Revision surgery for periprosthetic fracture of distal femur after endoprosthetic replacement of knee joint following resection of osteosarcoma.

Purpose: Periprosthetic fracture (PPF) is one of the severe complications in patients with osteosarcoma and carries the risk of limb loss. This study describes the characteristics, treatment strategies, and outcomes of this complication. Methods: Patients were consecutively included who were treated at our institution between 2016 and 2020 with a PPF of distal femur. The treatment strategies included two types: 1) open reduction and internal fixation with plates and screws and 2) replacement with long-stem endoprosthesis and reinforcement with wire rope if necessary. Results: A total of 11 patients (mean age 12.2 years (9-14)) were included, and the mean follow-up period was 36.5 (21-54) months. Most fractures were caused by direct or indirect trauma (n = 8), and others (n = 3) underwent PPF without obvious cause. The first type of treatment was performed on four patients, and the second type was performed on seven patients. The mean Musculoskeletal Tumor Society (MSTS) score was 20 (17-23). All patients recovered from the complication, and limb preservation could be achieved. Conclusion: PPF is a big challenge for musculoskeletal oncologists, particularly in younger patients. Additionally, PPF poses a challenge for orthopedic surgeons, as limb preservation should be an important goal. Hence, internal fixation with plates and endoprosthetic replacement are optional treatment strategies based on fracture type and patient needs.

HMGB1 Positive Feedback Loop Between Cancer Cells and Tumor-Associated Macrophages Promotes Osteosarcoma Migration and Invasion.

Numerous studies have demonstrated the key roles of tumor-associated macrophages (TAMs) in osteosarcoma metastasis. Higher levels of high mobility group box 1 (HMGB1) promote osteosarcoma progression. However, whether HMGB1 is involved in the polarization of M2 macrophages into M1 macrophages in osteosarcoma remains largely unknown. Here, HMGB1 and CD206 mRNA expression levels were measured by a quantitative reverse transcription-polymerase chain reaction in osteosarcoma tissues and cells. HMGB1 and receptor for advanced glycation end products (RAGE) protein expression levels were measured by western blotting. Osteosarcoma migration was measured using transwell and wound-healing assays, while a transwell assay determined osteosarcoma invasion. Macrophage subtypes were detected using flow cytometry. HMGB1 expression levels were aberrantly enhanced in osteosarcoma tissues compared with normal tissues and were positively correlated with AJCC III and IV stages, lymph node metastasis, and distant metastasis. Silencing HMGB1 inhibited the migration, invasion, and epithelial-mesenchymal transition (EMT) of osteosarcoma cells. Furthermore, reduced HMGB1 expression levels in conditioned media derived from osteosarcoma cells induced the polarization of M2 TAMs to M1 TAMs. In addition, silencing HMGB1 inhibited the liver and lung metastasis of tumors and reduced the expression levels of HMGB1, CD163, and CD206 in vivo. HMGB1 was found to regulate macrophage polarization through RAGE. Polarized M2 macrophages induced osteosarcoma migration and invasion, activating HMGB1 expression in osteosarcoma cells to form a positive feedback loop. In conclusion, HMGB1 and M2 macrophages enhanced osteosarcoma migration, invasion, and EMT through positive feedback regulation. These findings reveal the significance of tumor cell and TAM interactions in the metastatic microenvironment.

En bloc resection of huge primary tumors with epidural involvement in the mobile spine using the "rotation-reversion" technique: Feasibility, safety, and clinical outcome of 11 cases.

