Aims. Treatment of high-grade limb bone sarcoma that invades a joint requires en bloc extra-articular excision. MRI can demonstrate joint invasion but is frequently inconclusive, and its predictive value is unknown. We evaluated the diagnostic accuracy of direct and indirect radiological signs of intra-articular tumour extension and the performance characteristics of MRI findings of intra-articular tumour extension. Methods. We performed a retrospective case-control study of patients who underwent extra-articular excision for sarcoma of the knee, hip, or shoulder from 1 June 2000 to 1 November 2020. Radiologists blinded to the pathology results evaluated preoperative MRI for three direct signs of joint invasion (capsular disruption, cortical breach, cartilage invasion) and indirect signs (e.g. joint effusion, synovial thickening). The discriminatory ability of MRI to detect intra-articular tumour extension was determined by receiver operating characteristic analysis. Results. Overall, 49 patients underwent extra-articular excision. The area under the curve (AUC) ranged from 0.65 to 0.76 for direct signs of joint invasion, and was 0.83 for all three combined. In all, 26 patients had only one to two direct signs of invasion, representing an equivocal result. In these patients, the AUC was 0.63 for joint effusion and 0.85 for synovial thickening. When direct signs and synovial thickening were combined, the AUC was 0.89. Conclusion. MRI provides excellent discrimination for determining intra-articular tumour extension when multiple direct signs of invasion are present. When MRI results are equivocal, assessment of synovial thickening increases MRI’s discriminatory ability to predict intra-articular joint extension. These results should be interpreted in the context of the study’s limitations. The inclusion of only extra-articular excisions enriched the sample for true positive cases. Direct signs likely varied with tumour histology and location. A larger, prospective study of periarticular bone sarcomas with spatial correlation of histological and radiological findings is needed to validate these results before their adoption in clinical practice. Cite this article: Bone Jt Open 2024;5(10):944–952

Aims. The aim of this study was to identify factors associated with five-year cancer-related mortality in patients with limb and trunk soft-tissue sarcoma (STS) and develop and validate machine learning algorithms in order to predict five-year cancer-related mortality in these patients. Methods. Demographic, clinicopathological, and treatment variables of limb and trunk STS patients in the Surveillance, Epidemiology, and End Results Program (SEER) database from 2004 to 2017 were analyzed. Multivariable logistic regression was used to determine factors significantly associated with five-year cancer-related mortality. Various machine learning models were developed and compared using area under the curve (AUC), calibration, and decision curve analysis. The model that performed best on the SEER testing data was further assessed to determine the variables most important in its predictive capacity. This model was externally validated using our institutional dataset. Results. A total of 13,646 patients with STS from the SEER database were included, of whom 35.9% experienced five-year cancer-related mortality. The random forest model performed the best overall and identified tumour size as the most important variable when predicting mortality in patients with STS, followed by M stage, histological subtype, age, and surgical excision. Each variable was significant in logistic regression. External validation yielded an AUC of 0.752. Conclusion. This study identified clinically important variables associated with five-year cancer-related mortality in patients with limb and trunk STS, and developed a predictive model that demonstrated good accuracy and predictability. Orthopaedic oncologists may use these findings to further risk-stratify their patients and recommend an optimal course of treatment. Cite this article: Bone Joint J 2023;105-B(6):702–710

Aims. Radiotherapy is a well-known local treatment for spinal metastases. However, in the presence of postoperative systemic therapy, the efficacy of radiotherapy on local control (LC) and overall survival (OS) in patients with spinal metastases remains unknown. This study aimed to evaluate the clinical outcomes of post-surgical radiotherapy for spinal metastatic non-small-cell lung cancer (NSCLC) patients, and to identify factors correlated with LC and OS. Methods. A retrospective, single-centre review was conducted of patients with spinal metastases from NSCLC who underwent surgery followed by systemic therapy at our institution from January 2018 to September 2022. Kaplan-Meier analysis and log-rank tests were used to compare the LC and OS between groups. Associated factors for LC and OS were assessed using Cox proportional hazards regression analysis. Results. Overall, 123 patients with 127 spinal metastases from NSCLC who underwent decompression surgery followed by postoperative systemic therapy were included. A total of 43 lesions were treated with stereotactic body radiotherapy (SBRT) after surgery and 84 lesions were not. Survival rate at one, two, and three years was 83.4%, 58.9%, and 48.2%, respectively, and LC rate was 87.8%, 78.8%, and 78.8%, respectively. Histological type was the only significant associated factor for both LC (p = 0.007) and OS (p < 0.001). Treatment with targeted therapy was significantly associated with longer survival (p = 0.039). The risk factors associated with worse survival were abnormal laboratory data (p = 0.021), lesions located in the thoracic spine (p = 0.047), and lumbar spine (p = 0.044). This study also revealed that postoperative radiotherapy had little effect in improving OS or LC. Conclusion. Tumour histological type was significantly associated with the prognosis in spinal NSCLC metastasis patients. In the presence of post-surgical systemic therapy, radiotherapy appeared to be less effective in improving LC, OS, or quality of life in spinal NSCLC metastasis patients. Cite this article: Bone Jt Open 2024;5(4):350–360

