Chondrosarcoma of the Femur: Is Local Recurrence Influenced by the Presence of an Extraosseous Component?

BACKGROUND: Chondrosarcoma (CS) is the second most common surgically treated primary malignancy of the bone. The current study explored the effect of the margin and extraosseous tumor component in CS in the femur on local recurrence (LR), LR-free survival (LRFS), and disease-specific survival (DSS). METHODS: Among 202 patients, 115 were in the proximal extremity of the femur, 4 in the corpus of the femur, and 83 in the distal extremity of femur; 105 patients had an extraosseous tumor component. RESULTS: In the Kaplan-Meier analysis, factors significant for decreased LRFS were the extraosseous tumor component (p < 0.001), extraosseous tumor component arising from the superior aspect (p < 0.001), histological grade (p = 0.031), and narrow surgical margin < 3 mm (p < 0.001). Factors significantly affecting DSS were the histological grade (p < 0.001), extraosseous component (p < 0.001), LR (p < 0.001), metastases (p < 0.001), and surgical margin (p < 0.001). CONCLUSIONS: In CS of the femur, the presence of an extraosseous tumor component has a predictive role in LRFS, and extraosseous tumor component arising from the superior aspect was significant for decreased LRFS. Wide margins were more commonly achieved when the tumor had only an intraosseous component, and the rate of LR was significantly higher in cases with an extraosseous tumor component. When the extraosseous component arose from the superior aspect of the femur, LR occurred more frequently despite achieving adequate margins.

Chondrosarcoma of the Proximal Humerus: Does the Margin Affect Survival?

Chondrosarcoma (CS) is the second most common primary malignant bone tumour and, in the absence of reliable chemotherapy and radiotherapy, is effectively a surgical disease. Overall disease specific survival (DSS) is affected by tumour grade, whilst resection margin contributes to local recurrence free survival (LRFS). The aim of this study was to investigate factors that affect the local and systemic prognoses for conventional central CSs arising from the proximal humerus. A multi-centre, retrospective study from three international collaborative sarcoma centres identified 110 patients between 1995 and 2020 undergoing treatment for a conventional central CS of the proximal humerus; 58 patients (53%) had a grade 1 tumour, 36 (33%) had a grade 2 tumour, and 16 patients (13%) had a grade 3 CS. The mean age of patients was 50 years (range 10-85). The incidence of local recurrence (LR) was 9/110 (8.2%), and the disease specific mortality was 6/110 (5.5%). The grade was a statistically significant factor for LRFS (p < 0.001). None of the grade 1 tumours developed LR. The DSS was affected by the grade (p < 0.001) but not by the LR (p = 0.4). Only one patient with a grade 2 tumour died from the disease. The proximal humeral grade 1 CS behaved as a benign tumour, having no cases of LR nor death due to disease. Grade 2 CSs of the proximal humerus behaved in a more indolent way when compared with comparable grade tumours elsewhere in the appendicular skeleton, being locally aggressive with a higher LR rate than grade 1 CSs but still having very low mortality and a high rate of DSS. The LR in grade 2 CSs did not affect the DSS; therefore, surgical management in proximal humeral grade 2 CSs should have a greater emphasis on preserving function whilst maintaining an adequate margin for resection. The proximal humeral grade 3 CS was, as elsewhere in the skeleton, an aggressive, high-grade tumour. Therefore, surgical management should include en bloc resection with clear margins to avoid LR.

Anatomical distribution, the incidence of malignancy and diagnostic workup in the pathological lesions of the clavicle: a review of 410 cases.

