Aims. Ilium is the most common site of pelvic Ewing’s sarcoma (ES). Resection of the ilium and iliosacral joint causes pelvic disruption. However, the outcomes of resection and reconstruction are not well described. In this study, we report patients’ outcomes after resection of the ilium and iliosacral ES and reconstruction with a tibial strut allograft. Methods. Medical files of 43 patients with ilium and iliosacral ES who underwent surgical resection and reconstruction with a tibial strut allograft between January 2010 and October 2021 were reviewed. The lesions were classified into four resection zones: I. 1. , I. 2. , I. 3. , and I. 4. , based on the extent of resection. Functional outcomes, oncological outcomes, and surgical complications for each resection zone were of interest. Functional outcomes were assessed using a Musculoskeletal Tumor Society (MSTS) score and Toronto Extremity Salvage Score (TESS). Results. The mean age of the patients was 17 years (SD 9.1). At a mean follow-up of 70.8 months (SD 50), the mean functional outcomes were 24.2 points (SD 6.3) for MSTS and 81 points (SD 11) for TESS. The mean MSTS and TESS scores were associated with the iliac resection zone (< 0.001). Nine patients (20.9%) had local recurrence. The recurrence was not associated with the zone of iliac resection (p = 0.324). The two-year disease-free survival of the patients was 69.4%. The mean time to graft union was longer in patients with the I. 4. resection zone (p < 0.001). The complication rate was 34.9%, and nerve palsy (11.6%) was the most common. The rate of surgical complications was not associated with the resection zone. Conclusion. Reconstruction using tibial strut allograft is an efficient procedure after the resection of the ilium and iliosacral ES. Functional outcomes and complications of iliac ES depend on the resection zone, and inferior outcomes could be generally expected when more segments of the pelvic ring are resected, even if it is reconstructed. Cite this article: Bone Jt Open 2024;5(5):385–393

Ewing’s sarcoma principally arises in bone but can also present as a soft tissue tumour. Very few studies have assessed the outcomes of extra-skeletal Ewing’s sarcomas. This study compares the oncological outcomes of the two forms of Ewing’s sarcomas to see if there is any difference in prognostic factors. 198 patients with primary, non metastatic Ewing’s sarcoma diagnosed between 1980 and 2005 were identified from our database. There were 118 males and 80 females with a median age of 15 years. The three most common sites of diagnosis were the femur (24%), pelvis (15%) and tibia (13%). There were 169(85%) bony Ewing’s and 29 (15%) extra-skeletal Ewing’s sarcomas. All patients received chemotherapy. 86% of the patients had surgery for local control but 28(14%) patients had radiotherapy. The overall survival at five years was 89% and was related to the age of patient (92% < 16years p=0.005), size (p=0.03) and site of tumour (p=0.004) as well as the response to chemotherapy. There was no difference in the overall survival of patients with bony Ewing’s (90%) and extra-skeletal Ewing’s (85%) (p=0.85). There was a 10% risk of local recurrence at 5 years with site of tumour (p=0.01) and surgical excision (p=0.05) being significant prognostic factors. The risk of local recurrence was also not related to the type of Ewing’s sarcoma. This large series has shown that the oncological outcomes of Ewing’s sarcoma is related to tumour characteristics, patient age and treatment factors and not determined by the tissue component

Aim: To review the epidemiology, prognostic factors and outcome of treatment for extra-osseous Ewing’s sarcoma. Method: Thirty-four patients with a diagnosis of extra-osseous Ewing’s sarcoma were identified from a prospectively gathered national tumour database between 1961 and 2005. Patient demographics, clinical features, tumour stage, location and size, treatment received, local recurrence, metastasis and survival were all recorded. Survival was analysed using Kaplan-Meier methods. The average follow up was 45 months. Results: The annual incidence of extra-osseous Ewing’s was 0.2 per million of population between 1970 and 2004. The five-year survival rate for extra-osseous Ewing’s was 62%, which is significantly better than previously reported in the literature. Indicators of a poor prognosis were extra-compartment spread of tumour, local recurrence and metastasis. The recorded annual incidence of extra-osseous Ewing’s sarcoma increased during the period of this study. Conclusions: Extra-osseous Ewing’s sarcoma appears to have similar demographics and the outcome following modern treatment is better than previously reported and no worse than that reported for osseous Ewing’s

