A pan-cancer single-cell transcriptional atlas of tumor infiltrating myeloid cells.

Tumor-infiltrating myeloid cells (TIMs) are key regulators in tumor progression, but the similarity and distinction of their fundamental properties across different tumors remain elusive. Here, by performing a pan-cancer analysis of single myeloid cells from 210 patients across 15 human cancer types, we identified distinct features of TIMs across cancer types. Mast cells in nasopharyngeal cancer were found to be associated with better prognosis and exhibited an anti-tumor phenotype with a high ratio of TNF+/VEGFA+ cells. Systematic comparison between cDC1- and cDC2-derived LAMP3+ cDCs revealed their differences in transcription factors and external stimulus. Additionally, pro-angiogenic tumor-associated macrophages (TAMs) were characterized with diverse markers across different cancer types, and the composition of TIMs appeared to be associated with certain features of somatic mutations and gene expressions. Our results provide a systematic view of the highly heterogeneous TIMs and suggest future avenues for rational, targeted immunotherapies.

Deep learning model for measuring the sagittal Cobb angle on cervical spine computed tomography.

PURPOSES: To develop a deep learning (DL) model to measure the sagittal Cobb angle of the cervical spine on computed tomography (CT). MATERIALS AND METHODS: Two VB-Net-based DL models for cervical vertebra segmentation and key-point detection were developed. Four-points and line-fitting methods were used to calculate the sagittal Cobb angle automatically. The average value of the sagittal Cobb angle was manually measured by two doctors as the reference standard. The percentage of correct key points (PCK), matched samples t test, intraclass correlation coefficient (ICC), Pearson correlation coefficient, mean absolute error (MAE), and Bland‒Altman plots were used to evaluate the performance of the DL model and the robustness and generalization of the model on the external test set. RESULTS: A total of 991 patients were included in the internal data set, and 112 patients were included in the external data set. The PCK of the DL model ranged from 78 to 100% in the test set. The four-points method, line-fitting method, and reference standard measured sagittal Cobb angles were - 1.10 ± 18.29°, 0.30 ± 13.36°, and 0.50 ± 12.83° in the internal test set and 4.55 ± 20.01°, 3.66 ± 18.55°, and 1.83 ± 12.02° in the external test set, respectively. The sagittal Cobb angle calculated by the four-points method and the line-fitting method maintained high consistency with the reference standard (internal test set: ICC = 0.75 and 0.97; r = 0.64 and 0.94; MAE = 5.42° and 3.23°, respectively; external test set: ICC = 0.74 and 0.80, r = 0.66 and 0.974, MAE = 5.25° and 4.68°, respectively). CONCLUSIONS: The DL model can accurately measure the sagittal Cobb angle of the cervical spine on CT. The line-fitting method shows a higher consistency with the doctors and a minor average absolute error.

Vertebral MRI-based radiomics model to differentiate multiple myeloma from metastases: influence of features number on logistic regression model performance.

OBJECTIVES: This study aimed to use the most frequent features to establish a vertebral MRI-based radiomics model that could differentiate multiple myeloma (MM) from metastases and compare the model performance with different features number. METHODS: We retrospectively analyzed conventional MRI (T1WI and fat-suppression T2WI) of 103 MM patients and 138 patients with metastases. The feature selection process included four steps. The first three steps defined as conventional feature selection (CFS), carried out 50 times (ten times with 5-fold cross-validation), included variance threshold, SelectKBest, and least absolute shrinkage and selection operator. The most frequent fixed features were selected for modeling during the last step. The number of events per independent variable (EPV) is the number of patients in a smaller subgroup divided by the number of radiomics features considered in developing the prediction model. The EPV values considered were 5, 10, 15, and 20. Therefore, we constructed four models using the top 16, 8, 6, and 4 most frequent features, respectively. The models constructed with features selected by CFS were also compared. RESULTS: The AUCs of 20EPV-Model, 15EPV-Model, and CSF-Model (AUC = 0.71, 0.81, and 0.78) were poor than 10EPV-Model (AUC = 0.84, p < 0.001). The AUC of 10EPV-Model was comparable with 5EPV-Model (AUC = 0.85, p = 0.480). CONCLUSIONS: The radiomics model constructed with an appropriate small number of the most frequent features could well distinguish metastases from MM based on conventional vertebral MRI. Based on our results, we recommend following the 10 EPV as the rule of thumb for feature selection. KEY POINTS: • The developed radiomics model could distinguish metastases from multiple myeloma based on conventional vertebral MRI. • An accurate model based on just a handful of the most frequent features could be constructed by utilizing multiple feature reduction techniques. • An event per independent variable value of 10 is recommended as a rule of thumb for modeling feature selection.

