surveillance. Furthermore, our analysis revealed that key regulators, including C1QB, CEP55, HIST1H2BO, IFI6, KIAA0101, PBK, SPAG5, SPP1, DCN, FZD7, KRT5, and TGFBR3, were correlated to the OS time in BC patients. In addition, we analyzed TCGA database to further confirm the expression levels of these hub genes in breast cancer. Our results showed that these regulators were significantly differentially expressed in breast cancer, which were consistent with GSE22358 dataset analysis. Furthermore, our analysis demonstrated that CEP55 was remarkably upregulated in the advanced stage of breast cancer compared to the stage I breast cancer sample and was significantly upregulated in triple-negative breast cancers (TNBC) compared to other types of breast cancers, including luminal and HER2-positive cancers, demonstrating CEP55 may have a regulatory role in TNBC. Finally, our results showed that CEP55 was the most highly expressed in Basal-like 1 TNBC and Basal-like 2 TNBC samples but the most lowly expressed in mesenchymal stem-like TNBC samples. Although more studies are still needed to understand the functions of key regulators in BC, this study provides useful information to understand the mechanisms underlying BC spinal metastases.

Video-Assisted Thoracoscopic En Bloc Vertebrectomy for Spine Tumors: Technique and Outcomes in a Series of 33 Patients.

BACKGROUND: In en bloc vertebrectomy, the posterior approach is associated with limited access to anterior structures (vertebral body, esophagus, aorta, azygos vein). Video-assisted thoracoscopic surgery (VATS) might prove to be advantageous during thoracic en bloc vertebrectomy by allowing a combined anterior-posterior access in the prone position. We describe the technique and review the outcomes of 33 cases of video-assisted thoracoscopic en bloc vertebrectomy. METHODS: A retrospective, single-center cohort study included all cases of VATS with a minimum follow-up of 1 year. A team of thoracic and orthopaedic surgeons performed the surgical procedure with the patient in a single, prone position. Anterior release was carried out thoracoscopically, followed by posterior en bloc tumor removal. RESULTS: From 2003 to 2019, 33 patients were included. Nine patients underwent total vertebrectomy (8 had single-level and 1 had 3-level), and 24 patients underwent partial vertebrectomy (1 had single-level, 8 had 2-level, 13 had 3-level, and 2 had 4-level). Ten patients had pulmonary resection. Histology revealed 18 cases (55%) of primary bone tumors, 6 cases (18%) of lung cancer invading the spine, 6 cases (18%) of solitary metastasis, and 3 other cases (9%). The margins were tumor-free in 28 cases (85%). The median operative time was 240 minutes (range, 150 to 510 minutes), with a median blood loss of 1,200 mL (range, 400 to 6,700 mL), and there were 2 cases of conversion to thoracotomy. A total of 33 complications occurred in 18 patients (55%), and these were predominantly pulmonary. One death was surgery-related (infection). One patient had a persistent monoplegia. At a median follow-up of 63 months (range, 12 to 156 months), there were 21 surviving patients (64%) with 2 local recurrences and 1 distant recurrence, and 2 patients (6%) were lost to follow-up. The survival rates were 94% at 1 year, 71% at 2 years, and 68% at 5 years. CONCLUSIONS: VATS en bloc vertebrectomy may be indicated for T2-to-T11 spine tumors with the exception of massive tumors, substantial chest wall and/or mediastinal invasion, and lung cancer exceeding 7 cm. The technique yielded satisfactory surgical and oncologic outcomes. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Clinical outcomes and prognostic factors following the surgical resection of renal cell carcinoma spinal metastases.

The efficacy of surgical resection in metastatic renal cell carcinoma is an active and important research field in the postcytokine era. Bone metastases, especially in the spine, compromise patient performance status. Metastasectomy is indicated, if feasible, because it helps to achieve the best clinical outcomes possible compared with other treatments. This study examined the postoperative survival and prognostic factors in patients who underwent metastasectomy of spinal lesions. The retrospective study included 65 consecutive patients with metastatic renal cell carcinomas who were operated on by spinal metastasectomy between 1995 and 2017 at our institution. The cancer-specific survival times from the first spinal metastasectomy to death or the last follow-up (≥3 years) were determined using Kaplan-Meier analysis. Potential factors influencing survival were analyzed using Cox proportional hazard models. Planned surgical resection of all the spine tumors was achieved in all patients. Of these, 38 had complete metastasectomy of all visible metastases, including extraspinal lesions. In all patients, the estimated median cancer-specific survival time was 100 months. The 3-, 5-, and 10-year cancer-specific survival rates were 77%, 62%, and 48%, respectively. The survival times after spinal metastasectomy were similar in both cytokine and postcytokine groups. In multivariate analyses, postoperative disability, the coexistence of liver metastases, multiple spinal metastases, and incomplete metastasectomy were significant risk factors associated with short-term survival. Complete metastasectomy, including extraspinal metastases, was associated with improved cancer-specific survival. Proper patient selection and complete metastasectomy provide a better prognosis in metastatic renal cell carcinoma patients.