Cellular mechanisms that account for tumour osteolysis associated with Ewing’s sarcoma are uncertain. Osteoclasts are marrow-derived multinucleated cells that effect tumour osteolysis. Osteoclasts are known to form from macrophages by both receptor activator for nuclear factor κB ligand (RANKL)-dependent and RANKL-independent mechanisms. In this study our aim has been to determine whether tumour-associated macrophages (TAMs) isolated from Ewing’s sarcoma are capable of differentiating into osteoclasts and to characterise the cellular and humoral mechanisms whereby this occurs. TAMs were isolated from two Ewing’s sarcomas and cultured on both coverslips and dentine slices for up to 21 days with soluble RANKL and human macrophage colony stimulating factor (M-CSF). Osteoclast formation from TAMs (CD14+) was evidenced by the formation of tartrate–resistant acid phosphatase and vitronectin receptor-positive multinucleated cells which were capable of carrying out lacunar resorption. This osteoclast formation and resorption was inhibited by the addition of the bisphosphonate, zoledronate. Osteoclast formation was also seen when Ewing’s sarcoma-derived TAMs were cultured with TNF α in the presence of M-CSF. We also found that TC71 Ewing’s sarcoma cells were capable of independently stimulating osteoclast formation through the release of a soluble factor. These results indicate that TAMs in Ewing’s sarcoma are capable of osteoclast differentiation by both RANKL-dependent and RANKL-independent mechanisms and that Ewing’s sarcoma cells produce an osteoclastogenic factor. The role bisphosphonates may play in inhibiting osteoclast formation and osteolysis in Ewing’s sarcoma merits further investigation

Introduction: A retrospective analysis was performed to determine the oncological outcome of patients with Ewing’s sarcoma of the spine treated with combined chemotherapy and radiotherapy for definitive local control. Materials and Methods: Fifteen patients were identified from the Scottish Bone Tumour Registry with a histologically confirmed Ewing’s sarcoma affecting the axial skeleton. All case notes and imaging were retrospectively reviewed. Results: Primary vertebral Ewing’s sarcoma accounted for 8.3% of all malignant spinal lesions in our registry. The mean age was 17.8 years (between 4 and 39 years). There was a male predilection with 9 male and 6 female patients. Site was evenly distributed between cervical (4), dorsal (5) and lumbosacral (6) regions. Progressively worsening back pain was the first symptom in all the patients. Satisfactory imaging studies were available in all with plain radiographs (15), bone scan (11), CT-scan (12) and MR Scan (9) patients. Biopsy was performed in 11 patients and surgical treatment was carried out in 3 patients including curettage (2) and excision with bone grafting (1). All patients were treated with adjuvant radiotherapy while 87% also received adjuvant chemotherapy. Seven patients were alive with no evidence of disease at a mean 6 year follow-up. Six patients died of metastatic disease, one due to local recurrence and one with persistent primary disease. The mean follow-up time was 65 months (median 28 months; ranging from 12 to 218 months). Conclusions: Primary vertebral Ewing’s sarcoma comprised 8.3% of our National Registry’s primary malignant spinal lesions. Progressive vertebral pain in the late second decade and male gender should raise the suspicion of Ewing’s sarcoma. Ewing’s sarcoma of the spine treated with combined chemotherapy and radiotherapy for definitive local control achieved a 45% five year survival

Aims. Present the outcomes of those patients diagnosed with Ewing's Sarcoma of the foot within the past 10 years and treated at the Royal National Orthopaedic Hospital's Bone Tumour Unit, Stanmore. Methods. Retrospective study of the cases identified from the pathology database. Notes reviewed for presentation, treatment and follow up. TESS (Toronto Extremity Salvage Score) and MSTS (Musculoskeletal tumour score) were calculated. Results. 6 patients identified with positive diagnosis of Ewing's Sarcoma of the Foot. Male:Female ratio of 5:1. Age range 15–31 (Mode 25). 4 cases skeletal, 2 extra skeletal. All cases reviewed by supra-regional MDT and received adjuvant and neo-adjuvant chemotherapy. All except one patient underwent limb-salvage surgery. The MDT decision for the remaining patient was that amputation was the only viable surgical option but the patient and his parents requested radiotherapy without surgical treatment. Mean survival 40 months (15–107 months). All patients survive at time of submission. Mean MSTS/TESS scores 93% (80–100%) and 94.6% (85–100) respectively. Discussion. All patients reported a delay between first presentation and referral to the sarcoma unit. This experience is common across the literature for this rare pathology. Lowest scores were submitted by the two patients who had amputation of their great toe. All patients are happy with their outcome and decision to salvage their limb. All patients scored themselves as “not at all disabled” and two stated this would not have been their response if they had lost their foot. Conclusion. Amputation is psychologically difficult to accept and patients are more receptive to limb salvage surgery. Our patients demonstrate good functional outcome. Our experience at Stanmore suggests that limb salvage surgery with adequate MDT surveillance for Ewing's Sarcoma of the Foot can be a viable alternative to amputation

