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AimsThe aim of this study was to report the patterns of symptoms and insufficiency fractures in patients with tumour-induced osteomalacia (TIO) to allow the early diagnosis of this rare condition.MethodsThe study included 33 patients with TIO who were treated between January 2000 and June 2022. The causative tumour was detected in all patients. We investigated the symptoms and evaluated the radiological patterns of insufficiency fractures of the rib, spine, and limbs.ResultsThe mean age of the patients was 57 years (24 to 87), and the mean duration of pain from onset to time of presentation was 3.9 years (0.75 to 23). The primary symptoms were low back pain (ten patients), chest wall pain (eight patients), and hip pain (eight patients). There were symptoms at more sites at the time of presentation compared with that at the time of the onset of symptoms. Bone scans showed the uptake of tracer in the rib (100%), thoracic and lumbar vertebrae (83%), proximal femur (62%), distal femur (66%), and proximal tibia (72%). Plain radiographs or MRI scans identified femoral neck fractures in 14 patients, subchondral insufficiency fractures of the femoral head and knee in ten and six patients, respectively, distal femoral fractures in nine patients, and proximal tibial fractures in 12 patients. Thoracic or lumbar vertebral fractures were identified in 23 of 29 patients (79.3%) when using any imaging study, and a biconcave deformity was the most common type of fracture.ConclusionInsufficiency fractures in patients with TIO caused spinal pain, chest wall pain, and periarticular pain in the lower limbs. Vertebral fractures tended to be biconcave deformities, and periarticular fractures of the hips and knees included subchondral insufficiency fractures and epiphyseal or metaphyseal fractures. In patients with a tumour, the presence of one or more of these symptoms and an insufficiency fracture should suggest the diagnosis of TIO.Cite this article: Bone Joint J 2023;105-B(5):568–574.

Neurotropic tropomyosin receptor kinase (NTRK) gene rearrangements have been reported in limited cases of sarcomas; however, to date, there has been only one report of such rearrangements in malignant peripheral nerve sheath tumors (MPNSTs). Herein, we describe a 51-year-old male patient with a buttock tumor arising from the sciatic nerve, which was diagnosed as MPNST with positive S-100 staining, negative SOX10 staining, and loss of trimethylation at lysine 27 of histone H3 (H3K27me3) confirmed by immunohistochemistry. Soon after the resection of the primary tumor, the patient was found to have pulmonary and lymph node metastases. Chemotherapy with eribulin and trabectedin showed limited effects. However, the patient responded rapidly to pazopanib, but severe side effects caused discontinuation of the treatment. RNA panel testing revealed a novel fusion gene between Small Nuclear Ribonucleoprotein U1 Subunit 70 (SNRNP70) gene and NTRK3 gene. Furthermore, loss of NF1, SUZ12, and CDKN2A genes was confirmed by DNA panel testing, which is compatible with a histological diagnosis of MPNST. SNRNP70 possesses a coiled-coiled domain and seems to induce constitutive activation of NTRK3 through dimerization. In fact, immunohistochemistry revealed diffuse staining of pan-TRK within tumor cells. Treatment with entrectinib, which is an NTRK inhibitor, showed a quick and durable response for 10 months. Although NTRK rearrangements are very rare in MPNST, this case highlights the importance of genetic testing in MPNST, especially using an RNA panel for the detection of rare fusion genes.

Background Clinical characteristics of undifferentiated pleomorphic sarcoma of bone are not elucidated. Herein, we clarify its clinical features and analyze the efficacy of adjuvant chemotherapy in patients with undifferentiated pleomorphic sarcoma of bone. Methods Prognostic factors and estimated disease-specific survival in 247 patients with primary undifferentiated pleomorphic sarcoma of bone were identified from a registry in Japan. The effect of adjuvant chemotherapy was evaluated in localized resectable cases, and the characteristics of the two groups treated with or without chemotherapy were adjusted using propensity score matching. Results The 5-year disease-specific survival rates were 47.4% in the entire cohort and 56.4 and 16.9% in the M0 and M1 groups, respectively. Multivariate disease-specific survival analysis revealed that metastasis on initial presentation and age ≥ 65 years were poor prognostic factors. Overall, 132 localized and resectable primary lesions were extracted. Adjuvant chemotherapy administration was a favorable prognostic factor (hazard ratio: 0.43, P = 0.04), and it significantly prolonged disease-specific survival compared with no adjuvant chemotherapy (5-year disease-specific survival: 78.8% vs. 51.8%, P = 0.008). Adjuvant chemotherapy prolonged disease-specific survival in patients with tumor size Conclusions Metastasis in the initial presentation was the poorest prognostic factor. On evaluating localized and resectable cases only, adjuvant chemotherapy significantly improved disease-specific survival, although its effect decreased in cases with large tumors.

