Aims. Limb salvage in bone tumour patients replaces the bone with massive segmental prostheses where achieving bone integration at the shoulder of the implant through extracortical bone growth has been shown to prevent loosening. This study investigates the effect of multidrug chemotherapy on extracortical bone growth and early radiological signs of aseptic loosening in patients with massive distal femoral prostheses. Methods. A retrospective radiological analysis was performed on adult patients with distal femoral arthroplasties. In all, 16 patients were included in the chemotherapy group with 18 patients in the non-chemotherapy control group. Annual radiographs were analyzed for three years postoperatively. Dimensions of the bony pedicle, osseointegration of the hydroxyapatite (HA) collar surface, bone resorption at the implant shoulder, and radiolucent line (RLL) formation around the cemented component were analyzed. Results. A greater RLL score (p = 0.041) was observed at three years postoperatively, with those receiving chemotherapy showing greater radiological loosening compared with those not receiving chemotherapy. Chemotherapy patients experience osteolysis at the shoulder of the ingrowth collar over time (p < 0.001) compared with non-chemotherapy patients where osteolysis was not observed. A greater median percentage integration of the collar surface was observed in the non-chemotherapy group (8.6%, interquartile range (IQR) 0.0% to 37.9%; p = 0.021) at three years. Bone growth around the collar was observed in both groups, and no statistical difference in amount of extracortical bony bridging was seen. Conclusion. Multidrug chemotherapy affects the osseointegration of ingrowth collars and accelerates signs of radiological loosening. This may increase the risk of aseptic loosening in patients with massive segmental implants used to treat bone cancer. Cite this article: Bone Joint Res 2020;9(7):333–340

Total joint replacement (TJR) was one of the most revolutionary breakthroughs in joint surgery. The majority studies had shown that most implants could last about 25 years, anyway, there is still variation in the longevity of implants. In US, for all the hip revisions from 2012 to 2017 in the United States, 12.0% of the patients were diagnosed as aseptic loosening. Variable studies have showed that any factor that could cause a systemic or partial bone loss, might be the risk of periprosthetic osteolysis and aseptic loosening. Breast cancer is the most frequent malignancy in women, more than 2.1 million women were newly diagnosed with breast cancer, 626,679 women with breast cancer died in 2018. It's been reported that the mean incidence of THA was 0.29% for medicare population with breast cancer in USA, of which the incidence was 3.46% in Norwegian. However, the effects of breast cancer chemotherapy and hormonotherapy, such as aromatase inhibitors (AI), significantly increased the risk of osteoporosis, and had been proved to become a great threat to hip implants survival. In this case, a 46-year-old female undertook chemotherapy and hormonotherapy of breast cancer 3 years after her primary THA, was diagnosed with aseptic loosening of the hip prosthesis. Her treatment was summarized and analyzed. Breast cancer chemotherapy and hormonotherapy might be a threat to the stability of THA prosthesis. More attention should be paid when a THA paitent occurred with breast cancer. More studies about the effect of breast cancer treatments on skeleton are required

We studied the safety of external fixation during post-operative chemotherapy in 28 patients who had undergone distraction osteogenesis (17, group A) or vascularised fibular grafting (11, group B) after resection of a tumour. Four cycles of multi-agent post-operative chemotherapy were administered over a mean period of 14 weeks (6 to 27). The mean duration of external fixation for all patients was 350 days (91 to 828). In total 204 wires and 240 half pins were used. During the period of post-operative chemotherapy, 14 patients (11 in group A, 3 in group B) developed wire- and pin-track infection. A total of ten wires (4.9%) and 11 half pins (4.6%) became infected. Seven of the ten infected wires were in periarticular locations. External fixation during post-operative chemotherapy was used safely and successfully for fixation of a vascularised fibular graft and distraction osteogenesis in 27 of 28 patients. Post-operative chemotherapy for malignant bone tumours did not adversely affect the ability to achieve union or cause hypertrophy of the vascularised fibular graft and had a minimal effect on distraction osteogenesis. Only one patient developed osteomyelitis which required further surgery

Aims. To assess the correlation between the histological response to preoperative chemotherapy and event-free survival (EFS) or overall survival (OS) in patients with high-grade localized osteosarcoma. Methods. Out of 625 patients aged ≤ 40 years treated for primary high-grade osteosarcoma between 1997 and 2016, 232 patients without clinically detectable metastases at the time of diagnosis and treated with preoperative high-dose methotrexate, adriamycin and cisplatin (MAP) chemotherapy and surgery were included. Associations of chemotherapy-induced necrosis in the resected specimen and EFS or OS were assessed using Cox model and the Pearson’s correlation coefficients (r). Time-dependent receiver operating characteristic analysis was applied to determine the optimal cut-off value of chemotherapy-induced necrosis for EFS and OS. Results. OS was 74% (95% confidence interval (CI) 67 to 79) at five years. Median chemotherapy-induced necrosis was 85% (interquartile range (IQR) 50% to 97%). In multivariate Cox model, chemotherapy-induced necrosis was significantly associated with EFS and OS (hazard ratio (HR) = 0.99 (95% CI 0.98 to 0.99); p < 0.001 and HR = 0.98 (95% CI 0.97 to 0.99); p < 0.001, respectively). Positive correlation was observed between chemotherapy-induced necrosis and five-year EFS and five-year OS (r = 0.91; p < 0.001, and r = 0.85; p < 0.001, respectively). The optimal cut-off value of chemotherapy-induced necrosis for five-year EFS and five-year OS was 85% and 72%, respectively. Conclusion. Chemotherapy-induced necrosis in the resected specimen showed positive correlation with EFS and OS in patients with high-grade localized osteosarcoma after MAP chemotherapy. In our analysis, optimal cut-off values of MAP chemotherapy-induced necrosis in EFS and OS were lower than the commonly used 90%, suggesting the need for re-evaluation of the optimal cut-off value through larger, international collaborative research. Cite this article: Bone Joint J 2020;102-B(6):795–803

Introduction: Limb salvage surgery has all but replaced amputation as the treatment of choice for sarcomas of the extremities. This dramatic change came about as the result of two important developments: effective chemotherapy and precision imaging techniques.In high-grade sarcomas the most significant predictors of survival are the location of the primary lesion, local control of the tumor, and the degree of necrosis in the primary tumor after intravenous neoadjuvant chemotherapy (histologic response). Aim : To detect the response to preoperative chemotherapy and correlate with the biological characteristic of osteosarcoma. Materials and method:19 Patients wih primary osteo-sarcoma were studied (follow up 9 months to 7 years). Response to preoperative chemotherapy is made histologically according to the HUVOS staging system..Combination chemotherapy was used based on the Rosen T-10 protocol (high dose methotrexate) or the platine and adriamycine protocol. Conclusions :The best response to preoperative chemotherapy was found in osteoblastic osteosarcomas (12% grade IV, 33% grade III, 33% grade II and 22% grade I tumor necrosis).Chondroplastic osteosarcomas showed less sensitivity to chemotherapy (o% grade IV, 40 % grade III, 20% grade II and 40% grade I tumor necrosis) and paraosteal and periosteal osteosarcomas were resistant to preoperarive chemotherapy

High grade sarcoma present a systemic metastatic progression in approximaly 50% of cases. The effectiveness of palliative chemotherapy as a treatment of systemic metastases is still controversed. The main objectif of this study is to assess disease progression and survival of patients diagnosed with metastatic soft tissue sarcomas treated with palliative chemotherapy, analyse chemotherapy treatment patterns and response to different lines of treatment. Retrospective chart review of 75 patients treated with palliative chemotherapy for metastatic soft tissue sarcomas between 2003 and 2013 at Maisonneuve-Rosemont Hospital. Data for control group of 40 patients with metastatic soft tissue sarcomas not treated with chemotherapy was collected retrospectively. Collected data include demographic data, overall survival, time free survival, type of chemotherapy treatment, surgical treatment and adverse reaction to palliative chemotherapy. Overall survival was analysed with Kaplan-Meier test. Categorial variable were compared with Log-Rank test. Seventy-five patients (37% female; mean age 50.4 years) received minimally one line of chemotherapy for their metastatic sarcomas. The regimens most commonly used in first-line were doxorubicin (48%) and doxorubicin combined with ifosfamide (21.3%). Favorable response was achieved by 38.7% in first-line and 27.9% in second-line therapy. Median overall survival with chemotherapy treatments was more than two times overall survival without treatments. Median overall survival was 19 months with chemotherapy treatments and 7 months without chemotherapy (p<0.0001). There was no statistically significant difference between survivals for treated and untreated patients with chemotherapy when analysed in term of the histological subtype, age and monotherapy versus combined treatment. Event-free survival was statistically longer during the first year for the group of patients treated with combined chemotherapy (p=0.0125). Results have shown a significantly improved overall survival in all histological groups, resulting in an OS of 19 vs 7 months for the chemotherpy and non chemotherapy group respectively. Nevertheless, patients with favorable response to chemotherapy have poor outcomes. Additional treatment options are needed