We reviewed the treatment and clinical outcome of 32 consecutive patients with Ewing’s sarcoma who presented with or developed pathological fracture after biopsy between 1984 and 2004. The minimum follow-up was 18 months. The mean age at diagnosis was 20 years (5 – 51). There were 18 males and 14 females. All patients were newly diagnosed and had localized disease at the time of diagnosis. 21 patients presented with pathological fracture while 11 patients developed fracture during the course of chemotherapy. The femur was the most common location in 15 patients. All the patients had chemotherapy according to the protocol current at the time of treatment. 6 patients had radiotherapy alone while 26 patients underwent surgical excision and reconstruction. Of the patients who had surgery, 7 patients had adjuvant radiotherapy. Fracture healing was the norm after pre-operative chemotherapy. Surgical margins were wide in 17 patients, marginal in 4 and intralesional in 3 patients. Local recurrence developed in one patient (3%). Metastases occurred in 12 patients (37%). At the time of review 16 patients were free of disease, 3 were alive with disease and 13 patients had died of disease. The cumulative 5 year metastases free and overall survival in all the patients was 58% and 61 % respectively and similar to patients with Ewing’s sarcoma without fracture treated at our centre. The prognosis of patients who presented with fracture was exactly similar to those who developed fracture in the course of treatment. We conclude that limb preserving surgery is perfectly safe in patients with Ewing’s sarcoma who have associated pathological fracture and survival is not in any way compromised. Survival of patients who present with fracture is similar to those who develop fracture in the course of treatment. The exact role of adjuvant radiotherapy in these patients needs to be clarified

We reviewed the treatment and clinical outcome of 32 consecutive patients with Ewing’s sarcoma who presented with or developed pathological fracture after biopsy between 1984 and 2004. The minimum follow-up was 18 months. The mean age at diagnosis was 20 years (5 – 51). There were 18 males and 14 females. All patients were newly diagnosed and had localized disease at the time of diagnosis. 21 patients presented with pathological fracture while 11 patients developed fracture during the course of chemotherapy. The femur was the most common location in 15 patients. All the patients had chemotherapy according to the protocol current at the time of treatment. 7 patients had radiotherapy alone while 25 patients underwent surgical excision and reconstruction. Of the patients who had surgery, 7 patients had adjuvant radiotherapy. Fracture healing was the norm after pre-operative chemotherapy. Surgical margins were wide in 17 patients, marginal in 4 and intralesional in 3 patients. Local recurrence developed in one patient (3%). Metastases occurred in 12 patients (37%). At the time of review 16 patients were free of disease, 3 were alive with disease and 13 patients had died of disease. The cumulative 5 year metastases free and overall survival in all the patients was 58% and 61 % respectively and similar to patients with Ewing’s sarcoma without fracture treated at our centre. The prognosis of patients who presented with fracture was exactly similar to those who developed fracture in the course of treatment. We conclude that limb preserving surgery is perfectly safe in patients with Ewing’s sarcoma who have associated pathological fracture and survival is not in any way compromised. Survival of patients who present with fracture is similar to those who develop fracture in the course of treatment. The exact role of adjuvant radiotherapy in these patients needs to be clarified

