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

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

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

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

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

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

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

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

The orthopaedic surgeon is often consulted to manage pathologic fractures due to metastatic disease, even though he or she may not be an orthopaedic oncologist. A good understanding of the principles of management of metastatic disease is therefore important. The skeleton remains a common site for metastasis, and certain cancers have a predilection for bone, namely, tumors of the breast, prostate, lung, thyroid, and kidney. Myeloma and lymphoma also often involve bone. The proximal femur and pelvis are most commonly affected, so we will focus on those anatomic sites. The patient may present with pain and impending fracture, or with actual fracture. Careful preoperative medical optimization is recommended. If the lesion is solitary, or the primary is unknown, the diagnosis must be made by a full workup and biopsy before definitive treatment is planned. For patients with known metastasis (the most common situation), the options for treatment of pathologic lesions of the proximal femur generally center on internal fixation versus prosthetic replacement. Patients with breast or prostate metastasis can live for several years after pathologic fracture, so constructs must be relatively durable. If fixation is chosen, it must be stable enough to allow full weight bearing, since the overwhelming majority of pathologic fractures will never heal. In general, long constructs are chosen to protect the entire length of the bone. Nails should protect the femoral neck as well, so cephalomedullary devices are typically chosen. Megaprostheses can be useful in situations where bony destruction precludes stable internal fixation. Postoperative radiation is recommended after wound healing. Acetabular involvement typically requires reinforcement rings or cement augmentation with the Harrington technique. Careful multi-disciplinary medical management is recommended to minimise complications

Purpose. Due to the aging population, an increasing proportion of elderly patients with soft tissue sarcoma are presenting to cancer centers. This population appears to have a worse prognosis but the reasons for this has not been studied in depth. The purpose of this study is to examine the effect of age on the outcome of patients with extremity and trunk soft tissue sarcoma. Method. This is a multicenter study including 2071 patients with median age at operation of 57 years (1st quartile–3rd quartile: 42–70). The endpoints considered were local recurrence and metastasis with death as a competing event. Cox proportional hazards models were used to estimate hazard ratios across the age ranges with and without adjustment for known confounding factors. Results. Older patients presented with tumors that were larger and of higher grade. The proportion of positive margins increased progressively as patients aged, but radiation therapy was relatively underused in patients over 60 years old. Age was strongly associated with both local recurrence and metastasis. The 5-year cumulative incidences of local recurrence were 7.6% (4.2%–12.2%) for patients 30 years or younger and 13.8% (9.8%–18.5%) for patients 75 years and older; corresponding 5-year cumulative incidences of metastasis were 21.5% (15.7%–28%) and 32.5% (27%–38.2%) for the same groups. Age showed a non linear effect with a dramatic increase in the risk of local recurrence and metastasis after 60 years old. The increased risk of metastasis for older patients was explained by disparities in tumor characteristics at presentation, and additionally for local recurrence, by disparities in treatment. Conclusion. Age is associated with worse outcomes after resection of soft tissue sarcoma. Older patients have worse outcomes because they tend to present with tumors having more adverse prognostic features and they are also treated less aggressively. A significant effect of age that is not explained by known confounders remains

Ewing Sarcoma is the second most common primary bone sarcoma in young patients, however, there remains geographical variation in the treatment of these tumours. All patients receive neoadjuvant chemotherapy and, in most cases, the soft tissue mass diminishes significantly in volume. Controversy surrounds whether to then treat the pre- or post-chemotherapy tumour volume. Many centres advocate either (1) resection of the pre-chemotherapy volume or (2) treatment of the pre-chemotherapy volume with radiation followed by resection of the post-chemotherapy volume. These approaches increase both the short and long-term morbidity for this young patient population. In this study, we retrospectively reviewed our experience resecting only the post-chemotherapy volume without the use of (neo)adjuvant radiotherapy. A retrospective analysis of all patients with Ewing Sarcoma treated at a tertiary orthopaedic oncology centre was conducted. All patients were treated as per the consensus opinion of the multidisciplinary tumour board. Demographic and oncological variables were collected from our institutional database. Presentation and re-staging MRI scans were reviewed to evaluate pre- and post-chemotherapy tumour volumes. Operative and pathology reports were utilized to determine the extent of the surgical resection. Outcome variables included local recurrence free-, metastasis free- and overall survival. Sixty-five patients were identified in our institutional database of which 56 did not receive (neo)adjuvant radiotherapy. Median age at diagnosis was 24 years (range 13–64), 60% of patients were male and 67.6% of tumours were located in the appendicular skeleton. All 56 patients not treated with radiotherapy had resection of the post-chemotherapy tumour volume. There were 3 local recurrences in this group with a mean follow-up of 70.8 months (range 2 to 328). The median overall survival was 47 months and the mean of 70.8months. The rate of local recurrence is comparable to reports in the literature in which patients had their entire pre-chemotherapy tumour volume treated by radiation and/or surgery. Similarly, two-year overall survival for our patient cohort is not significantly different from previous studies in which more aggressive local control measures were employed. Resecting the post-chemotherapy tumour volume in Ewing Sarcoma without the use of (neo)adjuvant radiotherapy does not appear to increase the risk of local recurrence or negatively impact overall survival. This approach should be studied further as it reduces the risk of short and long-term complications for this patient population.”