The influence of advancements in imaging and chemotherapy on patient with dedifferentiated chondrosarcoma was determined. There were forty-two cases in which twenty-seven patients received adjuvant therapy. Median survival was eight months and five-year survival was 4.8%. There was no statistical difference (p=0.62) in survival between patients who did and did not receive chemotherapy, had wide versus radical resection, or had limb sparing versus sacrificing procedures. There were no statistically significant differences between patients treated prior to 1986 and those subsequently. Despite advances, dedifferentiated chondrosarcoma continues to carry a poor prognosis. The routine adjuvant chemotherapy in this population should be questioned. The long-term survival for patients that presented with dedifferentiated chondrosarcoma has historically been poor. A large clinical series has not been analyzed in the era of modern diagnostic and treatment modalities. The current study was performed to look at the influence of advancements in imaging and chemotherapy on patient outcome. A retrospective chart review of all cases of patients presenting with dedifferentiated chondrosarcoma at our institution from 1984–2000 was performed. This was done as an extension to a study published in 1986 prior to the era of modern chemotherapy. There were forty-two cases in twenty-five men and seventeen women of average age fifty-six (range twenty-four-eighty-three years). MSTS grades at presentation were IIA(5), IIB(27), and III(10). Three patients underwent biopsy only, nineteen had limb sacrificing surgery, and twenty had limb sparing procedures. Surgical margins were intralesional in three, marginal in two, wide in twenty, and radical in fourteen. Twenty-seven patients received adjuvant therapy (twenty-two chemotherapy only, two radiotherapy only, three combined therapy). Median survival was eight months and five-year survival was 4.8%. There was no statistical difference (p=0.62) in survival between patients who did and did not receive chemotherapy, had wide versus radical resection, or had limb sparing versus sacrificing procedures. There were no statistically significant differences between patients treated prior to 1986 and those subsequently. Despite advances in diagnostic modalities, surgical treatments, and adjuvant therapies, dedifferentiated chondrosarcoma continues to carry a poor prognosis. The routine use of current adjuvant chemotherapy and its inherent risks and benefits in this population should be questioned

The April 2023 Oncology Roundup. 360. looks at: Complete tumour necrosis after neoadjuvant chemotherapy defines good responders in patients with Ewing’s sarcoma; Monitoring vascularized fibular autograft: are radiographs enough?; Examining patient perspectives on sarcoma surveillance; The management of sacral tumours; Venous thromboembolism and major bleeding in the clinical course of osteosarcoma and Ewing’s sarcoma; Secondary malignancies after Ewing’s sarcoma: what is the disease burden?; Outcomes of distal radial endoprostheses for tumour reconstruction: a single centre experience over 15 years; Is anaerobic coverage during soft-tissue sarcoma resection needed?; Is anaerobic coverage during soft-tissue sarcoma resection needed?

Background. The discussion over the duration, type of therapy and regimen to be used in osteoarticular tuberculosis is losing importance in all orthopaedic gathering. Still little consensus is there over the universality of a treatment regime for osteoarticular tuberculosis. Material and Method. 340 new cases of osteoarticular tuberculosis were included in the study that were medically treated in the department of orthopaedics in a tertiary care center between 2001 and 2011. Out of which 202 cases were of spinal tuberculosis and 138 cases of extraspinal tuberculosis. 88 cases of spinal tuberculosis were treated by conventional method and 114 cases by short course chemotherapy. 60 cases of extraarticular tuberculosis were treated by conventional chemotherapy and 78 cases by short course and intermittent therapy. Results. All cases were evaluated on clinical, radiological and haematological basis. Cases who received conventional therapy received 18–24 months of treatment irrespective to the clinical, radiological and haematological parameters. Whereas those who received short course (2HRZE+4 HR) and intermittent therapy (DOTS) were evaluated for clinical improvement. Maximum follow up was of 12.8 years (conventional) minimum follow of 8 years (intermittent). The trend of fall in ESR, clinical and radiological parameters showed improvement beyond 2 years of initiation of treatment in cases that had stopped treatment at 6 months. But the improvement was slow after six months even in cases who received 24 months of chemotherapy. There were no relapses in all the three groups. Conclusion. This study reinforces that chemotherapy tailored to the response of treatment (6-9months) is the rational therapy. This study gives an insight over the evolution of different regimes as well as gives an understanding of the clinical treatment. Level of Evidence. Level 1. No relevant financial disclosures or conflicts of interest from any of the authors

We performed a randomised, controlled clinical trial to compare ambulant short-course chemotherapy with anterior spinal fusion plus short-course chemotherapy for spinal tuberculosis without paraplegia. Patients with active disease of vertebral bodies were randomly allocated to one of three regimens: a) radical anterior resection with bone grafting plus six months of daily isoniazid plus rifampicin (Rad6); b) ambulant chemotherapy for six months with daily isoniazid plus rifampicin (Amb6); or c) similar to b) but with chemotherapy for nine months (Amb9). Ten years from the onset of treatment, 90% of 78 Rad6, 94% of 78 Amb6 and 99% of 79 Amb9 patients had a favourable status. Ambulant chemotherapy for a period of six months with daily isoniazid plus rifampicin (Amb6) was an effective treatment for spinal tuberculosis except in patients aged less than 15 years with an initial angle of kyphosis of more than 30° whose kyphosis increased substantially

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. Socioeconomic and racial disparities have been recognized as impacting the care of patients with cancer, however there are a lack of data examining the impact of these disparities on patients with bone sarcoma. The purpose of this study was to examine socioeconomic and racial disparities that impact the oncological outcomes of patients with bone sarcoma. Methods. We reviewed 4,739 patients diagnosed with primary bone sarcomas from the Surveillance, Epidemiology and End Results (SEER) registry between 2007 and 2015. We examined the impact of race and insurance status associated with the presence of metastatic disease at diagnosis, treatment outcome, and overall survival (OS). Results. Patients with Medicaid (odds ratio (OR) 1.41; 95% confidence interval (CI) 1.15 to 1.72) and uninsured patients (OR 1.90; 95% CI 1.26 to 2.86) had higher risks of metastatic disease at diagnosis compared to patients with health insurance. Compared to White patients, Black (OR 0.63, 95% CI 0.47 to 0.85) and Asian/Pacific Islander (OR 0.65, 95% CI 0.46 to 0.91) were less likely to undergo surgery. In addition, Black patients were less likely to receive chemotherapy (OR 0.67, 95% CI 0.49 to 0.91) compared to White patients. In patients with chondrosarcoma, those with Medicaid had worse OS compared to patients with insurance (hazard ratio (HR) 1.65, 95% CI 1.06 to 2.56). Conclusion. In patients with a bone sarcoma, the cancer stage at diagnosis varied based on insurance status, and racial disparities were identified in treatment. Further studies are needed to identify modifiable factors which can mitigate socioeconomic and racial disparities found in patients with bone sarcomas. Cite this article: Bone Joint Res 2022;11(5):278–291

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

Objective: The aim of our study was to evaluate results of chemotherapy regimens and analyse prognostics factors in children with relapse of osteosarcoma. Patients and methods: From 2000–2007, we treated 57 patients with non metastatic osteosarcoma, median age 15,5 years (range 3–18). 29 pts relapsed. 26 pts with osteosarcoma relapse were treated, and 3 pts with OS relapse refused the treatment. In 24 pts pulmonary metastases were detected (7 solitary), while 2 pts had local relapse of disease. Disease free interval (DFI) was more than 1 year in 12 patients. Surgery was performed in 20 pts (17 thoracotomy, 3 amputation). Chemotherapy regimens administered were: HD IFO-VP16 (11 pts), HDMth/IFO-VP16 (6 pts), HDMth/Carbo-VP16 (9 pts). Results : During 8–116 months follow up period (Me=32 mts), disease free suvival rate was 33.12%. There was no significant difference in survival in relation to the type of chemotherapy regimen applied.Prognostic factors that influenced survival were: presence of a solitary metastasis (p= 0.026), local relapse of disease (p= 0.002), completeness of resection (p=0.043) and DFIlonger than 1 year (p= 0.039). Conclusion: The use of aggressive multimodal therapy (surgery/chemotherapy) and evaluation of prognostic factors are necessary for successful treatment in patients with osteosarcoma relapse. Chemotherapy regimen HD IFO-VP16 had better initial tumore response, but in longer follow up the survival rate was similar to other chemotherapy groups