Aims. The preoperative grading of chondrosarcomas of bone that accurately predicts surgical management is difficult for surgeons, radiologists, and pathologists. There are often discrepancies in grade between the initial biopsy and the final histology. Recent advances in the use of imaging methods have shown promise in the ability to predict the final grade. The most important clinical distinction is between grade 1 chondrosarcomas, which are amenable to curettage, and resection-grade chondrosarcomas (grade 2 and 3) which require en bloc resection. The aim of this study was to evaluate the use of a Radiological Aggressiveness Score (RAS) to predict the grade of primary chondrosarcomas in long bones and thus to guide management. Methods. A total of 113 patients with a primary chondrosarcoma of a long bone presenting between January 2001 and December 2021 were identified on retrospective review of a single oncology centre’s prospectively collected database. The nine-parameter RAS included variables from radiographs and MRI scans. The best cut-off of parameters to predict the final grade of chondrosarcoma after resection was determined using a receiver operating characteristic curve (ROC), and this was correlated with the biopsy grade. Results. A RAS of ≥ four parameters was 97.9% sensitive and 90.5% specific in predicting resection-grade chondrosarcoma based on a ROC cut-off derived using the Youden index. Cronbach’s α of 0.897 was derived as the interclass correlation for scoring the lesions by four blinded reviewers who were surgeons. Concordance between resection-grade lesions predicted from the RAS and ROC cut-off with the final grade after resection was 96.46%. Concordance between the biopsy grade and the final grade was 63.8%. However, when the patients were analyzed based on surgical management, the initial biopsy was able to differentiate low-grade from resection-grade chondrosarcomas in 82.9% of biopsies. Conclusion. These findings suggest that the RAS is an accurate method for guiding the surgical management of patients with these tumours, particularly when the initial biopsy results are discordant with the clinical presentation. Cite this article: Bone Joint J 2023;105-B(7):808–814

Aims. Intra-articular (IA) tumours around the knee are treated with extra-articular (EA) resection, which is associated with poor functional outcomes. We aim to evaluate the accuracy of MRI in predicting IA involvement around the knee. Methods. We identified 63 cases of high-grade sarcomas in or around the distal femur that underwent an EA resection from a prospectively maintained database (January 1996 to April 2020). Suspicion of IA disease was noted in 52 cases, six had IA pathological fracture, two had an effusion, two had prior surgical intervention (curettage/IA intervention), and one had an osseous metastasis in the proximal tibia. To ascertain validity, two musculoskeletal radiologists (R1, R2) reviewed the preoperative imaging (MRI) of 63 consecutive cases on two occasions six weeks apart. The radiological criteria for IA disease comprised evidence of tumour extension within the suprapatellar pouch, intercondylar notch, extension along medial/lateral retinaculum, and presence of IA fracture. The radiological predictions were then confirmed with the final histopathology of the resected specimens. Results. The resection histology revealed 23 cases (36.5%) showing IA disease involvement compared with 40 cases without (62%). The intraobserver variability of R1 was 0.85 (p < 0.001) compared to R2 with κ = 0.21 (p = 0.007). The interobserver variability was κ = 0.264 (p = 0.003). Knee effusion was found to be the most sensitive indicator of IA involvement, with a sensitivity of 91.3% but specificity of only 35%. However, when combined with a pathological fracture, this rose to 97.5% and 100% when disease was visible in Hoffa’s fat pad. Conclusion. MRI imaging can sometimes overestimate IA joint involvement and needs to be correlated with clinical signs. In the light of our findings, we would recommend EA resections when imaging shows effusion combined with either disease in Hoffa’s fat pad or retinaculum, or pathological fractures. Cite this article: Bone Joint J 2023;105-B(6):696–701

Aims. Clear cell sarcoma (CCS) of soft-tissue is a rare melanocytic subtype of mesenchymal malignancy. The aim of this study was to investigate the clinical and therapeutic factors associated with increased survival, stratified by clinical stage, in order to determine the optimal treatment. Methods. The study was a retrospective analysis involving 117 patients with histologically confirmed CCS, between July 2016 and November 2017, who were enrolled in the Bone and Soft Tissue Tumour Registry in Japan. Results. The five- and ten-year survival rates were 41% (95% confidence interval (CI) 29 to 52) and 37% (95% CI 25 to 49), respectively. On multivariable analysis, the size of the tumour of > 10 cm (p = 0.006), lymph node metastasis at the time of diagnosis (p < 0.001), distant metastases at the time of diagnosis (p < 0.001), and no surgery for the primary tumour (p = 0.019) were independently associated with a poor survival. For N0M0 CCS (n = 68), the development of distant metastases was an independent prognostic factor for survival (early (< 12 months), hazard ratio (HR) 116.78 (95% CI 11.69 to 1,166.50); p < 0.001; late (> 12 months), HR 14.79 (95% CI 1.66 to 131.63); p = 0.016); neoadjuvant/adjuvant chemotherapy (p = 0.895) and/or radiotherapy (p = 0.216) were not significantly associated with survival. The five-year cumulative incidence of local recurrence was 19% (95% CI 8 to 35) and the size of the tumour was significantly associated with an increased rate of local recurrence (p = 0.012). For N1M0 CCS (n = 18), the risk of mortality was significantly lower in patients who underwent surgery for both the primary tumour and lymph node metastases (HR 0.03 (95% CI 0.00 to 0.56); p = 0.020). For M1 CCS (n = 31), excision of the primary tumour was independently associated with better survival (HR 0.26 (95% CI 0.09 to 0.76); p = 0.013). There was no significant difference in survival between the different types of systemic treatment (p = 0.523). Conclusion. Complete excision of the primary tumour and lymph nodes is associated with a better survival in patients with CCS. Systemic treatment appears to provide limited benefits, demonstrating a pressing need for novel systemic agents. Cite this article: Bone Joint J 2023;105-B(11):1216–1225