A Novel Nomogram for Survival Prediction of Patients with Spinal Metastasis From Prostate Cancer.

STUDY DESIGN: A retrospective study of 84 patients with spinal metastasis from prostate cancer (SMPCa) was performed. OBJECTIVE: The aim of this study was to predict the survival of patients with SMPCa by establishing an effective prognostic nomogram model, associating with the affecting factors and compare its efficacy with the existing scoring models. SUMMARY OF BACKGROUND DATA: Prostate cancer (PCa) is the second most frequently malignant cancer causing death in men, and the spine is the most common site of bone metastatic burden. The aim of this study was to establish a prognostic nomogram for survival prediction of patients with SMPCa, explore associated factors, and compare the effectiveness of the new nomogram prediction model with the existing scoring systems. METHODS: Included in this study were 84 SMPCa patients who were admitted in our spinal tumor center between 2006 and 2018. Their clinical data were retrospectively analyzed by univariate and multivariate analyses to identify independent variables that enabled to predict prognosis. A nomogram, named Changzheng Nomogram for Survival Prediction (CNSP), was established on the basis of preoperative independent variables, and then subjected to bootstrap re-samples for internal validation. The predictive accuracy and discriminative ability were measured by concordance index (C-index). Receiver-operating characteristic (ROC) analysis with the corresponding area under the ROC was used to estimate the prediction efficacy of CNSP and compare it with the four existing prognostic models Tomita, Tokuhashi, Bauer, and Crnalic. RESULTS: A total of seven independent variables including Gleason score (P = 0.001), hormone refractory (P < 0.001), visceral metastasis (P < 0.001), lymphocyte to monocyte ratio (P = 0.009), prostate-specific antigen (P = 0.018), fPSA/tPSA (P = 0.029), Karnofsky Performance Status (P = 0.039) were identified after accurate analysis, and then entered the nomogram with the C-index of 0.87 (95% confidence interval, 0.84-0.90). The calibration curves for probability of 12-, 24-, and 36-month overall survival (OS) showed good consistency between the predictive risk and the actual risk. Compared with the previous prognostic models, the CNSP model was significantly more effective than the four existing prognostic models in predicting OS of the SMPCa patients (p < 0.05). CONCLUSION: The overall performance of the CNSP model was satisfactory and could be used to estimate the survival outcome of individual patients more precisely and thus help clinicians design more specific and individualized therapeutic regimens.Level of Evidence: 4.

Surgical Impacts of Metastatic Non-small Cell Lung Cancer to the Thoracic and Lumbar Spine.

BACKGROUND: Surgery for spinal metastasis is rapidly increasing in frequency with procedures ranging from laminectomy to spondylectomy combined with stabilization. This study investigated the effect of various surgical procedures for spinal metastasis of non-small cell lung cancer (NSCLC). METHODS: A single-center consecutive series of patients who underwent surgery for spinal metastasis of NSCLC were retrospectively reviewed. Patients' characteristics, radiographic parameters, operative data, clinical outcomes, and complications were analyzed. Surgical outcomes were assessed according to pain and performance status before and after surgery. Overall survival (OS) rate was estimated using the Kaplan-Meier method. Multivariate analysis was performed to detect factors independently associated with OS using a Cox proportional hazards model. RESULTS: Twenty-one patients were treated with laminectomy, 24 with corpectomy, 13 with spondylectomy (piecemeal or total en bloc fashion), and all procedures were combined with stabilization. Back pain and performance status improved significantly after surgical treatment among the three groups. Revision surgery due to tumor progression at the index level or spinal metastasis at another level were four patients (19.0%) in the laminectomy group, six patients (25.0%) in the corpectomy group, and one patient (7.7%) in the spondylectomy group. A Charlson comorbidity index and the number of spinal metastasis negatively affected OS (hazard ratio [HR], 19.613 and 2.244). Postoperative chemotherapy, time to metastasis, spondylectomy, and corpectomy had favorable associations with OS (HR, 0.455, 0.487, 0.619, and 0.715, respectively). CONCLUSION: Postoperative chemotherapy was the most critical factor in OS of patients with metastatic NSCLC to the spine. An extensive surgical procedure (corpectomy/spondylectomy) with stabilization also could be beneficial for limited patients with spinal metastasis of NSCLC.

Postoperative Stereotactic Body Radiotherapy for Spinal Metastasis and Predictors of Local Control.