Ewing sarcoma (ES) and Osteosarcoma (OS) are the 2 most common malignant primary bone tumors. A patient's response to neoadjuvant chemotherapy has important implications in subsequent patient management and prognosis, as a favourable response to chemotherapy allows orthopedic oncologists to be more aggressive in pursuing limb-sparing surgery. An accurate and non-invasive pre-operative marker of response would be ideal for planning surgical margins and as a prognostic tool. ES and OS have differing biological characterisitcs and respond differently to chemotherapy. We reviewed 18F-FDG PET imaging characteristics of ES and OS patients at baseline and following treatment to determine whether this biological variation is reflected in their imaging phenotype. A retrospective review of ES and OS patients treated with neoadjuvant chemotherapy and surgery was done, correlating PET results with histologic response to chemotherapy. Change in the maximum standardized Uptake Value (SUVmax) between baseline and post-treatment scanning was not significantly associated with histologic response for either ES or OS. Metabolic tumor volume (MTV) and the percentage of injected 18F-FDG dose (%ID) in the primary tumor were found to be different for ES and OS response subgroups. A 50% reduction in MTV (MTV2:1 < 0.5) was found to be significantly associated with histologic response in OS. Using the same criteria for ES incorrectly predicted good responders. Increasing the cut-offs for ES to a 90% reduction in MTV (MTV 2:1 < 0.1) resulted in association with histologic response. Response to neoadjuvant chemotherapy as reflected by changes in PET characteristics should be interpreted differently for ES and OS

The results are presented of thirty-seven patients with Ewing's sarcoma; ten were treated by a combination of operation, radiotherapy and cyclic chemotherapy, the remainder by radiotherapy and chemotherapy but without operation. The drugs, vincristine, cyclophosphamide and adriamycin were used in combination and were continued for two years. The follow-up ranged from twelve to sixty-two months. The mortality rate and the incidence of metastases were both markedly lower than in a comparable previous series treated by radiotherapy alone, or by operation plus radiotherapy, but all without chemotherapy. The percentage of local recurrences and of metastases was much higher in the twenty-seven patients who had radiotherapy and adjuvant chemotherapy, than in the ten in whom operation was also performed. It is suggested that on the basis of these results (and on theoretical grounds) treatment should consist of radiotherapy combined with chemotherapy plus, whenever feasible, operative excision of the primary tumour

Fifty-five cases of osteosarcoma of the extremities were treated between 1972 and 1976 by combined surgery and chemotherapy (vincristine, adriamycin and methotrexate in medium doses) for 18 months. The follow-up ranges from 30 to 80 months (mean = 48 months). Twenty-six patients remained free from any evidence of disease, two had local recurrences but no metastases and 27 had metastases (four of these also had local recurrences). In 12 patients, the metastases appeared after the end of chemotherapy. Both metastases and local recurrences were more frequent in patients who had segmental bone resection (7/8) than in those treated by more radical surgery (22/47). Comparison with an "historical" group (94 osteosarcoma patients treated by operation alone in our Institute between 1960 and 1971) showed that the percentage of patients free from evidence of disease was higher in the group who receiving chemotherapy. In addition, the appearance of metastases in this group was delayed (mean = 16 months) as compared with the historical controls (mean = 8 months). On the other hand, after the same kind of operative treatment, the rate of local recurrences and the time of their appearance was almost identical in both groups

We investigated the effect of adjuvant and neoadjuvant chemotherapy regimens on the tibial regenerate after removal of the external fixator in a rabbit model of distraction osteogenesis using New Zealand white rabbits. Forty rabbits were randomly distributed into two groups. In the neoadjuvant group, half of the rabbits received 1mg/kg cisplatinum & 2mg/kg adriamycin at eight weeks of age followed by 1mg/kg cisplatinum & 4mg/kg adriamycin at ten weeks of age. The remaining ten received an identical volume of normal saline using the same regimen. The adjuvant group differed only in the timing of the chemotherapy infusion. Half received the initial infusion ten days prior to the osteotomy, with the second infusion four days following the osteotomy. Again, the remaining ten rabbits received an identical volume of normal saline using the same regimen. This produced an identical interval between infusions and identical age at osteotomy in both groups. All rabbits underwent a tibial osteotomy at 12 weeks of age. Distraction started 24hours after osteotomy at a rate of 0.75mm a day for 10 days, followed by 18 days without correction to allow for consolidation of the regenerate. At week 16 there was no difference in Bone Mineral Density (BMD), Bone Mineral Content (BMC) or volumetric Bone Mineral Density (vBMD) in the adjuvant group. Neoadjuvant chemotherapy appears to have a significant detrimental effect on BMD, vBMD and BMC. Despite this there were no significant alterations in the mechanical properties of the regenerate. Histologically there was a trend for increased cortical thickness in the control groups compared to intervention however this did not prove statistically significant. In conclusion, adjuvant chemotherapy may be more beneficial for cases where distraction osteogenesis is being considered to replace segmental bone loss after tumour excision

We studied the CT and MR scans, and the histology of 50 patients with primary Ewing’s sarcoma of bone to determine the association between the change in tumour volume and necrosis after chemotherapy, and to ascertain their influence on prognosis. The mean age of the patients was 17 years. The limbs were involved in 40 and the axial bones in ten. The volume of the tumour at diagnosis varied from 31 to 1790 ml. There was a significant relationship between necrosis and the measured change in volume of the tumour after chemotherapy. Progression of the tumour despite chemotherapy was seen only in patients with necrosis of grades 4 to 6. Necrosis significantly influenced survival (p < 0.05), but the effect of change in volume was less significant. Change in volume of the tumour is a good predictor of necrosis induced by chemotherapy. Necrosis is a strong prognostic factor in Ewing’s sarcoma

Purpose. Ewings Sarcoma (ES) and Osteosarcoma (OS) behave and respond differently to chemotherapy and any interpretation of diagnostics tests to predict a patients response to treatment must consider this. We reviewed 18F-FDG PET imaging characteristics of consecutive series of ES and OS patients to determine if any differences in PET imaging existed between them. Method. A retrospective review was performed of 31 patients with ES and OS who received all their treatment by our group and who had pre- and post-chemotherapy 18F-FDG PET scans at the Peter MacCallum Cancer Centre from Jan 1, 1999 to December 1, 2009 (Table 1). Patients who did not have both their pre- and post-chemotherapy PET scans done at Peter MacCallum Cancer Centre were excluded from the study to remove bias from having different PET scanning protocols. Patients received neoadjuvant chemotherapy according to standard protocols, all starting within 2 weeks after the initial pre-chemotherapy PET scans (PET1). The PET scan taken after the last cycle of chemotherapy prior to surgery was considered as the post-chemotherapy scan (PET2). The ratio between pre and post-chemotherapy for each PET parameter was then associated with the histology response for both ES and OS, and positive (PPV) and negative predicting values (NPV) of each parameter were calculated. Results. Standardized Uptake Values (SUV) was not significantly associated with histologic response for both ES and OS. Metabolic tumor volume (MTV) and accumulation percentage of 18F-FDG (%ID) was found to be different for ES and OS. A 50% reduction in MTV (MTV2:1 < 0.5) was found to be significantly associated with histologic response in OS. Using the same criteria for ES incorrectly predicted good responders. Increasing the cut-offs for ES to a 90% reduction in MTV (MTV 2:1 < 0.1) resulted in association with histologic response. Conclusion. Response to neoadjuvant chemotherapy as reflected by changes in PET characteristics should be interpreted differently for ES and OS

The rising incidence of atraumatic fractures in patients either with Ewing's sarcoma or osteosarcoma years after chemotherapy revealed a growing population of childhood cancer survivors with a decreased bone mineral density (BMD) possibly due to a long-term effect of the chemotherapy. Therefore we started to screen our patients below 50y of age who were treated for bone malignancies between 1994 and 2009. The first series of measurements included 15 patients – eight Ewing's sarcoma, three female and five male, with a mean age of 18y (±13SD), and seven osteosarcoma, two female and five male, with a mean age of 19y(±9SD). We screened the patients for deficits in their bone status using DEXA (dual-energy-x-ray-absorptiometry) to gain the T-and Z-Scores of the proximal femur and the lumbal spine. Additionally we took blood samples for endocrinological analysis and utilised a questionnaire to scan the patient's liefestyle. The mean time between diagnosis and investigation was 95months (±79SD) in Ewing's sarcoma and 105months (±54 SD) in osteosarcoma. The results of the age and gender matched lumbal measurement (Z-Score) of the Ewing's sarcoma patients showed a reduction of the BMD in six cases (6/8), including three times osteopenia (3/8) and two times osteoporosis (2/8). The osteosarcoma patients presented a BMD-decline in four cases (4/7) with two times osteopenia (2/7) and one osteoporosis (1/7). In the proximal femur six Ewing's sarcoma (6/8) and six osteosarcoma patients (6/7) showed a BMD-decrease including three osteopenic (3/8) and one osteoporotic (1/8) Ewing's sarcoma and four osteopenic osteosarcoma (4/7). We found two cases of pathologic fractures (2/15), one Ewing's sarcoma 29 months after diagnosis with a fracture of the distal femur and the proximal Tibia (1/8) and one osteosarcoma with a fractured distal femur after 72 months (1/7). As presented in our case series osteoporosis after chemotherapy is an underestimated long-term effect of the chemotherapeutic treatment. In our series BMD-reduction seems to be independent of tumour-type and chemotherapeutic agent like MTX

