Molecular mechanisms of osteosarcoma metastasis and possible treatment opportunities.

In osteosarcoma patients, metastasis of the primary cancer is the leading cause of death. At present, management options to prevent metastasis are limited and non-curative. In this study, we review the current state of knowledge on the molecular mechanisms of metastasis and discuss promising new therapies to combat osteosarcoma metastasis. Genomic and epigenomic changes, metabolic reprogramming, transcription factors, dysregulation of physiologic pathways, and alterations to the tumor microenvironment are some of the changes reportedly involved in the regulation of osteosarcoma metastasis. Key factors within the tumor microenvironment include infiltrating lymphocytes, macrophages, cancer-associated fibroblasts, platelets, and extracellular components such as vesicles, proteins, and other secreted molecules. We conclude by discussing potential osteosarcoma-limiting agents and their clinical studies.

The pedicled sartorius flap and mesh (PSM) technique vs no reconstruction in repairing the defect after type III pelvic bone tumor resection: a retrospective study.

BACKGROUND: Type III pelvic bone tumor resections are often accompanied by postoperative complications. In order to reduce complications, we developed a novel pedicled sartorius flap and mesh (PSM) technique to reconstruct the pelvic ring defect. In this study, we evaluated the efficacy and risks of this PSM technique in type III pelvic bone tumor resections by comparing outcomes between patients that underwent PSM reconstruction and patients that did not receive any reconstruction. METHODS: We retrospectively reviewed a consecutive set of patients that underwent type III pelvic bone tumor surgeries in our center from January 2020 to January 2021 with either PSM reconstruction (designated as the PSM group) or without any reconstruction (designated as the control group). General information such as age, gender, tumor type, tumor size, and surgical-related information such as duration of surgery, blood loss, and the surgical margins was collected. Outcome data recorded included wound complications such as infection and dehiscence, local recurrence, and Musculoskeletal Tumor Society (MSTS) scores for postoperative functional evaluation. Statistical analysis between both groups was performed with GraphPad Prism v7. RESULTS: A total of 20 patients were included in this study (PSM group n = 12, control group n = 8). While no herniation was found in the PSM group, it occurred in 6 of 8 cases in the control group. The control group showed a significantly higher rate of bacterial infection (p = 0.03) and wound dehiscence (p = 0.02) but lower MSTS scores (p < 0.05) compared to the PSM group. CONCLUSIONS: The use of the PSM technique can significantly reduce postoperative complication rates and enhance postoperative function following type III pelvic bone tumor resection.

A Systematic Review of Perioperative Complications in en Bloc Resection for Spinal Tumors.

STUDY DESIGN: Systematic review. OBJECTIVE: En bloc resection is a major, invasive surgical procedure designed to completely resect a vertebral tumor with a sufficient margin. It is technically demanding and potentially poses risks of perioperative complications. In this systematic review, we investigated the incidence of complications after en bloc resection for spinal tumors. METHODS: We screened PubMed and Embase databases for relevant English publications, from 1980 to 2020, using the following terms: spine OR spinal AND en bloc AND tumor. Using a standard PRISMA template, after the initial screening, full-text articles of interest were evaluated. RESULTS: Thirty-six studies with 961 patients were included. The overall mean age of patients was 49.6 years, and the mean follow-up time was 33.5 months. There were 560 complications, and an overall complication rate of 58.3% (560/961). The 5 most frequent complications were neurological damage (12.7%), hardware failure (12.1%), dural tear and cerebrospinal fluid leakage (10.6%), wound-related complications (7.6%) and vascular injury and bleeding (7.3%). The complication-related revision rate was 10.7% (103/961). The average incidence of complication-related death was 1.2% (12/961). CONCLUSIONS: En bloc resection is a surgical procedure that is very invasive and technically challenging, and the possible risks of perioperative complications should not be neglected. The overall complication rate is high. However, complication-related death was rare. The advantages of surgery should be weighed against the serious perioperative morbidity associated with this technique.

Evaluation of different scoring systems for spinal metastases based on a Chinese cohort.