Solitary fibrous tumor (SFT) is a rare mesenchymal tumor with an intermediate tendency to metastasize, which is found in many different locations including head and neck, abdomen, chest cavity and extremities. Also, meningeal hemangiopericytoma (HPC) is considered an SFT which arises in the meningeal membranes. SFT family shows an undetermined biologic behavior varying from a silent indolent tumor to an aggressive malignant form; however, benign and malignant variants of SFT may have similar cytopathologic characteristics. In this study, we defined the factors correlated with SFT's aggressive behavior and patient's survival. This is a retrospective study based on medical records of 85 patients who were suffering from SFT and had been treated at McGill University Health Centre (MUHC) between 1984 and 2017. We used multivariate logistic regression analysis to address any association between the variables including patient's demographics, tumor size, primary location of the tumor, pathological features, treatment methods and outcomes. The median of the follow-up period was 60 months. The patient's age or gender had no association with tumor aggressive behavior or patient's survival. Anatomical origin of primary tumor had no strong correlation with the patient's disease related death (DRD); however, tumors originated from CNS showed more aggressive behavior. There was an association between tumor size more than 7 cm and distant metastasis (MT) (p= 0.03) and DRD (p=0.03). The tumor size also correlated with the 5-year disease-free survival (p=0.017). We had three histologic groups: 1- Benign SFT (30 cases), 2- cellular SFT or HPC (29 cases), 3- malignant SFT or anaplastic HPC (26 cases). Although univariate analysis demonstrates that patients suffering from cellular SFT and malignant SFT showed increased aggressive behavior of the tumor, multivariate analysis didn't verify the mentioned association. Patients with positive margins had increased odds ratio to experience tumor local recurrence (LR) (p= 0.05) and LR was correlated with DRD in our patients (p=0.006). Radiotherapy had no statistical association with LR, MT or DRD. Frequency of LR and MT in the study were 25.7% and 29.8% respectively. 5-year disease-free survival in our patients was 76%. The size of SFT is the most correlative predictor of the tumor's aggressive behavior. The local recurrence of SFT is associated with disease related death; therefore, resection of the tumor with negative margins provides the highest chance of cure. In addition, a cellular SFT should be treated like a malignant variant of the tumor

To set up an osteosarcoma mouse model with spontaneous lung metastasis and to identify a marker of osteosarcoma metastasis and to inhibit the marker against the invasive ability of an osteosarcoma cell line. A human osteosarcoma orthotopic mouse model was set up by injecting 143B human osteosarcoma cells into mouse tibia. Type I insulin-like growth factor receptor (IGF-1R) and its downstream signalling factors were measured in samples from the primary tumor and the lung secondaries by immunohistochemistry. Human Alu mRNA expression was tested using in situ hybridization assay. A Matrigel assay was used to assess cell invasion ability under the interference of a MEK/ERK pathway specific inhibitor, U0126. All fifteen mice showed tumour mass at the left tibia and lung metastasis. Human Alu expression in the primary and secondary tumours confirmed human origin of the tumour cells. Total IGF-1R, MEK, Akt, p38 and phosphorylated MEK (p-MEK), but not p-Akt and p-p38, were positive in both local tumours and lung secondaries. Leiomyosarcoma controls expressed p-Akt and p-MEK, but not p-p38. The 143B cells treated with U0126 had significantly lower in vitro invasion ability compared with controls. The IGF-1R-MEK signalling pathway, particularly Ras/Raf/MEK/ERK, may play an important role in osteosarcoma lung metastasis, and the targeting MEK/ERK by its specific inhibitor may have a potential use in the effective treatment of osteosarcoma

