Aims. This study aimed to evaluate the incidence and prognosis of patients with spinal metastasis as the initial manifestation of malignancy (SM-IMM). Patients and Methods. We retrospectively reviewed the electronic medical records of 338 patients who underwent surgical treatment for metastatic spinal disease. The enrolled patients were divided into two groups. The SM-IMM group included patients with no history of malignancy whose site of primary malignancy was diagnosed after the identification of spinal metastasis. The other group included patients with a history of treatment for primary malignancy who then developed spinal metastasis (SM-DTM). The incidence of SM-IMM by site of primary malignancy was calculated. The difference between prognoses after surgical treatment for SM-IMM and SM-DTM was established. Results. The median follow-up period was 11.5 months (interquartile range (IQR) 3.2 to 13.4) after surgical treatment. During the follow-up period, 264 patients died; 74 patients survived. The SM-IMM group consisted of 94 patients (27.8%). The site of primary malignancy in the SM-IMM group was lung in 35/103 patients (34.0%), liver in 8/45 patients (17.8%), kidney in 10/33 patients (30.3%), colorectum in 3/29 patients (10.3%), breast in 3/22 patients (13.6%), prostate in 3/10 patients (30%), thyroid in 4/8 patients (50%), and ‘other’ in 28/88 patients (31.8%). On Kaplan–Meier survival analysis, the SM-IMM group showed a significantly longer survival than the SM-DTM group (p = 0.013). The mean survival time was 23.0 months (95% confidence interval (CI) 15.5 to 30.5) in the SM-IMM group and 15.5 months (95% CI 11.8 to 19.2) in the SM-DTM group. Conclusion. Of the 338 enrolled patients who underwent surgical treatment for spinal metastasis, 94 patients (27.8%) underwent surgical treatment for SM-IMM. The SM-IMM group had an acceptable prognosis with surgical treatment. Cite this article: Bone Joint J 2019;101-B:1379–1384

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

We describe a case of intraneural metastasis of a synovial sarcoma, the first published case of a metastasis of a soft-tissue sarcoma to a peripheral nerve

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

Adamantinoma is a rare tumour of long bones that occurs most commonly in the tibia. Its pathogenesis is unknown. It is locally aggressive and recurrences are common after resection. Metastases have been reported in 10% to 20% of cases, most commonly in the lungs and rarely in the lymph nodes. We report a patient who developed a skeletal metastasis four years after resection of the primary tumour. There was no evidence of recurrence at the primary site or of secondary deposits in the lungs

We have developed a hollow perforated cannulated screw. One or more of these was implanted percutaneously in 11 patients with an osteolytic metastasis in the femoral neck and multiple metastases elsewhere. They were supplemented by one or two additional standard 6.5 mm cannulated screws in nine patients. Polymethylmethacrylate bone cement was injected through the screw into the neck of the femur using small syringes, as in vertebroplasty. The mean amount of cement injected was 23.2 ml (17 to 30). Radiotherapy was started on the fourth post-operative day and chemotherapy, on average, was resumed a day later. Good structural stability and satisfactory relief from pain were achieved in all the patients. This technique may be useful in the palliation of metastases in the femoral neck

We carried out excision of a solitary bony metastasis from renal-cell carcinoma in 25 patients in the hope that this would produce a prolonged disease-free interval. Two patients had excisions only, five had amputations and 18 had excision and endoprosthetic replacement. The one-, three- and five-year cumulative survival rates were 88%, 54% and 13%, respectively. There were three complications. One patient developed a local recurrence and three had problems related to the endoprosthesis. We recommend radical excision of a solitary bony metastasis from renal-cell carcinoma to achieve local control of the tumour for the remainder of the patient’s life

Between 1992 and 1999, we treated 350 patients with skeletal metastases. A multivariable analysis of the patients was conducted using the Cox proportional hazards model. We identified five significant prognostic factors for survival, namely, the site of the primary lesion, the performance status (Eastern Cooperative Oncology Group status 3 or 4), the presence of visceral or cerebral metastases, any previous chemotherapy, and multiple skeletal metastases. The score for each significant factor was derived from the corresponding estimated regression coefficients (natural logarithm of the hazard ratio). The prognostic score was calculated by adding all the scores for individual factors.

The rate of survival was 31% at six months and 11% at one year for the patients with a prognostic score of 6 or more. By contrast, patients with a prognostic score of 2 or less had a rate of survival of 98% at six months and 89% at one year. This scoring system can be used to determine the optimal treatment for patients with pathological fractures or epidural compression.

Many tumors metastasise to bone, therefore, pathologic fracture and impending pathologic fractures are common reasons for orthopedic consultation. Having effective treatment strategies is important to avoid complications, and relieve pain and preserve function. Thorough pre-operative evaluation is recommended for medical optimization and to ensure that the lesion is in fact a metastasis and not a primary bone malignancy. For impending fractures, various scoring systems have been proposed to determine the risk of fracture, and therefore the need for prophylactic stabilisation. Lower score lesions can often be treated with radiation, while more problematic lesions may require internal fixation. Intramedullary fixation is generally preferred due to favorable biomechanics. Arthroplasty may be required for lesions with massive bony destruction where internal fixation attempts are likely to fail. Radiation may also be useful postoperatively to minimise construct failure due to tumor progression.

Aims. 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. Methods. We conducted a retrospective study on a population-based cohort of all adult patients treated surgically for bony metastases of the appendicular skeleton between January 2014 and December 2019. We excluded patients in whom the status of bone metastases and resection margin was unknown. Patients were followed until the end of the study or to their death. We had no loss to follow-up. We used Kaplan-Meier analysis (with log-rank test) to evaluate patient survival. We identified 506 operations in 459 patients. A total of 120 operations (in 116 patients) were for solitary metastases and 386 (in 345 patients) for multiple metastases. Of the 120 operations, 70 (in 69 patients) had no/an unknown status of visceral metastases (solitary group) and 50 (in 49 patients) had visceral metastases. In the solitary group, 45 operations (in 44 patients) were R0 (resections for cure or complete remission) and 25 (in 25 patients) were R1/R2 (resections leaving microscopic or macroscopic tumour, respectively). The most common types of cancer in the solitary group were kidney (n = 27), lung (n = 25), and breast (n = 20). Results. The one-year patient survival was 47% (95% confidence interval (CI) 38 to 57) for the solitary bony metastases and 34% (95% CI 29 to 39) for multiple bone metastases (p < 0.001). The one-year patient survival was 64% (95% CI 52 to 75) for solitary bony metastases without/with unknown visceral metastases and 23% (95% CI 11 to 36) for solitary bony metastases with visceral metastases (p < 0.001). The one-year patient survival was 75% (95% CI 62 to 89) for a solitary bony metastasis after R0 surgery and 42% (95% CI 22 to 61) for a solitary bony metastasis with R1/R2 surgery (p < 0.001). Conclusion. Our study suggests that the surgical treatment of patients with a solitary bony metastasis to the appendicular skeleton results in better survival than for patients with multiple bony metastases. Furthermore, aggressive treatment of a solitary bony metastasis with R0 surgery may improve patient survival. Cite this article: Bone Joint J 2023;105-B(11):1206–1215

The February 2024 Oncology Roundup. 360. looks at: Does primary tumour resection improve survival for patients with sarcomas of the pelvis with metastasis at diagnosis?; Proximal femur replacements for an oncologic indication offer a durable endoprosthetic reconstruction option: a 40-year experience; The importance of awaiting biopsy results in solitary pathological proximal femoral fractures: do we need to biopsy solitary pathological fractures?; Effect of radiotherapy on local recurrence, distant metastasis, and overall survival in 1,200 extremity soft-tissue sarcoma patients; What to choose in bone tumour resections? Patient-specific instrumentation versus surgical navigation; Optimal timing of re-excision in synovial sarcoma patients: immediate intervention versus waiting for local recurrence; Survival differences of patients with resected extraskeletal osteosarcoma receiving two different (neo) adjuvant chemotherapy regimens; Solitary versus multiple bone metastases in the appendicular skeleton: should the surgical treatment be different?