INTRODUCTIONS: The spine is one of the most common sites of metastasis for malignancies. This study aimed to compare the predictive performance of seven commonly used prognostic scoring systems for surgically treated spine metastases. It is expected to assist surgeons in selecting appropriate scoring systems to support clinical decision-making and better inform patients. METHODS: We performed a retrospective study involving 268 surgically treated patients with spine metastases between 2017 and 2020 at a single regional oncology center in China. The revised Tokuhashi, Tomita, modified Bauer, revised Katagiri, van der Linden, Skeletal Oncology Research Group (SORG) nomogram, and SORG machine-learning (ML) scoring systems were externally validated. The area under the curve (AUC) of the receiver operating characteristic curve was used to evaluate sensitivity and specificity at different postoperative time points. The actual survival time was compared with the reference survival time provided in the original publication. RESULTS: In the present study, the median survival was 16.6 months. The SORG ML scoring system demonstrated the highest accuracy in predicting 90-day (AUC: 0.743) and 1-year survival (AUC: 0.787). The revised Katagiri demonstrated the highest accuracy (AUC: 0.761) in predicting 180-day survival. The revised Katagiri demonstrated the highest accuracy (AUC: 0.779) in predicting 2-year survival. Based on this series, the actual life expectancy was underestimated compared with the original reference survival time. CONCLUSIONS: None of the scoring systems can perform optimally at all time points and for all pathology types, and the reference survival times provided in the original study need to be updated. A cautious awareness of the underestimation by these models is of paramount importance in relation to current patients.

The predictive ability of routinely collected laboratory markers for surgically treated spinal metastases: a retrospective single institution study.

PURPOSE: We aimed to identify effective routinely collected laboratory biomarkers for predicting postoperative outcomes in surgically treated spinal metastases and attempted to establish an effective prediction model. METHODS: This study included 268 patients with spinal metastases surgically treated at a single institution. We evaluated patient laboratory biomarkers to determine trends to predict survival. The markers included white blood cell (WBC) count, platelet count, neutrophil count, lymphocyte count, hemoglobin, albumin, alkaline phosphatase, creatinine, total bilirubin, calcium, international normalized ratio (INR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR). A nomogram based on laboratory markers was established to predict postoperative 90-day and 1-year survival. The discrimination and calibration were validated using concordance index (C-index), area under curves (AUC) from receiver operating characteristic curves, and calibration curves. Another 47 patients were used as a validation group to test the accuracy of the nomogram. The prediction accuracy of the nomogram was compared to Tomita, revised Tokuhashi, modified Bauer, and Skeletal Oncology Research Group machine-learning (SORG ML). RESULTS: WBC, lymphocyte count, albumin, and creatinine were shown to be the independent prognostic factors. The four predictive laboratory markers and primary tumor, were incorporated into the nomogram to predict the 90-day and 1-year survival probability. The nomogram performed good with a C-index of 0.706 (0.702-0.710). For predicting 90-day survival, the AUC in the training group and the validation group was 0.740 (0.660-0.819) and 0.795 (0.568-1.000), respectively. For predicting 1-year survival, the AUC in the training group and the validation group was 0.765 (0.709-0.822) and 0.712 (0.547-0.877), respectively. Our nomogram seems to have better predictive accuracy than Tomita, revised Tokuhashi, and modified Bauer, alongside comparable prediction ability to SORG ML. CONCLUSIONS: Our study confirmed that routinely collected laboratory markers are closely associated with the prognosis of spinal metastases. A nomogram based on primary tumor, WBC, lymphocyte count, albumin, and creatinine, could accurately predict postoperative survival for patients with spinal metastases.

[Application of three-dimensional printed customized prosthesis with preserved epiphysis and articular surface in the reconstruction of large bone defects in treatment of adolescent femoral malignant tumors].