Aims. The aim of this study is to determine the predictors of overall survival (OS) and predictive factors of poor prognosis of conventional high-grade osteosarcoma of the limbs in a single-centre in South Africa. Methods. We performed a retrospective cross-sectional analysis to identify the prognostic factors that predict the OS of patients with histologically confirmed high-grade conventional osteosarcoma of the limbs over ten years. We employed the Cox proportional regression model and the Kaplan-Meier method for statistical analysis. Results. This study comprised 77 patients at a three-year minimum follow-up. The predictors of poor OS were: the median age of ≤ 19 years (hazard ratio (HR) 0.96; 95% confidence interval (CI) 0.92 to 0.99; p = 0.021); median duration of symptoms ≥ five months (HR 0.91; 95% CI 0.83 to 0.99; p < 0.037); metastasis at diagnosis (i.e. Enneking stage III) (HR 3.33; 95% CI 1.81 to 6.00; p < 0.001); increased alkaline phosphatase (HR 3.28; 95% CI 1.33 to 8.11; p < 0.010); palliative treatment (HR 7.27; 95% CI 2.69 to 19.70); p < 0.001); and amputation (HR 3.71; 95% CI 1.12 to 12.25; p < 0.032). In contrast, definitive surgery (HR 0.11; 95% CI 0.03 to 0.38; p < 0.001) and curative treatment (HR 0.18; 95% CI 0.10 to 0.33; p < 0.001) were a protective factor. The Kaplan-Meier median survival time was 24 months, with OS of 57.1% at the three years. The projected five-year event-free survival was 10.3% and OS of 29.8% (HR 0.76; 95% CI 0.52 to 1.12; p = 0.128). Conclusion. In this series of high-grade conventional osteosarcoma of the appendicular skeleton from South Africa, 58.4% (n = 45) had detectable metastases at presentation; hence, an impoverished OS of five years was 29.8%. Large-scale future research is needed to validate our results. Cite this article: Bone Jt Open 2024;5(3):210–217

Aims. Although chondrosarcomas (CSs) display true malignant features, including local recurrence (LR) and metastases, their behaviour in the hands and feet is thought to differ from that in other parts of the axial and appendicular skeleton by having a lower metastatic potential. The purpose of this study was to investigate the disease-specific and surgical factors that affect the local and systemic prognosis of CS of the hands and feet. Methods. A multicentre retrospective study was carried out at two tertiary sarcoma centres. A database search identified all patients with a CS treated between January 1995 and January 2018. There were 810 CSs of which 76 (9.4%) were located in the fingers, toes, metacarpals, and metatarsal bones. Results. The median age of the study population was 55 years (36 to 68) with a median follow-up of 52 months (22 to 87) months. Overall, 70% of the tumours were in the hand (n = 54) and 30% in the foot (n = 22). Predictors for LR were margin (p = 0.011), anatomical location (p = 0.017), and method of surgical management (p = 0.003). Anatomical location (p = 0.026), histological grade between 1 and 3 (p = 0.004) or 2 and 3 (p = 0.016), and surgical management (p = 0.001) were significant factors for LR-free survival. Disease-specific survival was affected by histological grade (p < 0.001), but not by LR (p = 0.397). Conclusion. Intralesional curettage of a low-grade CS is associated with an increased risk of LR, but LR does not affect disease-specific survival. Therefore, for low-grade CSs of the hands and feet, surgical management should aim to preserve function. In grade 2 CS, our study did not show any decreased disease-specific survival after recurrence; however, we suggest a more aggressive surgical approach to these tumours to prevent local recurrence, especially in the metacarpal and metatarsal bones. In high-grade tumours, the incidence of progressive disease is high and, therefore, the treatment of the primary tumour should be aggressive where possible, and patients observed closely for the development of metastatic disease. Cite this article: Bone Joint J 2021;103-B(3):562–568

Aims. The purpose of this study was to clarify the clinical behaviour, prognosis, and optimum treatment of dedifferentiated low-grade osteosarcoma (DLOS) diagnosed based on molecular pathology. Patients and Methods. We retrospectively reviewed 13 DLOS patients (six men, seven women; median age 32 years (interquartile range (IQR) 27 to 38)) diagnosed using the following criteria: the histological coexistence of low-grade and high-grade osteosarcoma components in the lesion, and positive immunohistochemistry of mouse double minute 2 homolog (MDM2) and cyclin-dependent kinase 4 (CDK4) associated with MDM2 amplification. These patients were then compared with 51 age-matched consecutive conventional osteosarcoma (COS) patients (33 men, 18 women; median age 25 years (IQR 20 to 38)) regarding their clinicopathological features. Results. The five-year overall survival (OAS) rates in the DLOS and COS patients were 85.7% and 77.1% (p = 0.728), respectively, and the five-year progression-free survival (PFS) rates were 57.7% and 44.9% (p = 0.368), respectively. A total of 12 DLOS patients received chemotherapy largely according to regimens for COS. Among the nine cases with a histological evaluation after chemotherapy, eight showed a poor response, and seven of these had a necrosis rate of < 50%. One DLOS patient developed local recurrence and five developed distant metastases. Conclusion. Based on our study of 13 DLOS cases that were strictly defined by histological and molecular means, DLOS showed a poorer response to a standard chemotherapy regimen than COS, while the clinical outcomes were not markedly different. Cite this article: Bone Joint J 2019;101-B:745–752

Aims. The purpose of this study was to describe the effect of histological grade on disease-specific survival in patients with chondrosarcoma. Patients and Methods. A total of 343 patients with a chondrosarcoma were included. The histological grade was assessed on the initial biopsy and on the resection specimen. Where the histology showed a mixed grade, the highest grade was taken as the definitive grade. When only small focal areas showed higher grade, the final grade was considered as both. Results. The concordance between the highest preoperative biopsy grading and the highest final grading of the resection specimen in total was only 43% (146/343). In 102 specimens (30%), a small number of cells or focal areas of higher grade were observed in contrast to the main histology. The disease-specific survival, stratified according to the predominant histological grade, showed greater variation than when stratified according to the highest grade seen in the resection specimen. Conclusion. The diagnostic biopsy in chondrosarcoma is unreliable in assessing the definitive grade and the malignant potential of the tumour. When categorizing the grade of the resection specimen, the prognosis for local recurrence and disease-specific survival should be based on the highest grade seen, even when seen in only a few cells. Cite this article: Bone Joint J 2018;100-B:662–6