Background: En bloc resection of spinal tumors provides better local control and survival outcomes than intralesional resection. Safe margins during en bloc resection of primary spinal tumors with epidural involvement are required for improved outcomes. The present study describes a "rotation-reversion" technique that has been used for en bloc resection of huge primary tumors in the mobile spine with epidural involvement and reported the clinical outcomes in these patients. Methods: All patients with primary spinal tumors who were treated with the rotation-reversion technique at our institution between 2015 and 2021 were evaluated retrospectively. Of the patients identified, those with both huge extraosseous soft-tissue masses and epidural involvement were selected for a case review. Clinical and radiological characteristics, pathologic findings, operative procedures, complications, and oncological and functional outcomes of these patients were reviewed. Results: Of the 86 patients identified with primary spinal tumors who underwent en bloc resection using the rotation-reversion technique between 2015 and 2021, 11 had huge extraosseous soft-tissue masses with epidural involvement in the mobile spine. The average maximum size of these 11 tumors was 8.1 × 7.5 × 9.7 cm. Median follow-up time was 28.1 months, mean operation time was 849.1 min (range 465-1,340 min), and mean blood loss was 6,972.7 ml (range 2,500-17,700 ml), with 10 (91%) of the 11 patients experiencing perioperative complications. The negative margin rate was 91%, with only one patient (9%) experiencing local recurrence. Ten patients were able to walk normally or with a crutch at the last follow-up, whereas one was completely paralyzed preoperatively. Conclusion: The rotation-reversion technique is an effective procedure for the en bloc resection of huge primary spinal tumors, with the extension of invasion in selected patients including not only the vertebral body but also the pedicle and part of the posterior arch.

Image-guided percutaneous biopsy and pathological diagnosis in atypical tuberculous spondylitis: a case series and clinical outcomes.

Background: Tuberculous spondylitis can be difficult to distinguish from alternative spinal pathologies such as malignancy, particularly if the imaging features are not typical. Biopsy and histopathological analysis are facilitative to the early and accurate diagnosis of atypical tuberculous spondylitis and the clinical management. The purpose of this study is to describe some of the atypical imaging features of tuberculous spondylitis diagnosed by image-guided percutaneous biopsy, as well as associated treatment outcomes. Methods: We performed a retrospective analysis of all patients diagnosed with tuberculous spondylitis after image-guided percutaneous biopsy at The Third Affiliated Hospital of Southern Medical University between 2013 and 2020. Of the patients identified, those with atypical imaging features were selected for case review. All patients were given anti-tuberculous medication treatment with or without surgery. The imaging features, histological and microbiological results, and clinical presentations and outcomes were evaluated. Neurological function was evaluated according to the Frankel grading system. The clinical outcomes were evaluated by Visual Analogic Scale (VAS) scores for pain, imaging [X-ray, computed tomography (CT), and magnetic resonance imaging (MRI)] results, and laboratory examinations. Comparison of VAS scores was made by Student t-test. Results: Of the 102 patients identified with tuberculous spondylitis between 2013 and 2020, eight patients (two females and six males) with a mean age of 41.6 years (range, 18-61 years) demonstrated atypical imaging findings, including central vertebral body lesion, multiple skip vertebral lesions, extradural mass lesion and anterior subperiosteal lesion. All eight patients received anti-tuberculous medication treatment, and six underwent surgery. One patient developed a pleural effusion after debridement of the thoracic lesion. The mean follow-up period was 16.2 months (6-37 months). The VAS scores before treatment and at the final follow-up showed significant differences (7.25±1.49 and 0.0±0.0, respectively, P<0.01). Improved neurological function were observed in all patients. Solid fusion and osteogenic osteosclerosis were observed at the final follow-up, and no recurrence was observed in any cases. Conclusions: All eight patients had a good prognosis. Image-guided biopsy and histopathological analysis are helpful for the early diagnosis of tuberculous spondylitis, especially when imaging features are not typical for this condition.