Primary tumor resection is the mainstay of treatment for undifferentiated pleomorphic sarcoma (UPS); however, the necessity of adjuvant chemotherapy has been debated. We aimed to clarify the effect of adjuvant chemotherapy on survival rates in patients with UPS with localized and resectable primary lesions.This retrospective analysis included data of 2112 patients with localized UPS arising in the extremities and trunk, extracted from a registry in Japan. We estimated overall survival (OS), identified prognostic factors, and adjusted patient characteristics in the two groups treated with or without chemotherapy using propensity score matching (PSM).The 5-year OS rate was 79.4%. In multivariate OS analysis, adjuvant chemotherapy was a good prognostic factor (hazard ratio 0.65; 95% confidence interval 0.48-0.9, P = 0.009). Large tumor size was the poorest prognostic factor, and OS decreased with the tumor size (P 0.0001). In all patients, adjuvant chemotherapy prolonged OS (5-year OS: 82.3% vs. 78.6%, P = 0.03). Adjuvant chemotherapy did not affect OS in patients with tumor size 5 cm; the benefit was strong in patients with tumor size 10 to 15 cm (5-year OS: 79.5% vs. 66.8%, P = 0.003). Adjuvant chemotherapy efficacy was not pronounced in patients with tumor size 5 to 10 cm (5-year OS: 87% vs. 80%, P = 0.06) and ≥ 15 cm (5-year OS: 60.7% vs. 49.5%, P = 0.08). After PSM, adjuvant chemotherapy was significantly associated with improved OS (P = 0.02).In patients with localized UPS, adjuvant chemotherapy tended to improve OS when tumors were ≥ 5 cm, especially when they were 10 to 15 cm.

The effect of margin quality as a barrier against infiltration of soft-tissue sarcomas (STSs) has been unclear. We aimed to investigate the effect of margin quantity and quality on local control for myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS).278 patients with a localised MFS and UPS were studied. Margin quality was categorized into five types; type 1, pseudocapsule/reactive zone; type 2, fat/fibrofatty tissue; type 3, muscle; type 4, fascia; type 5, periosteum.The 5-year cumulative LR incidence was 22% and 13% in patients with positive and 0.1-9.9 mm margins, respectively, but decreased to 3% with ≥10.0 mm margins (p = 0.009); the cumulative LR incidence was significantly lower in patients with ≥10.0 mm margins than those with positive margins (p = 0.033) but was not significantly different in those with 0.1-9.9 mm margins (p = 0.183). In patients with 0.1-9.9 mm margins, the cumulative LR incidence was affected by margin quality; type 4 and 5 provided an LR risk less than 5% (p 0.001), which was similar to those with margins ≥10.0 mm. Combining these two factors together, the LR risk in patients with positive or 0.1-9.9 mm margins without fascia/periosteum was approximately 11 × higher than patients with 0.1-9.9 mm margins with fascia/periosteum or margins ≥10.0 mm (p = 0.002).A resection margin of 0.1-9.9 mm with fascia or periosteum provided a similar LR risk profile to ≥10 mm margins with any margin quality, which provided the lowest LR risk. The quality of fascial or periosteal tissue margins may be equivalent to a margin quantity of 10 mm as a barrier to LR.

Acetabular reconstruction using an ice-cream cone prosthesis has been a reliable reconstruction option following pelvic tumour resection. However, it remains unknown which factor determines the success of this procedure. We aimed to determine risk factors for complications and functional loss in acetabular reconstruction using an ice-cream cone prosthesis. Fifty-four patients with malignant bone tumours who underwent acetabular reconstruction using an ice-cream cone prosthesis between 2004 and 2016 were studied. The bone–stem ratio was calculated as the ratio of the inserted length into the bone per the entire stem length. A total of 26 (48%) patients had at least one complication and 11 patients (20%) required surgical interventions. The complication rates were 71% and 40% with a bone–stem ratio ≤ 50% and > 50%, respectively (p = 0.026), and the bone–stem ratio significantly stratified the risk of complications (≤ 50%: OR, 4.67 versus > 50%; p = 0.048). The mean MSTS score at the final follow-up was 60% (range 23–97%): the scores were significantly lower in patients with complications/leg-length discrepancy (52%) than in those without (79%; p = 0.002). The mean score with a bone–stem ratio ≤ 50% was significantly lower than the score with a ratio > 50%, especially in patients who underwent non-navigated reconstructions (33% versus 64%; p = 0.001). The inserted length of the coned stem into residual bone was predictive of complications and functional outcome. Surgical indication for this procedure should be considered with the size of the remaining ilium to stabilise the prosthesis with a coned stem longer than half length.