Eight-lncRNA signature of cervical cancer were identified by integrating DNA methylation, copy number variation and transcriptome data.

BACKGROUND: Copy number variation (CNV) suggests genetic changes in malignant tumors. Abnormal expressions of long non-coding RNAs (lncRNAs) resulted from genomic and epigenetic abnormalities play a driving role in tumorigenesis of cervical cancer. However, the role of lncRNAs-related CNV in cervical cancer remained largely unclear. METHODS: The data of messenger RNAs (mRNAs), DNA methylation, and DNA copy number were collected from 292 cervical cancer specimens. The prognosis-related subtypes of cervical cancer were determined by multi-omics integration analysis, and protein-coding genes (PCGs) and lncRNAs with subtype-specific expressions were identified. The CNV pattern of the subtype-specific lncRNAs was analyzed to identify the subtype-specific lncRNAs. A prognostic risk model based on lncRNAs was established by least absolute shrinkage and selection operator (LASSO). RESULTS: Multi-omics integration analysis identified three molecular subtypes incorporating 617 differentially expressed lncRNAs and 1395 differentially expressed PCGs. The 617 lncRNAs were found to intersect with disease-related lncRNAs. Functional enrichment showed that 617 lncRNAs were mainly involved in tumor metabolism, immunity and other pathways, such as p53 and cAMP signaling pathways, which are closely related to the development of cervical cancer. Finally, according to CNV pattern consistent with differential expression analysis, we established a lncRNAs-based signature consisted of 8 lncRNAs, namely, RUSC1-AS1, LINC01990, LINC01411, LINC02099, H19, LINC00452, ADPGK-AS1, C1QTNF1-AS1. The interaction of the 8 lncRNAs showed a significantly poor prognosis of cervical cancer patients, which has also been verified in an independent dataset. CONCLUSION: Our study expanded the network of CNVs and improved the understanding on the regulatory network of lncRNAs in cervical cancer, providing novel biomarkers for the prognosis management of cervical cancer patients.

CMTM3 suppresses chordoma progress through EGFR/STAT3 regulated EMT and TP53 signaling pathway.

BACKGROUND: Chordomas are rare, slow-growing and locally aggressive bone sarcomas. At present, chordomas are difficult to manage due to their high recurrence rate, metastasis tendency and poor prognosis. The underlying mechanisms of chordoma tumorigenesis and progression urgently need to be explored to find the effective therapeutic targets. Our previous data demonstrates that EGFR plays important roles in chordoma development and CKLF-like MARVEL transmembrane domain containing (CMTM)3 suppresses gastric cancer metastasis by inhibiting the EGFR/STAT3/EMT signaling pathway. However, the roles and mechanism of CMTM3 in chordomas remain unknown. METHODS: Primary chordoma tissues and the paired adjacent non-tumor tissues were collected to examine the expression of CMTM3 by western blot. The expression of CMTM3 in chordoma cell lines was tested by Real-time PCR and western blot. CCK-8 and colony forming unit assay were performed to delineate the roles of CMTM3 in cell proliferation. Wound healing and Transwell assays were performed to assess cell migration and invasion abilities. A xenograft model in NSG mice was used to elucidate the function of CMTM3 in vivo. Signaling pathways were analyzed by western blot and IHC. RNA-seq was performed to further explore the mechanism regulated by CMTM3 in chordoma cells. RESULTS: CMTM3 expression was downregulated in chordoma tissues compared with paired normal tissues. CMTM3 suppressed proliferation, migration and invasion of chordoma cells in vitro and inhibited tumor growth in vivo. CMTM3 accelerated EGFR degradation, suppressed EGFR/STAT3/EMT signaling pathway, upregulated TP53 expression and enriched the TP53 signaling pathway in chordoma cells. CONCLUSIONS: CMTM3 inhibited tumorigenesis and development of chordomas through activating the TP53 signaling pathway and suppressing the EGFR/STAT3 signaling pathway, which suppressed EMT progression. CMTM3 might be a potential therapeutic target for chordomas.