METTL14-mediated epitranscriptome modification of MN1 mRNA promote tumorigenicity and all-trans-retinoic acid resistance in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumor in adolescents. The molecular mechanism behind OS progression and metastasis remains poorly understood, which limits the effectiveness of current therapies. RNA N6-methyladenosine (m6A) modification plays a critical role in influencing RNA fate. However, the biological significance of m6A modification and its potential regulatory mechanisms in the development of OS remain unclear. METHODS: Liquid chromatography-tandem mass spectrometry (LC-MS/MS), dot blotting, and colorimetric ELISA were used to detect m6A levels. Western blotting, quantitative real-time PCR (RT-qPCR) and immunohistochemistry (IHC) were used to investigate METTL14 expression levels. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptomic RNA sequencing (RNA-seq) were used to screen the target genes of METTL14. RNA pull-down and RNA immunoprecipitation (RIP) assays were conducted to explore the specific binding of target genes and relevant m6A "readers". RNA stability and polysome analysis assays were used to detect the half-lives and translation efficiencies of the downstream genes of METTL14. IHC and clinical data were applied to explore the clinical correlations of METTL14 and its downstream target genes with the prognosis of OS. FINDINGS: We observed the abundance of m6A modifications in OS and revealed that METTL14 plays an oncogenic role in facilitating OS progression. MeRIP-seq and RNA-seq revealed that MN1 is a downstream gene of METTL14. MN1 contributes to tumor progression and all-trans-retinoic acid (ATRA) chemotherapy resistance in OS. Mechanistically, MN1 is methylated by METTL14, specifically in the coding sequence (CDS) regions, and this modification is recognized by the specific m6A reader insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) to prevent MN1 mRNA degradation and promote it translation efficiency. IHC showed that MN1 expression was positively correlated with METTL14 and IGF2BP2 expression in OS tissues. The METTL14-IGF2BP2-MN1 panel demonstrated more promising prognostic value for OS patients than any of these molecules individually. INTERPRETATION: Our study revealed that METTL14 contributes to OS progression and ATRA resistance as an m6A RNA methylase by regulating the stability and translation efficiency of MN1 and thus provides both an underlying biomarker panel for prognosis prediction in OS patients. FUNDING: This work was supported by the National Natural Science Foundation of China (Grants 81972510 and 81772864).

A novel limb-salvage reconstruction strategy with a custom hemipelvic endoprosthesis and preserved femoral head following the resection of periacetabular tumors: A preliminary study.

The treatment of periacetabular malignancy frequently challenges surgeons. To simplify the surgical procedure, we performed a novel reconstruction strategy preserving the femoral head for patients with periacetabular malignancies. We retrospectively reviewed 14 patients who underwent total en bloc resection of a periacetabular tumor and reconstruction of the hip joint with an individualized hemipelvic endoprosthesis and remaining femoral head from July 2015 to January 2019 at our center. Regions of pelvic resection: region II-4 (28.6%), region I + II-5 (35.7%), region II + III-2 (14.3%) and region I + II + III-3 (21.4%). The oncological outcomes were that 13 patients survived without disease and one patient survived with lung metastasis. None of the patients experienced local recurrence (range: 20-62 months; mean: 32 months). The incidence of postoperative complications was 35.7%, including delayed wound healing and deep venous thrombosis. No prosthesis-related complications occurred until the last follow-up in this study (range: 20-62 months; mean: 32 months). The mean Musculoskeletal Tumor Society functional outcome score was 23.2. The mean Toronto Extremity Salvage Score of the patients was 75.7 points, with a mean limb discrepancy of 1.51 cm (range: 0.5-3.2 cm). Reconstruction with preservation of the femoral head showed acceptable early functional and oncological outcomes, and it had an acceptable complication rate.

Cordycepin augments the chemosensitivity of osteosarcoma to cisplatin by activating AMPK and suppressing the AKT signaling pathway.

BACKGROUND: Osteosarcoma is the most common primary bone tumor in children and adolescents. However, some patients with osteosarcoma develop resistance to chemotherapy, leading to a poor clinical prognosis. Hence, effective therapeutic agents that can improve the response to chemotherapy drugs to improve the prognosis of patients with osteosarcoma are urgently needed. Cordycepin has recently emerged as a promising antitumor drug candidate. This study aims to explore the effect of cordycepin in suppressing osteosarcoma in vivo and in vitro and the synergistic effect of cordycepin combined with cisplatin and to demonstrate the underlying molecular mechanism. METHODS: CCK-8 assay was performed to investigate the inhibition effect of cordycepin combined with cisplatin in osteosarcoma cell lines. The colony formation and invasion abilities were measured by colony formation assay and Transwell assay. Osteosarcoma cells apoptosis was detected by flow cytometry. Western blot analysis were used to detect the expression of cell apoptosis-related proteins and AMPK and AKT/mTOR signaling pathway-related proteins. Finally, we performed the in vivo animal model to further explore whether cordycepin and cisplatin exert synergistic antitumor effects. RESULTS: Notably, we found that treatment with cordycepin inhibited cell proliferation, invasion, and induced apoptosis in osteosarcoma cells in vitro and in vivo. Moreover, the combination of cordycepin and cisplatin led to marked inhibition of osteosarcoma cell proliferation and invasion and promoted osteosarcoma cell apoptosis in vitro and in vivo. Mechanistically, we demonstrated that cordycepin enhanced the sensitivity of osteosarcoma cells to cisplatin by activating AMPK and inhibiting the AKT/mTOR signaling pathway. CONCLUSIONS: In brief, this study provides comprehensive evidence that cordycepin inhibits osteosarcoma cell growth and invasion and induces osteosarcoma cell apoptosis by activating AMPK and inhibiting the AKT/mTOR signaling pathway and enhances the sensitivity of osteosarcoma cells to cisplatin, suggesting that cordycepin is a promising treatment for osteosarcoma.