BACKGROUND: The clavicle poses a diagnostic dilemma of the pathological lesions due to the wide range of pathologies seen at this site. This study aimed to identify and stratify various pathologies seen in the clavicle and to guide ways of investigation for diagnosis based on age, site and investigation findings. MATERIALS AND METHODS: Four hundred and ten cases with clavicle lesions were identified in our database. Data were collected about the patient's medical history, previous investigation, inflammatory markers radiological investigations and biopsy. All patients were worked up and managed after discussion in a multidisciplinary team meeting (MDT). RESULTS: Non-malignant lesions accounted for 79% of cases. Infection was the most common diagnosis (39%) and the commonest diagnosis in those less than 20 years of age. 73% of the lesions were found at the medial end of the clavicle. Malignant tumours were 21%, while primary benign bone tumours accounted for only 14%. 50% of the malignant lesions were due to metastatic disease. The risk of malignancy increases with advancing age. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were not sensitive as a diagnostic tool in cases of osteomyelitis confirmed by histology. Magnetic resonance imaging (MRI) was noted to have high sensitivity and specificity for identifying the nature of a lesion and diagnosis. CONCLUSION: We have identified age as a positive predictor of a malignant cause in pathological lesions of the clavicle. MRI should be considered in all these cases. CRP and ESR have poor predictive values in diagnosing infection in the clavicle. Patients presenting with clavicle lesions should be discussed in a specialist MDT and undergo a systemic diagnostic workup, still in some cases, diagnosis can be speculated based on the patient's age, location of the lesion within the clavicle and the features seen on the MRI scan. LEVEL OF EVIDENCE: IV.

Intralesional margin after excision of a high-grade osteosarcoma: Is it a catastrophe?

BACKGROUND AND OBJECTIVES: Treatment of high-grade osteosarcoma (OS) relies on a combination of systemic chemotherapy and radical surgical excision of the tumor. Little is known on what happens in case of an irrefutably inadequate (intralesional) margin. We aimed to describe the outcome of patients with high-grade OSs of the trunk and the extremities where planned wide resection resulted in an intralesional margin. METHODS: A retrospective study from the Scandinavian Sarcoma Group registry and the Royal Orthopaedic Hospital databases including data from 53 patients surgically treated between the years 1990 and 2017. RESULTS: Local recurrence was observed in 13/53 patients. All patients with local recurrence where the neoadjuvant chemotherapy response could be retrieved (n = 9) were shown to be poor responders. None of the patients with good response to chemotherapy relapsed. Postoperative radiotherapy was not associated with improved local control of the disease. Re-excision surgery was performed in only seven patients, and two of them had tumor relapse. CONCLUSIONS: Good response to chemotherapy salvages the outcome of surgical excision with a poor margin in patients with high-grade OSs and a watchful waiting strategy may be justified in these cases. Poor responders have a higher recurrence risk and their approach should be individualized.

Development and comparison of 1-year survival models in patients with primary bone sarcomas: External validation of a Bayesian belief network model and creation and external validation of a new gradient boosting machine model.

BACKGROUND: Bone sarcomas often present late with advanced stage at diagnosis and an according, varying short-term survival. In 2016, Nandra et al. generated a Bayesian belief network model for 1-year survival in patients with bone sarcomas. The purpose of this study is: (1) to externally validate the prior 1-year Bayesian belief network prediction model for survival in patients with bone sarcomas and (2) to develop a gradient boosting machine model using Nandra et al.'s cohort and evaluate whether the gradient boosting machine model outperforms the Bayesian belief network model when externally validated in an independent Danish population cohort. MATERIAL AND METHODS: The training cohort comprised 3493 patients newly diagnosed with bone sarcoma from the institutional prospectively maintained database at the Royal Orthopaedic Hospital, Birmingham, UK. The validation cohort comprised 771 patients with newly diagnosed bone sarcoma included from the Danish Sarcoma Registry during January 1, 2000-June 22, 2016. We performed area under receiver operator characteristic curve analysis, Brier score and decision curve analysis to evaluate the predictive performance of the models. RESULTS: External validation of the Bayesian belief network 1-year prediction model demonstrated an area under receiver operator characteristic curve of 68% (95% confidence interval, 62%-73%). Area under receiver operator characteristic curve of the gradient boosting machine model demonstrated: 75% (95% confidence interval: 70%-80%), overall model performance by the Brier score was 0.09 (95% confidence interval: 0.077-0.11) and decision curve analysis demonstrated a positive net benefit for threshold probabilities above 0.5. External validation of the developed gradient boosting machine model demonstrated an area under receiver operator characteristic curve of 63% (95% confidence interval: 57%-68%), and the Brier score was 0.14 (95% confidence interval: 0.12-0.16). CONCLUSION: External validation of the 1-year Bayesian belief network survival model yielded a poor outcome based on a Danish population cohort validation. We successfully developed a gradient boosting machine 1-year survival model. The gradient boosting machine did not outperform the Bayesian belief network model based on external validation in a Danish population-based cohort.