Introduction: The role of surgery for local control in the multimodal management of Ewing’s sarcoma has substantially increased during the past 20 years. However, selection bias due to location (extremities vs axial skeleton) and relatively non-homogeneous treatment received by patients in multi-institutional trials may limit objective evaluation and comparison of the relative role of surgery and radiation therapy in this setting. Purpose of this study was to review a large series of patients homogeneously treated at a single institution. Methods: 268 patients with non-metastatic Ewing’s sarcoma of the extremities treated by contemporary multimodal management were reviewed. Chemotherapy was administered according to 4 sequential protocols of adjuvant (1) and neoadjuvant (3) treatment. Local control consisted of surgery in 136 patients, surgery and radiation therapy in 70 patients, and radiation therapy in 60 patients. Two patients underwent only chemotherapy. Results: The 5-year event-free survival (EFS) and overall survival (OS) were 62 and 69 per cent respectively. The rates of 5-year EFS and local control were significantly lower in patients treated with radiation therapy compared to patients treated by surgery or surgery and radiation therapy (48 vs 66 per cent, p=0.002; 80 vs 94 per cent, p= 0,0001). In group 3 (Radiation Therapy only) there were also 6 secondary malignancies. Conclusion: Surgery was associated with better survival and local control in this series. In our opinion, surgery should always be considered in the local treatment of Ewing’s sarcoma of the extremities. Postoperative Radiation Therapy must be added in cases of inadequate surgical margins

The outcome for patients with Ewing's sarcoma recurrence is poor. Local recurrences occur in 8%-25%of these patients. The aim of the study was to analyze the patients who had a local recurrence to identify factors predicting the local recurrence and if it could be prevented. Methods. A retrospective analysis of 650 patients who had a diagnosis of Ewing's sarcoma treated between 1975 and 2009 at a single institution was performed and 64 patients (10%) who had a local recurrence were identified and analysed. Results. Fifteen patients had metastases at diagnosis.20 patients had chemotherapy and radiotherapy only while 44 had chemotherapy and surgery +/− post op radiotherapy. Thirteen patients who were suitable for post –operative radiotherapy could not receive the treatment due to various reasons like biological reconstruction. The estimated 5 years survival for the patients was 15%. The risk of local recurrence is higher if the tumour is located in the axial skeleton, treatment with chemotherapy and radiotherapy alone [location and size of the tumour precluding surgery]. The risk of local recurrence is higher if the tumour was in the fibula or radius. One out of three patients who have good response to chemotherapy still went on to develop a LR. The use of biological reconstruction and younger age group often resulted in deferral of post-operative radiotherapy. Location and type of treatment can predict LR. Surgery with clear margins and post-operative radiotherapy given when indicated may reduce the incidence of LR

Introduction and Aims: To assess and compare treatment of pelvic Ewing’s sarcoma, particularly extracorporeal irradiation (ECI) and re-implantation of bone segments. Method: We reviewed all patients presenting to the New South Wales Bone Tumor Service with Ewing’s sarcoma of the pelvis from 1995 until 2003. All received chemotherapy. There were 17 patients. Resection was performed in 14 cases: 12 were reconstructed by ECI and re-implantation of the bone segment; one with autograft and THR; one with allograft and THR. Three patients with sacral lesions had chemotherapy and radiotherapy only. All margins were clear. All patients were clinically and radiologically reviewed. Three scoring systems were used: The Musculoskeletal Tumor Society score (MSTS), the Toronto Extremity Salvage Score (TESS), and the Harris Hip Score (HHS). Results: The average age at presentation was 18 years (range six to 35). There were seven males and 10 females. One patient presented with metastatic disease. Survivor follow-up ranged from 25 to 105 months (mean 55). In those who developed metastases these were detected at a mean of 27 months (range one to 79). Deaths occurred at a mean 31 months (range eight to 65). Fourteen underwent surgery. Seven had THR as part of their reconstruction. There have been no local recurrences after surgery. Six patients have died, 11 patients are alive (65%), one with metastatic disease. Overall disease-free survival is 59%. The disease-free survival in those who underwent ECI and re-implantation is 75% (minimum two-year follow-up). Functional outcome is good. The TESS mean was 83 (range 60–100). The MSTS score mean 85 (range 60–97). The HHS mean 92 (range 67–100). Radiologically solid bony union at the osteotomy sites was the norm. Lysis existed at two periacetabular osteotomies, around the posterior iliac crest of one osteotomy, and a fibrous union occurred at one sacro-iliac joint with breakage of the sacro-iliac screws. There have been no graft fractures. Conclusion: The best surgical management for these difficult cases is extracorporeal irradiation and re-implantation of bone segments