Background Primary tumor resection is the mainstay of treatment for malignant peripheral nerve sheath tumors. However, the efficacy of perioperative chemotherapy and radiotherapy for malignant peripheral nerve sheath tumors has not been elucidated. Methods This retrospective analysis based on a Japanese registry included patients with localized malignant peripheral nerve sheath tumors arising at the extremities and trunk wall. Disease-specific overall survival and local recurrence-free survival were estimated using the Kaplan–Meier method. A Cox regression model was used to identify prognostic factors. Characteristics of groups with or without chemotherapy were adjusted using propensity score matching. Results In total, 291 patients were included. The 5-year disease-specific overall survival rate was 70.6%. Multivariate analysis of disease-specific overall survival revealed that deep-seated tumors were a poor prognostic factor, but perioperative chemotherapy was not associated with disease-specific overall survival (hazard ratio, 0.81; 95% confidence interval, 0.45–1.43, P = 0.46). Local recurrence was observed in 55 patients (19.0%), and surgical margins (R1 and R2) were significant risk factors. Overall, perioperative chemotherapy did not prolong disease-specific overall survival (5-year disease-specific overall survival: 74.1% vs. 69.3%, P = 0.75) and had limited efficacy in the group with tumor size ≥ 5 cm, although the difference was not statistically significant (5-year disease-specific overall survival: 77.2% vs. 68.6%, respectively, P = 0.13). After adjustment by propensity score matching, perioperative chemotherapy significantly prolonged disease-specific overall survival (5-year disease-specific overall survival: 74.9% vs. 57.1%, P = 0.03), but this effect was not observed in local recurrence-free survival. In all patients, perioperative radiotherapy did not correlate with local recurrence-free survival (hazard ratio, 1.43; 95% confidence interval 0.78–2.62, P = 0.25). Conclusions Perioperative chemotherapy had limited efficacy for disease-specific overall survival in patients with localized malignant peripheral nerve sheath tumors.

BACKGROUND Pulmonary metastases are a poor prognostic factor in patients with osteosarcoma; however, the clinical significance of subcentimeter lung nodules and whether they represent a tumor is not fully known. Because the clinician is faced with decisions regarding biopsy, resection, or observation of lung nodules and the potential impact they have on decisions about resection of the primary tumor, this remains an area of uncertainty in patient treatment. Surgical management of the primary tumor is tailored to prognosis, and it is unclear how aggressively patients with indeterminate pulmonary nodules (IPNs), defined as nodules smaller than 1 cm at presentation, should be treated. There is a clear need to better understand the clinical importance of these nodules. QUESTIONS/PURPOSES (1) What percentage of patients with high-grade osteosarcoma and spindle cell sarcoma of bone have IPNs at diagnosis? (2) Are IPNs at diagnosis associated with worse metastasis-free and overall survival? (3) Are there any clinical or radiologic factors associated with worse overall survival in patients with IPN? METHODS Between 2008 and 2016, 484 patients with a first presentation of osteosarcoma or spindle cell sarcoma of bone were retrospectively identified from an institutional database. Patients with the following were excluded: treatment at another institution (6%, 27 of 484), death related to complications of neoadjuvant chemotherapy (1%, 3 of 484), Grade 1 or 2 on final pathology (4%, 21 of 484) and lack of staging chest CT available for review (0.4%, 2 of 484). All patients with abnormalities on their staging chest CT underwent imaging re-review by a senior radiology consultant and were divided into three groups for comparison: no metastases (70%, 302 of 431), IPN (16%, 68 of 431), and metastases (14%, 61 of 431) at the time of diagnosis. A random subset of CT scans was reviewed by a senior radiology registrar and there was very good agreement between the two reviewers (κ = 0.88). Demographic and oncologic variables as well as treatment details and clinical course were gleaned from a longitudinally maintained institutional database. The three groups did not differ with regard to age, gender, subtype, presence of pathological fracture, tumor site, or chemotherapy-induced necrosis. They differed according to local control strategy and tumor size, with a larger proportion of patients in the metastases group presenting with larger tumor size and undergoing nonoperative treatment. There was no differential loss to follow-up among the three groups. Two percent (6 of 302) of patients with no metastases, no patients with IPN, and 2% (1 of 61) of patients with metastases were lost to follow-up at 1 year postdiagnosis but were not known to have died. Individual treatment decisions were determined as part of a multidisciplinary conference, but in general, patients without obvious metastases received (neo)adjuvant chemotherapy and surgical resection for local control. Patients in the no metastases and IPN groups did not differ in local control strategy. For patients in the IPN group, staging CT images were inspected for IPN characteristics including number, distribution, size, location, presence of mineralization, and shape. Subsequent chest CT images were examined by the same radiologist to reevaluate known nodules for interval change in size and to identify the presence of new nodules. A random subset of chest CT scans were re-reviewed by a senior radiology resident (κ = 0.62). The association of demographic and oncologic variables with metastasis-free and overall survival was first explored using the Kaplan-Meier method (log-rank test) in univariable analyses. All variables that were statistically significant (p < 0.05) in univariable analyses were entered into Cox regression multivariable analyses. RESULTS Following re-review of staging chest CTs, IPNs were found in 16% (68 of 431) of patients, while an additional 14% (61 of 431) of patients had lung metastases (parenchymal nodules 10 mm or larger). After controlling for potential confounding variables like local control strategy, tumor size, and chemotherapy-induced necrosis, we found that the presence of an IPN was associated with worse overall survival and a higher incidence of metastases (hazard ratio 1.9 [95% CI 1.3 to 2.8]; p = 0.001 and HR 3.6 [95% CI 2.5 to 5.2]; p < 0.001, respectively). Two-year overall survival for patients with no metastases, IPN, or metastases was 83% [95% CI 78 to 87], 65% [95% CI 52 to 75] and 45% [95% CI 32 to 57], respectively (p = 0.001). In 74% (50 of 68) of patients with IPNs, it became apparent that they were true metastatic lesions at a median of 5.3 months. Eighty-six percent (43 of 50) of these patients had disease progression by 2 years after diagnosis. In multivariable analysis, local control strategy and tumor subtype correlated with overall survival for patients with IPNs. Patients who were treated nonoperatively and who had a secondary sarcoma had worse outcomes (HR 3.6 [95% CI 1.5 to 8.3]; p = 0.003 and HR 3.4 [95% CI 1.1 to 10.0]; p = 0.03). The presence of nodule mineralization was associated with improved overall survival in the univariable analysis (87% [95% CI 39 to 98] versus 57% [95% CI 43 to 69]; p = 0.008), however, because we could not control for other factors in a multivariable analysis, the relationship between mineralization and survival could not be determined. We were unable to detect an association between any other nodule radiologic features and survival. CONCLUSION The findings show that the presence of IPNs at diagnosis is associated with poorer survival of affected patients compared with those with normal staging chest CTs. IPNs noted at presentation in patients with high-grade osteosarcoma and spindle cell sarcoma of bone should be discussed with the patient and be considered when making treatment decisions. Further work is required to elucidate how the nodules should be managed. LEVEL OF EVIDENCE Level III, prognostic study.