Aims. Time to treatment initiation (TTI) is generally defined as the time from the histological diagnosis of malignancy to the initiation of first definitive treatment. There is no consensus on the impact of TTI on the overall survival in patients with a soft-tissue sarcoma. The purpose of this study was to determine if an increased TTI is associated with overall survival in patients with a soft-tissue sarcoma, and to identify the factors associated with a prolonged TTI. Methods. We identified 23,786 patients from the National Cancer Database who had undergone definitive surgery between 2004 and 2015 for a localized high-grade soft-tissue sarcoma of the limbs or trunk. A Cox proportional hazards model was used to examine the relationship between a number of factors and overall survival. We calculated the incidence rate ratio (IRR) using negative binomial regression models to identify the factors that affected TTI. Results. Patients in whom the time to treatment initiation was prolonged had poorer overall survival than those with a TTI of 0 to 30 days. These were: 31 to 60 days (hazard ratio (HR) 1.08, p = 0.011); 61 to 90 days (HR 1.11, p = 0.044); and 91 days (HR 1.22; p = 0.003). The restricted cubic spline showed that the hazard ratio increased substantially with a TTI longer than 50 days. Non-academic centres (vs academic centres; IRR ranging from 0.64 to 0.86; p < 0.001) had a shorter TTI. Those insured by Medicaid (vs private insurance; IRR 1.34), were uninsured (vs private insurance; IRR 1.17), or underwent a transition in care (IRR 1.62) had a longer TTI. Conclusion. A time to treatment initiation of more than 30 days after diagnosis was independently associated with poorer survival. The hazard ratio showed linear increase, especially if the TTI was more than 50 days. We recommend starting treatment within 30 days of diagnosis to achieve the highest likelihood of cure for localized high-grade soft-tissue sarcomas in the limbs and trunk, even when a patient needs to be referred to a specialist centre. Cite this article: Bone Joint J 2021;103-B(6):1142–1149

Aims. Chondrosarcoma is the second most common primary sarcoma of bone: conventional chondrosarcoma accounts for 85% of all cases. Conventional chondrosarcoma may be central or peripheral. Most studies group central and peripheral chondrosarcomas together, although there is growing evidence that their clinical behaviour and prognosis differ. The aims of this study were to analyze any differences in characteristics between central and peripheral chondrosarcomas and to investigate the incidence and role of different syndromes. Methods. Data from two international tertiary referral sarcoma centres between January 1995 and December 2018 were retrospectively reviewed. The study population consisted of 714 patients with surgically treated conventional chondrosarcoma of the pelvis and limbs. Results. In patients with Ollier’s disease and Mafucci’s syndrome, 12/20 (60%) and 2/5 (60%) of malignancies, respectively, were in the limbs, most frequently in the proximal humerus, proximal tibia, and in the hands and feet. In patients with hereditary multiple exostosis (HME), 20/29 (69.0%) of chondrosarcomas were in the pelvis and scapula, specifically in the ilium in 13/29 (44.8%) and the scapula in 3/29 (10.3%). In central chondrosarcoma, survival of patients with Ollier’s disease and non-syndromic patients was the same (p = 0.805). In peripheral chondrosarcoma, survival among HME patients was similar (p = 0.676) in patients with tumours of the pelvis and limbs. Conclusion. Both central and peripheral chondrosarcoma have specific characteristics. HME is frequently seen in patients with a peripheral chondrosarcoma, in whom tumours are commonly located in the ilium and scapula. The incidence of Ollier’s disease is uncommon in patients with a central chondrosarcoma. Disease-specific survival is equal in different subtypes after adjustment for histological grade. The local recurrence-free survival is the same for different locations and subtypes after adjustment for surgical margin. Cite this article: Bone Joint J 2021;103-B(5):984–990

Aims. The aim of this study was to report the outcomes of patients who underwent definitive surgery for secondary chondrosarcomas arising from osteochondromas. Patients and Methods. A total of 51 patients with secondary chondrosarcomas occurring from osteochondromas were reviewed. Median age was 36 years (interquartile range (IQR) 15 to 82). Median follow-up was 6.9 years (IQR 2.8 to 10.6). The pelvis was the most commonly affected site (59%). Histological grades were grade I in 35 (69%), grade II in 13 (25%), and grade III in three patients (6%). Results. Preoperative biopsy histology correctly predicted the final histological grade in 27% of patients. The ten-year disease-specific survival (DSS) for all patients was 89.4%. Local recurrence occurred in 15 patients (29%), more commonly in pelvic tumours (37%) compared with limb tumours (19%). Four patients with pelvic tumours died from progression of local recurrence. No patient with limb tumours died of disease. Wide/radical margin was associated with improved local recurrence-free survival (p = 0.032) and local recurrence was associated with worse DSS (p = 0.005). Conclusion. We recommend that a secondary chondrosarcoma arising from osteochondroma of the pelvis is resected with wide/radical resection margins. The balance between the morbidity of surgery and risk of local recurrence needs to be considered in patients with limb secondary chondrosarcomas. Cite this article: Bone Joint J 2019;101-B:1313–1320

Aims. The aim of this study was to analyse a group of patients with non-metastatic Ewing’s sarcoma at presentation and identify prognostic factors affecting the development of local recurrence, in order to assess the role of radiotherapy. Patients and Methods. A retrospective review of all patients with a Ewing’s sarcoma treated between 1980 and 2012 was carried out. Only those treated with chemotherapy followed by surgery and/or radiotherapy were included. Patients were grouped according to site (central or limb) for further analysis of the prognostic factors. Results. A total of 388 patients were included in the study. Of these, 60 (15%) developed local recurrence at a mean median of 27 months (. sd. 24, range 7 to 150) and the five-year local recurrence-free survival (5yrLRFS) was 83%. For central tumours, the size of the tumour and histological response to chemotherapy were found to be significant factors for local recurrence. For limb tumours, local recurrence was affected by intralesional and marginal resections, but not by the histological response to chemotherapy. Radiotherapy in those with a marginal resection reduced the risk of local recurrence (5yrLRFS: 96% versus 81%, p = 0.044). Conclusion. Local recurrence significantly affects the overall survival in patients with a Ewing’s sarcoma. For those with a tumour in a limb, radiotherapy reduced the risk of local recurrence, especially in those with a marginal margin of excision, but the effect in central tumours was less clear. Radiotherapy for those who have had a wide margin of resection does not reduce the risk of local recurrence, regardless of the histological response to chemotherapy. Cite this article: Bone Joint J 2018;100-B: 247–55