Thirty-day Unplanned Reoperations After Posterior Surgery for Thoracic Spinal Stenosis: A Single-center Study Based on 1948 Patients.

STUDY DESIGN: A retrospective study. OBJECTIVE: The purpose of this study is to identify the incidences, causes, and risk factors of 30-day unplanned reoperation of posterior surgery for thoracic spinal stenosis (TSS) based on 1948 patients in a single center. SUMMARY OF BACKGROUND DATA: Unplanned reoperation is suggested to be a useful quality indicator for spine surgery. However, the incidences, causes, and risk factors of 30-day unplanned reoperation in patients who underwent posterior spinal surgery for TSS have not been well-established. MATERIALS AND METHODS: We retrospectively analyzed the clinical data of patients who underwent posterior spinal surgery for TSS from January 2011 to December 2021. Statistical methods including univariate and multivariate analyses were performed to assess the incidences, causes, and risk factors. RESULTS: A total of 1948 patients who underwent posterior spinal surgery for TSS in our institution were reviewed, and 77 (3.95%) required unplanned reoperations within 30 days because of epidural hematoma (1.64%), wound-related complications (1.02%), inadequate decompression (0.41%), and implant malposition or failure (0.36%), neurological deficit (0.26%), and other causes (0.26%). After univariate analysis, seven clinical factors were associated with unplanned reoperation ( P <0.05). Multivariate logistic regression analysis showed that upper thoracic spine surgery ( P =0.010), thoracic kyphosis ≥45° ( P =0.039), and intraoperative dural injury ( P =0.047) were independent risk factors for 30-day unplanned reoperation of posterior surgery for TSS. CONCLUSIONS: The incidence of 30-day unplanned reoperations after posterior surgical treatment for TSS was 3.95%. The most common causes were epidural hematoma, wound-related complications, inadequate decompression, and implant malposition or failure. Upper thoracic spine surgery, thoracic kyphosis ≥45°, and intraoperative dural injury led to an increased risk of unplanned reoperation within 30 days after posterior spinal surgery for TSS. LEVEL OF EVIDENCE: 4.

Thirty-day unplanned reoperations of thoracic spine surgery: 10 years of data from a single center with 3242 patients.

BACKGROUND CONTEXT: Unplanned reoperation is a useful quality indicator for spine surgery. However, the rates of a 30-day unplanned reoperation in patients undergoing thoracic spinal surgery are not well established. PURPOSE: To assess the rates, reasons, and risk factors of 30-day unplanned reoperations for thoracic spine surgeries in a single center study. STUDY DESIGN: A retrospective observational study. PATIENT SAMPLE: A total of 3242 patients who underwent thoracic spinal surgery at our institution in the past decade were included. OUTCOME MEASURES: The incidence, chief reasons, and risk factors for unplanned reoperations within 30 days after thoracic spinal surgery. METHODS: We retrospectively analyzed the data of all patients who underwent thoracic spinal surgery between January 2012 and December 2021. Statistical methods, including univariate and multivariate analyses, were performed to assess the incidence, reasons, and risk factors for thoracic degenerative diseases, spinal tumors, kyphosis deformity, and spinal trauma. RESULTS: Of the 3242 patients who underwent thoracic spinal surgery, 107 (3.30%) required unplanned reoperations within 30 days due to epidural hematoma (1.17%), wound complications (0.80%), implant complications (0.43%), inadequate decompression (0.25%), and other causes (0.65%). Patients with degenerative disease (3.88%), spinal tumor (2.98%), and kyphosis deformity (3.33%) had significantly higher incidences of reoperation than those with spinal trauma (1.47%). Unplanned reoperations were classified as hyperacute (30.84%), acute (31.76%), and subacute (37.38%). After univariate analysis, several factors were associated with unplanned reoperation in the 4 cohorts of thoracic spine diseases (p<.05). Multivariate logistic regression analysis revealed that upper thoracic spine surgery (p=.001), concomitant dekyphosis (p=.027), and longer activated partial thromboplastin time (p=.025) were risk factors of unplanned reoperation for thoracic degenerative disease. Whereas American Society of Anesthesiologists (ASA) grade III (p=.015), combined approach (p=.016), and operation time longer than 420 min (p=.042) for spinal tumor, and similar ankylosing spondylitis (p=.023) and operation time longer than 340 min (p=.041) were risk factors of unplanned reoperation for kyphosis deformity. CONCLUSIONS: The unplanned reoperation rate for thoracic spine surgery was 3.30%, with epidural hematoma and wound complications being the most common reasons. However, upper thoracic spine surgery, concomitant dekyphosis, underlying coagulation disorder, longer operation time, higher ASA grade, and comorbidities of ankylosing spondylitis led to an increased risk of unplanned reoperation within 30 days of thoracic spine surgery.