The April 2024 Oncology Roundup. 360. looks at: Midterm outcomes of total hip arthroplasty after internal hemipelvectomy and iliofemoral arthrodesis; Intraosseous conventional central chondrosarcoma does not metastasize irrespective of grade in pelvis, scapula, and in long bone locations; Oncological and functional outcomes after resection of malignant tumours of the scapula; Reconstruction following oncological iliosacral resection – a comparison of techniques; Does primary tumour resection improve survival for patients with sarcomas of pelvic bones, sacrum, and coccyx who have metastasis at diagnosis?; Older patients with Ewing’s sarcoma: an analysis of the National Cancer Database; Diagnostic challenges in low-grade central osteosarcoma; Effect of radiotherapy on local recurrence, distant metastasis, and overall survival in 1,200 limb soft-tissue sarcoma patients: a retrospective analysis using inverse probability of treatment weighting-adjusted models

Neck of femur fractures are a common trauma presentation and patients with a history of malignancy are sent for long leg femur views (LLF), to exclude a distal lesion which would alter the management plan (Intra-medullary nail/Long stem Hemiarthroplasty). The aim of this is to identify incidence of malignancy on LLF views, the length of time in between each xray (XR) and to identify demographics. Data was retrospectively collected from 01/01/2021 to 31/01/2021 from a single centre. All patients admitted to the Queen Elizabeth University Hospital had their electronic records (Bluespier, PACS, Clinical Portal) accessed. These confirmed if patients had a past medical history of malignancy, if they had LLF view and the time differences between diagnostic pelvis XR and LLF XR. A total of 784 patients were identified in the specified time period. Of these, 138 were identified with a malignancy and there were 85 LLF views completed. LLF views diagnosed 1 patient with known prostate cancer that had a new distal femoral metastasis (Incidence = 1.28 cases per 1000). This patient underwent further imaging (MRI Femur) and received a long stem hip hemiarthroplasty. The average length of wait between the images was 9 hours 27 minutes. LLF views can alter management of patients with malignancy and are therefore useful to perform. There can be a long delay between each image. Therefore we recommend imaging tumour with common bony metastasis (Renal, Thyroid, Breast, Prostrate, Lung) and other remaining tumours with known secondary metastasis. Imaging primary low risk (eg basal cell carcinoma) can lead to long delays in a frail patient cohort and consideration should be given to rationalise appropriate use of resources

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

Lymph node metastasis are a rare occurrence in soft tissue sarcomas of the extremity, arising in less than 5% of patients. Few studies have evaluated the prognosis and survival of patients with a lymph node metastasis. Early reports compared lymph node involvement to lung metastasis, while others suggested a slightly better outcome. The purpose of this study was to evaluate the impact of lymph node metastasis on patient survival and to investigate the histologic and clinical features associated with lymph node involvement. A retrospective review was done of the prospectively collected soft tissue sarcoma database at our institution. Two thousand forty-five patients had surgery for soft tissue sarcoma of an extremity between January 1986 and August 2017. Included patients either presented with a synchronous lymph node metastasis or were diagnosed with a lymph node metastasis after their initial treatment. Demographic, treatment, and outcome data for patients with lymph node involvement were obtained from the clinical and radiographic records. Lymph node metastases were identified as palpable adenopathy by physical examination and were further characterized on cross-sectional imaging by computed tomography (CT) or magnetic resonance imaging (MRI) scans. All cases were confirmed by pathologic examination of biopsy specimens. A pathologist with expertise in sarcoma determined the histologic type and graded tumors as 1, 2, or 3. One hundred eighteen patients with a mean age of 55.7 (SD=18.9) were included in our study. Seventy-two (61.3%) out of 119 patients were male. Thirty six patients (57.1%) had lymph node involvement at diagnosis. The mean follow-up from the date of the first surgery was 56.3 months. The most common histological diagnoses were Malignant fibrous histiocytoma (35) and liposarcoma (12). Ninety eight patients (89%) underwent surgical treatment of the lymph node metastasis while 21 (17.6%) were treated with chemotherapy and/or radiation therapy. The mean survival was 52.6 months (range 1–307). Our results suggest that patients with a lymph node metastasis have a better prognosis than previously described. Their overall survival is superior to patients diagnosed with lung metastasis. A signifant proportion of patients may expect long term survival after surgical excision of lymph node metastasis. Furthermore, our study also indicates that different histological subtypes such as liposarcoma or malignant peripheral nerve sheath tumor (MPNST) may also be responsible for lymph node metastasis. Additional studies to further improve the treatment of soft tissue sarcoma nodal metastasis are warranted

Aims. Most patients with advanced malignancy suffer bone metastases, which pose a significant challenge to orthopaedic services and burden to the health economy. This study aimed to assess adherence to the British Orthopaedic Oncology Society (BOOS)/British Orthopaedic Association (BOA) guidelines on patients with metastatic bone disease (MBD) in the UK. Methods. A prospective, multicentre, national collaborative audit was designed and delivered by a trainee-led collaborative group. Data were collected over three months (1 April 2021 to 30 June 2021) for all patients presenting with MBD. A data collection tool allowed investigators at each hospital to compare practice against guidelines. Data were collated and analyzed centrally to quantify compliance from 84 hospitals in the UK for a total of 1,137 patients who were eligible for inclusion. Results. A total of 846 patients with pelvic and appendicular MBD were analyzed, after excluding those with only spinal metastatic disease. A designated MBD lead was not present in 39% of centres (33/84). Adequate radiographs were not performed in 19% of patients (160/846), and 29% (247/846) did not have an up-to-date CT of thorax, abdomen, and pelvis to stage their disease. Compliance was low obtaining an oncological opinion (69%; 584/846) and prognosis estimations (38%; 223/846). Surgery was performed in 38% of patients (319/846), with the rates of up-to-date radiological investigations and oncology input with prognosis below the expected standard. Of the 25% (215/846) presenting with a solitary metastasis, a tertiary opinion from a MBD centre and biopsy was sought in 60% (130/215). Conclusion. Current practice in the UK does not comply with national guidelines, especially regarding investigations prior to surgery and for patients with solitary metastases. This study highlights the need for investment and improvement in care. The recent publication of British Orthopaedic Association Standards for Trauma (BOAST) defines auditable standards to drive these improvements for this vulnerable patient group. Cite this article: Bone Joint J 2023;105-B(10):1115–1122

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. 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. Methods. We retrospectively analyzed the medical records of 49 patients with LGCOS (Broder’s grade 1 to 2) treated between January 1985 and December 2017 in a single institute. We examined the presence of malignant features on imaging (periosteal reaction, cortical destruction, soft-tissue invasion), the diagnostic accuracy of biopsy, surgical treatment, and oncological outcome. Results. Based on imaging, 35 of 49 patients (71.4%) exhibited malignant features. Overall, 40 of 49 patients (81.6%) had undergone a biopsy before en-bloc resection: 27 of 40 patients (67.5%) were diagnosed on the first biopsy, which was more accurate when carried out by open rather than needle biopsy (91.3% vs 35.3% diagnostic accuracy, respectively; p < 0.001). Of the 40 patients treated by en-bloc resection, surgical margins were wide in 38 (95.0%) and marginal in two (5.0%). Furthermore, nine of 49 patients (18.4%) underwent curettage (intralesional margin) without previous biopsy. All patients with a positive margin developed local recurrence. Distant metastases occurred in five of 49 patients (10.2%). The mean five-year overall survival (OS) and distant relapse-free survival (D-RFS) were 89.3% (SD 5.1%) and 85.7% (SD 5.5%), respectively. Univariate analysis showed that the occurrence of distant metastasis was a poor prognostic factor for OS (hazard ratio 11.54, 95% confidence interval (CI) 1.92 to 69.17; p < 0.001). Local recurrence was a poor prognostic factor for D-RFS (HR 8.72, 95% CI 1.69 to 45.0; p = 0.002). Conclusion. The diagnosis of LGCOS can be challenging because it may present with non-malignant features and has a low diagnostic accuracy on biopsy. If precisely diagnosed, LGCOS can be successfully treated by surgical excision with wide margins. Cite this article: Bone Joint J 2024;106-B(1):99–106

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

En bloc resection for primary bone tumours and isolated metastasis are complex surgeries associated with a high rate of adverse events (AEs). The primary objective of this study was to explore the relationship between frailty/sarcopenia and major perioperative AEs following en bloc resection for primary bone tumours or isolated metastases of the spine. Secondary objectives were to report the prevalence and distribution of frailty and sarcopenia, and determine the relationship between these factors and length of stay (LOS), unplanned reoperation, and 1-year postoperative mortality in this population. This is a retrospective study of prospectively collected data from a single quaternary care referral center consisting of patients undergoing an elective en bloc resection for a primary bone tumour or an isolated spinal metastasis between January 1st, 2009 and February 28th, 2020. Frailty was calculated with the modified frailty index (mFI) and spine tumour frailty index (STFI). Sarcopenia, determined by the total psoas area (TPA) vertebral body (VB) ratio (TPA/VB), was measured at L3 and L4. Regression analysis produced ORs, IRRs, and HRs that quantified the association between frailty/sarcopenia and major perioperative AEs, LOS, unplanned reoperation and 1-year postoperative mortality. One hundred twelve patients met the inclusion criteria. Using the mFI, five patients (5%) were frail (mFI ³ 0.21), while the STFI identified 21 patients (19%) as frail (STFI ³ 2). The mean CT ratios were 1.45 (SD 0.05) and 1.81 (SD 0.06) at L3 and L4 respectively. Unadjusted analysis demonstrated that sarcopenia and frailty were not significant predictors of major perioperative AEs, LOS or unplanned reoperation. Sarcopenia defined by the CT L3 TPA/VB and CT L4 TPA/VB ratios significantly predicted 1-year mortality (HR of 0.32 per one unit increase, 95% CI 0.11-0.93, p=0.04 vs. HR of 0.28 per one unit increase, 95% CI 0.11-0.69, p=0.01) following unadjusted analysis. Frailty defined by an STFI score ≥ 2 predicted 1-year postoperative mortality (OR of 2.10, 95% CI 1.02-4.30, p=0.04). The mFI was not predictive of any clinical outcome in patients undergoing en bloc resection for primary bone tumours or isolated metastases of the spine. Sarcopenia defined by the CT L3 TPA/VB and L4 TPA/VB and frailty assessed with the STFI predicted 1-year postoperative mortality on univariate analysis but not major perioperative AEs, LOS or reoperation. Further investigation with a larger cohort is needed to identify the optimal measure for assessing frailty and sarcopenia in this spine population