Experience with periprosthetic infection after limb salvage surgery for patients with osteosarcoma.

BACKGROUND: The rate of postoperative infection developing is higher after limb salvage surgery (LSS) following sarcoma resection compared with conventional arthroplasty. The goal of this study is to summarize our experience in management of periprosthetic joint infection (PJI) and the risk factors of early PJI after LSS. METHODS: Between January 2010 and July 2019, 53 patients with osteosarcoma in the lower extremities who encountered periprosthetic infection after segmental tumor endoprosthetic replacement in our center were analyzed. Detailed patient characteristics and therapeutic information were collected from database of our institution or follow-up data and we divided patients according to the interval time between infection and tumor resection (surgery-infection interval) and investigate potential risk factors. RESULTS: A total of 53 (5.08%) patients were suffered postoperative infection. The average interval between surgery and clinical signs of deep infections are 27.5 days. For the drainage culture, positive results were only presented in 11 patients (20.8%). Almost half of this study's (47.2%) patients underwent a traditional two-stage revision, that was, after the removal of the infected prosthesis, we applied antibiotic-loaded bone cements as a spacer. The mean blood loss during initial implantation surgery and operation time both correlated with interval period between PJI and initial implantation significantly (P = 0.028, P = 0.046). For several patients which infection marker was hardly back to normal after spacer implantation, we conservatively introduced an improved combination of bone cement and prosthesis for the second-stage surgery (5.6%). There were six patients needing re-operation, of which three were due to the aseptic loosening of the prosthesis, one developed periprosthetic infection again, and two patients encountered local recurrence and underwent amputation. Two patients were dead from distal metastasis. CONCLUSIONS: A two-stage revision strategy remains effective and standardized methods for PJI patients. Total operation time and blood loss during LSS of osteosarcoma are the main risk factors of early PJI. For the patients without confirmed eradiation of microorganisms, an improved combination of bone cement and prosthesis applied in the second-stage surgery could achieve satisfied functional and oncologic results.

Plastic lengthening amputation with vascularized bone grafts in children with bone sarcoma: a preliminary report.

BACKGROUND: At present, amputation was widely adopted for young patients when limb salvage was deemed risky with several surgical strategy such as rotationplasty. However, leg length discrepancies and unfavorable cosmetic results were indispensable complication of this strategy. The purpose of this study was to propose a novel reconstruction strategy and evaluate the early clinical and functional outcomes of the strategy. METHODS: Plastic lengthening amputation (PLA) has been developed by lengthening the stump to preserve one additional distal joint for fixing the artificial limb well. The surgical technique and postoperative management were documented, and the functional outcomes were compared with those of traditional amputation (TA). Six pairs of patients matched for age, sex, location, pathological type, and final prosthesis underwent individually designed plastic lengthening amputation with vascularized autografts or traditional amputation between January 2005 and December 2007. All patients were followed, and the locomotor index and the musculoskeletal tumor society score (MSTS) were used to describe and quantitatively grade limb functional outcomes after amputation. The complications and functional outcomes of the patients taken two kinds of procedures were compared. RESULTS: Twelve patients with osteosarcoma or Ewing's sarcoma of either the femur or tibia were included in the study. Six patients underwent plastic lengthening amputations, three of whom also underwent vascular anastomosis. Patients were followed for an average of 48.17 months; bone healing required an average of 3.3 months. No local recurrence was found. The average postoperative locomotor index functional score of the affected limb was 32.67 ± 5.89 in the plastic lengthening amputation group while was 19.50 ± 7.87 in the traditional amputation group. The MSTS functional scores were 22.67 ± 1.33 and 24.17 ± 1.45 at 6 and 12 months for patients in PLA group while 17.00 ± 1.549 and 17.83 ± 1.64 at 6 and 12 months for patients in TA group. CONCLUSIONS: Plastic lengthening amputations with vascularized autografts could preserve the knee joint to improve the function of the amputated limb in selected bone sarcoma patients.