Proteomics and phosphoproteomics of chordoma biopsies reveal alterations in multiple pathways and aberrant kinases activities.

Background: Chordoma is a slow-growing but malignant subtype of bone sarcoma with relatively high recurrence rates and high resistance to chemotherapy. It is urgent to understand the underlying regulatory networks to determine more effective potential targets. Phosphorylative regulation is currently regarded as playing a significant role in tumorigenesis, and the use of tyrosine kinase inhibitors in clinical practice has yielded new promise for the treatment of a variety of sarcoma types. Materials and methods: We performed comprehensive proteomic and phosphoproteomic analyses of chordoma using four-dimensional label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) and bioinformatics analysis. The potential aberrantly expressed kinases and their functions were validated using western blotting and CCK-8 assays. Results: Compared with paired normal muscle tissues, 1,139 differentially expressed proteins (DEPs) and 776 differentially phosphorylated proteins (DPPs) were identified in chordoma tumor tissues. The developmentally significant Wnt-signaling pathway and oxidative phosphorylation were aberrant in chordoma. Moreover, we predicted three kinases (AURA, CDK9, and MOK) with elevated activity by kinase-pathway network analysis (KiPNA) and verified their increased expression levels. The knockdown of these kinases markedly suppressed chordoma cell growth, and this was also the case for cells treated with the CDK9 inhibitor AZD4573. We additionally examined 208 proteins whose expression and phosphorylation levels were synergetically altered. Conclusions: We herein depicted the collective protein profiles of chordomas, providing insight into chordomagenesis and the potential development of new therapeutic targets.

Imaging Features of Aggressive Giant Cell Tumors of the Mobile Spine: Retrospective Analysis of 101 Patients From Single Center.

STUDY DESIGN: Retrospective study. OBJECTIVES: Giant cell tumors (GCTs) of the mobile spine can be locally aggressive. This study described and classified the typical and atypical appearance of aggressive spinal GCTs according to imaging findings to help the imaging diagnosis, especially for patients with rapid neurological deficit that may require emergent surgery without biopsy. METHODS: Computed tomography (CT) and magnetic resonance imaging (MRI) scans of patients diagnosed with aggressive spinal GCTs at single center were reviewed. RESULTS: Overall, 101 patients with 100 CT images and 94 MR images were examined. All lesions were osteolytic with cortical destruction; 95 lesions showed epidural extension; 90 were centered in the vertebral body; 82 showed pathological fracture and/or collapse of the vertebral body; 78 had pseudotrabeculation on CT; 80 showed low-to-iso signal intensity or heterogeneous high-signal intensity with cystic areas on the T2-weighted images; 9 showed fluid-fluid level on T2-weighted images; and 61 patients showed marked enhancement on contrast-enhanced CT and/or MRI. Forty-one lesions (40.6%) had at least 1 atypical radiographic feature: 19 involved ≥2 segments; 11 were centered in the posterior neural arch; 10 had a paravertebral mass over 2 segments; 16 showed partial margin sclerosis with partial cortical destruction on CT scans; and 3 showed mineralization within the tumor on CT. Eighty-eight patients underwent CT-guided biopsy with a diagnostic accuracy rate of 94.3%. CONCLUSIONS: Spinal GCTs might appear more radiologically atypical, and about 40% of the lesions may have at least 1 atypical feature. CT-guided biopsies are recommended for definitive diagnosis.

Incidences, causes and risk factors of unplanned reoperations within 30 days of spine surgery: a single-center study based on 35,246 patients.