Aims The existing clinical guidelines do not describe a clear indication for adjuvant radiotherapy (RT) in the treatment of superficial soft tissue sarcomas (STSs). We aimed to determine the efficacy of adjuvant RT for superficial STSs. Methods We retrospectively studied 304 patients with superficial STS of the limbs and trunk who underwent surgical resection at a tertiary sarcoma centre. The efficacy of RT was investigated according to the tumour size and grade: group 1, ≤ 5 cm, low grade; group 2, ≤ 5cm, high grade; group 3, > 5 cm, low grade; group 4, > 5 cm, high grade. Results The five- and ten-year local recurrence-free survival (LRFS) for all patients was 88% and 81%, respectively. While the efficacy of adjuvant RT was not proven in local control of all patients (five-year LRFS; RT+, 90% versus RT-, 83%; p = 0.074), the LRFS was significantly improved by adjuvant RT in group 2 (five-year LRFS; RT+, 96% versus RT-, 82%; p = 0.019), and group 4 (five-year LRFS; RT+, 87% versus RT-, 73%; p = 0.027). In groups 2 and 4, adjuvant RT significantly reduced the LR risk if the resection margin was clear but less than 5 mm; the LR rate was 7% with adjuvant RT compared with 26% with surgery alone (p = 0.003). There was no statistical relationship with the use of adjuvant RT and survival in every group. Conclusion Adjuvant RT reduces the risk of local recurrence in patients with superficial high-grade STS regardless of tumour size, especially when resection margin is less than 5 mm. Cite this article: Bone Joint J 2020;102-B(8):1088–1094.

Objectives There remains no consensus on what constitutes an adequate margin of resection for non-infiltrative soft-tissue sarcomas (STSs). We aimed to investigate the role of resection margins in millimetres for non-infiltrative STSs. Methods 502 patients who underwent surgical resection for a localized, non-infiltrative, high-grade STSs were studied. The prognostic significance of margin width was analysed and compared with the conventional R- and R+1-classification of surgical margins. Results The overall local recurrence (LR) rate was 13%; 9% and 27% with negative and positive margins, respectively (p < 0.001). In patients with negative margins, the LR rates were greater than 10% in patients with margins ≤5.0 mm but reduced to less than 4% with margins >5.0 mm. When classified by the R- (or R+1)-classification, the 5-year cumulative LR incidence was 8%, 23% (16%), and 31% for R0, R1, and R2, respectively, which did not stratify the LR risk with negative margins. On the other hand, an accurate risk stratification was possible by metric distance; the 5-year cumulative incidence of LR was 29%, 10%, and 1% with 0 mm, 0.1–5.0 mm, and >5.0 mm, respectively (p < 0.001). This classification also stratified the LR risk in patients with or without adjuvant radiotherapy. Conclusion While a negative margin is essential to optimize local control in patients with non-infiltrative STSs, surgical margin width greater than 5 mm minimises the risk of local failure regardless of the use of adjuvant radiotherapy.