Neoadjuvant therapy in soft-tissue sarcomas is still a controversial issues regarding indications, patients selection and treatment protocols. In the last fifteen years (1990–2005) at our Institution more than 600 patients affected by soft tissue sarcomas of the limbs and superficial trunk were surgically treated. Among these patients, 49 received preoperative chemotherapy (epirubicin plus ifosfamide, according to Italian Sarcoma Group protocol), associated to preoperative conventional external beam radiationtherapy in 36 cases (73.5%). The histologic types were liposarcoma (30,6%), synovial sarcoma (20,4%), fibrosarcoma (16,3%), pleomorphic sarcoma or malignant fibrous histiocitoma (12,1%), leiomyosarcoma (8,2%), other histotypes (12,1%). Tumor size was 10 cm or larger in 21 cases, 6 to 9 cm in 23 patients and 5 cm or smaller in 5 cases. Neoplasms were high-grade (Broders grade 3 or 4) in all cases but five. After neoadjuvant treatment we performed a limb-sparing surgical excision of the tumor in 47 patients (96%), while a primary amputation of the limb was necessary in only two cases (4.1%). A vascularized miocutaneous flap was used in 8 cases, and adequate surgical margins were achieved in more than 70% of the cases. Postoperative chemotherapy was given in 26 cases (53%), postoperative radiotherapy just in 5 (10%). We report the outcome data on these 49 cases, regarding overall survival, local or distant relapse, local and systemic complications, early and long-term limb salvage rate. According to histologic examination of the resection specimen, average percent of necrosis after neoadjuvant treatment was 70.6% (range 30 – 99%). Wound dehiscence occurred in 6 patients but ultimately healed succesfully in all of them. At an average follow-up of 23 months (range 3 – 82), 37 patients were continuously disease free (76%), two patients had local recurrence (one amputated), four patients were alive with metastatic disease, five patients had died with disseminated disease (at 4, 19, 28, 37 and 61 months after surgery), one patient had died of unrelated disease. Due to the inconstant tumor response, neoadjuvant treatment in soft tissue tumors is still a controversial issue. On the basis of data presently available, we think that it can be a useful treatment in high-risk tumors (larger than 5 cm; high grade). In these cases, at a low and acceptable rate of local complications, the conjoined use of preoperative chemotherapy and radiotherapy can help to make a limb-salvage surgery possible and at the same time can maybe reduce the risk of distant metastasis

Amalignant peripheral nerve-sheath tumour developed in the right S1 nerve root in a man aged 30 causing back pain and sciatica. CT and MRI revealed a destructive tumour of the sacrum invading the retroperitoneal space. The tumour was not resectable with an adequate margin. Chemotherapy, consisting of high-dose ifosfamide followed by a combination of vincristine, doxorubicin and cyclophosphamide, was given with success. Malignant peripheral nerve-sheath tumours are thought to respond weakly to chemotherapy, but the response in our patient was complete

In 36 patients was carried out short-lived hyperglycemia and local hyperthermic prolonged intraarterial chemotherapy on the background of modificators of short-lived hyperglycemia in the department of general oncology of R. O.S. C of the H.M of the Republic of Uzbekistan. Tumour has localized in distal part of femoral bones in 18 patients, in proximal part of cannon bones in 13. Treatment was carried out by the scheme of Syclophosphan 1000 mg/m2 doxorubicin 90 mg/ m2 48-hourly unbroken infusion, cycplatin 100 mg2 in the dependence from efficacy of the treatment has been carried out from 1 to 4 courses In 3–4 hours time after beginning prolonged intraarterial chemotherapy unbrokenly began short-lived hyperglycemia by the way of introduction i/v solution of glucose 20% to1500ml. Maximal concentration of the blood sugar level has composed 18–23ml in the period of treatment. Then local hyperthermia with USD apparatus was carried out in 30MG frequency regime with exposition of 20 min. time. Control group of the patients has composed patients, who has performed system chemotherapy by analogical scheme CAP (in 34 patients). In the patients group, who received prolonged intraarterial chemotherapy with modificators (short-lived hyperglycemia with local hyperthermia) in 4 (11, 1%) patients have been observed full effect, in 25 patients (69, 4%) partial effect, in 5 (13,9%) stabilization, and in 2 (5,6%) progressing of tumour process. Safe operation was performed in 17 patients (47, 2%), crippling in 4 (11,4%) patients, conservative treatment in 15 patients (41,6%) in this group. In patients, who was carried out system chemotherapy full effect was marked in 2 (5,9%) patients, partial effect in 8 (23,5%), stabilization in 15 (44,1%) and progressing in 9 (26,5%) patients. Safe operations were carried out in 3 (8,8%), crippling operations in 19 (55,9%), other 12 (35,3%) patients are under observation after conducting 9 courses of chemotherapy and beam therapy without operation in conservative treatment. Endovascular chemotherapy in combination with local hyperthermia and short – lived hyperglycemia allows overcoming medicinal steadiness and increases quantity of safe operations. That’s why combination prolonged intraarterial chemotherapy with modifications is aimed

Chondrosarcomas are malignant hyaline cartilage tumours of bone. They are clinically resistant to conventional chemo- and radiotherapy and the underlying mechanism is poorly studied. Chemoresistance is a multifactorial process and the inaccessibility due to abundant hyaline cartilaginous matrix surrounding the cells, presence of multi-drug resistance pumps, and expression of anti-apoptotic proteins such as BCL2, have been suggested. Our aim was to study chemoresistance mechanisms in chondrosarcoma. We first studied the sensitivity of chondrosarcoma cell lines (SW1353, CH2879, JJ012, OUMS27) and 2 primary cultures for doxorubicin and cisplatin. We used a 3D pellet model of CH2879 to study doxorubicin incorporation. To investigate whether chondrosarcoma cells could be resensitised to chemotherapy we tested the BH3 mimetic ABT737 inhibiting anti-apoptotic BCL2 family proteins. Cell viability was assessed using a WST assay for mitochondrial activity. Dose response curves showed that chondrosarcoma cell lines and cultures are partially resistant to doxorubicin, while primary cultures were completely resistant to cisplatin. In 3D cell pellets, with morphology strongly resembling high grade chondrosarcoma, doxorubicin incorporation was confirmed. Chondrosarcoma cells responded to ABT737 with a >60% reduction in cell viability at high concentrations (25μM). Combination treatment allowing 2 days between ABT737 and chemotherapy addition led to a complete reduction of cell viability in all cell cultures. In conclusion, chondrosarcoma cell lines show a partial response to doxorubicin and less response to cisplatin. The incorporation of doxorubicin in the cells in a 3D pellet model indicates that resistance is not caused by inaccessibility of the cells for the drugs nor by multi-drug resistance pump activity. By combining BCL2 inhibition with Doxorubicin treatment, a complete reduction of cell viability was obtained. This suggests that BCL2 overexpression plays an important role in chemoresistance of chondrosarcoma, and turning on the apoptotic machinery by BCL 2 inhibition can render them chemosensitive

The purpose of study was to evaluate retrospectively the efficacy of Ifosfamide-Carboplatin containing chemotherapy in recurrent/refractory osteosarcoma and MFH of the extremities. Twenty seven osteosarcoma and 2 MFH pts who had achieved complete surgical remission after multimodal treatment and then progressed soon after en-bloc bone resection or developed recurrent disease were included in two chemotherapy protocols. There were 20M/9F with ages ranging from 15 to 36 yrs (mean 20). Chemotherapy consisted of ifosfamide (median dose per cycle 7.5 g/m2) + carboplatin (median dose 350 mg/m2) + etoposide (median dose 450 mg/m2) – (regimen ICE) or doxorubicin 60 mg/m2 (regimen ICA). Response was evaluated according to RECIST. Survival was calculated from the time of R1 to death and analyzed as February 11, 2009. In total 93 (from 1 to 5. mean 3) cycles were administrated between October 2003 and December 2008. Of 17 ICE pts 3 had PR (17.6%), 10 had SD (58.8%) and 4 (23.5%) – PD. Among 12 ICA pts 3 (25%) had PR, 6 (50%) had SD and 3 (25%) had PD. Sixteen pts (55%) without progression during chemotherapy achieved second surgical remission. At last follow-up 12 pts died of disease, 8 are AWD and 9 are NED. Actuarial 5-year survival was 35±16%, median 38 mos. Outcome was related to relapse-free interval. Five-year survival was 23±18% among patients who relapsed < 12 mos after CR1 and 64±18% among pts who relapsed later, p=0.3. 5-year survival was significantly better in pts in whom chemotherapy was followed by surgery for distant metastases − 37.8±27% (median 38 mos), versus 23.3±19% (median 11 mos.) in patients treated without surgery, p< 0.05. We conclude that retrieval chemotherapy stopped disease progression in the majority of cases. Followed by surgery it was associated with better survival. These regimens and treatment strategy need further investigation in prospective trials