Benign aggressive tumors are common and can be debilitating for patients especially if they are in peri-articular regions or cause pathological fracture as is common for giant cell tumor of bone (GCT). Although GCT rarely metastasize, the literature reports many series with high rates of local recurrence, and evidence about which risk factors influence recurrence is lacking. This study aims to evaluate the recurrence rate and identify local recurrence risk factors by reviewing patient data from a single high-volume orthopedic oncology center. A retrospective analysis of all patients treated for GCT at a tertiary orthopedic oncology center was conducted. In total 413 patients were treated for GCT between 1989 and 2017. Multiple patient and tumour characteristics were analysed to determine if they influenced local recurrence including: age, gender, anatomical site, Campanacci stage, soft tissue extension, presence of metastasis, pathologic fractures, and prior local recurrence. Additional variables that were analysed included type of treatment (en bloc resection or aggressive intralesional curettage) and use of local adjuvants. The main outcome parameters were local recurrence- free survival, metastasis-free survival and complications. Patients treated with Denosumab were excluded from analysis given its recently documented association with high rates of local recurrence. “There were 63/413 local recurrences (15.3%) at a mean follow-up of 30.5 months. The metastatic rate was 2.2% at a mean 50.6 months follow-up and did not vary based on type of treatment. Overall complication rate of 14.3% was not related to treatment modality. Local recurrence was higher (p=0.019) following curettage (55/310; 17.7%) compared to resection (8/103; 7.8%) however, joint salvage was possible in 87% of patients (270/310) in the curettage group. Use of adjuvant therapy including liquid nitrogen, peroxide, phenol, water versus none did not show any effect on local recurrence rates (p= 0.104). Pathological fracture did not affect local recurrence rates regardless of treatment modality (p= 0.260). Local recurrence at presentation was present in 16.3% (58/356) patients and did not show any significance for further local recurrence (p= 0.396). Gender was not associated with local recurrence (p=0.508) but younger patient age, below 20 years (p = 0.047) or below 30 years (p = 0.015) was associated with higher local recurrence rates. GCT in distal radius demonstrated the highest rate of local recurrence at 31.6% compared to other sites, although this was not significant (p=0.098). In addition, Campanacci stage and soft tissue extension were not risk factors for recurrence. The overall GCT local recurrence rate was 15.3%, but varied based on the type of resection: 17.7% following joint sparing curettage compared to 7.8% following resection. Local recurrence was also higher with younger patient age (30 years or less) and in distal radius lesions. In addition, neither Campanacci stage, soft tissue extension or presence of a pathologic fracture affected local recurrence. Most patients with GCT can undergo successful curettage and joint sparing, while only a minority require resection +/− prosthetic reconstruction. Even in the presence of soft tissue extension or a pathologic fracture, most joints can be salvaged with curettage

Osteosarcoma (OS) is the most prevalent bone tumor in children and young adults. Most tumors arise from the metaphysis of the long bones and easily metastasize to the lungs. Current therapeutic strategies of osteosarcoma are routinely surgical resection and chemotherapy, which are limited to the patients suffering from metastatic recurrence. Therefore, to investigate molecular mechanisms that contribute to osteosarcoma progression is very important and may shed light on targeted therapeutic approach to improve the survival of patients with this disease. Several miRNAs have been found expressed differentially in osteosarcoma (OS), In this study, we found that miR-144 significantly suppresses osteosarcoma cell proliferation, migration andinvasion ability in vitro, and inhibited tumor growth and metastasisin vivo. The function and molecular mechanism of miR-144 in Osteosarcoma was further investigated. Tissue samples from fifty-one osteosarcoma patients were obtained from Shanghai Ninth People's Hospital. The in vitro function of miR-144 in Osteosarcoma was investigated by cell viability assay, wound healing assay, invasion assay, the molecular mechanism was identified by Biotin-coupled miRNA capture, Dual-luciferase reporter assays, etc. the in vivo function of miR-144 in osteosarcoma was confirmed by osteosarcoma animal model and miR-144−/− zebrafish model. Mechanically, we demonstrated that Ras homolog family member A (RhoA) and its pivotal downstream effector Rho-associated, coiled-coil containing protein kinase 1 (ROCK1) were both identified as direct targets of miR-144. Moreover, the negative co-relation between downregulated miR-144 and upregulated ROCK1/RhoA was verified both in the osteosarcoma cell lines and clinical patients' specimens. Functionally, RhoA with or without ROCK1 co-overexpression resulted a rescue phenotype on the miR-144 inhibited cell growth, migration and invasion abilities, while individual overexpression of ROCK1 had no statistical significance compared with control in miR-144 transfected SAOS2 and U2-OS cells. This study demonstrates that miR-144 inhibited tumor growth and metastasis in osteosarcoma via dual-suppressing of RhoA and ROCK1, which could be a new therapeutic approach for the treatment ofosteosarcoma