Background Massive intraoperative blood loss is common in pelvic malignant bone tumor surgery, and preoperative arterial embolization may be used in selected cases. Preoperative arterial embolization reportedly increases wound complications in pelvic fracture surgery, but little evidence is available regarding pelvic bone tumor surgery. Methods Using a Japanese nationwide database (Diagnosis Procedure Combination database), we searched for patients who underwent pelvic malignant bone tumor surgery between July 2010 and March 2018. The primary endpoint was wound complications, defined as any wound requiring re-operation, negative pressure wound therapy or both. Univariate analyses (the chi-squared test for categorical variables, the unpaired t-test for continuous variables) and multivariate logistic regression analyses were performed to examine the association between preoperative arterial embolization and wound complications. Results Among the 266 eligible patients, 43 (16%, 43/266) underwent embolization and 69 (26%, 69/266) developed wound complications. In the univariate analyses, preoperative arterial embolization (P Conclusions Preoperative arterial embolization may be associated with increased wound complications after pelvic malignant tumor surgery.

Effective classification and visualization of multiple antimicrobial resistance plasmids can be challenging, and few tools to analyze similarities among plasmids depending on the location of genes are available. We created a new plasmid mapping program called Bird's-eye MApping of plasmids (BeMAp) to map antimicrobial resistance genes across multiple plasmids onto a spreadsheet and visualize their similarities based on gene types, locations, alignments, and organization. We analyzed plasmids containing various antimicrobial resistance genes, together with genes coding for IMP-type metallo-β-lactamases. Moreover, the mapping of plasmids with antimicrobial resistance genes and Incompatibility (Inc) groups showed that clustered plasmids with a similar organization of antimicrobial resistance genes were not always classified into the same Inc groups, indicating that the program displays multiple plasmids regardless of the Inc group classification. Our results showed that this calculation protocol and mapping strategy could provide a valuable tool for the practical and convenient visualization and comparison of the genomic structure of multiple plasmids in parallel.

Cases. Case 1 was a 58-year-old man who presented with an incidentally detected, slowly growing mass in the right hypochondrium area. An imaging study showed the mass arising from the 11th rib, with ill-defined margins and cortical destruction. Differential diagnoses included chondrosarcoma and metastatic malignant tumor. Open biopsy was associated with moderate bleeding (300 mL) despite small incision. Microscopic findings showed numerous irregular, dilated, and thin-walled vessels, consistent with the diagnosis of hemangioma of bone, and en bloc excision was performed with no surgical complication. Case 2 was a 49-year-old man who presented with an incidentally detected 4th rib mass with calcification on computed tomography scan. Chondrosarcoma was suspected according to imaging features. An open biopsy was considered to have a risk of tumor seeding because the tumor was located behind the scapula. En bloc excision of the tumor without biopsy was performed. The pathological findings were consistent with hemangioma of bone. Conclusion. We reported two cases of rare hemangioma arising from the rib, which mimicked chondrosarcoma. The preoperative diagnosis was challenging, both clinically and radiologically. Because biopsy for hemangioma of the rib is associated with a bleeding risk, the en bloc excision without biopsy can be a practical treatment option.

Aims While a centralized system for the care of patients with a sarcoma has been advocated for decades, regional variations in survival remain unclear. The aim of this study was to investigate regional variations in survival and the impact of national policies in patients with a soft-tissue sarcoma (STS) in the UK. Methods The study included 1,775 patients with a STS who were referred to a tertiary sarcoma centre. The geographical variations in survival were evaluated according to the periods before and after the issue of guidance by the National Institute for Health and Care Excellence (NICE) in 2006 and the relevant evolution of regional management. Results There had been a significant difference in survival between patients referred from the North East, North West, East Midlands, West Midlands, South West, and Wales in the pre-NICE era (five-year disease-specific survival (DSS); South West, 74% vs North East, 47% (p = 0.045) or West Midlands, 54% (p = 0.049)), which was most evident for patients with a high-grade STS. However, this variation disappeared in the post-NICE era, in which the overall DSS for high-grade STS improved from 47% to 68% at five years (p < 0.001). Variation in the size of the tumour closely correlated with the variation in DSS, and the overall size of the tumour and incidence of metastasis at the time of diagnosis also decreased after the national policies were issued. Conclusion The survival of patients with a STS improved and regional variation corrected after the introduction of national policies, as a result of a decreasing size of tumour and incidence of metastasis at the time of diagnosis, particularly in patients with a high-grade STS. This highlights the positive impact of national guidelines on regional variation in the presentation, management, and outcome in patients with a STS. Cite this article: Bone Joint J 2021;103-B(9):1541–1549.