Between 1948 and 2004, we report 34 patients with Ewing’s sarcoma of pelvis accrued from Scottish Bone Tumour Registry, aiming to identify the prognostic factors and the influence of various treatment modalities on outcome. There were 19 male and 15 female patients at a mean age of 19 years (range, 3 to 48 years). The Pain was main presenting symptom in 30, swelling in 12 and restriction of hip movements in 11 patients. The commonest anatomical site was ilium. Local control was achieved by surgery, radiotherapy (n=25), chemotherapy (n=23) or a combination. The survival correlated significantly with chemotherapy protocols in favour of the group that received ifosamide (p< 0.01). Metastases at presentation was the most important factor determining survival (P< 0.01). Among the patients who presented without metastases (n=25), there was no statistically significant difference in survival based on the anatomical location of the tumour, age or sex. The mean time to lung metastases from the date of presentation was 13 months, while bone metastases presented at an average of 20 months. None of the patients with the metastasis or local recurrence survived. There were 5 local and 17 systemic (metastatic) relapses. The mean duration of survival was 13 months. With advances in imaging, aggressive chemotherapy, surgery and conformal radiotherapy which can deliver high dose of radiation with precision, it is possible to achieve a cure rate of more that 50% in non-metastatic pelvic Ewing’s sarcoma. The results of this study favour a middle-path regime combining all treatment modalities

Aim. To determine the overall survival of patients with Pelvic Ewing's Sarcoma treated in our unit and to identify prognostic factors in pelvic primaries that could be used to select patients who would most likely benefit from high intensity treatment. Method. Between 1977 and 2009, 80 male and 66 female patients aged 2 to 60 (mean, 18) years with Pelvic Ewing's Sarcomas were retrospectively reviewed from the Royal Orthopaedic Hospital Oncology Service Registry. Treatments included surgery, radiotherapy, chemotherapy, or any of them in combination. Event-free (from presentation to recurrence) and overall (from presentation to death/latest follow-up) survival rates were calculated using the Kaplan- Meier method. Influence of various factors (age at diagnosis, gender, tumour site, metastasis at presentation, surgery (and surgical margins), radiotherapy, and type of treatment on survival was assessed using SPSS 14.0 statistical software. Results. Out of the 146 patients, 128 had available follow up and were eventually included in the analysis. Ninety two patients died (63%) within a mean follow-up of 51 months (range, 3-343). In multivariate analysis, metastases at diagnosis and development of metastases were associated with decreased survival. In terms of the type of treatment received, chemotherapy and surgery was found to be associated with increased survival rates compared to chemotherapy and radiotherapy (p=0.04). Factors that were statistically significant associated with the development of metastasis were location at the periacetabular region and development of local recurrence. In multivariate analysis, only the development of local recurrence was significantly associated with increased risk for metastasis development (p=0.003). No factor was found to associate significantly with the development of local recurrence. Conclusion. Currently, the optimal management of Pelvic Ewing's Sarcoma is controversial but our study shows increased survival rates with chemotherapy and surgery treatment

Introduction: Ewing’s sarcoma is the second commonest primary tumor in childhood and its 5-year survival is currently just over 70%. The aim of the current study was to identify the prognostic significance of p53 and hsp70 overexpression into the nuclei of tumor cells. Method: 30 patients treated for Ewing’s in a 15-year period, in a Children’s hospital, were included in the study. Treatment protocols included always Neo-adjuvant Chemo and did not considerably change in time. The male to female ratio was 1.8: 1. The average age was 10.5 years (range 2–18y). Central axis and extremities were equally affected, with pelvis being the commonest site. Expression of P53 and HSP70 in > 20% and > 15% of the tumor nuclei respectively, was considered compatible with mutation. The mean follow up was 7.2 years. Results: Seventeen patients eventually died. HSP70 trace was negative, meaning that at the time of biopsy the tumor nuclei were not expressing the protein. Mutated p53 was traced in 13% of the tumor nuclei and had significant negative prognostic value in 5-year survival (p=0.039) and in Event Free Survival (p=0.006). Discussion: The search of factors that could independently affect the prognosis in Ewing’s sarcoma continues. Identification of these factors would lead to application of more intense therapeutic means only to those patients with a poorer prognosis without getting everyone in the risk of adverse effects