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. The aim of this study was to investigate the incidence and characteristics of instrumentation failure (IF) after total en bloc spondylectomy (TES), and to analyze risk factors for IF. Methods. The medical records from 136 patients (65 male, 71 female) with a mean age of 52.7 years (14 to 80) who underwent TES were retrospectively reviewed. The mean follow-up period was 101 months (36 to 232). Analyzed factors included incidence of IF, age, sex, BMI, history of chemotherapy or radiotherapy, tumour histology (primary or metastasis; benign or malignant), surgical approach (posterior or combined), tumour location (thoracic or lumbar; junctional or non-junctional), number of resected vertebrae (single or multilevel), anterior resection line (disc-to-disc or intravertebra), type of bone graft (autograft or frozen autograft), cage subsidence (CS), and local alignment (LA). A survival analysis of the instrumentation was performed, and relationships between IF and other factors were investigated using the Cox regression model. Results. A total of 44 patients (32.4%) developed IF at a median of 31 months (interquartile range 23 to 74) following TES. Most IFs were rod fractures preceded by a mean CS of 6.1 mm (2 to 18) and LA kyphotic enhancement of 10.8° (-1 to 36). IF-free survival rates were 75.8% at five years and 56.9% at ten years. The interval from TES to IF peaked at two to three years postoperatively and continued to occur over a period of time thereafter; the early IF-developing group had greater CS at one month postoperatively (CS1M) and more lumbar TES. CS1M ≥ 3 mm and sole use of frozen autografts were identified as independent risk factors for IF. Conclusion. IF is a common complication following TES. We have demonstrated that robust spinal reconstruction preventing CS, and high-quality bone grafting are necessary for successful reconstruction. Cite this article: Bone Joint J 2023;105-B(2):172–179

Aims. The aims of this study were to determine the incidence and factors for developing periprosthetic joint infection (PJI) following hemiarthroplasty (HA) for hip fracture, and to evaluate treatment outcome and identify factors associated with treatment outcome. Methods. A retrospective review was performed of consecutive patients treated for HA PJI at a tertiary referral centre with a mean 4.5 years’ follow-up (1.6 weeks to 12.9 years). Surgeries performed included debridement, antibiotics, and implant retention (DAIR) and single-stage revision. The effect of different factors on developing infection and treatment outcome was determined. Results. A total of 1,984 HAs were performed during the study period, and 44 sustained a PJI (2.2%). Multiple logistic regression analysis revealed that a higher CCI score (odds ratio (OR) 1.56 (95% confidence interval (CI) 1.117 to 2.187); p = 0.003), peripheral vascular disease (OR 11.34 (95% CI 1.897 to 67.810); p = 0.008), cerebrovascular disease (OR 65.32 (95% CI 22.783 to 187.278); p < 0.001), diabetes (OR 4.82 (95% CI 1.903 to 12.218); p < 0.001), moderate-to-severe renal disease (OR 5.84 (95% CI 1.116 to 30.589); p = 0.037), cancer without metastasis (OR 6.42 (95% CI 1.643 to 25.006); p = 0.007), and metastatic solid tumour (OR 15.64 (95% CI 1.499 to 163.087); p = 0.022) were associated with increasing PJI risk. Upon final follow-up, 17 patients (38.6%) failed initial treatment and required further surgery for HA PJI. One-year mortality was 22.7%. Factors associated with treatment outcome included lower preoperative Hgb level (97.9 g/l (SD 11.4) vs 107.0 g/l (SD 16.1); p = 0.009), elevated CRP level (99.1 mg/l (SD 63.4) vs 56.6 mg/l (SD 47.1); p = 0.030), and type of surgery. There was lower chance of success with DAIR (42.3%) compared to revision HA (66.7%) or revision with conversion to total hip arthroplasty (100%). Early-onset PJI (≤ six weeks) was associated with a higher likelihood of treatment failure (OR 3.5 (95% CI 1.2 to 10.6); p = 0.007) along with patients treated by a non-arthroplasty surgeon (OR 2.5 (95% CI 1.2 to 5.3); p = 0.014). Conclusion. HA PJI initially treated with DAIR is associated with poor chances of success and its value is limited. We strongly recommend consideration of a single-stage revision arthroplasty with cemented components. Cite this article: Bone Jt Open 2022;3(12):924–932

Purpose. Extraskeletal chondrosarcoma is a rare tumor with an indolent course and high propensity for local recurrence and metastasis. This tumor most commonly presents in the proximal extremities of middle-aged males, and is commonly asymptomatic. Although slow growing, these tumors have a significant risk of eventual relapse and metastases, especially to the lung. There are no clinical trials that investigated the best treatment options for this tumor given its very low incidence. The aim of this study is to present the surgical and clinical results of extraskeletal chondrosarcoma, which is a rare tumor. Methods. In our clinic, the information of 13 patients who were diagnosed with extra-skeletal chondrosarcoma between 2006 and 2018 were retrospectively reviewed. Demographic information, tumor size, surgical treatments, chemotherapy and radiotherapy status, follow-up times, recurrence and metastases of the patients were recorded. Results. This study included 13 patients with an average age of 53.6 ± 15 (range, 28 to 73) years diagnosed with extraskelatal chondrosarcoma. In 8 of the patients, the tumor was located in the lower limbs and it was observed that the thigh was located mostly (46.2%). The mean follow-up period of the patients was 52.8 ± 19.9 (range, 24 to 96) months. All patients underwent extensive resection and only one patient had a positive surgical margin. In the follow-up, 5 (38.5%) of the patients developed recurrence, while 6 patients had lung metastasis (46.2%) and 53.8% (7 patients) of the patients exitus. The mean tumor size was 10.4 ± 3.2 (range, 5 to 17) cm. The median survival time of the patients in the study was 61 (50.5–71.4) months. The 5-year survival rate is 51.8%. There was no significant difference between survival times according to age, gender, side, limb location, postoperative RT, recurrence and presence of lung metastasis (log rank tests p > 0.05). The cut off value for exitus obtained by ROC analysis of tumor size was determined as 11 cm (fig 1). Accordingly, the survival time of patients with 11 cm and above tumor size was observed to be statistically significantly shorter. Conclusion. Consequently, ECM is a rare soft tissue sarcoma with high local recurrence and metastasis capacity. Therefore, close follow-up is recommended. The first option should be extensive resection. Studies with large patient series on the prognostic factors of the future ECM are needed. For any figures or tables, please contact the authors directly

Aims. 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. Methods. This is a retrospective analysis of 151 patients (with median follow-up in survivors of 44 months (interquartile range 12 to 77)) who underwent hemipelvectomy with iliosacral resection at a single centre between 2007 and 2019. The proposed classification differentiates the extent of iliosacral resection and defines types S1 to S6 (S1 resection medial and parallel to the sacroiliac joint, S2 resection through the ipsilateral sacral lateral mass to the neuroforamina, S3 resection through the ipsilateral neuroforamina, S4 resection through ipsilateral the spinal canal, and S5 and S6 contralateral sacral resections). Descriptive statistics and the chi-squared test were used for categorical variables, and the Kaplan-Meier survival analysis were performed. Results. Resections were S1 in 25/151 patients (17%), S2 in 70/151 (46%), S3 in 33/151 (22%), S4 in 77/151 (11%), S5 in 4/151 (3%), and S6 in 2/151 (1%). An internal hemipelvectomy was performed in 113/151 patients (75%), and 38/151 patients (25%) had an external hemipelvectomy. The predominant types of sarcoma were high-grade osteosarcoma in 48/151 patients (32%), chondrosarcoma in 41/151 (27%), Ewing sarcoma in 33/151 (22%), pleomorphic sarcoma in 17/151 (11%), and others in 2/151 (8%). LR was found in 24/151 patients (15%) with S3, S5, with S6 resections showing the highest rate of LR (p = 0.038). Overall, 19/151 patients (16%) had evidence of metastastic disease at the time of surgery and these patients showed poorer survival when compared to patients with no metastasis. Conclusion. The proposed classification can help to report and compare different surgical and reconstructive approaches in these difficult cases who are still have a considerable risk of LR. Cite this article: Bone Joint J 2022;104-B(2):290–296