Objectives What constitutes an adequate margin of resection for infiltrative subtypes of soft-tissue sarcomas remains unclear. We aimed to determine the prognostic significance of the margin in millimetres for myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS). Methods 305 patients diagnosed with either a high-grade, localised MFS (n = 98) or UPS (n = 207) were included. The relationship of closest margin in millimetres to viable tumour and oncological outcomes was analysed. Results The overall local recurrence (LR) rate for all patients were 12%: 19% with positive margin and 10% with negative margin (p = 0.051). The LR rate was similar in patients with negative but Conclusion The resection margin, when measured as a metric distance, correlates with a reduction in LR, and appears to be more significant on local control than radiotherapy. To minimise the risk of LR, a margin distance of at least 10 mm is advocated for MFS and UPS.

Background The survival and prognostic factors in non-metastatic, radiation-induced bone sarcomas of bone have not been described. Moreover, the quantitative data about surgical outcomes and complications after limb-salvage surgery versus amputation are quite limited. Methods Twenty-five patients with non-metastatic, radiation-induced sarcoma of bone who underwent definitive surgery were analysed. Histological diagnosis was osteosarcoma in 19 and undifferentiated pleomorphic sarcoma in six. The definitive surgery was limb-salvage surgery in 15 patients and an amputation in 10. Results The 5-year overall survival rate (OS) and the 5-year event-free survival rate (EFS) were 53% (95% CI 31%–70%) and 40% (21%–59%), respectively. Patients with wide or radical surgical margins (n = 13) showed significantly better OS compared with those with marginal (n = 8) or intralesional (n = 2) margins (5-year OS, radical or wide = 74%, marginal = 17%, intralesional = 0%, p = 0.044). The risk of local recurrence was significantly higher in the limb-salvage group compared to the amputation group (49% vs 0%, p = 0.011). OS and EFS were not significantly different between limb-salvage group and an amputation group (p = 0.188 and 0.912, respectively). Conclusions We believe non-metastatic, radiation-induced sarcoma of bone should be resected with the aim of achieving wide or radical margins. Although limb-salvage surgery was related to higher rates of local recurrence compared with those of the amputation group, OS and EFS were not different among two groups. Surgeons need to discuss the higher risk of local recurrence in limb-salvage surgery.

BACKGROUND AND OBJECTIVES We aimed to identify the overall survival (OS), surgical complications, survival of reconstruction, and functional outcome of patients who underwent extra-articular resection of the shoulder joint for primary bone sarcomas. The OS and local recurrence rates in patients who underwent an amputation were also evaluated for comparison. METHODS Thirty-two patients treated between 1988 and 2017 were studied. The tumours were located in the humerus in 22 (69%) and scapula in 10 patients (31%). The resection types were Malawer type IV in 6 (19%), type V in 21 (66%), and type VI in 5 patients (15%). Reconstruction was performed with endoprosthesis in 23 patients (72%) while excision arthroplasty with the suspension of the humerus to the clavicle was performed in 9 patients (28%). Surgical margins were wide in 16, marginal in 8, intralesional in 3, and not available in 5 patients. During the study period, 40 patients underwent a forequarter amputation and 11 patients underwent a shoulder disarticulation. RESULTS The 5-year OS for patients who underwent extra-articular resection of the shoulder joint was 42% which was not statistically different compared with that of patients who underwent amputation (5-year OS = 30%; P = .091). The 5-year survival of the reconstruction was 94%, similar for endoprosthesis and excision arthroplasty. Local recurrence and complications developed in 6 (19%) and 10 patients (31%), respectively. Failures of the reconstruction requiring revision surgery occurred in two patients (6%). Limb salvage was achieved in 30 patients (94%). The median Musculoskeletal Tumour Society functional score was 61% (interquartile range, 57%-70%) and was similar in the endoprosthesis and excision arthroplasty group. CONCLUSIONS Extra-articular resection of the shoulder joint for bone sarcomas is an effective limb-salvage method. However, local recurrence remains a principal concern.

Purpose Chondrosarcomas typically present in adults during the fifth to seventh decades and are rare in young patients. The biological behaviour and oncological outcomes may be different in children and adolescents. Methods We retrospectively evaluated the outcomes of all patients with chondrosarcoma of bone who were younger than 18 years of age at the time of diagnosis and were treated at our centre between 1995 and 2018. Results The 15 consecutive patients studied included nine male and six female cases, with a mean age at diagnosis of 13 years (7 to 17). The median follow-up was 117 months (30 to 277). The tumours were primary and secondary in ten and five patients, respectively. The tumours were central in 13 and surface in two patients. The tumour locations were the humerus in five, digits in five, femur in three, radius in one and pelvis in one patient. The histological grades were grade I in seven, grade II in seven and grade III in one patient. The surgical treatments were limb salvage in ten patients and ray amputation in five patients. The surgical margins were wide in eight, marginal in two and intralesional in five patients. All the patients were alive and continuously free of disease at the time of the last follow-up. No patient developed metastases or local recurrence. Conclusion Chondrosarcoma of bone in children and adolescent patients has a very good prognosis and is less aggressive compared with published outcomes in older patients. Level of evidence IV