The purpose of this study was to investigate the importance of the timing of surgery for disease-free survival (DFS). The increasing efficacy of neo-adjuvant chemotherapy in Ewing’s sarcoma modifies the prognostic factors. In a recent monocentric study the classical prognostic value of size and location of the primary disappeared (. Delepine G, Alkallaf S. . J. Chem. 1997. ;. 9. :. 352. –63. ). This study confirmed the value of histologic response and pointed out the importance of dose intensity of VCR and ACTD. However, the role of local treatment could not be significantly demonstrated because the number of patients was too small. Seventy-five patients with an average age of 19 years (range 4 to 40) years with Ewing’s sarcoma of bone fulfilled the inclusion criteria for this study: localised tumour at first screening (CT of lungs + bone scan) and location of the tumour in resectional bones (limb, scapula, innominate, rib, maxilla, skull). Metastatic patients and vertebral locations were excluded. The patients received multi-drug chemotherapy and were treated by surgery and radiotherapy in cases of bad responders and/or marginal surgery. The histologic response was evaluated according to Picci’s criteria (. Picci, A. . J Clin Oncol. 1993. ;. 11. :. 1793. –99. ). The duration of local treatment was calculated from biopsy to surgery in weeks. After a mean follow-up of 54 months, 41 patients were in first complete remission. Patients operated before the tenth week had a higher chance (68%) of first complete remission than patients operated later (DFS: 43%). The difference is significant (p< 0.03). Further analysis shows that the difference is due to late local control, which causes a dismal prognosis for bad responders. Local treatment must be performed early, especially when histologic response is incomplete or uncertain. Preoperative chemotherapy that is too long increases the risk of metastases in bad responders. These factors must be taken into account when analysing multicentre protocols

The purpose of this study was to investigate the importance of the timing of surgery for disease-free survival (DFS). The increasing efficacy of neo-adjuvant chemotherapy in Ewing’s sarcoma modifies the prognostic factors. In a recent monocentric study the classical prognostic value of size and location of the primary disappeared (. Delepine G, Alkallaf S. . J. Chem. 1997. ;. 9. :. 352. –63. ). This study confirmed the value of histologic response and pointed out the importance of dose intensity of VCR and ACTD. However, the role of local treatment could not be significantly demonstrated because the number of patients was too small. Seventy-five patients with an average age of 19 years (range 4 to 40) years with Ewing’s sarcoma of bone fulfilled the inclusion criteria for this study: localised tumour at first screening (CT of lungs + bone scan) and location of the tumour in resectional bones (limb, scapula, innominate, rib, maxilla, skull). Metastatic patients and vertebral locations were excluded. The patients received multi-drug chemotherapy and were treated by surgery and radiotherapy in cases of bad responders and/or marginal surgery. The histologic response was evaluated according to Picci’s criteria (. Picci, A. . J Clin Oncol. 1993. ;. 11. :. 1793. –99. ). The duration of local treatment was calculated from biopsy to surgery in weeks. After a mean follow-up of 54 months, 41 patients were in first complete remission. Patients operated before the tenth week had a higher chance (68%) of first complete remission than patients operated later (DFS: 43%). The difference is significant (p< 0.03). Further analysis shows that the difference is due to late local control, which causes a dismal prognosis for bad responders. Local treatment must be performed early, especially when histologic response is incomplete or uncertain. Preoperative chemotherapy that is too long increases the risk of metastases in bad responders. These factors must be taken into account when analysing multicentre protocols

Pathological fracture occurs in 5–10% of all primary malignant bone tumours. It is thought that they unfavourably influence survival, because the fracture haema-toma may contaminate adjacent tissues. Management is often more aggressive and one is less inclined to consider limb saving surgery. Aim of this study was to determine whether the presence of pathological fracture had an effect on rate of limb salvage surgery, role of adjuvant treatment and survival. A retrospective study was done on all patients with a pathological fracture through localised Ewing’s sarcoma, treated between 1979 and 2001. Of 289 patients with localised Ewing’s sarcoma, 27 had a pathological fracture. Eighteen presented with fracture, in 9 fracture occurred after biopsy. All were treated with chemotherapy according to protocol. Two fractures were already treated by osteosynthesis elsewhere, the rest healed with conservative treatment. After chemotherapy, 20 patients were treated surgically: 19 with limb saving surgery, 1 with amputation. Apart from chemotherapy, treatment was surgery alone in 15, surgery and radiotherapy in 5, and radiotherapy alone in 7 patients. Indications for radiotherapy were close margins, poor chemotherapy response, or pelvic tumours. Surgical margins were wide in 16 patients, marginal in 2, and intralesional in 1 patient. Local recurrence occurred in 2 patients, primarily treated with chemotherapy and radiotherapy alone. Five year survival was 60%, metastasis free survival 59%, both comparable with rates reported in literature. Conclusion: Chemotherapy allows fractures to consolidate with conservative treatment. Adequate surgical margins can be achieved in the majority of patients with limb saving surgery. Adjuvant radiotherapy does not seem necessary if margins are wide. Survival is not negatively influenced by pathological fracture. The survival rate following limb saving surgery in these patients is similar to that of patients in literature where amputation is done. Limb saving surgery seems a safe option