Aims. The aim of this study is to evaluate the clinical results of operative intervention for femoral metastases which were selected based on expected survival and to discuss appropriate surgical strategies. Methods. From 2002 to 2017, 148 consecutive patients undergoing surgery for femoral metastasis were included in this study. Prognostic risk assessments were performed according to the Katagiri and revised Katagiri scoring system. In general, the low-risk group underwent resection and reconstruction with endoprosthetic replacement (EPR), while the high-risk group underwent internal fixation (IF) and radiation therapy. For the intermediate-risk group, the operative choice depended on the patient’s condition, degree of bone destruction, and radio-sensitivity. Overall survival, local failure, walking ability, and systemic complications were evaluated. Results. A total of 83 patients underwent EPR (low-risk, 23%; intermediate-risk, 60%; high-risk, 17%) and 65 patients underwent IF (low-risk, 0%; intermediate-risk, 32%; high-risk, 68%). The one-year survival rate was 71% for EPR and 15% for IF (p < 0.001). The one-year local failure-free survival was 93% for EPR and 67% for IF, and the two-year and five-year local failure-free survival for EPR were both 88% (p = 0.016). Although the ambulatory rate was 99% for EPR and 60% for IF, the median time to ambulation was shorter in the IF (EPR, 28 days, interquartile range (IQR) 25 to 35; IF, 23 days, IQR 18 to 28; p < 0.001) The cause of non ambulation was mainly due to progression of cancer (89%). The rate of systemic complications was comparable between the two groups (EPR, 18%; IF, 22%; p = 0.598). Conclusion. Selective use of EPR where survival is expected to be good offers correspondingly good long-term results. IF is less invasive with shorter treatment period, which is beneficial for patients with short-term expected survival. Prognosis is an important indicator in selecting operative procedures for femoral metastasis. Cite this article: Bone Joint J 2020;102-B(3):285–292

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

Abstract. Background. Reconstruction following resection of sarcomas of the upper extremity with methods described in the prevalent literature may not be possible in few selected cases. We describe Surgical Phocomelia or Phoco-reduction as a method of limb salvage in such cases of extensive sarcomas of the upper limb with its functional and oncological outcomes. Methods. Evaluation of functional and oncological outcomes was performed for 11 patients who underwent surgical phocomelia or phocoreduction for extensive sarcomas of the upper limb between 2010 and 2019. Results. Mean follow-up period in the study was27.8 months. Five patients required a segmental resection including the entire humerus while 6 patients underwent segmental resection around the elbow with a mean resection length of 21.5 cm. Mean MSTS 93 score was 22 depicting a good functional outcome. Mean hand grip strength on the operated side was 62% of the contralateral side with preservation of useful hand function. Mean time to humero-ulnar union was 6.7 months. Radial nerve palsy and implant failure occurred in 1 patient each. No patient developed local recurrence while 3 patients died of metastasis. Conclusion. Surgical phocomelia is a prudent alternative to severely incapacitating amputations in situations where other reconstruction methods are not feasible

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

Osteosarcoma is a highly malignant primary tumor of bone tissue. The 5-year survival rate of patients with metastasis is below 20% and this scenario is unchanged in the last two decades, despite great efforts in pre-clinical and clinical research. Traditional preclinical models of osteosarcoma do not consider the whole complexity of its microenvironment, leading to poor correlation between in vitro/in vivo results and clinical outcomes. Spheroids are a promising in vitro model to mimic osteosarcoma and perform drug-screening tests, as they (i) reproduce the microarchitecture of the tumor, (ii) are characterized by hypoxic regions and necrotic core as the in vivo tumor, (iii) and recapitulate the chemo-resistance phenomena. However, to date, the spheroid model is scarcely used in osteosarcoma research. Our aim is to develop a customized culture dish to grow and characterize spheroids and to perform advanced drug-screening tests. The resulting platform must be adapted to automated image acquisition systems, to overcome the drawbacks of commercial spheroids platforms. To this purpose, we designed and developed a micro-patterned culture dish by casting agarose on a 3D printed mold from a CAD design. We successfully obtained viable and reproducible homotypic osteosarcoma spheroids, with two different cells lines from osteosarcoma (i.e., 143b and MG-63). Using the platform, we performed viability assays and live fluorescent stainings (e.g., Calcein AM) with low reagent consumption. Moreover, the culture dish was validated as drug screening platform, administrating Doxorubicin at different doses, and evaluating its effect on OS spheroids, in terms of morphology and viability. This platform can be considered an attractive alternative to the highly expensive commercial spheroid platforms to obtain homogeneous and reproducible spheroids in a high-throughput and cost effective mode

The NZ Standards of Service Provision for Sarcoma patients were developed by the NZ Sarcoma working group and published by the Ministry of Health (MOH) in 2013. Although not formally enacted by the MOH we aimed to determine the impact of these published standards and referral pathways on disease-specific survival of patients with soft-tissue sarcoma in NZ. The Middlemore Musculoskeletal Tumour Unit database was searched. Patients referred for treatment in our centre with a diagnosis of soft tissue sarcoma in the five-year period before (n=115) and after (n=155) were included. We excluded patients with bone sarcomas and retroperitoneal soft tissue sarcomas. The rate of referral after inappropriate treatment reduced after implementation of the Standards (24% vs 12%, p=0.010). The number of patients referred with tumours larger than 50mm decreased (74.8% vs 72.3%, p=0.021) and fewer had metastases at diagnosis (11.3% vs 3.2%, p=0.017). Mortality was lower in the group after introduction of the Standards (45% vs 30%, p=0.017). The estimated disease-specific survival curve between the two groups shows a trend towards increased survival in the post-standards group, although not reaching statistical significance. Local recurrence rate and metastasis rate after definitive treatment were similar between the two groups. Patients had a shorter duration of symptoms before referral in the post-Standards group although this was not statistically significant. Since implementation of the Standards, patients have been referred more promptly, with fewer inappropriate treatments. The time to mortality curve indicates a trend towards improved disease-specific survival. We conclude that the pathway for investigation and referral for this condition has become clearer, supporting the ongoing use of the Sarcoma Standards, and that these should be formally implemented by the MOH

Macrophages (Mφ) are immune cells that play a crucial role in both innate and adaptive immunity as they are involved in a wide range of physiological and pathological processes. Depending on the microenvironment and signals present, Mφ can polarize into either M1 or M2 phenotypes, with M1 macrophages exhibiting pro-inflammatory and cytotoxic effects, while M2 macrophages having immunosuppressive and tissue repair properties. Macrophages have been shown to play key roles in the development and progression or inhibition of various diseases, including cancer. For example, macrophages can stimulate tumor progression by promoting immunosuppression, angiogenesis, invasion, and metastasis. This work aimed to investigate the effect of extracellular vesicles (EVs)-derived from polarized macrophages on an osteosarcoma cell line. Monocytes were extracted from buffy coats and cultured in RPMI medium with platelet lysate or M-CSF. After 6 days of seeding, Mφ were differentiated into M1 and M2 with INF-γ/LPS and IL-4/IL-13, respectively. The medium with M1 or M2 derived EVs was collected and EVs were isolated by differential centrifugation and size exclusion chromatography and its morphology and size were characterized with SEM and NTA, respectively. The presence of typical EVs markers (CD9, CD63) was assessed by Western Blot. Finally, EVs from M1 or M2-polarized Mφ were added onto osteosarcoma cell cultures and their effect on cell viability and cell cycle, proliferation, and gene expression was assessed. The EVs showed the typical shape, size and surface markers of EVs. Overall, we observed that osteosarcoma cells responded differentially to EVs isolated from the M1 and M2-polarized Mφ. In summary, the use of Mφ-derived EVs for the treatment of osteosarcoma and other cancers deserves further study as it could benefit from interesting traits of EVs such as low immunogenicity, nontoxicity, and ability to pass through tissue barriers. Acknowledgements: Carlos III Health Institute and the European Social Fund for contract CP21/00136 and project PI22/01686