BACKGROUND CONTEXT: Unplanned reoperation, a quality indicator in spine surgery, has not been sufficiently investigated in a large-scale, single-center study. PURPOSE: To assess the incidences, causes, and risk factors of unplanned reoperations within 30 days of spine surgeries in a single-center study. STUDY DESIGN: Retrospective observational study. PATIENT SAMPLE: A cohort of 35,246 patients who underwent spinal surgery in our hospital were included. OUTCOME MEASURES: The rates, chief reasons, and risk factors for unplanned reoperations within 30 days of spine surgery. METHODS: We retrospectively analyzed the data for patients who underwent spine surgeries for degenerative spinal disorders, tumor, or deformity and had subsequent unplanned operations within 30 days at a single tertiary academic hospital from January 2016 to July 2021. Univariate and multivariate analyses were performed to assess the incidences, causes, and risk factors. RESULTS: Out of 35,246 spinal surgery patients, 297 (0.84%) required unplanned reoperations within 30 days of spine surgery. Patients with a thoracic degenerative disease (3.23%), spinal tumor (1.63%), and spinal deformity (1.50%) had significantly higher rates of reoperation than those with atlantoaxial (0.61%), cervical (0.65%), and lumbar (0.82%) degenerative disease. The common causes for reoperation included epidural hematoma (0.403%), wound infections (0.148%), neurological deficit (0.108%), and pedicle screw malposition (0.077%). Unplanned reoperations were classified as hyperacute (45.45%), acute (30.98%), subacute (15.82%), or chronic (7.74%). Univariate analysis indicated that 20 clinical factors were associated with unplanned reoperation (p<.05). Multivariate Poisson regression analysis revealed that anemia (p<.001), osteoporosis (p=.048), ankylosing spondylitis (p=.008), preoperative foot drop (p=.011), deep venous thrombosis (p<.001), and previous surgical history (p<.001) were independent risk factors for unplanned spinal reoperation. CONCLUSIONS: The incidence of unplanned spinal reoperations was 0.84%. The chief common causes were epidural hematoma, wound infections, neurological deficit, and pedicle screw malposition. Anemia, osteoporosis, ankylosing spondylitis, preoperative foot drop, deep venous thrombosis, and previous surgical history led to an increased risk of unplanned reoperation within 30 days of spine surgery.

Benign and malignant diagnosis of spinal tumors based on deep learning and weighted fusion framework on MRI.

BACKGROUND: The application of deep learning has allowed significant progress in medical imaging. However, few studies have focused on the diagnosis of benign and malignant spinal tumors using medical imaging and age information at the patient level. This study proposes a multi-model weighted fusion framework (WFF) for benign and malignant diagnosis of spinal tumors based on magnetic resonance imaging (MRI) images and age information. METHODS: The proposed WFF included a tumor detection model, sequence classification model, and age information statistic module based on sagittal MRI sequences obtained from 585 patients with spinal tumors (270 benign, 315 malignant) between January 2006 and December 2019 from the cooperative hospital. The experimental results of the WFF were compared with those of one radiologist (D1) and two spine surgeons (D2 and D3). RESULTS: In the case of reference age information, the accuracy (ACC) (0.821) of WFF was higher than three doctors' ACC (D1: 0.686; D2: 0.736; D3: 0.636). Without age information, the ACC (0.800) of the WFF was also higher than that of the three doctors (D1: 0.750; D2: 0.664; D3:0.614). CONCLUSIONS: The proposed WFF is effective in the diagnosis of benign and malignant spinal tumors with complex histological types on MRI.

Evaluation of Deep Learning-Based Automated Detection of Primary Spine Tumors on MRI Using the Turing Test.

Background: Recently, the Turing test has been used to investigate whether machines have intelligence similar to humans. Our study aimed to assess the ability of an artificial intelligence (AI) system for spine tumor detection using the Turing test. Methods: Our retrospective study data included 12179 images from 321 patients for developing AI detection systems and 6635 images from 187 patients for the Turing test. We utilized a deep learning-based tumor detection system with Faster R-CNN architecture, which generates region proposals by Region Proposal Network in the first stage and corrects the position and the size of the bounding box of the lesion area in the second stage. Each choice question featured four bounding boxes enclosing an identical tumor. Three were detected by the proposed deep learning model, whereas the other was annotated by a doctor; the results were shown to six doctors as respondents. If the respondent did not correctly identify the image annotated by a human, his answer was considered a misclassification. If all misclassification rates were >30%, the respondents were considered unable to distinguish the AI-detected tumor from the human-annotated one, which indicated that the AI system passed the Turing test. Results: The average misclassification rates in the Turing test were 51.2% (95% CI: 45.7%-57.5%) in the axial view (maximum of 62%, minimum of 44%) and 44.5% (95% CI: 38.2%-51.8%) in the sagittal view (maximum of 59%, minimum of 36%). The misclassification rates of all six respondents were >30%; therefore, our AI system passed the Turing test. Conclusion: Our proposed intelligent spine tumor detection system has a similar detection ability to annotation doctors and may be an efficient tool to assist radiologists or orthopedists in primary spine tumor detection.