BACKGROUND: Spine surgery is indicated for select patients with mechanical instability, pain, and/or malignant epidural spinal cord compression, with or without neurological compromise. Stereotactic body radiotherapy (SBRT) is an option for durable local control (LC) for metastatic spine disease. OBJECTIVE: To determine factors associated with LC and progression-free survival (PFS) for patients receiving postoperative stereotactic spine radiosurgery. METHODS: We analyzed consecutive patients from 2013 to 2019 treated with surgical intervention followed by SBRT. Surgical interventions included laminectomy and vertebrectomy. SBRT included patients treated with 1 to 5 fractions of radiosurgery. We analyzed LC, PFS, overall survival (OS), and toxicity. Univariate and multivariate analyses were performed. RESULTS: A total of 63 patients were treated with a median follow-up of 12.5 mo. Approximately 75% of patients underwent vertebrectomy and 25% underwent laminectomy. One-year cumulative incidence of local failure was 19%. LC was significantly improved for patients receiving radiosurgery ≤40 d from surgery compared to that for patients receiving radiosurgery ≥40 d from surgery, 94% vs 75%, respectively, at 1 yr (P = .03). Patients who received preoperative embolization had improved LC with 1-yr LC of 88% vs 76% for those who did not receive preoperative embolization (P = .037). Significant predictors for LC on multivariate analysis were time from surgery to radiosurgery, higher radiotherapy dose, and preoperative embolization. The 1-yr PFS and OS was 56% and 60%, respectively. CONCLUSION: Postoperative radiosurgery has excellent and durable LC for spine metastasis. An important consideration when planning postoperative radiosurgery is minimizing delay from surgery to radiosurgery. Preoperative embolization and higher radiotherapy dose were associated with improved LC warranting further study.

Prognostic Factors Associated With Surviving Less Than 3 Months vs Greater Than 3 Years Specific to Spine Stereotactic Body Radiotherapy and Late Adverse Events.

BACKGROUND: Patient selection is critical for spine stereotactic body radiotherapy (SBRT) given potential for serious adverse effects and the associated costs. OBJECTIVE: To identify prognostic factors associated with dying within 3 mo, or living greater than 3 yr, following spine SBRT, to better inform patient selection. METHODS: Patients living ≤3 mo after spine SBRT and >3 yr after spine SBRT were identified, and multivariable regression analyses were performed. We report serious late toxicities observed, including vertebral compression fractures (VCF) and plexopathy. RESULTS: A total of 605 patients (1406 spine segments) were treated from 2009 to 2018. A total of 51 patients (8.4%) lived ≤3 mo, and 79 patients (13%) survived >3 yr. Significant differences in baseline features were observed. On multivariable analysis, nonbreast/prostate primaries (odds ratio [ORs]: 28.8-104.2, P = .0004), eastern cooperative oncology group (ECOG) ≥2 (OR: 23.7, 95% CI: 3.2-177, P = .0020), polymetastatic disease (OR: 6.715, 95% CI: 1.89-23.85, P = .0032), painful lesions (OR: 3.833-8.898, P = .0118), and paraspinal disease (OR: 2.874, 95% CI: 1.118-7.393, P = .0288) were prognostic for ≤3 mo survival. The 3- and 5-yr rates of VCF were 10.4% and 14.4%, respectively, and 3- and 5-yr rates of plexopathy were 2.2% and 5.1%, respectively. A single duodenal perforation was observed, and there was no radiation myelopathy events. CONCLUSION: Shorter survival after spine SBRT was seen in patients with less radiosensitive histologies (ie, not breast or prostate), ECOG ≥2, and polymetastatic disease. Pain and paraspinal disease were also associated with poor survival. Fractionated spine SBRT confers a low risk of late serious adverse events.

Long-Term Results of Dose-Intensified Fractionated Stereotactic Body Radiation Therapy (SBRT) for Painful Spinal Metastases.

PURPOSE: To report long-term outcome of fractionated stereotactic body radiation therapy (SBRT) for painful spinal metastases. METHODS AND MATERIALS: This prospective, single-arm, multicenter phase 2 clinical trial enrolled 57 patients with 63 painful, unirradiated spinal metastases between March 2012 and July 2015. Patients were treated with 48.5 Gy in 10 SBRT fractions (long life expectancy [Mizumoto score ≤4]) or 35 Gy in 5 SBRT fractions (intermediate life expectancy [Mizumoto score 5-9]). Pain response was defined as pain improvement of a minimum of 2 points on a visual analog scale, and net pain relief was defined as the sum of time with pain response (complete and partial) divided by the overall follow-up time. RESULTS: All 57 patients received treatment per protocol; 32 and 25 patients were treated with 10- and 5-fraction SBRT, respectively. The median follow-up of living patients was 60 months (range, 33-74 months). Of evaluable patients, 82% had complete or partial pain response (responders) at 3 months' follow-up (primary endpoint), and pain response remained stable over 5 years. Net pain relief was 74% (95% CI, 65%-80%). Overall survival rates of 1, 3, and 5 years were 59.6% (95% CI, 47%-72%), 33.3% (95% CI, 21%-46%), and 21% (95% CI, 10%-32%), respectively. Freedom from local spinal-metastasis progression was 82% at the last imaging follow-up. Late grade-3 toxicity was limited to pain in 2 patients (nonresponders). There were no cases of myelopathy. SBRT resulted in long-term improvements of all dimensions of the 5-level EuroQol 5-Dimension Questionnaire except anxiety/depression. CONCLUSIONS: Fractionated SBRT achieved durable pain response and improved quality of life at minimum late toxicity.