In the treatment of osteosarcoma, many reports in the literature outline that tumor response to chemotherapy directly correlates with disease-free survival and/or mortality. The aim of this study is to evaluate if the percentage of tumor necrosis is a sole prognostic indicator of overall survival in osteosarcoma patients. We retrospectively studied 33 osteosarcoma cases treated in our institution from 1997 to 2006. All patients were treated preoperatively with HDMTX chemotherapy. The percent necrosis of the excised specimen were compared with survival rates of the patients. Sixteen patients were good responders (Huvos III, IV- > 90% necrosis), 16 patients were poor responders (Huvos I, II- < 90% necrosis), and one patient died during preop. chemotherapy. With a mean follow-up of 5,48 years (3–12 years) 22 patients are NOD (not evident disease), in 8 patient disease progressed, 8 patients died. Statistical analysis could not establish a significant correlation between percent necrosis and patient survival. Outcome of osteosarcoma may be dependent on a variety of factors s.a. tumor size, location, metastasis, surgical therapy, pathologic fracture. Tumor necrosis itself may be dependent on the histological subtype of the tumor and P-glycoprotein expression. In this series we could not establish tumor necrosis as a sole prognostic factor of patient survival

Aim: To investigate the possibility of using polymethylmethacrylate (PMMA) bone cement as a delivery vehicle for anti-tumour chemotherapy. Methods: Doxorubicin was incorporated into PMMA pellets and incubated in physiological medium at 37°C. Release of Doxorubicin from the pellets continued for eight weeks as demonstrated by high performance liquid chromatography (HPLC). Doxorubicin-containing pellets were incubated with sarcoma cultures at 37°C for 24 hours. A significantly higher cell death rate(as measured by flow cytometry) was seen in the plates exposed to Doxorubicin compared to those exposed only to plain PMMA, indicating that the Doxorubicin released from the cement pellets retained its cytotoxic capability. PMMA-Doxorubicin cement pellets were implanted in rat tibiae and the animals killed at intervals over three weeks. HPLC analysis showed that this technique produced high concentrations of Doxorubicin adjacent to the implant but negligible systemic levels(heart, kidney, lung, liver). Four groups of rats had sarcomas established in their tibiae and then treated either by excision of tumour and Doxorubicin/PMMA implantation, excision and plain PMMA implantation, excision only or no treatment. The animals were then observed for tumour regrowth. A survival advantage was demonstrated for those animals treated by tumour excision and Doxorubicin/PMMA implantation. Conclusion: These experiments demonstrate that PMMA is an effective medium for the delivery of cytotoxic chemotherapy. This method has scope for early translation to the human situation

Osteosarcomas represent a heterogeneous group of primary bone tumours that affect predominantly the long bones of patients in the first two decades of life. We aim to describe the secondary effects of a poor response (⋋90% necrosis) to chemotherapy on the effectivity of other treatment outcomes, local recurrence and survival rates. 182 cases of osteosarcoma with necrosis of less than 90% and no metastases at diagnosis have been seen at our institution over 24 years. There were 60 amputations. 122 patients underwent limb salvage, with 105 marginal margins and 17 contaminated. There was no difference in size or location between the two groups. In the 122 patients with LSS, 21 had adjuvant radiotherapy and 101 did not. In the entirety of patients with ⋋90% necrosis, survival was 64% at 2 years and 37% at 5 years. When LSS Marginal resections were compared with amputation there was a significant (P=0.006) difference in survival. LSS with a marginal margin had a 25% risk of LR. In these patients there was 25% survival, whereas the absence of a local recurrence, conferred a benefit of a 40% survival XRT was used in 21 of the 122 who underwent limb salvage. The decision to use XRT was made by the local oncologist at the treating unit. There was a 24% rate of recurrence in the XRT group and 25% with no XRT. These data demonstrated that patients who had a poor response to chemotherapy and underwent an amputation faired poorly when compared to patients with LSS. There is a selection bias in patients selected to undergo amputation. Additionally, patients who underwent amputation had a lower rate of local recurrence, but still had a poorer survival when compared to LSS

High-dose methothrexate, a standard agent in the therapy protocols for osteosarcoma, has long been suspected to have a negative long-term effect on bone metabolism and bone mineral density, especially in children and young adults. Recent literature questioned this association as also the BMD of Ewing‘s sarcoma patients treated without methothrexate is known to be decreased. We therefore wanted to screen our patients treated for Ewing‘s sarcoma and osteosarcoma for osteopenia/osteoporosis-associated fractures. Between 1994 and 2008 107 patients below 50y of age were treated for bone malignancies including 51 Ewing’s sarcomas – 31 male and 20 female – with a mean age at diagnosis of 17y(±11SD) and 56 osteosarcomas – 36 male and 20 female – with a mean age of 23y(±12SD). We screened the patients‘ files for fractures after chemotherapy. We found five patients with not trauma-associated fractures – one Ewing‘s sarcoma(1/51;2%) and four osteosarcoma patients(4/56;7%). They presented one fracture of the proximal femur 107 months after tumour diagnosis, three fractures of the distal femur after 29, 51, and 72 months and two fractures of the proximal tibia after 29 and 32 months (one patient suffered from fractures affecting both – the distal femur and the proximal tibia). As presented in our case series fractures due to an osteoporotic process after chemotherapy for bone sarcomas are well known late effects. Although described in several studies therapeutic recommendations for pro-phylaxis are sparse. Furthermore the fact that fractures occurred in both types of sarcoma casts MTX as the main cause of chemotherapy-induced osteoporosis into doubt. Additionally we estimate a high number of unreported cases of premature osteoporosis because sarcoma patients are usually not tested for their BMD-levels. Therefore further studies using DEXA (dual-energy-x-ray-absorptiometry) to measure the patients BMDs after chemotherapy are needed

Osteosarcoma and other types of bone cancers often require bone resection, and backfill with cement. A novel silorane-based cement without PMMA's drawbacks, previously developed for dental applications, has been reformulated for orthopedic use. The aim of this study is to assess each cement's ability to elute doxorubicin, maintain its potency, and maintain suitable weight-bearing strength.

The silorane-based epoxy cement was synthesized using a platinum-based Lamoreaux's catalyst. Four groups of cement were prepared. Two PMMA groups, one without any additives, one with 200 mg of doxorubicin. Two silorane groups: one without any additive, one with doxorubicin, added so that the w% of drug into both cements were equal. Pellets 6 × 12 mm were used for testing (ASTM F451). n=10. Ten pellets from each group were kept dry. All others were placed into tubes containing 2.5 mL of PBS and stored at 37 °C. Elution from doxorubicin-containing groups were collected every day for 7 days, with daily PBS changeout. Antibiotic concentrations were determined via HPLC. Compressive strength and compressive modulus of all groups were determined for unsoaked specimens, and those soaked for 7 and 14 days. MTT assays were done using an MG63 osteosarcoma cell line.

Both cements were able to elute doxorubicin over 7 days in clinically-favorable quantities. For PMMA samples, the incorporation of doxorubicin was shown to significantly affect the compressive strength and modulus of the samples (p<0.01). Incorporation of doxorubicin into silorane had no significant effect on either (p>.05). MTT assays indicated that doxorubicin incorporated into the silorane cement maintained its effectiveness whereas that into PMMA did not. At the dosing used, both cements remained above the 70 MPa.

Both PMMA and silorane-based cements can deliver doxorubicin. Doxorubicin, however, interacts chemically with PMMA, inhibiting polymerization and lowering the chemotherapeutic's effectiveness.

Hyperactivation of the epidermal growth factor receptor (EGFR) by gene amplification, mutation as well as overexpression is a hallmark of multiple human carcinomas. However, in recent years data have accumulated that EGFR-mediated signals might also contribute to malignant progression and therapy resistance of human sarcomas. Consequently we have investigated if human osteosarcoma cell lines (n=9) express functional EGFR and its useability as therapeutic target. Osteosarcoma cells expressed distinctly differing level of EGFR reaching in some cases high amounts. However, even low expression levels were sufficient to activate both MAPK and PI3K pathways (determined by phosphorylation of ERK1/2 and S6, respectively) following EGF exposure of serum-starved cells. The EGFR-specific inhibitor gefitinib completely blocked EGF-mediated and attenuated serum-induced downstream signal activation. While gefitinib applied as single agent demonstrated only limited growth inhibiting activity in short term experiments (72h drug exposure), it led to reduced colony formation in long term experiments in the majority of cell lines. Importantly, gefitinb sensitized EGFR-expressing osteosarcoma cell lines against chemotherapy with doxorubicin and methotrexate, while it antagonised cisplatin-induced cell death. Summarizing, our data suggest that EGFR-mediated survival signals protect human osteosarcoma cells against the cytotoxic activity of several antineoplastic drugs. Consequently, combination approaches including EGFR inhibitors in addition to chemotherapy should be evaluated for treatment of high grade osteosarcoma patients