Purpose Chordoma is a rare but highly aggressive primary bone sarcoma that arises commonly from the sacrum. While en bloc resection has been the mainstay of the treatment, the role of resection margin in millimetres with/without adjuvant radiotherapy (RT) has been unknown. We investigated the prognostic impact of surgical margin width, adjuvant RT, and their combined factor for sacral chordoma. Methods Forty-eight patients who underwent surgical treatment between 1996 and 2016 were studied. Of these, 11 patients (23%) received adjuvant RT; photon RT in 7 (15%) and proton RT in 4 (8%). Margins were microscopically measured in millimetres from the resection surface to the closest tumour on histologic slides. Results The five year and ten year disease-specific survival was 88% and 58%, respectively, and the local recurrence (LR) rate was 48%. The LR rate with 0-mm, Conclusion This study identified the lowest risk of local failure in tumour resection with ≥ 1.5-mm margin or negative but

The molecular hallmark of Ewing sarcoma (ES) is a fusion involving the EWSR1 gene and a member of the ETS family of transcription factors. EWSR1-FLI1 is the most common variant, occurring in 90% of cases, followed by EWSR1-ERG. In a small subset, the FUS gene can substitute for EWSR1 in these fusions. Only rare case reports have been described to date of ES with FEV gene rearrangements. In this study, we investigate the clinicopathologic and molecular features of 10 ES patients with FEV-rearrangements, either fused to EWSR1 (n = 4) or to FUS (n = 6). The median age at diagnosis was 38 years (range, 5-61 years); occurring in six males and four females. All tumors were located at extraskeletal sites, occurring more often in the axial soft tissues. Tumors had a similar morphologic appearance and immunophenotype as ES with more common EWSR1-ETS fusions. Of six patients with follow-up data, five patients (83%) developed metastasis and two patients (33%) died of their diseases. The diagnosis was confirmed either by fluorescence in situ hybridization and/or targeted RNA sequencing. In the five cases tested by targeted sequencing, the fusion transcripts were composed of EWSR1 or FUS fused to either exon 1 or 2 of FEV, retaining the FEV ETS DNA binding domain. This is the largest study to date investigating the ES subset with EWSR1/FUS-FEV fusions showing a predilection for extraskeletal sites and aggressive behavior.

Aims The aim of this study was to present the long-term surgical outcomes, complications, implant survival, and causes of implant failure in patients treated with the modified Harrington procedure using antegrade large diameter pins. Patients and Methods A cohort of 50 consecutive patients who underwent the modified Harrington procedure for periacetabular metastasis or haematological malignancy between January 1996 and April 2018 were studied. The median follow-up time for all survivors was 3.2 years (interquartile range 0.9 to 7.6 years). Results The five-year overall survival rate was 33% for all the patients. However, implant survival rates were 100% and 46% at five and ten years, respectively. Eight patients survived beyond five years. There was no immediate perioperative mortality or complications. A total of 15 late complications occurred in 11 patients (22%). Five patients (10%) required further surgery to treat complications. The most frequent complication was pin breakage without evidence of acetabular loosening (6%). Two patients (4%) underwent revision for aseptic loosening at 6.5 and 8.9 years after surgery. Ambulatory status and pain level were improved in 83% and 89%, respectively. Conclusion The modified Harrington procedure for acetabular destruction has low complication rates, good functional outcome, and improved pain relief in selected patients Cite this article: Bone Joint J 2019;101-B:1557–1562

Background Extendable endoprostheses are used to reconstruct segmental defects following resection of bone sarcomas in skeletally immature patients. However, there remains a paucity of studies with regard to long-term outcomes. Methods We retrospectively reviewed 124 skeletally immature children who underwent an extendable endoprosthetic replacement and survived more than 10 years after the surgical procedures. Anatomical sites included the distal part of the femur (n = 66), the proximal part of the femur (n = 13), the proximal part of the tibia (n = 29), and the proximal part of the humerus (n = 16). Complications and implant survival were classified according to the modified Henderson criteria. Results The mean follow-up was 24 years (range, 10 to 36 years). The mean age at the time of the extendable endoprosthetic replacement was 9 years (range, 2 to 16 years). All patients had reached skeletal maturity at the last follow-up. The 10-year endoprosthetic failure-free survival rate was 28%. A total of 243 complications occurred in 90% of patients; these complications were most frequently related to soft-tissue problems (27% of complications). The incidence of and cumulative survival with respect to each failure mode varied between anatomical sites. Soft-tissue failures occurred most frequently in the proximal part of the femur (77%; p = 0.003), and the distal part of the femur was the most frequent site of aseptic loosening (52%; p = 0.014) and structural failure (55%; p = 0.001). Excluding lengthening procedures, 105 patients (85%) underwent an additional surgical procedure, with a mean of 2.7 surgical procedures per patient (range, 0 to 7 surgical procedures per patient). The mean limb-length discrepancy at the final follow-up was 1 cm (range, 0 to 9 cm). Limb salvage was achieved in 113 patients (91%). The mean Musculoskeletal Tumor Society functional score (the percentage of a total score of 30 points) was 82% (range, 40% to 100%) in 115 patients with available data at the last follow-up. Conclusions Extendable endoprostheses are associated with a high complication rate and a need for additional surgical procedures over time. Despite this, successful limb salvage with reasonable function and small limb-length discrepancy is achievable in the long term. Our study provides benchmark data for individual anatomical sites for further improvements of outcomes. Level of evidence Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