Ewing’s sarcoma family tumors (ESFT) express the EWS-FLI1 fusion gene generated by the chromosomal translocation t(11;22)(q24;q12). Expression of the EWS-FLI-1 fusion protein in a permissive cellular environment is believed to play a key role in ESFT pathogenesis. However, EWS-FLI1 induces growth arrest or apoptosis in differentiated primary cells and the identity of permissive primary human cells that can support its expression and function has until now remained elusive. Here we show that expression of EWS-FLI1 in primary human mesenchymal stem cells (hMSC) is not only stably maintained without inhibiting proliferation, but that it induces a gene expression profile bearing striking similarity to that of ESFT, including genes that are among the highest ESFT discriminators. Expression of EWS-FLI-1 in MSCs may recapitulate the initial steps of Ewing’s sarcoma development, allowing identification of genes that play an important role early in its pathogenesis. These observations are consistent with our recent findings using mouse mesenchymal progenitor cells and provide compelling evidence that hMSCs are candidate cells of origin of ESFT

Purpose: Treatment results in patients with Ewing tumors of the vertebrae were analyzed. Patients and Methods: Between June 2000 and April 2007 7 patients with primary tumors of the thoracic or lumbar vertebrae were treated. No one patient had primary tumor of the cervical vertebra. The median ageat diagnosis was 13 years (range, 12 to 18 yrs.). Primary sites: thoracic5, lumbar 2. No one had metastases at diagnosis. Surgery was performed in 5 pts. Complete surgical excision in 2 and maximal tumor reduction in 3.Only biopsy was in 2pts. After surgery all pts. received chemotherapy: EICESS 92 (EVAIA chemotherapy regimen) in 4 pts. and Euro Ewing 99 in 3 pts. Radiotherapy was performed in 6 patients: after 2 cycles of chemotherapy in 2 pts., after 3 cycles in 4 pts. Median dose 5040cGy (range 5018–5400cGy) in conventional fractionation. Daily fractionation from 180–193cGy. Results/Discussion: The mean follow-up was 41 months (range 4–104 months). Overall survival (OS) rate was 71,42 %. One patient progressed and died after complete treatment, another one died during chemotherapy before radiotherapy. In our series of Ewing’s Sarcoma of the vertebrae, good surgery initialy, early definitve radiotherapy and aggressive multimodal therapy (surgery/radiotherapy/chemotherapy) may be effective in disease control and survival

The development of multidisciplinary therapy for Ewing’s sarcoma (ES) has increased current long-term survival rates to greater than 50%, but only 20% for patients with clinically detectable metastases at diagnosis, or not responding to therapy or with disease relapse. Anti-bone resorption bisphosphonates (BP) may represent promising adjuvant molecules to limit the osteolytic component of bone tumor. The combination of zoledronic acid (ZOL) and ifosfamide (IFOS) or mafosfamide (MAFOS) was studied in ES models and in 8 human cell lines all expressing the EWS-FLI1 fusion gene. Cell proliferation, viability, apoptosis and cell cycle distribution were analysed. The ES models were developed in immuno-deficient mice by inoculating the human tumor cells either intra-muscular (soft tissue tumor development) or intra-osseous (bone tumor development). Mice were then treated with ZOL (100 μg/kg twice or 4 times/week) and/or ifosfamide (IFOS 30 mg/kg, one to 3 sequences of 3 injections). All the cell lines studied were more or less sensitive to ZOL and MAFOS in terms of cell proliferation. Both drugs induced cell cycle arrest respectively in S and G2M phase and final apoptosis associated to caspase 3 activation. In vivo, ZOL had no effect on soft tumor progression although it dramatically inhibits ES development in bone site. When combined with IFOS, ZOL exerts synergistic effects in the soft tissue model leading to a similar quantitative inhibitory effect when associated with 1 sequence IFOS as compared to 3 sequences of IFOS alone. In the bone model, ZOL prevents tumor recurrence observed with a lonely sequence of IFOS. Combination of ZOL with conventional chemotherapy showed promising results in both ES models and could allow the clinicians to diminish the doses of chemotherapy. Moreover, as ZOL and MAFOS induce cell death by different pathways, respective resistance may be circumvented