Aims. Tenosynovial giant cell tumour (TGCT) is one of the most common soft-tissue tumours of the foot and ankle and can behave in a locally aggressive manner. Tumour control can be difficult, despite the various methods of treatment available. Since treatment guidelines are lacking, the aim of this study was to review the multidisciplinary management by presenting the largest series of TGCT of the foot and ankle to date from two specialized sarcoma centres. Methods. The Oxford Tumour Registry and the Leiden University Medical Centre Sarcoma Registry were retrospectively reviewed for patients with histologically proven foot and ankle TGCT diagnosed between January 2002 and August 2019. Results. A total of 84 patients were included. There were 39 men and 45 women with a mean age at primary treatment of 38.3 years (9 to 72). The median follow-up was 46.5 months (interquartile range (IQR) 21.3 to 82.3). Localized-type TGCT (n = 15) predominantly affected forefoot, whereas diffuse-type TGCT (Dt-TGCT) (n = 9) tended to panarticular involvement. TGCT was not included in the radiological differential diagnosis in 20% (n = 15/75). Most patients had open rather than arthroscopic surgery (76 vs 17). The highest recurrence rates were seen with Dt-TGCT (61%; n = 23/38), panarticular involvement (83%; n = 5/8), and after arthroscopy (47%; n = 8/17). Three (4%) fusions were carried out for osteochondral destruction by Dt-TGCT. There were 14 (16%) patients with Dt-TGCT who underwent systemic treatment, mostly in refractory cases (79%; n = 11). TGCT initially decreased or stabilized in 12 patients (86%), but progressed in five (36%) during follow-up; all five underwent subsequent surgery. Side effects were reported in 12 patients (86%). Conclusion. We recommend open surgical excision as the primary treatment for TGCT of the foot and ankle, particularly in patients with Dt-TGCT with extra-articular involvement. Severe osteochondral destruction may justify salvage procedures, although these are not often undertaken. Systemic treatment is indicated for unresectable or refractory cases. However, side effects are commonly experienced, and relapses may occur once treatment has ceased. Cite this article: Bone Joint J 2021;103-B(4):788–794

Aims. Bone metastasis ultimately occurs due to a complex multistep process, during which the interactions between cancer cells and bone microenvironment play important roles. Prior to colonization of the bone, cancer cells must succeed through a series of steps that will allow them to gain migratory and invasive properties; epithelial-to-mesenchymal transition (EMT) is known to be integral here. The aim of this study was to determine the effects of G protein subunit alpha Q (GNAQ) on the mechanisms underlying bone metastasis through EMT pathway. Methods. A total of 80 tissue samples from patients who were surgically treated during January 2012 to December 2014 were used in the present study. Comparative gene analysis revealed that the GNAQ was more frequently altered in metastatic bone lesions than in primary tumour sites in lung cancer patients. We investigated the effects of GNAQ on cell proliferation, migration, EMT, and stem cell transformation using lung cancer cells with GNAQ-knockdown. A xenograft mouse model tested the effect of GNAQ using micro-CT analyses and histological analyses. Results. GNAQ-knockdown showed down-regulation of tumour growth through mitogen-activated protein kinase (MAPK) signalling in lung cancer cells, but not increased apoptosis. We found that GNAQ-knockdown induced EMT and promoted invasiveness. GNAQ-knockdown cells injected into the bone marrow of murine tibia induced tumour growth and bone-to-lung metastasis, whereas it did not in control mice. Moreover, the knockdown of GNAQ enhanced cancer stem cell-like properties in lung cancer cells, which resulted in the development of resistance to chemotherapy. Conclusion. The present study reveals that the GNAQ-knockdown induced cancer stem cell-like properties. Cite this article: Bone Joint Res 2021;10(5):310–320

Aims. To assess the correlation between the histological response to preoperative chemotherapy and event-free survival (EFS) or overall survival (OS) in patients with high-grade localized osteosarcoma. Methods. Out of 625 patients aged ≤ 40 years treated for primary high-grade osteosarcoma between 1997 and 2016, 232 patients without clinically detectable metastases at the time of diagnosis and treated with preoperative high-dose methotrexate, adriamycin and cisplatin (MAP) chemotherapy and surgery were included. Associations of chemotherapy-induced necrosis in the resected specimen and EFS or OS were assessed using Cox model and the Pearson’s correlation coefficients (r). Time-dependent receiver operating characteristic analysis was applied to determine the optimal cut-off value of chemotherapy-induced necrosis for EFS and OS. Results. OS was 74% (95% confidence interval (CI) 67 to 79) at five years. Median chemotherapy-induced necrosis was 85% (interquartile range (IQR) 50% to 97%). In multivariate Cox model, chemotherapy-induced necrosis was significantly associated with EFS and OS (hazard ratio (HR) = 0.99 (95% CI 0.98 to 0.99); p < 0.001 and HR = 0.98 (95% CI 0.97 to 0.99); p < 0.001, respectively). Positive correlation was observed between chemotherapy-induced necrosis and five-year EFS and five-year OS (r = 0.91; p < 0.001, and r = 0.85; p < 0.001, respectively). The optimal cut-off value of chemotherapy-induced necrosis for five-year EFS and five-year OS was 85% and 72%, respectively. Conclusion. Chemotherapy-induced necrosis in the resected specimen showed positive correlation with EFS and OS in patients with high-grade localized osteosarcoma after MAP chemotherapy. In our analysis, optimal cut-off values of MAP chemotherapy-induced necrosis in EFS and OS were lower than the commonly used 90%, suggesting the need for re-evaluation of the optimal cut-off value through larger, international collaborative research. Cite this article: Bone Joint J 2020;102-B(6):795–803