Objective: To investigate the clinical application and effectiveness of three-dimensional (3D) printed customized prosthesis with preserved epiphysis and articular surface in the reconstruction of large bone defects in treatment of adolescent femoral malignant tumors. Methods: The clinical data of 10 adolescent patients with femoral primary malignant tumor who met the selection criteria and underwent limb salvage surgery with 3D printed customized prosthesis with preserved epiphysis and articular surface between January 2020 and October 2021 were retrospectively analyzed. There were 6 males and 4 females with an average age of 12.5 years ranging from 7 to 18 years. There were 8 cases of osteosarcoma and 2 cases of Ewing's sarcoma. Enneking stage was Ⅱb. The length of the lesions ranged from 76 to 240 mm, with an average of 138.0 mm. The length of osteotomy (i. e. length of customized prosthesis) ranged from 130 to 275 mm, with an average of 198.5 mm; the distance between distal osteotomy end and epiphyseal line ranged from 0 to 15 mm, with an average of 8.8 mm; the bone defect after osteotomy accounted for 37.36% to 79.02% of the total length of the lesion bone, with a mean of 49.43%. The operation time, intraoperative blood loss, complications, tumor outcome (refered to RESIST1.1 solid tumor efficacy evaluation criteria), and limb length discrepancy were recorded. The Musculoskeletal Cancer Society (MSTS) 93 score was used to evaluate the function at 6 months after operation, and visual analogue scale (VAS) score was used to evaluate the pain before and after operation. Results: The operation was successfully performed in all the 10 patients, and the postoperative pathological results were consistent with the preoperative pathological results. The operation time was 165-440 minutes, with an average of 263 minutes; and the intraoperative blood loss was 100-800 mL, with an average of 350 mL. All patients were followed up 7-26 months, with an average of 11.8 months. No tumor was found on the osteotomy surface; the customized prosthesis were firmly installed and closely matched with the retained articular surface. The tumor outcome of neoadjuvant chemotherapy was stable in 4 cases and partial remission in 6 cases. No local recurrence or distant metastasis was found in 9 cases after postoperative adjuvant chemotherapy; pulmonary metastasis was found in 1 case at 12 months after operation. Two patients had local incision fat liquefaction, superficial infection, and delayed healing at 14 days after operation; 1 patient had local bone absorption at the contact surface of the prosthesis, and the screw and prosthesis did not loosen at 7 months after operation; the other patients had good incision healing, with no infection, prosthesis loosening, fracture, or other complications. At 6 months after operation, the MSTS93 score was 19-28, with an average of 24.1; 8 cases were excellent and 2 cases were good. The VAS score was 0.9±1.0, which significantly improved when compared with before operation (5.9±1.0) ( t=23.717, P<0.001). The height of the patients increased by 1-12 cm, with an average of 4.6 cm. At last follow-up, 4 patients had limb length discrepancy, with a length difference of 1 cm in 2 cases and 2 cm in 2 cases. Conclusion: The application of 3D printed customized prosthesis in the resection and reconstruction of adolescents femoral primary malignant tumors can achieve the purpose of preserving epiphysis and articular surface, and obtain good effectiveness.

Experience in utilizing a novel 3D digital model with CT and MRI fusion data in sarcoma evaluation and surgical planning.

OBJECTIVE: To assess sarcoma margins with more accuracy and aid surgical planning, we constructed three-dimensional (3D) digital models with computed tomography(CT) and magnetic resonance imaging (MRI) image fusion data and validated the preciseness of the models by comparing them with 3D models constructed with CT only data. MATERIALS AND METHODS: We retrospectively reviewed a consecutive set of patients treated in our center who were preoperatively evaluated with the fusion image model. Models based on fusion images or CT-only data were constructed. Volumes of both tumors were calculated and the tumors were overlapped to see the location of differences between the two models. RESULTS: A consecutive 12 cases (4 male vs. 8 female) were included in this study. Most of the tumors were located in the pelvic bone or spine. The volume of the two tumor models was different and the differences were mainly in the peripheral region of the tumor. CONCLUSION: CT and MRI fusion image 3D models are more accurate than models with CT-only data and can be very helpful in preoperative planning of sarcoma patients.

3D-printed vertebral body for anterior spinal reconstruction in patients with thoracolumbar spinal tumors.

OBJECTIVE: A 3D-printed vertebral prosthesis can be used to reconstruct a bone defect more precisely because of its tailored shape, with its innermost porous structure inducing bone ingrowth. The aim of this study was to evaluate the clinical outcomes of using a 3D-printed artificial vertebral body for spinal reconstruction after en bloc resection of thoracolumbar tumors. METHODS: This was a retrospective analysis of 23 consecutive patients who underwent surgical treatment for thoracolumbar tumors at our hospital. En bloc resection was performed in all cases, based on the Weinstein-Boriani-Biagini surgical staging system, and anterior reconstruction was performed using a 3D-printed artificial vertebral body. Prosthesis subsidence, fusion status, and instrumentation-related complications were evaluated. Stability of the anterior reconstruction method was evaluated by CT, and CT Hounsfield unit (HU) values were measured to evaluate fusion status. RESULTS: The median follow-up was 37 (range 24-58) months. A customized 3D-printed artificial vertebral body was used in 10 patients, with an off-the-shelf 3D-printed artificial vertebral body used in the other 13 patients. The artificial vertebral body was implanted anteriorly in 5 patients and posteriorly in 18 patients. The overall fusion rate was 87.0%. The average prosthesis subsidence at the final follow-up was 1.60 ± 1.79 mm. Instrument failure occurred in 2 patients, both of whom had substantial subsidence (8.47 and 3.69 mm, respectively). At 3 months, 6 months, and 1 year postoperatively, the mean CT HU values within the artificial vertebral body were 1930 ± 294, 1997 ± 336, and 1994 ± 257, respectively, with each of these values being significantly higher than the immediate postoperative value of 1744 ± 321 (p < 0.05). CONCLUSIONS: The use of a 3D-printed artificial vertebral body for anterior reconstruction after en bloc resection of the thoracolumbar spinal tumor may be a feasible and reliable option. The low incidence of prosthesis subsidence of 3D-printed endoprostheses can provide good stability instantly. Measurement of HU values with CT is a valuable method to evaluate the osseointegration at the bone-metal interface of a 3D-printed vertebral prosthesis.