Impact of the national sarcoma guidelines on the prevalence and outcome of inadvertent excisions of soft tissue sarcomas: An observational study from a UK tertiary referral centre.

OBJECTIVES: This study aims to investigate the impact of the national guideline on the prevalence and outcome in patients with soft-tissue sarcoma (STS) who had undergone inadvertent excisions. METHODS: A total of 2336 patients were referred to a tertiary sarcoma centre from six regions (North East, North West, East Midlands, West Midlands, Wales, and South West) in the United Kingdom with a diagnosis of STS between 1996 and 2016, of whom 561 patients (24.0%) had undergone inadvertent excisions. Patients were categorised into two groups of 10-year periods pre and post the National Institute for Health and Clinical Excellence (NICE) guideline implementation in 2006. RESULTS: The proportion of inadvertent excisions decreased after the NICE guideline implementation: 27.2% (pre-NICE) versus 19.8% (post-NICE) (p = 0.001). A substantial regional variation (17.4%-34.5%) in the proportion of inadvertent excisions in the pre-NICE era was reduced in the post-NICE era (14.3%-22.4%). The 5-year disease-specific survival was 77.7% (pre-NICE) versus 75.6% (post-NICE) (p = 0.961) and there was a trend toward lower incidence of local recurrence in the post-NICE era; 13.5% (pre-NICE) versus 10.5% (post-NICE) (p = 0.522). Multivariate analyses revealed that residual tumours in re-resection specimens were independently associated with an increased risk of disease-specific mortality (HR, 3.35; p < 0.001) and local recurrence (HR, 1.99; p = 0.017), which was significantly reduced after the NICE guideline implementation (53.2% versus 42.0%; p = 0.022). CONCLUSIONS: The NICE guideline implementation reduced the proportion of patients with STS who had undergone inadvertent excisions and residual tumour in re-resection specimens, indicating an improved pre-referral management of STSs.

Regional variation in the survival of patients with a soft-tissue sarcoma of the extremity and trunk wall under a centralized care system : what has been the impact of national policies in the UK?

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.

Limb-salvage reconstruction following resection of pelvic bone sarcomas involving the acetabulum.

AIMS: Limb salvage for pelvic sarcomas involving the acetabulum is a major surgical challenge. There remains no consensus about what is the optimum type of reconstruction after resection of the tumour. The aim of this study was to evaluate the surgical outcomes in these patients according to the methods of periacetabular reconstruction. METHODS: The study involved a consecutive series of 122 patients with a periacetabular bone sarcoma who underwent limb-salvage surgery involving a custom-made prosthesis in 65 (53%), an ice-cream cone prosthesis in 21 (17%), an extracorporeal irradiated autograft in 18 (15%), and nonskeletal reconstruction in 18 (15%). RESULTS: The rates of major complications necessitating further surgery were 62%, 24%, 56%, and 17% for custom-made prostheses, ice-cream cone prostheses, irradiated autografts and nonskeletal reconstructions, respectively (p = 0.001). The ten-year cumulative incidence of failure of the reconstruction was 19%, 9%, 33%, and 0%, respectively. The major cause of failure was deep infection (11%), followed by local recurrence (6%). The mean functional Musculoskeletal Tumour Society (MSTS) scores were 59%, 74%, 64%, and 72%, respectively. The scores were significantly lower in patients with major complications than in those without complications (mean 52% (SD 20%) vs 74% (SD 19%); p < 0.001). For periacetabular resections involving the ilium, the mean score was the highest with custom-made prostheses (82% (SD 10%)) in patients without any major complication; however, nonskeletal reconstruction resulted in the highest mean scores (78% (SD 12%)) in patients who had major complications. For periacetabular resections not involving the ilium, significantly higher mean scores were obtained with ice-cream cone prostheses (79% (SD 17%); p = 0.031). CONCLUSION: Functional outcome following periacetabular reconstruction is closely associated with the occurrence of complications requiring further surgery. For tumours treated with periacetabular and iliac resection, skeletal reconstruction may result in the best outcomes in the absence of complications, whereas nonskeletal reconstruction is a reasonable option if the risk of complications is high. For tumours requiring periacetabular resection without the ilium, reconstruction using an ice-cream cone prosthesis supported by antibiotic-laden cement is a reliable option. Cite this article: Bone Joint J 2021;103-B(4):795-803.