Dermatofibrosarcoma protuberans (DFSP) is a rare, monoclonal dermal neoplasm. DFSP is known to be locally aggressive and infiltrative, but with a very low systemic recurrence risk. It is reported to be associated with high local recurrence rates following surgical excision. Positive or marginal resection margins can lead to a high risk of local recurrence. The objective was to determine the oncologic outcome for DFSP treated at our institution. We reviewed our prospectively collected database for all DFSP treated at our unit between 1990 and 2016. Patients were included whether or not they had excision prior to referral (“whoops” procedure). Those with fibrosarcomatous degeneration at presentation to our unit or less than 1 year of follow-up were excluded. The goal of surgery was a negative margin with a minimum margin of 2 cm where possible. Patients were followed up after surgery to monitor complications, recurrence, transformation and/or metastasis. 139 patients with a mean age of 42.7 (SD=14.1) were included. Mean follow-up was 56 months.101 patients had prior “whoops” surgery before referral. 14 patients were also treated with radiotherapy (13 preoperatively, 1 postoperatively). Following surgery, 6 patients had positive margins, 4 underwent radiation treatment while the other 2 had no further treatment. One patient who presented to our unit with a local recurrence developed a further local recurrence, which demonstrated fibrosarcomatous degeneration at the time of resection (1/139, 0.7%). 1 other patient developed a lesion at another site. The recurrence rate in our DFSP cohort is significantly lower than previous reports. Wide margin resection following oncologic principles can result in a very low recurrence rate. After the initial recovery phase, these patients do not require ongoing, frequent follow-up. Future studies should look at if closer margins can also produce similar treatment outcome

Spinal metastases are seen in 10–30% of cancer patients. Twenty percent of these metastases occur in the lumbo-sacral spine. Lumbo-sacral spine has different mechanical properties and encloses the cauda equina. Few studies took interest in this spinal segment. The objective of this study is to evaluate prognostic factors of lumbo-sacral spinal metastasis treated in our center. We retrospectively reviewed 376 patients who were operated in our center from 2010 to 2018. Eighty-nine patients presented lumbo-sacral metastases and thus were included. Data collected included age, smoking, tumor histology, American spinal injury association (ASIA) score, modified Tokuhashi score, modified Bauer score, ambulation status and adjuvant treatment. The mean population age was 60.9 years old (35–85). The tumor histology was predominantly lung (19 patients, 21.3%), breast (13 patients, 14.6%), kidney (11 patients, 12.4%) and prostate (9 patients 10.1%). Twenty-two patients (24.7%) were unable to walk preoperatively. Seventy-nine patients (88.8%) underwent a posterior open approach with corpectomy in 65 patients (73%). Eighteen patients regained ambulation post-operatively (81.8%). The mean survival was 24.03 months (CI95% 17,38–30,67, Range 0–90) and the median of survival was 9 months (CI95% 4.38–13.62). Better preoperative ASIA score had a significant favorable effect (p=0.03) on survival. Patients who regained their ability to walk had better survival (25.1 months (CI95% 18.2–32) VS 0.5 months (CI95% 0–1.1). Postoperative radiotherapy had a benefic effect on survival (p=0.019): Survival Increased from 10.5 months (CI95% 2.4–18.7) to 27.6 months (CI95% 19.5–35.8). The modified Tokuhashi and the modified Bauer scores underestimated the survival of the patients with lumbosacral metastases. Lumbosacral spinal metastases has better survival than expected by Tokuhashi and Bauer score. Surgical procedure have an important impact on survival and the ability to walk