Undifferentiated Pleomorphic Sarcoma with Neoplastic Fever: A Retrospective Study.

BACKGROUND: Although the annual incidence of undifferentiated pleomorphic sarcoma (UPS) is extremely low, it can be subdivided into different subtypes. UPS with fever of unknown origin (also known as neoplastic fever) is a specific subtype of UPS, which shows certain clinical features that differentiate it from other UPS subtypes. However, no studies have focused on this rare UPS subtype. This study retrospectively analyzed the clinical data of patients with UPS to provide a reference for the diagnosis and treatment of UPS with neoplastic fever. METHODS: This study included patients with UPS who were diagnosed and treated between June 2012 and June 2018. We examined whether these patients had a history of neoplastic fever. The characteristics of patients with UPS with neoplastic fever were summarized and analyzed. RESULTS: We reviewed the medical records of 183 patients with UPS. Seven (3.83%) of these patients had neoplastic fever. In patients with UPS with neoplastic fever, the primary lesions were located in the extremities and across the muscle space. In these patients, magnetic resonance imaging showed necrosis within the tumor body and extensive soft tissue edema around the tumor body. Patients with UPS with neoplastic fever had a lower metastasis rate (14.29% vs 44.94%) and a higher 3-year survival rate (85.71% vs 59.55%) than those without neoplastic fever. CONCLUSION: UPS with neoplastic fever is characterized by intratumoral necrosis and extensive edema of the surrounding soft tissues. Patients with UPS with neoplastic fever may have a better prognosis than those without neoplastic fever.

Reliability and validity of the simplified Chinese version of the Early Onset Scoliosis-24-Item Questionnaire (EOSQ-24).

BACKGROUND: It is important to use standard assessment tools to quantify the impact of early-onset scoliosis (EOS) on the health-related quality of life of these children and their caregivers. In this study we aimed to translate and validate the simplified Chinese version of the Early Onset Scoliosis Questionnaire-24 (EOSQ-24) in order to assess the health-related quality of life (HRQoL) and caregiver burden among patients with EOS from mainland China. METHODS: EOSQ-24 was forward-and-backward translated according to standard protocols, culturally adapted, and administered to patients fulfilling specific inclusion criteria and recruited between February and December 2015. Response distribution was assessed by their median and standard deviation. Floor and ceiling effects were calculated. Reliability was established using Cronbach's α and discriminative validity was determined using the Mann-Whitney U test and the Kruskal-Wallis test. RESULTS: A total of 63 children and their parents participated in this study. Most responses were left skewed towards normal physical and psychosocial well-being. No floor effect was observed but ceiling effect was found in questions regarding pain and pulmonary function. Cronbach's α for all questions and all domains was 0.950, and 0.927, respectively. EOSQ-24 scores were negatively correlated with curve severity and ambulatory status. Based on these preliminary results, EOSQ-24 could be used to distinguish patients in these regards. CONCLUSIONS: The simplified Chinese version of EOSQ-24 is a reliable and valid tool for HRQoL assessment among caregivers (parents) of children with EOS in mainland China. It could potentially be incorporated into routine clinical care in this patient population and as a standard assessment tool for research purposes.

Upper cervical spine reconstruction using customized 3D-printed vertebral body in 9 patients with primary tumors involving C2.