Prolonged survival have been reached in the last two decades in patients with Ewing’s sarcoma due to combination of chemotherapy and radiotherapy. We report the analysis of 493 patients treated according to 4 different protocols in 23 years (Jan1983- Dec 2006).Aim of this study was to evaluate the occurrence of late toxicities as Second Malignant Neoplasms (SMN), Cardiomyopathies and sterility. Methods: We reviewed our database to find out all those patients aged from 1 to 40 yrs with localized Ewing’s sarcoma who were treated with chemotherapy according to 4 different protocols from 1983 to December 2006. Data were updated at Dec 2008. Results: 493 patients had adequate follow up and meet the eligibility criteria. Median age was 16 yrs (1–40) female/male: 183/310.Median overall survival 69 ms (4–302).220 patients died and 273 are alive. 44 pts received HDCT + PBSCR.Eleven SMN were found : 2 AMLeukemia, 2 parotid adenocarcinoma, 1 melanoma, 1 thyroid cancer and 5 radioinduced osteosarcoma. The interval between Ewing’s sarcoma diagnosis and leukaemia diagnosis was shorter then interval between Ewing’s sarcoma and RT osteosarcoma. Six patients reported a Cardiomyopathy : in 4 cases it was mild and pts are well compensated,2 patients needed heart transplant,. One of these two pts received also a kidney transplant due to chronic renal failure due to previous chemotherapy. Fertility: 17 women became pregnant after chemotherapy, 20 women experienced postTx amenorrea: 7 pts received RT in pelvic area, 9 did HDCT, 3 pts were over 30 yrs old. 9 male became father. 8 male patients did sperm analysis 3 azospermia, 4 oligospermia and 1 normal sperm count. No congenital abnormalities in offsprings were reported. Conclusions: In this casuistic the Cumulative Risk to have a SMN at 5 yrs is 1.8% and 2.9% at 10 yr. The SMN cumulative incidence in Ewing’s sarcoma seems to be lower then in our previous casistic in osteosarcoma patients (ASCO 2006)

Summary. Methotrexate chemotherapy (commonly used in treating cancers and rheumatoid arthritis) creates an inflammatory condition in bone, decreasing osteogenesis, enhancing adipogenesis, increasing osteoclastogenesis, leading to bone loss and marrow adiposity; treatment with fish oil or folinic acid counteracts these negative effects and prevents bone loss. Introduction. Chemotherapy with anti-metabolite methotrexate (MTX) is commonly used in treating cancers and rheumatoid arthritis; however it is known to cause bone loss for which currently there are no adjunct preventative treatments. Methods and Materials. Using a rat model, this study investigated the damaging effects in bones caused by daily MTX injections (0.75mg/kg) for 5 consecutive days (mimicking induction phase treatment for childhood leukaemia) and also the potential protective benefits of omega-3 fatty acid-rich fish oil at different doses (0.25, 0.5 or 0.75 mL/100g BW) in comparison to antidote folinic acid (given i.p at 0.75mg/kg 6 hours post MTX, which is clinically used to reduce MTX toxicities in soft tissues). Results. Histological analysis showed that MTX significantly reduced primary spongiosa bone height and metaphyseal trabecular bone volume. MTX also significantly reduced density of osteoblasts at the secondary spongiosa. Ex vivo differentiation assays with bone marrow stromal cell populations of treated rats revealed a significant reduction in osteogenic differentiation but an increase in adipogenesis. Consistently, RT-PCR gene expression study within the stromal cell population revealed a lower expression of osteogenic transcription factors Runx2 and Osx and bone matrix protein osteocalcin but a significantly upregulated adipogenesis-related genes FABP4 and PPARγ, indicating that MTX chemotherapy induces a switch in the differentiation potential towards adipogenesis at the expense of osteogenesis. MTX increased the density of osteoclasts within the metaphyseal bone as revealed by histological analysis and osteoclast precursor cell pool as shown by ex vivo osteoclastogenesis assay with bone marrow samples. Consistently, mRNA expression of proinflammatory and osteoclastogenic cytokines IL-1, IL-6, TNF-α, and the RANKL/OPG ratio were significantly upregulated by MTX. Supplementary treatment with fish oil (0.5mL/100g BW) or folinic acid significantly preserved metaphyseal trabecular bone volume, osteoblast density, and bone marrow stromal cell osteogenic differentiation and suppressed MTX-induced adipogenesis. These supplements also prevented MTX-induced increased osteoclast density, osteoclastogenesis, and expression of proinflammatory and osteoclastogenic cytokines. Conclusion. These results suggest that MTX chemotherapy creates an inflammatory condition in bone resulting in increased osteoclast formation and decreased osteoblast formation thus leading to bone loss, and that supplementary treatment with fish oil at 0.5mL/100g BW or folinic acid counteract these negative effects, helping to conserve bone formation, suppress bone resorption and bone marrow adiposity, and thus prevent bone loss during MTX chemotherapy

We describe a patient who developed avascular necrosis of both humeral trochleae after combination chemotherapy for acute lymphoblastic leukaemia. This presented as progressive stiffness of both elbows with little pain. Radiography and MRI confirmed the presence of avascular necrosis at both sites. This region corresponds to a watershed between the medial and lateral vascular arcades which supply the distal humerus and may explain the susceptibility of this bony region to avascular necrosis. Treatment involved capsulectomy of the elbow and removal of osteophytes giving a good functional outcome on both sides

Surgical treatment of hydatid bone disease is rarely completely successful because radical excision is only possible at certain sites and secondary infection frequently occurs. Antihelmintic drugs have in the past been only palliative due to poor absorption and consequent low concentration in serum or cysts. We report five patients with Echinococcus granulosus infestation treated with a new chemotherapeutic agent albendazole; in two it was given postoperatively, in two pre-operatively and one child is being followed expectantly. We believe that a combination of chemotherapy and surgery may be efficacious in the treatment of hydatid bone disease

Our purpose was to assess the role of preoperative radio-therapy +/− neoadjuvant chemotherapy in nonmetastatic soft tissue sarcoma of extremities for limb-sparing surgery and identify the role of neoadjuvant therapies on local control and survival rate. Forty-seven patients with soft tissue sarcoma of extremities who were treated at Cerrahpasa Medical Faculty within a limb salvage protocol, including preoperative radiotherapy +/− chemotherapy were retrospectively analized. Median age was 45 years (17–72 years). The tumor size was between 5–33 cm. Seventeen patients were in stage I, 11 in stage II, 19 in stage III. The most common histology was synovial sarcoma. Nine patients were treated for locally recurrent tumour. The tumour and surrounding tissues with probable microscopic tumour involvement observed clinically and radiologically, were irradiated. Thirty-two patients, with a high grade tumour and/or tumours larger than 8 cm, also received neoadjuvant chemotherapy. Neoadjuvant chemotherapy regimen was consisted of doxorubicine and ifosphamide with mesna. Preoperative radiotherapy was applied, usually between the second and third cycles of chemotherapy. Definitive surgery was administered 2–6 weeks after radiotherapy or after the third cycle of chemotherapy. Chemotherapy was completed to 6 courses after the surgery. Postoperative external beam radio-therapy boost of 16 Gy was given who had close or positive surgical margins. Median follow-up time was 67 months (12–217 months). All of the patients had limb-sparing surgery. Patients had; 30 marginal excision, 13 wide local excision, 4 radical resection. Nine patients locally recurred. Limb-sparing surgery was performed for 8 patients. 25 patients had distant metastases. Metastasectomy were applied for 10 patients with lung metastasis. The 5-year local control, disease free survival and overall survival rates were 82.3%, 50.1% and 67.2%, respectively. Preoperative radiotherapy +/− chemotherapy seems to increase the chance of extremity-sparing surgery with good local control and the survival rates which were comparable with the literature

Tumour volume reduction (i.e. response), assessed following induction chemotherapy, has been identified as a prognostic factor for localized embryonal rhabdomyosarcoma (RME) in the CWS studies. In combination with other risk factors, it has been used to stratify secondary local and systemic treatment. It is however unclear whether the poor outcome of non-responders is due to insufficient local and/or systemic post-induction treatment. We analyzed post-induction therapy of RME-patients < 21 years with unresected localized tumours (IRS-III) and poor response (NR, i.e. < 33% tumour volume reduction) treated 1980–2005 in five consecutive CWS-trials. The NR were reviewed and subclassified (Objective Response (OR; i.e.< 33%–0%) vs. Stable Disease/Progression (PD; i.e. no reduction)). From 758 IRS-III RME-patients, 59 were NR (n=34 OR, n=25 PD). Induction for NR included dactinomycin, vincristine, alkylators ± anthracyclines in all patients. There were no significant differences in comparison of the control group and NR with regard to age, size, TN-classification, apart from site (p=0.04), and no differences regarding these parameters between OR and PD. Twenty-four NR received continued induction chemotherapy, n=32 other combinations, and n=3 no further chemotherapy following response assessment. Four patients were treated with additional high-dose chemotherapy. Fourty-two NR were irradiated with a median dose of 48Gy (control group: 45Gy). In 20 NR, the tumours were completely resected. As of 9/2008, with a median follow-up of 4.5 years (range: 0.9–12.1) for NR survivors, 34 NR are alive in CR. Reasons for the 25 deaths were: local/combined failure (n=21), systemic failure (n=1), and other reasons (n= 3). 5-yrs-OS was 71±4% for the control group, 78±15% for OR, but only 43±15% for PD (p< 0.01). Response is an important surrogate marker of outcome, but per se associated with a poor prognosis only in tumours without any volume regression to induction chemotherapy. Ineffective local control drives mortality in these patients

Prediction tools are instruments which are commonly used to estimate the prognosis in oncology and facilitate clinical decision-making in a more personalized manner. Their popularity is shown by the increasing numbers of prediction tools, which have been described in the medical literature. Many of these tools have been shown to be useful in the field of soft-tissue sarcoma of the extremities (eSTS). In this annotation, we aim to provide an overview of the available prediction tools for eSTS, provide an approach for clinicians to evaluate the performance and usefulness of the available tools for their own patients, and discuss their possible applications in the management of patients with an eSTS.