Aims. Survival rates and local control after resection of a sarcoma of the pelvis compare poorly to those of the limbs and have a high incidence of complications. The outcome for patients who need a hindquarter amputation (HQA) to treat a pelvic sarcoma is poor. Our aim was to evaluate the patient, tumour, and reconstructive factors that affect the survival of the patients who undergo HQA for primary or recurrent pelvic sarcoma. Methods. We carried out a retrospective review of all sarcoma patients who had undergone a HQA in a supraregional sarcoma unit between 1996 and 2018. Outcomes included oncological, surgical, and survival characteristics. Results. A total of 136 patients, with a mean age of 51 (12 to 83) underwent HQA, 91 for a bone sarcoma and 45 for a soft tissue sarcoma. The overall survival (OS) after primary HQA for a bone sarcoma was 90.7 months (95% confidence interval (CI) 64.1 to 117.2). In patients undergoing a secondary salvage HQA it was 90.3 months (95% CI 58.1 to 122.5) (p = 0.727). For those treated for a soft tissue sarcoma (STS), the mean OS was 59.3 months (95% CI 31.1 to 88.6) for patients with a primary HQA, and 12.5 months (95% CI 9.4 to 15.5) for those undergoing a secondary salvage HQA (p = 0.038). On multivariate analysis, high histological grade (hazard ratio (HR) 2.033, 95% CI 1.127 to 3.676; p = 0.018) and a diagnosis of STS (HR 1.653, 95% CI 1.027 to 2.660; p = 0.039) were associated with a poor prognosis. The 30-day mortality for patients with curative intent was 0.8% (1/128). For those in whom surgery was carried out with palliative intent it was 33.3% (2/6) (p = 0.001). In total, 53.7% (n = 73) of patients had at least one complication with 23.5% (n = 32) requiring at least one further operation. Direct closure was inferior to flap reconstruction in terms of complete primary wound healing (60.0% (3/5) vs 82.0% (82/100); p = 0.023). Conclusion. In carefully selected patients HQA is associated with satisfactory overall survival, with a low risk of perioperative mortality, but considerable morbidity. However, caution must be exercised when considering the procedure for palliation due to the high incidence of early postoperative mortality. Cite this article: Bone Joint J 2020;102-B(6):788–794

Aims

The scapula is a rare site for a primary bone tumour. Only a small number of series have studied patient outcomes after treatment. Previous studies have shown a high rate of recurrence, with functional outcomes determined by the preservation of the glenohumeral joint and deltoid. The purpose of the current study was to report the outcome of patients who had undergone tumour resection that included the scapula.

The pre-operative differentiation between enchondroma, low-grade chondrosarcoma and high-grade chondrosarcoma remains a diagnostic challenge. We reviewed the accuracy and safety of the radiological grading of cartilaginous tumours through the assessment of, first, pre-operative radiological and post-operative histological agreement, and second the rate of recurrence in lesions confirmed as high-grade on histology. We performed a retrospective review of major long bone cartilaginous tumours managed by curettage as low grade between 2001 and 2012. A total of 53 patients with a mean age of 47.6 years (8 to 71) were included. There were 23 men and 30 women. The tumours involved the femur (n = 20), humerus (n = 18), tibia (n = 9), fibula (n = 3), radius (n = 2) and ulna (n = 1). Pre-operative diagnoses resulted from multidisciplinary consensus following radiological review alone for 35 tumours, or with the addition of pre-operative image guided needle biopsy for 18. The histologically confirmed diagnosis was enchondroma for two (3.7%), low-grade chondrosarcoma for 49 (92.6%) and high-grade chondrosarcoma for two (3.7%). Three patients with a low-grade tumour developed a local recurrence at a mean of 15 months (12 to 17) post-operatively. A single high-grade recurrence (grade II) was treated with tibial diaphyseal replacement. The overall recurrence rate was 7.5% at a mean follow-up of 4.7 years (1.2 to 12.3). Cartilaginous tumours identified as low-grade on pre-operative imaging with or without additional image-guided needle biopsy can safely be managed as low-grade without pre-operative histological diagnosis. A few tumours may demonstrate high-grade features histologically, but the rates of recurrence are not affected. Cite this article: Bone Joint J 2014; 96-B:1098–105

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The aim of this study was to investigate the safety and efficacy of 3D-printed modular prostheses in patients who underwent joint-sparing limb salvage surgery (JSLSS) for malignant femoral diaphyseal bone tumours.

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This study aimed to compare the performance of survival prediction models for bone metastases of the extremities (BM-E) with pathological fractures in an Asian cohort, and investigate patient characteristics associated with survival.

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We performed a systematic literature review to define features of patients, treatment, and biological behaviour of multicentric giant cell tumour (GCT) of bone.

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The modern prevalence of primary tumours causing metastatic bone disease is ill-defined in the oncological literature. Therefore, the purpose of this study is to identify the prevalence of primary tumours in the setting of metastatic bone disease, as well as reported rates of pathological fracture, postoperative complications, 90-day mortality, and 360-day mortality for each primary tumour subtype.

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Venous tumour thrombus (VTT) is a rare finding in osteosarcoma. Despite the high rate of VTT in osteosarcoma of the pelvis, there are very few descriptions of VTT associated with extrapelvic primary osteosarcoma. We therefore sought to describe the prevalence and presenting features of VTT in osteosarcoma of both the pelvis and the limbs.

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Low-grade central osteosarcoma (LGCOS), a rare type of osteosarcoma, often has misleading radiological and pathological features that overlap with those of other bone tumours, thereby complicating diagnosis and treatment. We aimed to analyze the clinical, radiological, and pathological features of patients with LGCOS, with a focus on diagnosis, treatment, and outcomes.