BACKGROUND: Reconstruction following resection of the primary tumors of the upper cervical spine is challenging, and conventional internal implants develop complications in this region. 3D printing, also known as additive manufacturing, can produce patient-specific porous implants in a particular shape for bone defect reconstruction. This study aimed to describe the clinical outcomes of upper cervical spine reconstruction using customized 3D-printed vertebral body in 9 patients with primary tumors involving C2. METHODS: Patients with primary tumors involving C2 who were treated in our institution between July 2014 and November 2018 were enrolled. A two-stage intralesional spondylectomy was performed using the posterior-anterior approach. Anterior reconstruction was accomplished using a customized 3D-printed vertebral body, which was fabricated by successive layering of melted titanium alloy powder using electron beam melting. No bone graft was used. RESULTS: Nine patients (2 males and 7 females) were included in the study with a mean age of 31.4 years (12 to 59 years). Seven patients demonstrated tumors located in C2 and 2 showed involvement of C2 and C3. During a mean follow-up of 28.6 months (range, 12-42 months), 1 patient died of systemic metastasis and 1 had local tumor recurrence, the other 7 patients were alive and functional in their daily living until the last follow-up without evidence of disease. The 3D-printed vertebral bodies were all stable with no sign of displacement or subsidence, evidence of implant osseointegration was observed on the imaging studies. For the posterior instrumentation systems, no screw loosening or rod breakage was found. CONCLUSIONS: Spinal reconstruction in the upper cervical region using customized 3D-printed vertebral body is reliable. The tailored shape matching with the contact surfaces and the porous structure conductive to osseointegration provide both short- and long-term stability to the implant.

Risk Factors for Instrumentation Failure After Total En Bloc Spondylectomy of Thoracic and Lumbar Spine Tumors Using Titanium Mesh Cage for Anterior Reconstruction.

OBJECTIVE: The present study investigated the risk factors for instrumentation failure (IF) after total en bloc spondylectomy (TES) of thoracic and lumbar spine tumors using a titanium mesh cage (TMC) for anterior reconstruction. METHODS: The data from patients who had undergone TES for thoracic and lumbar spine tumors in our institution were retrospectively reviewed. Anterior reconstruction was performed using a TMC filled with morcelized allograft or morcelized autograft. Posterior reconstruction was performed using pedicle fixation. Survival analysis from TES to IF was conducted. The Kaplan-Meier method was used for univariate analysis. Factors of statistical significance were included in the multivariate analysis using Cox regression analysis. RESULTS: A total of 30 patients (20 men and 10 women), with a mean age of 37.1 ± 14.3 years (range, 14-65 years) were included. The mean follow-up period was 41.8 ± 21.3 months (range, 13-120 months). Bone fusion was achieved in 23 patients (76.7%). IF occurred in 8 patients. The mean interval from TES to the first IF was 31.8 ± 15.1 months (range, 13-64 months). On univariable analysis, a body mass index >28 kg/m2, perioperative radiotherapy, and the TMC in an oblique position were associated with IF. On multivariable analysis, these 3 factors were entered into the Cox regression model and were also significant. CONCLUSIONS: The use of TES can achieve durable oncological control. However, IF, a not uncommon late complication that leads to reoperation, should be a cause for concern. We found perioperative radiotherapy, a TMC in an oblique position, and a body mass index >28 kg/m2 were significant predictive factors for IF.

A Cross-sectional Study on the Symptom Burden of Patients With Spinal Tumor: Validation of the Chinese Version of the M.D. Anderson Symptom Inventory-Spine Tumor Module.

CONTEXT: Tumors involving the spine are associated with unique symptoms affecting both patient survival and health-related quality of life. Currently, there is no disease-specific instrument in Chinese to assess the symptom burden of these patients. OBJECTIVES: The objective of this study was to translate and validate a Chinese version of the M.D. Anderson Symptom Inventory-Spine Tumor Module (MDASI-SP-C) to assess the symptom burden of Chinese-speaking patients with spinal tumors. METHODS: MDASI-SP-C was forward-and-backward translated according to standard protocols and administered to patients fulfilling study criteria at a major referral center of spine tumor between November 2014 and September 2015. The generic instruments of Short Form 36 Quality of Life Questionnaire (SF-36), Functional Assessment of Cancer Therapy-General Version (FACT-G), and Karnofsky Performance Scale were used along with MDASI-SP-C. Prevalence and severity distribution of each item were analyzed. Psychometric assessment and hierarchical cluster analysis were performed for the translated instrument. RESULTS: One hundred forty-two patients were enrolled. High interdependency and relatively low intra-cluster distances were identified. Cronbach's alpha of the entire instrument, the symptom severity subscale, and the interference subscale was 0.93, 0.91, and 0.92, respectively. Principal axis factoring resulted in a four-factor solution, which was reduced to a three-factor (general symptoms, spine-specific symptoms, and gastrointestinal symptoms) solution on account of clinical interpretation. Correlation coefficients between MDASI-SP-C items and their corresponding domains in SF-36 and/or FACT-G were all greater than 0.3. MDASI-SP-C was able to distinguish patients with different Karnofsky Performance Scale levels. CONCLUSION: MDASI-SP-C demonstrated satisfactory psychometric properties and could be used to better assess the symptom burden of Chinese-speaking patients with spine tumors for improved management of their medical needs.