Cite this article: Bone Joint J 2022;104-B(9):1011–1016.

Synovial sarcoma is the most common NRSTS, that typically affects the extremities of adolescents. To improve the results of the treatment of synovial sarcoma for children and adolescents is the target of this study. 19 children and adolescents at the mean age of 10,84±3,28 years (9 males, 10 females) with synovial sarcoma were treated between 1999 and 2008 years at the Research Institution of Pediatric Oncology in the Russian Cancer Center. Histologically, 5 patients had the biphasic,12 had the monophasic, and 2 of them had the poorly differentiated pattern. The most often affected area was the area of the lower extremity – 10 cases, the area of the upper extremity was affected in 3 cases, and the trunk – 6 cases. According to the staging systems adopted, the size > 5cm (TB) was reported in 12 cases. Five patients (non-staging) had relapse of disease. Four patients had nodal involvement, and 4 had distant metastases (mostly at lungs). The general scheme of the treatment included: 8 courses of chemotherapy (used ifosfamide or cyclophosphamide, ethoposide, carboplatine); the harvesting and preservation of the stem cells after the stimulation of the haemophoesis by G-CSF, the stage of the local control of the tumor consisting of the surgical ablation of the primary lesion (in 1 case it was not available) and the radiotherapy of the initial tumor and metastasis left after the induction. The partial effect was registered by most of the patients – 80%. We observed 1 case of progression of the disease during inductive CT. The toxicity of intensive chemotherapy was reduced by support of sub transplantation doses of peripheral blood stem cells – 0,9-1,5±0,1·106 per kg. In our research we have analyzed the 5-year overall and disease free survival. Thus, 5-year disease-free survival was 66,1±11,3 %, overall 5-year survival −75,6±10,6%

Aims. To report the outcome observed in 34 dogs with non metastatic distal radial osteosarcoma (OSA) treated by a combination of adjuvant chemotherapy and limb-sparing surgery. Limb-sparing procedures were based on the use of a frozen bone cortical allograft (group A; 18 cases) and of a pasteurised tumoral autograft (group B; 16 cases), respectively. Methods. In group A, limb-sparing procedure was performed using a fresh-frozen cortical allograft from a bone bank. In the group B, the bone graft was realized from the excised tumoral segment after its pasteurisation at 65A1C for 40 minutes. Adjuvant chemotherapy (cisplatin or cisplatin and doxorubicin) was administered in all dogs. Results. In group A, mean and median survival times were 478-266 days, respectively (range 80–2611 days). Overall survival was 78% at 6 months, 35% at 12 months, 23% at 18 months and 19% at 24 months. Lung metastasis occurred in 10 cases (55%). Observed complications were local recurrence (28%), graft infection (39%) and implant failure (11%). In group B, mean and median survival times were 533-368 days, respectively (range 137–1944 days). Overall survival was 100% at 6 months, 57% at 12 months, 45% at 18 months and 20% at 24 months. Metastasis were observed in 7 dogs (44%). Complications were local recurrence (12%), graft infection (44%) and implant failure (19%). Limb function was good in 72% (group A), and 92% (group B) of the dogs, respectively. Conclusions. Limb-sparing techniques with bone grafts represent an alternative to amputation in the treatment of selected cases of distal radial osteosarcoma. Limb sparing techniques are not free of complication (infection, implant failure, recurrence) if compared to amputation. The latter represents the elective option in most cases of appendicular OSA and is usually free of complication. Comparing the two treatment groups, pasteurised bone autograft derived from the tumoral bone segment represents an effective alternative to cortical bone allograft coming from a bone bank, considering the difficulties encountered in finding donor dogs and national legal limitations on establishing a canine cortical bone graft bank. Alternative limb sparing procedures (metallic implant, Ilizarov) will be also discussed

We investigated the possible use of acrylic cement containing chemotherapeutic drugs in the treatment of malignant lesions in bone. The diffusion of methotrexate (MTX) from methylpolymethacrylate implants was studied in vitro: polymerisation of the cement did not destroy the drug; liberation began immediately and about 10% was released by 18 hours. Some release continued for as long as six months. In vivo experiments on rats with induced osteosarcoma showed that MTX in cement had both local and general effects which were dependent on the dosage. A series of 17 large dogs with spontaneous osteosarcoma were then treated by local resection and cement containing MTX. General chemotherapeutic effects were detectable from 2 hours to 5 days, survival was increased and local recurrence was reduced, but there were four cases of delayed wound healing. Preliminary studies in human patients confirm the possibility that this method of local chemotherapy could be a useful addition to the treatment of malignant tumours of bone

The role of radiotherapy and/or surgery in the local treatment of Ewing’s sarcoma has still to be determined. The outcome of Ewing’s sarcoma may differ according to its location and a selection bias towards surgery limits the ability to compare methods of local treatment. We have carried out a retrospective review of 91 consecutive patients treated for non-metastatic Ewing’s sarcoma of the femur. They received chemotherapy according to four different protocols. The primary lesion was treated by surgery alone (54 patients), surgery and radiotherapy (13) and radiotherapy alone (23). One was treated by chemotherapy alone. At a median follow-up of ten years, 48 patients (53%) remain free from disease, 39 (43%) have relapsed, two (2%) have died from chemotherapeutic toxicity and two (2%) have developed a radio-induced second tumour. The probability of survival without local recurrence was significantly (p = 0.01) higher in patients who were treated by surgery with or without radiotherapy (88%) than for patients who received radiotherapy alone (59%). The five- and ten-year overall survival rates were 64% and 57%, respectively. Patients who were treated by surgery, with or without radiotherapy, had a five- and ten-year overall survival of 64%. Patients who received only radiotherapy had a five- and ten-year survival of 57% and 44%, respectively. Our results indicate that in patients with Ewing’s sarcoma of the femur, better local control is achieved by surgical treatment (with or without radiotherapy) compared with the use of radiotherapy alone. Further studies are needed to verify the impact of this strategy on overall survival

Desmoid tumours are a rare fibroblastic proliferation of monoclonal origin, arising in deep soft-tissues. Histologically, they are characterized by locally aggressive behaviour and an inability to metastasize, and clinically by a heterogeneous and unpredictable course. Desmoid tumours can occur in any anatomical site, but commonly arise in the limbs. Despite their benign nature, they can be extremely disabling and sometimes life-threatening, causing severe pain and functional limitations. Their surgical management is complex and challenging, due to uncertainties surrounding the biological and clinical behaviour, rarity, and limited available literature. Resection has been the first-line approach for patients with a desmoid tumour but, during the last few decades, a shift towards a more conservative approach has occurred, with an initial ‘wait and see’ policy. Many medical and regional forms of treatment are also available for the management of this condition, and others have recently emerged with promising results. However, many areas of controversy remain, and further studies and global collaboration are needed to obtain prospective and randomized data, in order to develop an appropriate shared stepwise approach.

Cite this article: Bone Joint J 2023;105-B(7):729–734.