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Acridine orange (AO) demonstrates several biological activities. When exposed to low doses of X-ray radiation, AO increases the production of reactive radicals (radiodynamic therapy (AO-RDT)). We elucidated the efficacy of AO-RDT in breast and prostate cancer cell lines, which are likely to develop bone metastases.

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The risk of postoperative complications after resection of soft-tissue sarcoma in the medial thigh is higher than in other locations. This study investigated whether a vessel sealing system (VSS) could help reduce the risk of postoperative complications after wide resection of soft-tissue sarcoma in the medial thigh.

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Due to its indolent clinical behaviour, the treatment paradigm of atypical cartilaginous tumours (ACTs) in the long bones is slowly shifting from intralesional resection (curettage) and local adjuvants, towards active surveillance through wait-and-scan follow-up. In this retrospective cohort study performed in a tertiary referral centre, we studied the natural behaviour of ACT lesions by active surveillance with MRI. Clinical symptoms were not considered in the surveillance programme.

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The ulna is an extremely rare location for primary bone tumours of the elbow in paediatrics. Although several reconstruction options are available, the optimal reconstruction method is still unknown due to the rarity of proximal ulna tumours. In this study, we report the outcomes of osteoarticular ulna allograft for the reconstruction of proximal ulna tumours.

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Endoprosthetic reconstruction following distal femur tumour resection has been widely advocated. In this paper, we present the design of an uncemented endoprosthesis system featuring a short, curved stem, with the goal of enhancing long-term survivorship and functional outcomes.

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The epiphyseal approach to a chondroblastoma of the intercondylar notch of a child’s distal femur does not provide adequate exposure, thereby necessitating the removal of a substantial amount of unaffected bone to expose the lesion. In this study, we compared the functional outcomes, local recurrence, and surgical complications of treating a chondroblastoma of the distal femoral epiphysis by either an intercondylar or an epiphyseal approach.

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The sacroiliac joint (SIJ) is the only mechanical connection between the axial skeleton and lower limbs. Following iliosacral resection, there is debate on whether reconstruction of the joint is necessary. There is a paucity of data comparing the outcomes of patients undergoing reconstruction and those who are not formally reconstructed.

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Ilium is the most common site of pelvic Ewing’s sarcoma (ES). Resection of the ilium and iliosacral joint causes pelvic disruption. However, the outcomes of resection and reconstruction are not well described. In this study, we report patients’ outcomes after resection of the ilium and iliosacral ES and reconstruction with a tibial strut allograft.

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Surgical site infection (SSI) after soft-tissue sarcoma (STS) resection is a serious complication. The purpose of this retrospective study was to investigate the risk factors for SSI after STS resection, and to develop a nomogram that allows patient-specific risk assessment.

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Advances in treatment have extended the life expectancy of patients with metastatic bone disease (MBD). Patients could experience more skeletal-related events (SREs) as a result of this progress. Those who have already experienced a SRE could encounter another local management for a subsequent SRE, which is not part of the treatment for the initial SRE. However, there is a noted gap in research on the rate and characteristics of subsequent SREs requiring further localized treatment, obligating clinicians to extrapolate from experiences with initial SREs when confronting subsequent ones. This study aimed to investigate the proportion of MBD patients developing subsequent SREs requiring local treatment, examine if there are prognostic differences at the initial treatment between those with single versus subsequent SREs, and determine if clinical, oncological, and prognostic features differ between initial and subsequent SRE treatments.

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We first sought to compare survival for patients treated surgically for solitary and multiple metastases in the appendicular skeleton, and second, to explore the role of complete and incomplete resection (R0 and R1/R2) in patients with a solitary bony metastasis in the appendicular skeleton.

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Surgical limb sparing for knee-bearing paediatric bone sarcoma is considered to have a clinically significant influence on postoperative function due to complications and leg-length discrepancies. However, researchers have not fully evaluated the long-term postoperative functional outcomes. Therefore, in this study, we aimed to elucidate the risk factors and long-term functional prognosis associated with paediatric limb-sparing surgery.

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Due to their radiolucency and favourable mechanical properties, carbon fibre nails may be a preferable alternative to titanium nails for oncology patients. We aim to compare the surgical characteristics and short-term results of patients who underwent intramedullary fixation with either a titanium or carbon fibre nail for pathological long-bone fracture.

Deep-seated lipomas are often atypical histologically and are considered by some to have a high risk of recurrence after excision. We reviewed 215 deep-seated lipomas of the extremities and trunk wall with reference to histology, cytogenetics, clinical features and local recurrence. We classified tumours with atypical features and/or ring chromosomes as atypical lipomas. These were more common in men, larger than ordinary lipomas and more often located in the upper leg. The annual incidence was estimated as ten per million inhabitants and the ratio of atypical to ordinary lipomas was 1:3. In total, six tumours (3%), recurred locally after a median of eight years (1 to 16); of these, four were classified as atypical. The low recurrence rate of deep-seated lipomas of the extremity or trunk wall, irrespective of histological subtype, implies that if surgery is indicated, the tumour may be shelled out, that atypical lipomas in these locations do not deserve the designation well-differentiated liposarcoma, and that routine review after surgery is not required

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Iliosacral sarcoma resections have been shown to have high rates of local recurrence (LR) and poor overall survival. There is also no universal classification for the resection of pelvic sarcomas invading the sacrum. This study proposes a novel classification system and analyzes the survival and risk of recurrence, when using this system.

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Socioeconomic and racial disparities have been recognized as impacting the care of patients with cancer, however there are a lack of data examining the impact of these disparities on patients with bone sarcoma. The purpose of this study was to examine socioeconomic and racial disparities that impact the oncological outcomes of patients with bone sarcoma.

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The modified Glasgow Prognostic Score (mGPS) uses preoperative CRP and albumin to calculate a score from 0 to 2 (2 being associated with poor outcomes). mGPS is validated in multiple carcinomas. To date, its use in soft-tissue sarcoma (STS) is limited, with only small cohorts reporting that increased mGPS scores correlates with decreased survival in STS patients.