The Spine Surgery Unit of IRCCS Istituto Ortopedico Rizzoli is dedicated to the diagnosis and the treatment of vertebral pathologies of oncologic, degenerative, and post-traumatic origin. To achieve increasingly challenging goals, research has represented a further strength for Spinal Surgery Unit for several years. Thanks to the close synergy with the Complex Structure Surgical Sciences and Technologies, IRCCS Istituto Ortopedico Rizzoli, extensive research was carried out. The addition of the research activities intensifies a complementary focus and provides a unique opportunity of innovation. The overall goal of spine research for the Spine Surgery Unit and for the Complex Structure Surgical Sciences and Technologies is and has been to:. - investigate the factors that influence normal spine function;. - engineer and validate new and advanced strategies for improving segmental spinal instrumentation, fusion augmentation and grafting;. - develop and characterize advanced and alternative preclinical models of vertebral bone metastasis to test drugs and innovative strategies, taking into account patient individual characteristics and specific tumour subtypes so predicting patient specific responses;. - evaluate the clinical characteristics, treatment modalities, and potential contributing and prognostic factors in patients with vertebral bone metastases;. - realize customized prosthesis to replace vertebral bodies affected by tumours or major traumatic events, specifically engineered to reduce infections, and increase patients’ surgical options. These efforts have made possible to obtain important results that favour the translation of basic research to application at the patient's bedside, and from here to routine clinical practice (without excluding the opposite pathway, in which the evidence generated by clinical practice helps to guide research). Although translational research can provide patients with valuable therapeutic resources, it is not risk-free. Thus, it is therefore necessary an always close collaboration between researchers and clinicians in order to guarantee the ethicality of translational research, by promoting the good of individuals and minimising the risks

Impaired bone healing biology secondary to soft tissue deficits and chemotherapy contribute to non-union, fracture and infection following limb salvage surgery in Osteosarcoma patients. Approved bone healing augments such as recombinant human bone morphogenetic protein-2 (rhBMP-2) have great potential to mitigate these complications. rhBMP-2 use in sarcoma surgery is limited, however, due to concerns of pro-oncogenic signalling within the tumour resection bed. To the contrary, recent pre-clinical studies demonstrate that BMP-2 may induce Osteosarcoma differentiation and limit tumour growth. Further pre-clinical studies evaluating the oncologic influences of BMP-2 in Osteosarcoma are needed. The purpose of this study is to evaluate how BMP-2 signalling affects Osteosarcoma cell proliferation and metastasis in an active tumour bed. Two Osteosarcoma cell lines (143b and SaOS-2) were assessed for proliferative capacity and invasion. 143b and SaOS-2 cells were engineered to upregulate BMP-2. In vitro proliferation was assessed using a cell viability assay, motility was assessed with a scratch wound healing assay, and degree of osteoblastic differentiation was assessed using qRT-PCR of Osteoblastic markers (CTGF, ALP, Runx-2 and Osx). For in vivo evaluation, Osteosarcoma cells were injected into the intramedullary proximal tibia of immunocompromised (NOD-SCID) mice and local tumour growth and metastases were assessed using weekly bioluminescence imaging (BLI) and tumour volume measurements for 4–6 weeks. At the experimental end point we assessed radiographic tumour burden using ex-vivo micro-CT, as well as tibial and pulmonary gross and histologic pathology. SaOS-2 was more differentiated than 143b, with increased expression of Runx-2 (p = 0.009), Osx (p = 0.004) and ALP (p = 0.035). BMP-2 upregulation did not stimulate an osteoblast differentiation response in 143b, but stimulated an increase in Osx expression in SaOS-2 (p = 0.002). BMP-2 upregulation in 143b cells resulted in increased proliferation in vitro (p = 0.014), faster in vitro wound healing (p = 0.03), significantly increased tumour volume (p = 0.001) with enhanced osteolysis detected on micro-CT, but did not affect rates of lung metastasis (67% vs. 71%, BMP-2 vs. Control). BMP-2 over-expression in SaOS-2 cells reduced in vitro proliferation when grown in partial osteogenic-differentiation media (p < 0.001), had no effect on in vitro wound healing (p = 0.28), reduced in vivo SaOS-2 tumour burden at 6 weeks (photon counts, p < 0.0001), decreased tumour-associated matrix deposition as assessed by trabecular thickness (p = 0.02), and did not affect rates of lung metastasis (0% vs. 0%). Our results indicate BMP-2 signalling incites a proliferative effect on a poorly differentiated Osteosarcoma cell line (143b), but conditionally reduces proliferative capacity and induces a partial differentiation response in a moderately-differentiated Osteosarcoma cell line (SaOS-2). This dichotomous effect may be due to the inherent ability for Osteosarcoma cells to undergo BMP-2 mediated terminal differentiation. Importantly, these results do not support the clinical application of BMP-2 in Osteosarcoma limb salvage surgery due to the potential for stimulating growth of poorly differentiated Osteosarcoma cells within the tumour bed. Additional studies assessing the effects of BMP-2 in an immune-competent mouse model are ongoing

Aims. 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. Methods. Data from 2006 to 2016 was obtained from the BSTT registry. Only patients with STS of the limb were included in the study. Patients with distant metastasis at the initial presentation and patients with dermatofibrosarcoma protuberans and well-differentiated liposarcoma were excluded from the study. Results. A total of 4,483 patients with STS of the limb were identified before propensity score matching. There were 355 patients who underwent UE and 4,128 patients who underwent PE. The five-year disease-specific survival (DSS) rate was significantly better in the patients who received additional excision after UE than in those who underwent PE. There was no significant difference in local recurrence-free survival (LRFS) between the two groups. After propensity score matching, a new cohort of 355 patients was created for both PE and UE groups, in which baseline covariates were appropriately balanced. Reconstruction after tumour excision was frequently performed in patients who underwent additional excision after UE. There were no significant differences in DSS and LRFS between the patients who underwent PE and those who had an additional excision after UE. Conclusion. Using propensity score matching, patients with STS of the limb who underwent additional excision after UE did not experience higher mortality and local failure than those who underwent PE. Reconstruction may be necessary when additional excision is performed. Cite this article: Bone Joint J 2021;103-B(12):1809–1814

Impaired bone healing biology secondary to soft tissue deficits and chemotherapy contribute to non-union, fracture and infection following limb salvage surgery in Osteosarcoma patients. Approved bone healing augments such as recombinant human bone morphogenetic protein-2 (rhBMP-2) have great potential to mitigate these complications. rhBMP-2 use in sarcoma surgery is limited, however, due to concerns of pro-oncogenic signalling within the tumour resection bed. To the contrary, recent pre-clinical studies demonstrate that BMP-2 may induce Osteosarcoma differentiation and limit tumour growth. Further pre-clinical studies evaluating the oncologic influences of BMP-2 in Osteosarcoma are needed. The purpose of this study is to evaluate how BMP-2 signalling affects Osteosarcoma cell proliferation and metastasis in an active tumour bed. Two Osteosarcoma cell lines (143b and SaOS-2) were assessed for proliferative capacity and invasion. 143b and SaOS-2 cells were engineered to upregulate BMP-2. In vitro proliferation was assessed using a cell viability assay, motility was assessed with a scratch wound healing assay, and degree of osteoblastic differentiation was assessed using qRT-PCR of Osteoblastic markers (CTGF, ALP, Runx-2 and Osx). For in vivo evaluation, Osteosarcoma cells were injected into the intramedullary proximal tibia of immunocompromised (NOD-SCID) mice and local tumour growth and metastases were assessed using weekly bioluminescence imaging and tumour volume measurements for 4–6 weeks. At the experimental end point we assessed radiographic tumour burden using ex-vivo micro-CT, as well as tibial and pulmonary gross and histologic pathology. SaOS-2 was more differentiated than 143b, with significantly increased expression of the Osteoblast markers Osx (p = 0.004) and ALP (p = 0.035). BMP-2 upregulation did not stimulate an osteoblast differentiation response in 143b, but stimulated an increase in Osx expression in SaOS-2 (p = 0.002). BMP-2 upregulation in 143b cells resulted in increased proliferation in vitro (p = 0.014), faster in vitro wound healing (p = 0.03), significantly increased tumour volume (p = 0.001) with enhanced osteolysis detected on micro-CT, but did not affect rates of lung metastasis (67% vs. 71%, BMP-2 vs. Control). BMP-2 over-expression in SaOS-2 cells reduced in vitro proliferation when grown in osteogenic-differentiation media (p < 0.001), had no effect on in vitro wound healing (p = 0.28), reduced in vivo SaOS-2 tumour burden at 6 weeks (photon counts, p < 0.0001), decreased tumour-associated matrix deposition as assessed by trabecular thickness (p = 0.02), but did not affect rates of lung metastasis (0% vs. 0%). Our results indicate BMP-2 signalling incites a proliferative effect on a poorly differentiated Osteosarcoma cell line (143b), but conditionally reduces proliferative capacity and induces a partial differentiation response in a moderately-differentiated Osteosarcoma cell line (SaOS-2). This dichotomous effect may be due to the inherent ability for Osteosarcoma cells to undergo BMP-2 mediated terminal differentiation. Importantly, these results do not support the clinical application of BMP-2 in Osteosarcoma limb salvage surgery due to the potential for stimulating growth of poorly differentiated Osteosarcoma cells within the tumour bed. Additional studies assessing the effects of BMP-2 in an immune-competent mouse model are ongoing