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.

Pan-cancer single-cell landscape of tumor-infiltrating T cells.

T cells play a central role in cancer immunotherapy, but we lack systematic comparison of the heterogeneity and dynamics of tumor-infiltrating T cells across cancer types. We built a single-cell RNA-sequencing pan-cancer atlas of T cells for 316 donors across 21 cancer types and revealed distinct T cell composition patterns. We found multiple state-transition paths in the exhaustion of CD8+ T cells and the preference of those paths among different tumor types. Certain T cell populations showed specific correlation with patient properties such as mutation burden, shedding light on the possible determinants of the tumor microenvironment. T cell compositions within tumors alone could classify cancer patients into groups with clinical trait specificity, providing new insights into T cell immunity and precision immunotherapy targeting T cells.

Reossification and prognosis following radiotherapy with/without surgery for spinal solitary plasmacytoma of the bone: a retrospective study of 39 patients.

BACKGROUND CONTEXT: Solitary plasmacytoma of bone (SPB) can progress to multiple myeloma (MM). Little attention has been paid to the reossification findings on computed tomography (CT) and their correlation with prognosis after radiotherapy with/without surgery. PURPOSE: To evaluate reossification after radiotherapy and prognostic factors of spinal SPB using single-center data. STUDY DESIGN: Retrospective observational study. PATIENT SAMPLE: Patients who had spinal SPB and received radiotherapy with/without surgery, without chemotherapy, denosumab or zoledronic acid. OUTCOME MEASURES: MM progression rate, mortality rate, and reossification rate at 12 months. METHODS: This retrospective clinical review included 39 patients who underwent radiotherapy as first-line treatment for SPB in the spine. External radiation was divided into 20-25 fractions with a total dose of 35-46 Gy. At the 12-month follow-up after the index radiotherapy, significant and mild reossification, defined as bone formation with ≥30% or 0%-30% increase, respectively, in bony area based on increase in CT values were documented, along with progressive disease, which was a decrease in bony area with lesion enlargement. This study was funded by AO Foundation, AOSpine (AOSDIA2019-026) (CHF45,000), Peking University Medicine Seed Fund for Interdisciplinary Research (BMU2018MX022) (¥40,000), and Peking University Third Hospital (No. Y71508-01) (¥400,000). RESULTS: Twenty-six men and 13 women (mean age, 51.5 years) were included. Solitary plasmacytomas were located in the cervical, thoracic, and lumbar vertebrae in 16, 17, and 6 patients, respectively. The mean clinical follow-up period after treatment was 72 (range 12-216) months. Sixteen patients (41.0%) had significant reossification after radiotherapy, 21 (53.8%) showed mild reossification, and 2 (5.2%) had progressive bony destruction (after 7 and 23 months, respectively). There were no significant differences in age among the three groups (p=.127). At a mean follow-up of 37 (range 6-90) months after radiosurgery, 14 (35.8%) patients developed MM, including 9 patients who died at a mean duration of 55 (range 19-102) months. In the significant reossification group, only 1 patient (6.3%, 1 of 16) had MM progression 82 months after treatment (p=.044). In the mild reossification group, 56.5% (13 of 23) of patients had MM progression. The significant reossification rates of the radiotherapy dose groups of <40 Gy and ≥40 Gy were 35.7% and 44% (p=.614), respectively. In the univariate analysis, age ≥65 years (p<.001), tumor ≥5 cm (p=.009), Spinal Instability Neoplastic Score scores ≥11.5 (p=.040), radiotherapy (RT) combined with surgery (p<.001), and progression to MM (p=.007) were the independent prognostic factors for overall survival; whereas, age >44 years (p=.045) and RT combined with surgery (p<.001) were for multiple myeloma-free survival. In the multivariate analyses, age >65 years (p=.004) and progression to MM (p=.007) were the unfavorable independent factors for overall survival, whereas RT combined with surgery (p=.004) was the only factor for multiple myeloma-free survival. CONCLUSIONS: In patients with spinal SPB, 41.0% lesions showed significant reossification after radiotherapy. Patients with significant reossification had a better prognosis with less possibility of MM progression. Radiotherapy may be a safe and effective treatment choice for spinal SPB; more attention should be paid to reossification.