CB-5083, an inhibitor of P97, suppresses osteosarcoma growth and stem cell properties by altering protein homeostasis.

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents, and its treatment still needs to be improved. Here, we assessed the antitumor ability of CB-5083, an oral inhibitor of P97, in osteosarcoma. MTT, colony formation, sphere formation, cell cycle and apoptosis assays and animal studies showed that CB-5083 significantly inhibited osteosarcoma cell growth in vitro and in vivo. The inhibition of P97 also led to suppression of endoplasmic reticulum-associated degradation (ERAD), thereby resulted in activation of the apoptosis function of the unfolded protein response (UPR), and ultimately induced the death of osteosarcoma cells. Furthermore, an analysis of clinical patient samples confirmed that P97 can predict the outcomes of patients with osteosarcoma. Our studies showed that CB-5083 inhibited the growth and stem cell abilities of osteosarcoma cells both in vitro and in vivo and might be a promising drug for osteosarcoma treatment.

Clinical Significance of the Radiological Relationship between the Tumor and the main blood vessels in Enneking IIB Osteosarcoma of the extremities.

Aim: Osteosarcoma is one of the most prevalent primary bone malignancies in children and adolescents. Magnetic resonance imaging (MRI) has been considered a very critical tool to provide anatomical information of tumor and surrounding main blood vessels. To evaluate the prognostic significance of the radiological vascular involvement according to the pre-treatment MRI in patients with Enneking IIB osteosarcoma. Methods: In this retrospective study, we included 482 patients younger than 50 years old with Enneking IIB primary osteosarcoma of the extremities with complete clinical records from 2005 to 2015.Univariate and multivariable analyses were conducted to identify the risk factors for OS (Overall survival) and EFS (Event-free survival). The correlations between the risk factors was performed using Spearman analysis. The Kaplan-Meier method was used to calculate survival curves. Based on the radiological relationship between the tumor lesion and the surrounding reactive area with the main blood vessels as shown on pretreatment MRI findings. Results: Radiological vascular involvement assessed via pretreatment MRI is an important risk factor for Enneking IIB primary patients with osteosarcoma (HROS=2.32/HREFS=1.81 P<0.01) according to the univariate and multivariable analyses. Enneking IIB patients with osteosarcoma were assigned to three subtypes based on the radiological relationship between the main blood vessels and the lesion or reactive area. The 5-year cumulative OS of patients classified by the three types were 81.6% (type I), 67.1% (type II) and 44.8% (type III)(P<0.01). The 5-year cumulative EFS of the three types were 60.2% (type I), 46.7% (type II) and 30.2% (type III)(P<0.05). The total 5-year cumulative OS and EFS for all patients were 68.3% and 48.3%, respectively. Conclusion: Vascular involvement according to radiological findings from pretreatment MRI is an independent risk factor for cumulative OS and EFS in patients with Enneking IIB primary osteosarcoma of the extremities. The new subtyping based on the relationship between the tumors and surrounding reactive area with the main blood vessels based on pretreatment MRI can predict the prognosis of patients with osteosarcoma and provide certain directive information for selecting the appropriate surgical procedure for individual patients.

Comparison of local control and survival outcomes between surgical and non-surgical local therapy on pelvic Ewing's sarcoma patients: a meta-analysis.