Pelvic reconstruction using an ice-cream cone prosthesis: correlation between the inserted length of the coned stem and surgical outcome.

BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Impact of NICE guidelines on the survival of patients with soft-tissue sarcomas.

AIMS: Urgent referral to a specialist centre for patients with a soft-tissue sarcoma (STS) has been recommended by the National Institute for Health and Care Excellence (NICE) in the UK since 2006. However, the impact of this recommendation on the prognosis for these patients remains unclear. We aimed to determine the impact of the NICE guidelines on the disease-specific survival (DSS) of patients with an STS. METHODS: A total of 2,427 patients with an STS referred to a supraregional centre in the ten-year periods before (n = 1,386) and after (n = 1,041) the issue of the NICE guidelines were evaluated. RESULTS: The mean size of the tumour was significantly smaller at the time of diagnosis (10.3 cm (SD 6.5) vs 9.1 cm (SD 6.2); p < 0.001) and the number of patients who had undergone an inadvertent excision significantly decreased (28% (n = 389) vs 20% (n = 204); p < 0.001) following the introduction of the NICE guidelines. The five-year DSS was 63% in the pre-NICE and 71% in post-NICE groups (p < 0.001). The improved survival was more significant for those with a high-grade tumour (pre-NICE, 48%; post-NICE, 68%; p < 0.001). In those with a high-grade tumour, the mean size of the tumour (11.6 cm (SD 6.2) vs 9.6 cm (SD 5.8); p < 0.001) and the number of patients with metastasis at the time of diagnosis (15% (n = 124 vs 10% (n = 80); p = 0.007) significantly decreased in the post-NICE group. CONCLUSION: An improvement in survival was seen after the introduction of the NICE guidelines, especially in patients with a high-grade STS. More patients were referred at an earlier stage, indicating a clearer pathway after the issue of national policy for the management of STSs in the UK. Cite this article: Bone Joint J 2021;103-B(3):569-577.

The importance of surgical margins in malignant Triton tumour of the trunk and extremities.

Malignant Triton tumour (MTT) is a rare variant of malignant peripheral nerve sheath tumour with partial rhabdomyosarcomatous differentiation. To the best of our knowledge, the importance of the surgical resection margins on the outcome of patients with MTT is unknown. The present study is a retrospective review of 24 patients treated for MTT of the trunk and the extremities between 1997 and 2015 in two institutions. The association of surgical margins with overall and tumour recurrence-free survival was analysed. Furthermore, the typical morphological and immunohistochemical characteristics of the tumour were described. In patients treated with curative intent (17/24), a surgical margin exceeding 1 mm was significantly associated with better overall survival and local recurrence-free survival. The oncological outcome was however poor, with only 28% of patients surviving at 5 years. Histopathologically, necrosis was a common feature, and most tumours displayed focal positivity for S100 protein and focal or strong positivity for desmin. The present results highlight the aggressive behaviour of MTTs and underline the importance of adequate surgical treatment.

Navigation-assisted pelvic resections and reconstructions for periacetabular chondrosarcomas.

OBJECTIVES: Survival in patients with chondrosarcomas has not improved over 40 years. Although emerging evidence has documented the efficacy of navigation-assisted surgery, the prognostic significance in chondrosarcomas remains unknown. We aimed to assess the clinical benefit of navigation-assisted surgery for pelvic chondrosarcomas involving the peri-acetabulum. METHODS: We studied 50 patients who underwent limb-sparing surgery for periacetabular chondrosarcomas performed with navigation (n = 13) without it (n = 37) at a referral musculoskeletal oncology centre between 2000 and 2015. RESULTS: The intralesional resection rates in the navigated and non-navigated groups were 8% (n = 1) and 19% (n = 7), respectively; all bone resection margins were clear in the navigated group. The 5-year cumulative incidence of local recurrence was 23% and 56% in the navigated and non-navigated groups, respectively (p = 0.035). There were no intra-operative complications related to use of navigation. There was a trend toward better functional outcomes in the navigated group (mean MSTS score, 67%) than the non-navigated group (mean MSTS score, 60%; p = 0.412). At a mean follow-up of 63 months, the 5-year disease-specific survival was 76% and 53% in the navigated and non-navigated group, respectively (p = 0.085), whilst the 5-year progression-free survival was 62% and 28% in the navigated and non-navigated group, respectively (p = 0.032). CONCLUSION: This study confirmed improved local control and progression-free survival with the use of computer navigation in patients with limb-salvage surgery for periacetabular chondrosarcomas, although the advancement in other treatment modalities is required for improvement of disease-specific survival.