Comparison of 5 × 5 Gy and 10 × 3 Gy for metastatic spinal cord compression using data from three prospective trials.

BACKGROUND: In a palliative situation like metastatic spinal cord compression (MSCC), overall treatment time of radiotherapy should be as short as possible. This study compared 5 × 5 Gy in 1 week to 10 × 3 Gy in 2 weeks in a prospective cohort. METHODS: Forty patients receiving 5 × 5 Gy in a phase II trial were matched 1:2 to 213 patients receiving 10 × 3 Gy in two previous prospective studies for tumor type, ambulatory status, time developing motor deficits, interval between tumor diagnosis and MSCC and visceral metastases. These factors were consistent in all three patients (triple) used for each 1:2 matching. Groups were compared for local progression-free survival (LPFS), motor function, ambulatory status, and overall survival (OS). RESULTS: After matching, 32 triples remained for analyses (N = 96 in total). Six-month LPFS-rates were 94% after 5 × 5 Gy and 87% after 10 × 3 Gy (p = 0.36), 6-month OS-rates 43% and 35% (p = 0.74). Improvement of motor function was achieved in 59% and 34% of patients (p = 0.028); overall response rates (improvement or no further progression of motor deficits) were 94% and 89% (p = 0.71). Post-treatment ambulatory rates were 81% after 5 × 5 Gy and 85% after 10 × 3 Gy (p = 0.61). Of non-ambulatory patients, 50% (6/12) and 46% (11/24) regained the ability to walk (p = 1.00). CONCLUSIONS: 5 × 5 Gy in 1 week appeared similarly effective as 10 × 3 Gy in 2 weeks. These results may not be applicable to long-term survivors and should be confirmed in a randomized trial directly comparing 5 × 5 Gy and 10 × 3 Gy. Trial registration clinicaltrials.gov NCT03070431. Registered 27 February 2017.

Delayed postoperative radiotherapy increases the incidence of radiographic local tumor progression before radiotherapy and leads to poor prognosis in spinal metastases.

BACKGROUND: Most previous studies focused on the minimum interval between surgery and radiotherapy in spinal metastases, leaving the maximum interval under-investigated. However, in real world, limited radiotherapist and equipment cannot meet the needs of a large patient population to obtain timely radiotherapy after the index spine surgery in developing countries. This study aimed to estimate the clinical risks of delayed radiotherapy after surgery in patients with spinal metastases in developing country. METHODS: Data from 89 patients who underwent surgery and postoperative radiotherapy at a single site in a developing country were retrospectively reviewed. Patients were divided into the progression before radiotherapy (PBR) and no progression before radiotherapy (NPBR) groups. Kaplan-Meier analysis and log-rank tests were used to compare the local control (LC) and overall survival (OS) between groups. RESULTS: Within 1 month after surgery, only 20.2% of patients underwent radiotherapy. Risk of local progression before radiotherapy at 1, 3, and 6 months was 1.2%, 24.1%, and 45.1%, respectively. The LC rate at 1 year was lower in the PBR group than in the NPBR group (53.3% vs. 76.3%, P = 0.040). The OS rate at 1 year was 61.9% and 79.6% in the PBR and NPBR groups, respectively (P = 0.001). The Karnofsky performance status significantly improved only in the NPBR group (52.5 ± 17.6 vs. 66.8 ± 26.3, P < 0.001). The sphincter dysfunction significantly improved in the NPBR group (0.3 ± 0.5 vs. 0.1 ± 0.3, P = 0.007) but it tended to be deteriorated in the PBR group (0.1 ± 0.4 vs. 0.3 ± 0.5, P = 0.500). CONCLUSIONS: In real world, about 80% of patients had delayed radiotherapy 1 month after spine surgery for metastases in our developing country. Patients had a higher risk for radiographic local progression before radiotherapy and poorer LC, OS, and quality of life as time to radiotherapy increased.