BACKGROUND: The efficacy of surgical therapy to nonsurgical therapy is still a controversial topic in pelvic Ewing's sarcoma (ES) management. We perform a systemic review and meta-analysis to compare the effect of local control (LC) and survival outcomes between surgical and nonsurgical local therapy on pelvic ES patients with systemic chemotherapy. METHODS: Published retrospective studies searched from PubMed, Embase, Cochrane and Web of Science databases that investigated the effects of surgical and nonsurgical local therapy on the LC and survival outcomes of patients with pelvic ES treated with chemotherapy were included in our study. Our primary outcome was the LC rate and progression-free survival (PFS) rate. The effect of confounders of extend of disease, surgical margin and chemotherapy respond on PFS was analyzed in subgroups. RESULTS: Ten studies with 782 pelvic ES patients were included in our analysis. Surgical patients showed higher LC and PFS rate comparing to nonsurgical patients [LC: risk ratio (RR) 0.72, 95% CI: 0.52-1.00, P=0.05, I2=0%; PFS: RR 0.72, 95% CI: 0.61-0.86, P=0.000, I2=15%]. Localized patients showed higher PFS with surgical therapy than nonsurgical patients (RR 0.67, 95% CI: 0.51-0.88, P=0.003).Patients with adequate resection and good chemotherapy respond improved PFS comparing to nonsurgical patients (adequate resection vs. nonsurgical: RR 0.59, 95% CI: 0.46-0.76, P<0.001, I2=0%; good respond vs. nonsurgical: RR 0.56, 95% CI: 0.41-0.77, P<0.001, I2=21%). But patients with inadequate resection and poor chemotherapeutic respond shows no statistical different PFS comparing to nonsurgical patients (inadequate resection vs. nonsurgical: RR 1.11, 95% CI: 0.87-1.41, P=0.41, I2=0%; poor respond vs. nonsurgical: RR 1.17, 95% CI: 0.90-1.52, P=0.25, I2=0%). CONCLUSIONS: Surgical therapy is primarily recommended in localized, resectable, good chemotherapeutic respond pelvic ES. Inadequate resection and poor chemotherapeutic respond are negative prognostic factors in surgical patients and their surviving are not improved comparing with nonsurgical patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020149224.

Regional lymph node involvement is associated with poorer survivorship in patients with upper extremity osteosarcoma than with lower extremity osteosarcoma: a SEER analysis.

BACKGROUND: Although the upper limb is the second most common site of osteosarcoma, investigations into clinical manifestation differences between upper and lower limb patients are still sporadic. We retrospectively investigated the characteristics of these patients to gain a better understanding of the differences between upper and lower limb osteosarcoma patients. METHODS: This retrospective study involved patients diagnosed with extremity osteosarcoma between 1997 and 2016 collected from the Surveillance, Epidemiology, and End Results (SEER) database. Patient characteristics were analyzed with t-tests, rank sum tests and chi-square tests. Log-rank tests were applied to evaluate univariate significance, and Cox hazards models were performed in multivariate analysis. A binary logistics regression model was used to screen the risk factors related to lymph node involvement. RESULTS: In total, 1,882 patients, 1,588 (84.4%) with lower limb lesions and 294 (15.6%) with upper limb lesions were enrolled in our study. The patients with upper limb osteosarcoma exhibited poorer 5-year overall survival (OS) than patients with lower limb osteosarcoma (54.8% vs. 63.2%, P=0.02). The upper limb patients had more lymph node involvement (5.6% vs. 2.7%, P=0.03), which was found to be an independent prognostic factor (P=0.000). Tumors located in the upper limbs and the presence of distal metastasis were risk factors related to lymph node involvement in the extremity (P<0.05). The upper limb patients were tended to suffer greater risk of being affected by both metastasis and lymph node involvement (15.7% vs. 9.4%, P=0.18). CONCLUSIONS: Upper limb osteosarcoma patients are characterized by more lymph node involvement than lower limb patients, leading to poorer OS. In addition, upper limb patients are at greater risk for both lymph node involvement and distal metastasis. Our results suggest that upper limb patients should be screened more thoroughly for regional lymph node involvement.

Multimodal Risk-Adapted Treatment in Surgical Patients With Synovial Sarcoma: A Preoperative Nomogram-Guided Adjuvant Treatment Strategy.