Acetabular reconstruction with an ice-cream cone prosthesis following resection of pelvic tumors: Does computer navigation improve surgical outcome?

BACKGROUND AND OBJECTIVES: Acetabular reconstruction with a coned-stem prosthesis has been one of the reliable procedures following pelvic tumor resections but is associated with a risk of complications and postoperative morbidity. We investigated whether navigated reconstruction could decrease the complication rate and optimize outcomes. METHODS: A retrospective study was conducted on 33 patients who underwent acetabular resection and reconstruction with ice-cream cone prostheses; outcomes were compared between the navigated and nonnavigated groups. RESULTS: A clear margin was obtained in 91% and 82% of the navigated and nonnavigated groups, respectively. The local recurrence (LR) rate was 12%, and all LRs occurred in the nonnavigated group. The rate of major complications requiring surgical intervention was significantly lower in the navigated group (9%) than in the nonnavigated group (50%; P = .024). Two implant failures occurred in the nonnavigated group. Functional outcomes were significantly correlated with the occurrence of major complications (P = .010) and the use of navigation (P = .043); superior functional scores were observed in the navigated group (Musculoskeletal Tumor Society, 73% vs 55%; Toronto Extremity Salvage Score, 73% vs 56%). CONCLUSION: Ice-cream cone prosthesis is an acceptable reconstruction modality following periacetabular tumor resections, and computer navigation are useful to facilitate proper resection margins and implant position.

Denosumab in giant cell tumour of bone in the pelvis and sacrum: Long-term therapy or bone resection?

INTRODUCTION: Surgery of GCTB in sacrum and pelvis is challenging, with high rates of complications and local recurrence. Denosumab can consolidate the peripheral rim of the tumour, thus reducing the rate of morbidities of surgery. The aim of this paper is to evaluate the use of denosumab in pelvic/sacrum giant cell tumours of bone (GCTB). PATIENTS AND METHODS: We retrospectively reviewed a cohort of 26 patients with aggressive GCTB in sacrum or pelvis treated with denosumab at two referral centres. Clinical response and local recurrence were recorded and the radiologic responses were evaluated with the MDA criteria. RESULTS: 69% of the pelvic GCTB treated with denosumab presented partial or good radiologic responses (type 2A or 2B) after 49 weeks of treatment. Denosumab was administered as adjuvant therapy prior and after surgery in 11 patients (group A), and as the only treatment in 15 patients (group B). In group A, 62% of local recurrence was observed in patients treated with intralesional curettage. No recurrences were identified after en bloc resection. In group B, 9 patients were on continuous bimonthly long term denosumab administration with type 2A and 2B responses. Six patients stopped denosumab and 66% remained stable after 10 months of follow-up. CONCLUSIONS: Long-term denosumab therapy can be considered with curative intent for pelvic and sacrum GCTB. If surgical intervention is required wide resection may be advisable to reduce the risk of recurrence.

Denosumab in patients with giant-cell tumour of bone: a multicentre, open-label, phase 2 study.