Osteolysis, fractures, and bone destruction caused by osteomyelitis or metastasis can cause large bone defects and present major challenges during acetabular reconstruction in total hip arthroplasty. We sought to evaluate the survivorship and radiographic outcomes of an acetabular reconstruction consisting of a polyethylene liner (semi-constrained) embedded in cement filling bone defect(s) reinforced with screws and/or plates for enhanced fixation (HiRISC). Retrospective chart review of 59 consecutive acetabular reconstructions as described above performed by 4 surgeons in a single institution (10/18/2018-1/5/2023) was performed. After radiographs and operative reports were reviewed, cases were classified following the Paprosky classification for acetabular defects. Paprosky type 1 cases (n=26) were excluded, while types 2/3 (n=33) were included for analysis. Radiographic loosening was evaluated up to latest follow-up. Mean follow-up was: 487 days (range, 20–1,539 days). Out of 33 cases, 2 (6.1%) cases were oncological (metastatic disease) and 22 (66.7%) had deep infection diagnosis (i.e., periprosthetic joint infection [PJI] or septic arthritis). In total, 7 (21.2%) reconstructions were performed on native acetabula (3 septic, 4 aseptic). At a mean follow-up of 1.3 years, 5 (15.2%) constructs were revised: 4 due to uncontrolled infection (spacer exchange) and 1 for instability. On follow-up radiographs, only 1 non-revised construct showed increased radiolucencies, but no obvious loosening. When compared to patients with non-revised constructs, those who underwent revision (n=5) were significantly younger (mean 73.8 vs. 60.6 years, p=0.040) and had higher body mass index (24.1 vs. 31.0 Kg/m. 2. , p=0.045), respectively. Sex, race, ethnicity, American-Society-of-Anesthesiologist classification, infection diagnosis status (septic/aseptic), and mean follow-up (449.3 vs. 695.6 days, respectively, p=0.189) were not significantly different between both groups. HiRISC construct may be a viable short-term alternative to more expensive implants to treat large acetabular defects, particularly in the setting of PJI. Longer follow up is needed to establish long term survivorship

Aims. Our aim was to develop and validate nomograms that would predict the cumulative incidence of sarcoma-specific death (CISSD) and disease progression (CIDP) in patients with localized high-grade primary central and dedifferentiated chondrosarcoma. Methods. The study population consisted of 391 patients from two international sarcoma centres (development cohort) who had undergone definitive surgery for a localized high-grade (histological grade II or III) conventional primary central chondrosarcoma or dedifferentiated chondrosarcoma. Disease progression captured the first event of either metastasis or local recurrence. An independent cohort of 221 patients from three additional hospitals was used for external validation. Two nomograms were internally and externally validated for discrimination (c-index) and calibration plot. Results. In the development cohort, the CISSD at ten years was 32.9% (95% confidence interval (CI) 19.8% to 38.4%). Age at diagnosis, grade, and surgical margin were found to have significant effects on CISSD and CIDP in multivariate analyses. Maximum tumour diameter was also significantly associated with CISSD. In the development cohort, the c-indices for CISSD and CIDP at five years were 0.743 (95% CI 0.700 to 0.819) and 0.761 (95% CI 0.713 to 0.800), respectively. When applied to the validation cohort, the c-indices for CISSD and CIDP at five years were 0.839 (95% CI 0.763 to 0.916) and 0.749 (95% CI 0.672 to 0.825), respectively. The calibration plots for these two nomograms demonstrated good fit. Conclusion. Our nomograms performed well on internal and external validation and can be used to predict CISSD and CIDP after resection of localized high-grade conventional primary central and dedifferentiated chondrosarcomas. They provide a new tool with which clinicians can assess and advise individual patients about their prognosis. Cite this article: Bone Joint J 2020;102-B(12):1752–1759

Aims. 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. Methods. A total of 60 patients (25 females, 35 males; mean age 39 years (SD 18)) undergoing iliosacral resection were reviewed. Most resections were performed for primary malignant tumours (n = 54; 90%). The mean follow-up for surviving patients was nine years (2 to 19). Results. Overall, 27 patients (45%) were reconstructed, while 33 (55%) had no formal reconstruction. There was no difference in the use of chemotherapy (p = 1.000) or radiotherapy (p = 0.292) between the groups. Patients with no reconstruction had a mean larger tumour (11 cm (SD 5) vs 8 cm (SD 4); p = 0.014), mean shorter operating times (664 mins (SD 195) vs 1,324 mins (SD 381); p = 0.012), and required fewer blood units (8 (SD 7) vs 14 (SD 11); p = 0.012). Patients undergoing a reconstruction were more likely to have a deep infection (48% vs 12%; p = 0.003). Nine reconstructed patients had a hardware failure, with five requiring revision. Postoperatively 55 (92%) patients were ambulatory, with no difference in the proportion of ambulatory patients (89% vs 94%; p = 0.649) or mean Musculoskeletal Tumor Society Score (59% vs 65%; p = 0.349) score between patients who did or did not have a reconstruction. The ten-year disease-specific survival was 69%, with no difference between patients who were reconstructed and those who were not (78% vs 45%; p = 0.316). There was no difference in the rate of metastasis between the two groups (hazard ratio (HR) 2.78; p = 0.102). Conclusion. Our results demonstrate that SIJ reconstruction is associated with longer operating times, greater need for blood transfusion, and more postoperative infections, without any improvement in functional outcomes when compared to patients who did not have formal SIJ reconstruction. Cite this article: Bone Joint J 2024;106-B(1):93–98

Giant cell tumors of bone (GCTs) are locally aggressive tumors with recurrence potential that represent up to 10% of primary tumors of the bone. GCTs pathogenesis is driven by neoplastic mononuclear stromal cells that overexpress receptor activator of nuclear factor kappa-B/ligand (RANKL). Treatment with specific anti-RANKL antibody (denosumab) was recently introduced, used either as a neo-adjuvant in resectable tumors or as a stand-alone treatment in unresectable tumors. While denosumab has been increasingly used, a percentage of patients do not improve after treatment. Here, we aim to determine molecular and histological patterns that would help predicting GCTs response to denosumab to improve personalized treatment. Nine pre-treatment biopsies of patients with spinal GCT were collected at 2 centres. In 4 patients denosumab was used as a neo-adjuvant, 3 as a stand-alone and 2 received denosumab as adjuvant treatment. Clinical data was extracted retrospectively. Total mRNA was extracted by using a formalin-fixed paraffin-embedded extraction kit and we determined the transcript profile of 730 immune-oncology related genes by using the Pan Cancer Immune Profiling panel (Nanostring). The gene expression was compared between patients with good and poor response to Denosumab treatment by using the nSolver Analysis Software (Nanostring). Immunohistochemistry was performed in the tissue slides to characterize cell populations and immune response in CGTs. Two out of 9 patients showed poor clinical response with tumor progression and metastasis. Our analysis using unsupervised hierarchical clustering determined differences in gene expression between poor responders and good responders before denosumab treatment. Poor responding lesions are characterized by increased expression of inflammatory cytokines as IL8, IL1, interferon a and g, among a myriad of cytokines and chemokines (CCL25, IL5, IL26, IL25, IL13, CCL20, IL24, IL22, etc.), while good responders are characterized by elevated expression of platelets (CD31 and PECAM), coagulation (CD74, F13A1), and complement classic pathway (C1QB, C1R, C1QBP, C1S, C2) markers, together with extracellular matrix proteins (COL3A1, FN1,. Interestingly the T-cell response is also different between groups. Poor responding lesions have increased Th1 and Th2 component, but good responders have an increased Th17 component. Interestingly, the checkpoint inhibitor of the immune response PD1 (PDCD1) is increased ~10 fold in poor responders. This preliminary study using a novel experimental approach revealed differences in the immune response in GCTs associated with clinical response to denosumab. The increased activity of checkpoint inhibitor PD1 in poor responders to denosumab treatment may have implications for therapy, raising the potential to investigate immunotherapy as is currently used in other neoplasms. Further validation using a larger independent cohort will be required but these results could potentially identify the patients who would most benefit from denosumab therapy