Recurrence Factors in Giant Cell Tumors of the Spine.

BACKGROUND: Giant cell tumors (GCTs) are benign, locally aggressive tumors. We examined the rate of local recurrence of spinal GCTs and sought to identify recurrence factors in patients who underwent surgery. METHODS: Between 1995 and 2014, 94 mobile spine GCT patients were treated at our hospital, comprising 43 male and 51 female patients with an average age of 33.4 years. Piecemeal intralesional spondylectomy and total en bloc spondylectomy (TES) were performed. Radiotherapy was suggested for recurrent or residual GCT cases. Since denosumab was not available before 2014 in our country, only interferon and/or zoledronic acid was suggested. RESULTS: Of the 94 patients, four underwent conservative treatment and 90 underwent operations. Seventy-five patients (79.8%) were followed up for a minimum of 24 months or until death. The median follow-up duration was 75.3 months. The overall recurrence rate was 37.3%. Ten patients (13.3%) died before the last follow-up (median: 18.5 months). Two patients (2.6%) developed osteogenic sarcoma. The local recurrence rate was 80.0% (24/30) in patients who underwent intralesional curettage, 8.8% (3/34) in patients who underwent extracapsular piecemeal spondylectomy, and 0 (0/9) in patients who underwent TES. The risk factors for local recurrence were lesions located in the cervical spine (P = 0.049), intralesional curettage (P < 0.001), repeated surgeries (P = 0.014), and malignancy (P < 0.001). Malignant transformation was a significant risk factor for death (P < 0.001). CONCLUSIONS: Cervical spinal tumors, curettage, and nonintact tumors were risk factors for local recurrence. Intralesional curettage and malignancy were the most important significant factors for local recurrence and death, respectively.

Surgical treatment of 21 patients with spinal metastases of differentiated thyroid cancer.

BACKGROUND: Differentiated thyroid cancer (DTC) is a common primary cancer for spinal metastases (SM). The treatments for DTC spinal metastases (SM) have evolved from simple surgery and radiotherapy to a multidisciplinary comprehensive therapeutic strategy of combined spinal surgery, general surgery, radiotherapy, nuclear medicine and endocrinology. The purpose of this study was to discuss the efficacy and prognosis associated with different surgical treatments of SM patients with DTC. METHODS: A total of 21 consecutive patients with SM of DTC that were treated between 1999 and 2013 were studied. Biopsy was routinely performed to achieve the pathological diagnosis before treatment. Three patients underwent total spondylectomy intralesionally or piecemeally, and 18 had curettage. Postoperative recurrence and survival times were analyzed by the Kaplan-Meier methods. RESULTS: Nineteen patients (90%) had an average of 42.7 months (range, 7-170 months) follow-up. The median visual analogue scale for pain reduced from 5 points to 1 point (P < 0.01), and the median Karnofsky performance score increased from 70 to 90 points after surgery (P < 0.01). Seventeen patients with neurological deficits attained improvements after surgeries, of at least one level according to the Frankel classification (P < 0.01). Eight patients with curettage had recurrence. Four patients died of DTC, 12 patients lived with disease, and three patients were disease-free. No significant effects on postoperative recurrence or survival were observed between surgery combined with conservative treatment, total spondylectomy, the number of bone metastases and visceral metastasis. CONCLUSIONS: DTC-SM have a relatively favorable prognosis, and curettage and stabilization can effectively relieve the pain and improve the quality of life and neurological status of the patients. For patients with Tomita scores of ≤3, total spondylectomy may have better clinical outcomes. Comprehensive therapeutic strategies including surgery, radioiodine, external beam radiation therapy and embolization should be considered for most patients.