BACKGROUND: Giant-cell tumour of bone (GCTB) is a rare, locally aggressive osteoclastogenic stromal tumour of the bone. This phase 2 study aimed to assess the safety and activity of denosumab in patients with surgically salvageable or unsalvageable GCTB. METHODS: In this multicentre, open-label, phase 2 study done at 30 sites in 12 countries we enrolled adults and skeletally mature adolescents (aged ≥12 years) weighing at least 45 kg with histologically confirmed and radiographically measurable GCTB, Karnofsky performance status 50% or higher (Eastern Cooperative Oncology Group status 0, 1, or 2), and measurable active disease within 1 year of study enrolment. Patients had surgically unsalvageable GCTB (cohort 1), had surgically salvageable GCTB with planned surgery expected to result in severe morbidity (cohort 2), or were enrolled from a previous study of denosumab for GCTB (cohort 3). Patients received 120 mg subcutaneous denosumab once every 4 weeks during the treatment phase, with loading doses (120 mg subcutaneously) administered on study days 8 and 15 to patients in cohorts 1 and 2 (patients in cohort 3 did not receive loading doses). The primary endpoint was safety in terms of the type, frequency, and severity of adverse events; secondary endpoints included time to disease progression from cohort 1 and the proportion of patients without surgery at month 6 for cohort 2. The safety analysis set included all enrolled patients who received at least one dose of denosumab. This study is registered with ClinicalTrials.gov, number NCT00680992, and has been completed. FINDINGS: Between Sept 9, 2008, and Feb 25, 2016, 532 patients were enrolled: 267 in cohort 1, 253 in cohort 2, and 12 in cohort 3. At data cutoff on Feb 24, 2017, median follow-up was 58·1 months (IQR 34·0-74·4) in the overall patient population, and 65·8 months (40·9-82·4) in cohort 1, 53·4 months (28·2-64·1) in cohort 2, and 76·4 months (61·2-76·5) in cohort 3. During the treatment phase, the most common grade 3 or worse adverse events were hypophosphataemia (24 [5%] of 526 patients), osteonecrosis of the jaw (17 [3%], pain in extremity (12 [2%]), and anaemia (11 [2%]). Serious adverse events were reported in 138 (26%) of 526 patients; the most common were osteonecrosis of the jaw (17 [3%]), anaemia (6 [1%]), bone giant cell tumour (6 [1%]), and back pain (5 [1%]). 28 (5%) patients had positively adjudicated osteonecrosis of the jaw, four (1%) had atypical femur fracture, and four (1%) had hypercalcaemia occurring 30 days after denosumab discontinuation. There were four cases (1%) of sarcomatous transformation, consistent with historical data. Ten (2%) treatment-emergent deaths occurred (two of which were considered treatment-related; bone sarcoma in cohort 2 and sarcoma in cohort 1). Median time to progression or recurrence for patients in cohort 1 during the first treatment phase was not reached (28 [11%] of 262 patients had progression or recurrence). 227 (92%; 95% CI 87-95) of 248 patients who received at least one dose of denosumab in cohort 2 had no surgery in the first 6 months of the study. INTERPRETATION: The types and frequencies of adverse events were consistent with the known safety profile of denosumab, which showed long-term disease control for patients with GCTB with unresectable and resectable tumours. Our results suggest that the overall risk to benefit ratio for denosumab treatment in patients with GCTB remains favourable. FUNDING: Amgen.

Surgical treatment for pelvic Ewing sarcoma: What is a safe and functional acetabular reconstruction when combined with modern multidisciplinary treatments?

PURPOSE: The purpose of this study was to clarify which local treatment is oncologically and functionally effective in pelvic Ewing sarcoma (ES). METHODS: A consecutive series of patients who underwent pelvic resections and acetabular reconstructions after chemotherapy between 1986 and 2016 at a supra-regional center were evaluated. RESULTS: The cohort consisted of 35 patients. The 5-year overall survival (OS) and local recurrence-free survival (LRFS) was 61% and 72%, respectively. Preoperative radiotherapy (RT) and surgery provided an excellent/good histological response in 92% and achieved significantly better OS (5 years, 64%) and LRFS (5 years, 100%) than surgery alone or surgery with postoperative RT. The Musculoskeletal Tumor Society functional scores were significantly better in patients with hip transposition than those with structural reconstructions (74% vs 57%; P = .031) using custom-made prostheses, irradiated autografts, and ice-cream cone prostheses. These scores were significantly lower if patients had deep infection (P = .035), which was the most common complication (28%) in structural reconstructions but did not occur in hip transposition even when performed after preoperative RT. CONCLUSION: Acetabular reconstruction with hip transposition resulted in no deep infection and superior function in patients with pelvic ES even when combined with preoperative RT, which improved tumor necrosis and rate of local control and survival.

Inadvertent excision of malignant soft tissue tumours.