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

Background/aim We analyzed the process of healing at osteotomy sites and timing of achievement of full weight-bearing in sarcoma patients who underwent hemicortical or intercalary reconstruction using the extracorporeal irradiated autologous bone graft technique. Patients and methods We studied 10 patients who had undergone tumor resection and reconstruction with hemicortical extracorporeal irradiated autologous bone graft at mid-shaft femur or tibia. The control group consisted of 30 patients who received the reconstruction using intercalary bone graft. Results Full weight-bearing was achieved in all 10 patients at a median time of 4.8 months. Function was excellent in all patients. When comparing the clinical outcome among the patients who received intercalary and hemicortical grafts, the duration to full weight-bearing achievement in patients who received hemicortical graft was shorter than that in those with intercalary graft. Conclusion Early full weight-bearing may be achieved in patients undergoing hemicortical resection and reconstruction using extracorporeal irradiated autologous bone graft.

AimsThe aim of this study was to report the results of custom-made endoprostheses with extracortical plates plus or minus a short, intramedullary stem aimed at preserving the physis after resection of bone sarcomas in children.Patients and MethodsBetween 2007 and 2017, 18 children aged less than 16 years old who underwent resection of bone sarcomas, leaving ≤ 5 cm of bone from the physis, and reconstruction with a custom-made endoprosthesis were reviewed. Median follow-up was 67 months (interquartile range 45 to 91). The tumours were located in the femur in 11 patients, proximal humerus in six, and proximal tibia in one.ResultsThe five-year overall survival rate was 78%. No patient developed local recurrence. The five-year implant survival rate was 79%. In all, 11 patients (61%) developed a complication. Seven patients (39%) required further surgery to treat the complications. Implant failures occurred in three patients (17%) including one patient with aseptic loosening and two patients with implant or periprosthetic fracture. The preserved physis continued to grow at mean 3.3 cm (0 to 14). The mean Musculoskeletal Society score was 88% (67% to 97%).ConclusionCustom-made endoprostheses that aim to preserve the physis are a safe and effective option for preserving physeal growth, limb length, and joint function with an acceptable rate of complications. Cite this article: Bone Joint J 2019;101-B:1144–1150

Aims The aim of this study was to determine the risk of local recurrence and survival in patients with osteosarcoma based on the proximity of the tumour to the major vessels. Patients and Methods A total of 226 patients with high-grade non-metastatic osteosarcoma in the limbs were investigated. Median age at diagnosis was 15 years (4 to 67) with the ratio of male to female patients being 1.5:1. The most common site of the tumour was the femur (n = 103) followed by tibia (n = 66). The vascular proximity was categorized based on the preoperative MRI after neoadjuvant chemotherapy into four types: type 1 > 5 mm; type 2 ≤ 5 mm, > 0 mm; type 3 attached; type 4 surrounded. Results Limb salvage rate based on the proximity type was 92%, 88%, 51%, and 0% for types 1 to 4, respectively, and the overall survival at five years was 82%, 77%, 57%, and 67%, respectively (p < 0.001). Local recurrence rate in patients with limb-salvage surgery was 7%, 8%, and 22% for the types 1 to 3, respectively (p = 0.041), and local recurrence at the perivascular area was observed in 1% and 4% for type 2 and 3, respectively. The mean microscopic margin to the major vessels was 6.9 mm, 3.0 mm, and 1.4 mm for types 1 to 3, respectively. In type 3, local recurrence-free survival with limb salvage was significantly poorer compared with amputation (p = 0.025), while the latter offered no overall survival benefit. In this group of patients, factors such as good response to chemotherapy or limited vascular attachment to less than half circumference or longitudinal 10 mm reduced the risk of local recurrence. Conclusion The proximity of osteosarcoma to major blood vessels is a poor prognostic factor for local control and survival. Amputation offers better local control for tumours attached to the blood vessels but does not improve survival. Limb salvage surgery offers similar local control if the tumour attachment to blood vessels is limited. Cite this article: Bone Joint J 2019;101-B:1024–1031.