Background: Synovial sarcoma is characterized by heterogeneous clinical manifestations, making it difficult to evaluate individual patients' prognoses and design personal treatment schemes. We established an effective preoperative nomogram to predict cancer-specific survival (CSS) and present a risk-adapted adjuvant treatment strategy in surgical patients with synovial sarcoma. Methods: This retrospective study included patients from the Surveillance, Epidemiology, and End Results (SEER) database who were diagnosed with synovial sarcoma between 1996 and 2015. The patients were randomly divided into training and validation groups. The predictors were selected using univariate and multivariate Cox hazards models. The nomogram performance was verified for its discriminatory ability and calibration. We further stratified the patients into different risk groups according to the nomogram scores and compared the efficacy of chemotherapy, radiotherapy, and combination of radiotherapy and chemotherapy. Results: There were 915 patients enrolled in our study, with 874 patients either alive or dead due to synovial sarcoma. We established a nomogram to predict 5-year CSS based on independent factors, including sex, age, grade, tumor size, location, and extent (all p < 0.05). Our model showed a consistently good discriminatory ability and calibration for predicting 5-year CSS in both the training (c-index = 0.78, 95% CI 0.75-0.81) and validation (c-index = 0.73, 95% CI 0.68-0.78). Based on their nomogram scores, we divided patients into 5 groups. Compared to patients without adjuvant treatment, nomogram I patients with adjuvant treatment had no improvements in 5-year CSS (100.0% vs. 100.0%), nomogram II patients had higher 5-year CSS with radiotherapy or chemotherapy (92.9% vs. 72.2%, p = 0.015), nomogram III patients had higher 5-year CSS with combination of chemotherapy and radiotherapy (70.1% vs. 47.2%, p = 0.004), nomogram IV patients had higher 5-year CSS with radiotherapy (41.3% vs. 15.6%, p = 0.015), and nomogram V patients had no improvements in 5-year CSS rates with adjuvant treatment (28.9% vs. 16.9%, p = 0.18). Conclusion: The nomogram showed a satisfactory discriminatory ability and calibration for predicting 5-year CSS in synovial sarcoma patients. Based on this nomogram, we stratified synovial sarcoma patients according to risk levels, which enabled us to provide a useful grouping scheme that can inform multimodal risk-adapted treatment in synovial sarcoma.

Comparison of clinical features, management and outcomes of osteosarcoma located in proximal fibula and proximal tibia: a propensity score matching analysis.

BACKGROUND: The aim of this study was to compare proximal fibular and proximal tibial sites regarding osteosarcoma in the proximal crus. Furthermore, we proposed a hypothesis explaining the differences. METHODS: From Jaunary 2000 to February 2015, 28 patients with non-metastatic proximal fibular osteosarcoma and 214 patients with non-metastatic proximal tibial osteosarcoma underwent surgery were identified in our center. All clinical data were analyzed retrospectively. Propensity score matching of patients in a 1:2 ratio was conducted based on age, gender and Enneking stage. To analyze possible factors resulting in amputation, we investigated extraosseous tumor volumes (ETVS), the nearest of the blood vessel to reactive zone (NBR) and the nearest of the blood vessel to tumor (NBT). RESULTS: Amputation rates were higher in the proximal fibula cohort (35.7%) than in the proximal tibia cohort (14.3%; p = 0.046). Comparing possible clinical characteristics related with amputation between two cohorts, the proximal fibula cohort had larger ETVS (p = 0.000). Moreover, the proximal fibula cohort had a smaller NBT for anterior tibial vessels (p = 0.025), a smaller NBR for posterior tibial vessels (p = 0.013) and a smaller NBT for posterior tibial vessels (p = 0.007) than the proximal tibia cohort. Univarite and multivariable analyses showed that NBT for posterior tibial vessels was the only independent factor associated with amputation. The 3-year event-free survival (EFS) and overall survival (OS) rates for the proximal fibula cohort vs. the proximal tibia cohort were 52.6% vs. 78.0% (p = 0.045) and 63.7% vs. 81.2% (p = 0.177), respectively. The MSTS scores for the functional evaluation of limb-salvaging surgery were similar in both groups (p = 0.212). CONCLUSIONS: Amputation rates among patients were higher when osteosarcoma was located in proximal fibula than in proximal tibia. A smaller NBT for posterior tibial vessels was associated with higher amputation rates. Prognosis of the proximal fibula cohort was poorer than that of the proximal tibia cohort of osteosarcoma patients.