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Current literature suggests that survival outcomes and local recurrence rates of primary soft-tissue sarcoma diagnosed in the very elderly age range, (over 90 years), are comparable with those in patients diagnosed under the age of 75 years. Our aim is to quantify these outcomes with a view to rationalizing management and follow-up for very elderly patients.

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Patients with soft-tissue sarcoma (STS) who undergo unplanned excision (UE) are reported to have worse outcomes than those who undergo planned excision (PE). However, others have reported that patients who undergo UE may have similar or improved outcomes. These discrepancies are likely to be due to differences in characteristics between the two groups of patients. The aim of the study is to compare patients who underwent UE and PE using propensity score matching, by analyzing data from the Japanese Bone and Soft Tissue Tumor (BSTT) registry.

Aims. The purpose of this retrospective study was to differentiate between the MRI features of normal post-operative change and those of residual or recurrent disease after intralesional treatment of an atypical cartilage tumour (ACT)/grade I chondrosarcoma. Patients and Methods. We reviewed the case notes, radiology and histology of 75 patients, who had been treated for an ACT/grade I chondrosarcoma by curettage, phenolisation and bone allografting between 1994 and 2005. The first post-operative Gd-enhanced MRI scan was carried out within one year of surgery. Patients had a minimum of two scans and a mean follow-up of 72 months (13 to 169). Further surgery was undertaken in cases of suspected recurrence. Results. In 14 patients (18.6%) a second procedure was undertaken after a mean period of 59 months (8 to 114). Radio frequency ablation (RFA) was used in lesions of < 10 mm and curettage, phenolisation and bone grafting for those ≥ 10 mm. Only six of these (8% of total) had a histologically-proven recurrence. No increase in tumour grade was seen at time of recurrence. Conclusion. Based on this study, we have been able to classify the post-operative MRI appearances into four groups. These groups differ in follow-up, and have a different risk of recurrence of the lesion. Follow-up and treatment vary for the patients in each group. We present a flow diagram for the appropriate and safe follow-up for this specific group of patients. Cite this article: Bone Joint J 2016;98-B:1674–81

We investigated the use of hypoxia-inducible factor (HIF) proteins as prognostic markers in chondrosarcoma and the relationship of HIF to the biological characteristics of cartilage tumours. The expression of HIF-1α, HIF-2α, proliferating cell nuclear antigen (PCNA) and microvessel density (MVD) were measured immunohistochemically in 29 specimens of cartilage tumour. There was no HIF-1α and HIF-2α staining in any of the nine benign cartilage tumours. In 20 specimens of chondrosarcoma, the rate of HIF-1α and HIF-2α expression was 40% and 25%, respectively. The tumour size (≥ 8 cm), histological grade (grade 2 and grade 3) surgical margin (marginal and intralesional) and HIF-1α expression (positive) correlated significantly with a shorter disease-free survival. There was a significant association between HIF-1α and the MVD and a strong trend towards a correlation between HIF-1α and the PCNA index or histological grade. Our findings suggest that HIF-1α protein may be a useful objective marker in the assessment of the prognosis in chondrosarcoma, since it plays an important role in tumour angiogenesis and cell proliferation

In this case study, we describe the clinical presentation and treatment of 36 patients with periosteal chondrosarcoma collected over a 59-year period by the archive of the Netherlands Committee on Bone Tumours. The demographics, clinical presentation, radiological features, treatment and follow-up are presented with the size, location, the histological grading of the tumour and the survival. We found a slight predominance of men (61%), and a predilection for the distal femur (33%) and proximal humerus (33%). The metaphysis was the most common site (47%) and the most common presentation was with pain (44%). Half the tumours were classified histologically as grade 1. Pulmonary metastases were reported in one patient after an intra-lesional resection. A second patient died from local recurrence and possible pulmonary and skin metastases after an incomplete resection. It is clearly important to make the diagnosis appropriately because an incomplete resection may result in local recurrence and metastatic spread. Staging for metastatic disease is recommended in grade II or III lesions. . These patients should be managed with a contrast-enhanced MRI of the tumour and histological confirmation by biopsy, followed by en-bloc excision. Cite this article: Bone Joint J 2014;96-B:823–8

Aims. The purpose of this study was to review a large cohort of patients and further assess the correlation between the histological response to chemotherapy in patients with Ewing’s sarcoma with the overall (OS) and event-free survival (EFS). Patients and Methods. All patients treated for Ewing’s sarcoma between 1980 and 2012 were reviewed. Of these, 293 patients without metastases at the time of diagnosis and treated with chemotherapy and surgery were included. Patients were grouped according to the percentage of necrosis after chemotherapy: Group I: 0% to 50%, Group II: 51% to 99% and Group III: 100%. Results. The mean age at diagnosis was 16 years (1 to 62) and the mean follow-up was 9.1 years (six months to 32.6 years). The OS and EFS for the series were 75% and 65% at five years. There were significant differences in survival between the groups of necrosis: 0% to 50% (OS: 49% and EFS: 45% at five years, respectively) compared with 51% to 99% (OS: 72% and EFS: 59% at five years, respectively) and 100% (OS: 94% and EFS: 81% at five years, respectively) (p <  0.001). There were no significant differences in survival between patients treated between 1980 and 1989 compared with those treated between 1990 and 1999, and those treated between 2000 and 2012 (p = 0.55). Conclusion. Only patients with 100% necrosis after chemotherapy should be classified as having a good response to chemotherapy because they have significantly better rates of survival compared with those with any viable tumour in the surgical specimen. Cite this article: Bone Joint J 2016;98-B:1138–44

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Cell-free DNA (cfDNA) and circulating tumour DNA (ctDNA) are used for prognostication and monitoring in patients with carcinomas, but their utility is unclear in sarcomas. The objectives of this pilot study were to explore the prognostic significance of cfDNA and investigate whether tumour-specific alterations can be detected in the circulation of sarcoma patients.