Evaluate the complications and outcomes of off-hours spinal metastasis surgery. Retrospective analysis of a prospective collected data. Preoperative, operative and post-operative data were collected as well as the complications and Frankel score at all time checkpoints. Off-hours surgery was defined as surgery starting between 17:00 and 8:00 the following day or surgery during the weekend. p < 0 .05 was defined as statistical significance threshold. 376 patients were included with an incidence of off-hours surgery of 32%. There was an increase of neurologic complication in the off hours group. This was associated with a higher ASA score and older population group. Oddly, there was decreased operative time with off-hours surgery with no difference in bleeding and number of fusion levels. Nonetheless, there was a higher percentage of neurologic improvement with off hours surgery compared to in-hours surgery. Finally, there were no effect on patients' survival in this patient population. To our knowledge, this is the first report of the effect of off-hours surgery on complications and outcomes of spinal metastasis. Greater neurological compromise and higher age and ASA scores were associated with higher incidence of off-hours surgery. It is associated with decreased surgical time with higher percentage of neurological improvement. Finally, there is no effect of surgical timing on survival rates

The reconstruction of peri-acetabular defects after severe bone loss or pelvic resection for tumor is among the most challenging surgical intervention. The Lumic® prosthesis (Implantcast, Buxtehude, Germany) was first introduced in 2008 in an effort to reduce the mechanical complications encountered with the classic peri-acetabular reconstruction techniques and to improve functional outcomes. Few have evaluated the results associated with the use of this recent implant. A retrospective study from five Orthopedic Oncology Canadian centers was conducted. Every patient in whom a Lumic® endoprosthesis was used for reconstruction after peri-acetabular resection or severe bone loss with a minimal follow-up of three months was included. The charts were reviewed and data concerning patients’ demographics, peri-operative characteristics and post-operative complications was collected. Surgical and functional outcomes were also assessed. Sixteen patients, 11 males and five females, were included and were followed for 28 months [3 – 60]. Mean age was 55 [17–86], and mean BMI reached 28 [19.6 – 44]. Twelve patients (75%) had a Lumic® after a resection of a primary sarcoma, two following pelvic metastasis, one for a benign tumor and one after a comminuted acetabular fracture with bone loss. Twelve patients (75%) had their surgery performed in one stage whereas four had a planned two-stage procedure. Mean surgical time was 555 minutes [173-1230] and blood loss averaged 2100 mL [500-5000]. MSTS score mean was 60.3 preoperatively [37.1 – 97] and 54.3 postoperatively [17.1-88.6]. Five patients (31.3%) had a cemented Lumic® stem. All patients got the dual mobility bearing, and 10 patients (62.5%) had the largest acetabular cup implanted (60 mm). In seven of these 10 patients the silver coated implant was used to minimize risk of infection. Five patients (31.3%) underwent capsular reconstruction using a synthetic fabric aiming to reduce the dislocation risk. Five patients had per-operative complications (31.3%), four were minor and one was serious (comminuted iliac bone fracture requiring internal fixation). Four patients dislocated within a month post-operatively and one additional patient sustained a dislocation one year post-operatively. Eight patients (50%) had a post-operative surgical site infection. All four patients who had a two-stage surgery had an infection. Ten patients (62.5%) needed a reoperation (two for fabric insertion, five for wash-outs, and three for implant exchange/removal). One patient (6.3%) had a septic loosening three years after surgery. At the time of data collection, 13 patients (81.3%) were alive with nine free of disease. Silver coating was not found to reduce infection risk (p=0.2) and capsuloplasty did not prevent dislocation (p=1). These results are comparable to the sparse data published. Lumic® endoprosthesis is therefore shown to provide good functional outcomes and low rates of loosening on short to medium term follow-up. Infection and dislocation are common complications but we were unable to show benefits of capsuloplasty and of the use of silver coated implants. Larger series and longer follow-ups are needed

The reconstruction of peri-acetabular defects after severe bone loss or pelvic resection for tumor is among the most challenging surgical intervention. The Lumic® prosthesis (Implantcast, Buxtehude, Germany) was first introduced in 2008 in an effort to reduce the mechanical complications encountered with the classic peri-acetabular reconstruction techniques and to improve functional outcomes. Few have evaluated the results associated with the use of this recent implant. A retrospective study from five Orthopedic Oncology Canadian centers was conducted. Every patient in whom a Lumic® endoprosthesis was used for reconstruction after peri-acetabular resection or severe bone loss with a minimal follow-up of three months was included. The charts were reviewed and data concerning patients’ demographics, peri-operative characteristics and post-operative complications was collected. Surgical and functional outcomes were also assessed. Sixteen patients, 11 males and five females, were included and were followed for 28 months [3 – 60]. Mean age was 55 [17-86], and mean BMI reached 28 [19.6 – 44]. Twelve patients (75%) had a Lumic® after a resection of a primary sarcoma, two following pelvic metastasis, one for a benign tumor and one after a comminuted acetabular fracture with bone loss. Twelve patients (75%) had their surgery performed in one stage whereas four had a planned two-stage procedure. Mean surgical time was 555 minutes [173-1230] and blood loss averaged 2100 mL [500-5000]. MSTS score mean was 60.3 preoperatively [37.1 – 97] and 54.3 postoperatively [17.1-88.6]. Five patients (31.3%) had a cemented Lumic® stem. All patients got the dual mobility bearing, and 10 patients (62.5%) had the largest acetabular cup implanted (60 mm). In seven of these 10 patients the silver coated implant was used to minimize risk of infection. Five patients (31.3%) underwent capsular reconstruction using a synthetic fabric aiming to reduce the dislocation risk. Five patients had per-operative complications (31.3%), four were minor and one was serious (comminuted iliac bone fracture requiring internal fixation). Four patients dislocated within a month post-operatively and one additional patient sustained a dislocation one year post-operatively. Eight patients (50%) had a post-operative surgical site infection. All four patients who had a two-stage surgery had an infection. Ten patients (62.5%) needed a reoperation (two for fabric insertion, five for wash-outs, and three for implant exchange/removal). One patient (6.3%) had a septic loosening three years after surgery. At the time of data collection, 13 patients (81.3%) were alive with nine free of disease. Silver coating was not found to reduce infection risk (p=0.2) and capsuloplasty did not prevent dislocation (p=1). These results are comparable to the sparse data published. Lumic® endoprosthesis is therefore shown to provide good functional outcomes and low rates of loosening on short to medium term follow-up. Infection and dislocation are common complications but we were unable to show benefits of capsuloplasty and of the use of silver coated implants. Larger series and longer follow-ups are needed

Aims. Local recurrence remains a challenging and common problem following curettage and joint-sparing surgery for giant cell tumour of bone (GCTB). We previously reported a 15% local recurrence rate at a median follow-up of 30 months in 20 patients with high-risk GCTB treated with neoadjuvant Denosumab. The aim of this study was to determine if this initial favourable outcome following the use of Denosumab was maintained with longer follow-up. Methods. Patients with GCTB of the limb considered high-risk for unsuccessful joint salvage, due to minimal periarticular and subchondral bone, large soft tissue mass, or pathological fracture, were treated with Denosumab followed by extended intralesional curettage with the goal of preserving the joint surface. Patients were followed for local recurrence, metastasis, and secondary sarcoma. Results. A total of 25 patients with a mean age of 33.8 years (18 to 67) with high-risk GCTB received median six cycles of Denosumab before surgery. Tumours occurred most commonly around the knee (17/25, 68%). The median follow-up was 57 months (interquartile range (IQR) 13 to 88). The joint was salvaged in 23 patients (92%). Two required knee arthroplasty due to intra-articular fracture and arthritis. Local recurrence developed in 11 patients (44%) at a mean of 32.5 months (3 to 75) following surgery, of whom four underwent repeat curettage and joint salvage. One patient developed secondary osteosarcoma and another benign GCT lung metastases. Conclusion. The use of Denosumab for joint salvage was associated with a higher than expected rate of local recurrence at 44%. Neoadjuvant Denosumab for joint-sparing procedures should be considered with caution in light of these results. Cite this article: Bone Joint J 2021;103-B(1):184–191

The aim of this study was to define the treatment criteria for patients with recurrent chondrosarcoma. We reviewed the data of 77 patients to examine the influence of factors such as the intention of treatment (curative/palliative), extent of surgery, resection margins, status of disease at the time of local recurrence and the grade of the tumour. A total of 70 patients underwent surgery for recurrent chondrosarcoma. In seven patients surgery was not a viable option. Metastatic disease occurred in 41 patients, appearing synchronously with the local recurrence in 56% of cases. For patients without metastasis at the time of local recurrence, the overall survival at a mean follow-up after recurrence of 67 months (0 to 289) was 74% (5 of 27) compared with 19% (13 of 50) for patients with metastasis at or before the development of the recurrence. Neither the type/extent of surgery, site of tumour, nor the resection margins for the recurrent tumour significantly influenced the overall survival. . With limited survival for patients with metastatic disease at the time of local recurrence (0% for patients with grade III and de-differentiated chondrosarcoma), palliative treatment, including local radiation therapy and debulking procedures, should be discussed with the patients to avoid long hospitalisation and functional deficits. For patients without metastasis at the time of local recurrence, the overall survival of 74% justifies an aggressive approach including wide resection margins and extensive reconstruction