Inadvertent excision of lumps which turn out to be sarcomas is not uncommon.Imaging has a limited role in detecting microscopic residual disease but can show the extent of the previous surgical field.Standard treatment is wide re-excision, usually combined with radiotherapy.Residual tumour is found in an average of 50% of reported cases.The presence of residual disease is an adverse prognostic factor.All lumps bigger than a golf ball should have a diagnosis prior to excision. Cite this article: EFORT Open Rev 2019;4 DOI: 10.1302/2058-5241.4.180060.

Survival and prognosis with osteosarcoma: outcomes in more than 2000 patients in the EURAMOS-1 (European and American Osteosarcoma Study) cohort.

BACKGROUND: High-grade osteosarcoma is a primary malignant bone tumour mainly affecting children and young adults. The European and American Osteosarcoma Study (EURAMOS)-1 is a collaboration of four study groups aiming to improve outcomes of this rare disease by facilitating randomised controlled trials. METHODS: Patients eligible for EURAMOS-1 were aged ≤40 years with M0 or M1 skeletal high-grade osteosarcoma in which case complete surgical resection at all sites was deemed to be possible. A three-drug combination with methotrexate, doxorubicin and cisplatin was defined as standard chemotherapy, and between April 2005 and June 2011, 2260 patients were registered. We report survival outcomes and prognostic factors in the full cohort of registered patients. RESULTS: For all registered patients at a median follow-up of 54 months (interquartile range: 38-73) from biopsy, 3-year and 5-year event-free survival were 59% (95% confidence interval [CI]: 57-61%) and 54% (95% CI: 52-56%), respectively. Multivariate analyses showed that the most adverse factors at diagnosis were pulmonary metastases (hazard ratio [HR] = 2.34, 95% CI: 1.95-2.81), non-pulmonary metastases (HR = 1.94, 95% CI: 1.38-2.73) or an axial skeleton tumour site (HR = 1.53, 95% CI: 1.10-2.13). The histological subtypes telangiectatic (HR = 0.52, 95% CI: 0.33-0.80) and unspecified conventional (HR = 0.67, 95% CI: 0.52-0.88) were associated with a favourable prognosis compared with chondroblastic subtype. The 3-year and 5-year overall survival from biopsy were 79% (95% CI: 77-81%) and 71% (95% CI: 68-73%), respectively. For patients with localised disease at presentation and in complete remission after surgery, having a poor histological response was associated with worse outcome after surgery (HR = 2.13, 95% CI: 1.76-2.58). In radically operated patients, there was no good evidence that axial tumour site was associated with worse outcome. CONCLUSIONS: In conclusion, data from >2000 patients registered to EURAMOS-1 demonstrated survival rates in concordance with institution- or group-level osteosarcoma trials. Further efforts are required to drive improvements for patients who can be identified to be at higher risk of adverse outcome. This trial reaffirms known prognostic factors, and owing to the large numbers of patients registered, it sheds light on some additional factors to consider.

Synovial sarcoma: Do children do better?

OBJECTIVES: Synovial sarcoma, a distinct subtype of soft tissue sarcomas (STS), is typically found in young patients. Long history of symptoms and heterogeneous clinical presentation sometimes delays diagnosis. Children have been reported to have a better prognosis than adults in some series. The main emphasis of this study was to determine differences between children and adults and to investigate prognostic factors regarding cancer specific survival (CSS). METHODS: 248 patients treated between 1982 and 2014 at one department were included. Mean age was 37.0 years, including 43 patients <16 years. Demographic, pathology- and treatment-related information was ascertained. Median follow-up was 5.2 years. RESULTS: Median duration of symptoms was 11.5 months in children and 12 months in adults (p = 0.238). Patients with a prior unplanned excision had a significantly longer duration of symptoms (p = 0.001). No difference was present between children and adults regarding tumour size, site, grade and superficial/deep location. Treatment was with surgical excision and (usually) adjuvant radiotherapy but five patients received preoperative radiotherapy and 43 patients chemotherapy. In patients treated with curative intent, five-year CSS rates were 75.5% for adults and 89.0% for children, with 10-year CSS rates of 56.1% and 82.2% (p = 0.026). In multivariate analysis, large tumour size (p < 0.005) and patient age (p = 0.024) were associated with worse CSS, irrespective of tumour location and site. CONCLUSION: Clinical presentation of synovial sarcoma is similar in children and adults, with no significant difference in tumour size, site, grade or location. Small tumour size and young patient age are independent positive prognostic factors influencing CSS.