Breast cancer is the most frequent malignancy in women with an estimation of 2.1 million new diagnoses in 2018. Even though primary tumours are usually efficiently removed by surgery, 20–40% of patients will develop metastases in distant organs. Bone is one of the most frequent site of metastases from advanced breast cancer, accounting from 55 to 58% of all metastases. Currently, none of the therapeutic strategies used to manage breast cancer bone metastasis are really curative. Tailoring a suitable model to study and evaluate the disease pathophysiology and novel advanced therapies is one of the major challenges that will predict more effectively and efficiently the clinical response. Preclinical traditional models have been largely used as they can provide standardization and simplicity, moreover, further advancements have been made with 3D cultures, by spheroids and artificial matrices, patient derived xenografts and microfluidics. Despite these models recapitulate numerous aspects of tumour complexity, they do not completely mimic the clinical native microenvironment. Thus, to fulfil this need, in our study we developed a new, advanced and alternative model of human breast cancer bone metastasis as potential biologic assay for cancer research. The study involved breast cancer bone metastasis samples obtained from three female patients undergoing wide spinal decompression and stabilization through a posterior approach. Samples were cultured in a TubeSpin Bioreactor on a rolling apparatus under hypoxic conditions at time 0 and for up to 40 days and evaluated for viability by the Alamar Blue test, gene expression profile, histology and immunohistochemistry. Results showed the maintenance and preservation, at time 0 and after 40 days of culture, of the tissue viability, biological activity, as well as molecular markers, i.e. several key genes involved in the complex interactions between the tumour cells and bone able to drive cancer progression, cancer aggressiveness and metastasis to bone. A good tis sue morphological and microarchitectural preservation with the presence of lacunar osteolysis, fragmented trabeculae locally surrounded by osteoclast cells and malignant cells and an intense infiltration by tumour cells in bone marrow compartment in all examined samples. Histomorphometrical data on the levels of bone resorption and bone apposition parameters remained constant between T0 and T40 for all analysed patients. Additionally, immunohistochemistry showed homogeneous expression and location of CDH1, CDH2, KRT8, KRT18, Ki67, CASP3, ESR1, CD8 and CD68 between T0 and T40, thus further confirming the invasive behaviour of breast cancer cells and indicating the maintaining of the metastatic microenvironment. The novel tissue culture, set-up in this study, has significant advantages in comparison to the pre-existent 3D models: the tumour environment is the same of the clinical scenario, including all cell types as well as the native extracellular matrix; it can be quickly set-up employing only small samples of breast cancer bone metastasis tissue in a simple, ethically correct and cost-effective manner; it bypasses and/or decreases the necessity to use more complex preclinical model, thus reducing the ethical burden following the guiding principles aimed at replacing/reducing/refining (3R) animal use and their suffering for scientific purposes; it can allow the study of the interactions within the breast cancer bone metastasis tissue over a relatively long period of up to 40 days, preserving the tumour morphology and architecture and allowing also the evaluation of different biological factors, parameters and activities. Therefore, the study provides for the first time the feasibility and rationale for the use of a human-derived advanced alternative model for cancer research and testing of drugs and innovative strategies, taking into account patient individual characteristics and specific tumour subtypes so predicting patient specific responses

Aims. The early mortality in patients with hip fractures from bony metastases is unknown. The objectives of this study were to quantify 30- and 90-day mortality in patients with proximal femoral metastases, and to create a mortality prediction tool based on biomarkers associated with early death. Methods. This was a retrospective cohort study of consecutive patients referred to the orthopaedic department at a UK trauma centre with a proximal femoral metastasis (PFM) over a seven-year period (2010 to 2016). The study group were compared to a matched control group of non-metastatic hip fractures. Minimum follow-up was one year. Results. There was a 90-day mortality of 46% in patients with metastatic hip fractures versus 12% in controls (89/195 and 24/192, respectively; p < 0.001). Mean time to surgery was longer in symptomatic metastases versus complete fractures (9.5 days (SD 19.8) and 3.4 days (SD 11.4), respectively; p < 0.05). Albumin, urea, and corrected calcium were all independent predictors of early mortality and were used to generate a simple tool for predicting 90-day mortality, titled the Metastatic Early Prognostic (MEP) score. An MEP score of 0 was associated with the lowest risk of death at 30 days (14%, 3/21), 90 days (19%, 4/21), and one year (62%, 13/21). MEP scores of 3/4 were associated with the highest risk of death at 30 days (56%, 5/9), 90 days (100%, 9/9), and one year (100%, 9/9). Neither age nor primary cancer diagnosis was an independent predictor of mortality at 30 and 90 days. Conclusion. This score could be used to predict early mortality and guide perioperative counselling. The delay to surgery identifies a potential window to intervene and correct these abnormalities with the aim of improving survival. Cite this article: Bone Joint J. 2020;102-B(1):72–81

In our database of 7935 patients referred for investigation of a soft-tissue mass, only 100 were found to have a soft-tissue metastasis (1.3%). Our aim was to define the clinical features of such patients and to identify the site of their primary tumour. The most common presentation was a painful lump, deep to the fascia, ranging between 2 cm and 35 cm (mean 8.3 cm) with 78% of the lumps located deep to the fascia. The mean age of the patients at presentation was 64 years (22 to 84) and there were almost equal numbers of men and women. Of 53 patients with a history of malignancy, 52 had metastases from the same primary (lung in 12, melanoma in ten, kidney in nine, gastrointestinal track in four, breast in five, bladder in four, and others in eight). The other 47 had no history of malignancy and the metastasis was the first presentation. The primary sites in these cases were the lung in 19, gastro-intestinal track in four, kidney in two, melanoma in nine, other in three, and unknown (despite investigations) in ten. There was no correlation between the site of the metastases and the primary tumour. Of the 7935 patients, 516 had a history of malignancy. Of these, only 10% had a soft-tissue metastasis, 29% had a benign diagnosis, 55% a soft-tissue sarcoma and 6% another malignancy. Patients with soft-tissue metastases have similar clinical features to those with soft-tissue sarcomas and should be considered for assessment at appropriate diagnostic centres for patients with suspicious soft-tissue lumps

All patients referred to our unit with previously untreated metastatic renal cancer were included in this review. We investigated likely prognostic factors including age, sex, site, synchronous or metachronous metastasis, stage of the disease and the type of treatment received. From 1976 until 2004, a total of 198 patients were treated by our unit for renal metastases. 15 patients were excluded because they were referred after failure of previous treatment or only had advice. 96 patients were already known to have renal metastasis with their diagnosis having been made between 0.2 and 17 years from the diagnosis of primary cancer (mean 4 years). 33 patients presented to us with a pathological fracture and were found to have renal cancer. A total of 54 patients had multiple metastases and 129 had a solitary metastasis. The cumulative survival from the time of diagnosis of the bone metastasis is 70 percent at 1 year, 40% at 3 years and 18% at 5 years. In patients with a solitary metastasis, the overall survival was 74% at 1 year and 45% at 3 years, whereas in patients with multiple metastases it was 55% at 1 year and 22% at 3 years. (p=0.02) In patients with a solitary metastasis treated by excision of the metastasis, the survival at 1 year was 86% as compared to 38% for those that were treated with just a local procedure. Cox multivariate analysis shows that survival was better in those with solitary metachronus metastasis who underwent a radical procedure. Conclusion. We recommend a radical procedure for patients who present with a solitary renal metastasis, particularly those with a disease-free interval of more than one year

Aims. The aim of this study was to identify factors that determine outcomes of treatment for patients with chondroblastic osteosarcomas (COS) of the limbs and pelvis. Patients and Methods. The authors carried out a retrospective review of prospectively collected data from 256 patients diagnosed between 1979 and 2015. Of the 256 patients diagnosed with COS of the pelvis and the limbs, 147 patients (57%) were male and 109 patients (43%) were female. The mean age at presentation was 20 years (0 to 90). Results. In all, 82% of the patients had a poor response to chemotherapy, which was associated with the presence of a predominantly chondroblastic component (more than 50% of tumour volume). The incidence of local recurrence was 15%. Synchronous or metachronous metastasis was diagnosed in 60% of patients. Overall survival was 51% and 42% after five and ten years, respectively. Limb localization and wide surgical margins were associated with a lower risk of local recurrence after multivariable analysis, while the response to chemotherapy was not. Local recurrence, advanced patient age, pelvic tumours, and large volume negatively influenced survival. Resection of pulmonary metastases was associated with a survival benefit in the limited number of patients in whom this was undertaken. Conclusion. COS demonstrates a poor response to chemotherapy and a high incidence of metastases. Wide resection is associated with improved local control and overall survival, while excision of pulmonary metastases is associated with improved survival in selected patients. Cite this article: Bone Joint J 2019;101-B:739–744