The aim of our study was to increase of survival of children with osteosarcoma by intensification of chemotherapy by inclusion of high dose methotrexate. 53 patients were treated in our centre between 2003 and 2007. Age are ranged from 5 to 16 years. 23 (43,4%) patients had metastetic disease. Polychemotherapy consist of alternating courses of CDDP, adriamicin, ifosfamide and etoposide and high-dose methotrexate (8–12 g/m. 2. ). In 25 (51%) cases have been received objective response (CR+PR). 38 (71,7%) patients alive at present time. 2 patients died from complications of treatment. 7 patients had PD, 1 — local relapse, 4 — metastatic relapse, 1 — combined relapse. 2-year OAS was 75,2±6,8%, 2-year RFS was 65±7,8%

After exclusions, 265 patients with tuberculosis of the thoracic and/or lumbar spine were followed for three years from the start of treatment. They were randomly allocated to four daily regimens of chemotherapy: 1) isoniazid plus rifampicin for 6 months (6HR, 65); 2) the same drugs as in 1) but for 9 months (9HR, 71); 3) isoniazid plus paraaminosalicylic acid (PAS) or ethambutol for 9 months (9P/EH, 62); or 4) the same drugs as in 3) but for 18 months (18P/EH, 67). All patients were ambulatory from the start of chemotherapy and no form of splintage or support or operation was used in any case. Over half (55%) the patients were children and one-third had sinuses or clinically evident abscesses. At three years a favourable status, defined as no sinus nor clinically evident abscess, no myelopathy with functional impairment, no surgery nor additional chemotherapy, full physical activity with disease quiescent clinically and radiographically, was achieved in 203 patients (77%) and in another 41 (15%) in all respects except radiographically. Only 20 patients (8%) had an unfavourable status the proportion being highest (19%) in the 9P/EH series. Thirteen of these were classified as unfavourable solely because they had needed additional chemotherapy; only seven still had an unfavourable status at three years. The clinical results at three years were thus excellent in all series except the 9P/EH, in which more patients had required additional chemotherapy. In the 88 patients with sinuses or abscesses on admission, the rate of resolution was similar in all the series; most lesions (83%) had resolved by 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)

A case of advanced retroperitoneal leiomyosarcoma is reported in a patient, who experienced a complete regression of her fatal illness. A 66-year old woman presented with a 1-year history of intermittent lower abdominal pain. An ultrasonogram (USG) and computed tomography (CT-scan) revealedmultiple soft tissue masses particularly in the lower retroperitoneal space and also 3 liver nodules. USG-guided biopsy was done and histologically confirmed poorly differentiated leiomyosarcoma. The patient underwent successful macroscopically complete en bloc resection of all tumor masses with the exception of 12 liver metastases which had been resected 6 weeks after the initial surgery. 11 months later USG showed disease progression with diffuse inoperable liver metastases, intraperitoneal and retroperitoneal tumor nodules. We introduced salvage chemotherapy (ChT), using intravenous infusion of ifosfamide 1.8 g/m2 on days 1–3 with mesna, and intravenous bolus injection of doxorubicin 60 mg/m2 on day 1. After 4 courses of treatment USG showed partial regression of metastatic disease. When the patient received the 8th, i.e. the last cycle of ChT, USG confirmed further disease regression with only 2 residual metastases in liver. 6 months later USG showed further regression of liver metastases. Another follow-up USG at 9 months and 12 months did not reveal evidence of residual metastases. Almost 2 years after the end of ChT the patient is asymptomatic, well and has no evidence of disease at 41 months after the diagnosis. The “spontaneous” further regression of metastatic leiomyosarcoma after the end of salvage ChT in our patient would be exceptional phenomena. Although we cannot exclude the remote possibility of “delayed” further response to ChT, generally poor response rate to ChT in leiomyosarcoma would make it very unlikely

Soft tissue sarcomas (STS) include a spectrum of his-tologically and clinically different tumors. Patients are typically relatively young and the course of disease is characterized by early metastasis as well as limited response to chemotherapy. However, a few subtypes such as small round cell tumors (SRCTs) and rhabdomyosarcoma (except from pleomorphic), are considered chemotherapy-sensitive. In addition, reflecting successful translational research of recent years, gastrointestinal stromal tumor (GIST) and dermatofibrosarcoma protuberans have become model diseases for targeted oncological therapy. With a very limited number of active compounds at hand, treatment choices in metastatic STS with inkonsistent genomic alterations were easy to overview until only a few years ago. However, with novel therapeutic strategies such as the antiangiogenic approach and a multitude of novel compounds available both outside and within clinical studies, it may have become more difficult to keep track of currently available treatment options and their clinical safety and efficacy. Anthracyclines with or without ifosfamide are still considered standard of care in most STS-subtypes, especially in high-grade tumors. There is no evidence-based recommendation as to second-line treatment options. However, a number of established compounds, including dacarbazine/temozolomide, gemcitabine, taxanes, trofosfamide, DNA topoisomerase I inhibitors, DNA minor groove binders, and bendamustine, have shown activity. Recently, trabectedin, a DNA minor groove binder initially isolated from a sea sponge, has proven effective and received European approval for use in treatment-refractory STS. In addition, novel compounds such as bevacizumab, multityrosine kinase inhibitors, mTOR inhibitors, imatinib mesylate, and the thrombospondin agonist ABT 510 represent attractive partners for the above-mentioned cytostatic agents or may even be effective single agents in the clinically advanced setting. Novel combinations are being evaluated in clinical studies. In order to be successful, we may have to combine not only different compounds but also different targets beyond the proliferation machinery of sarcoma cells such as tumor angiogenesis, the tumor stromal compartment or tumor cell oncogene products

1. Two hundred young Korean patients with a diagnosis of tuberculosis of the spine were allocated at random to in-patient rest in bed (IP) for six months followed by out-patient treatment, or to ambulatory out-patient treatment (OP) from the start. A second random allocation was made to chemotherapy with streptomycin for three months and PAS plus isoniazid for eighteen months (SPH), or to PAS plus isoniazid for eighteen months (PH). For various reasons twenty-nine patients had to be excluded from the study. The main analyses of this report therefore concern 171 patients, namely, forty IP/SPH, forty-six IP/PH, forty-two OP/SPH and forty three OP/PH. The comparisons made are a) of in-patient and out-patient treatment, and b) of the SPH and PH regimens. 2. The clinical and radiographic condition of the four groups on admission was similar. Many patients had extensive lesions. 3. Two in-patients died, probably from miliary tuberculosis, but neither had evidence of residual activity of the spinal lesion. 4. For the eighty-six in-patients the mean stay in hospital was 199 days and five were later readmitted. Of the eighty-five out-patients twenty-one (fourteen SPH, seven PH) were admitted to hospital in the first six months for complications of the spinal disease, for other medical conditions, or for domestic or geographical reasons; after the first six months eight more were admitted. 5. Three in-patients and five out-patients received chemotherapy beyond eighteen months for abscess or for paraparesis. 6. An abscess or sinus was either present initially or developed during treatment in 76 per cent of the in-patients and 72 per cent of the out-patients. Complete resolution occurred in most of the patients, some abscesses being aspirated. At three years 11 per cent of the in-patients and 5 per cent of the out-patients still had residual abscesses or sinuses. 7. On admission the mean total vertebral loss was 1·79 in the in-patients and 1·33 in the out-patients, and increased over the three-year period by 0·15 and 0·31 respectively. 8. The mean angulation of the spine at the start of treatment was 37 degrees for the in-patients and 27 degrees for the out-patients, the mean increase over the three-year period being 8 and 18 degrees respectively. 9. On admission six in-patients and four out-patients had incomplete motor paraplegia. This resolved completely within nine months in eight patients, as did the one cauda equina lesion. Only two patients (both out-patients) developed paraparesis during the course of the study; both recovered. 10. At eighteen months 66 per cent of the in-patients and 58 per cent of the out-patients had responded favourably. The corresponding percentages at thirty-six months were 84 and 88. 11. There was little difference in behaviour between the SPH and the PH series; at thirty-six months 82 per cent of eighty SPH and 90 per cent of eighty-eight PH patients had a favourable response. 12. A multiple regression analysis failed to identify any factor of clearly prognostic importance on admission

Osteosarcoma is a common primary bone sarcoma and distal femur its most frequent site. Between 2003 and 2008 at Rizzoli, 66 patients with osteosarcoma of the distal femur had neoadjuvant chemotherapy, resection and reconstruction with modular uncemented mega-prostheses. Series included 37 males and 29 females. Mean follow up was 2 years. To measure “subjective” outcome Karnofsky scale (KPS) was assessed for each patient pre and post-treatment. Also a functional evaluation according to the MSTS system was performed. To find out the current quality of life, a questionnaire on life at work, study and sport before and after treatment was sent to 64 alive patients. Before treatment 7 patients had a Karnofsky index (KI) of 60%, 31 of 50%, 25 of 40% and 3 of 30%. After treatment 19 patients had a Karnofsky index performance of 90%, 28 of 80%, 11 of 70%, 5 of 50% and 1 of 40%. Two patients died of disease. The most represented index of KPS after teatment was “Able to carry on normal activity; minor symptoms”. Poor results were related with amputation (2), knee stiffness (3), infection (2), aseptic loosening (1). After treatment 91% of patients had a KI over 70%, while 89% a KI lower than 50% pre-treatment. MSTS system showed excellent or good results in 85% and fair or poor in 15% of the patients. Average score at MSTS evaluation was 22 (73%). Questionnaires (some still pending) confirm previous analysis. KPS is simple and effective in evaluating quality of life in patients treated for distal femur osteosarcoma. In this study it confirmed the satisfactory MSTS assessed results. It is an easy method, useful and accessible for patients. The reported analysis shows that patients treated for osteosarcoma of the distal femur can have a good quality of life

In two centres in Korea 350 patients with a diagnosis of tuberculosis of the thoracic and/or lumbar spine were allocated at random: in Masan to in-patient rest in bed (IP) for six months followed by out-patient treatment or to ambulatory out-patient treatment (OP) from the start; in Pusan to out-patient treatment with a plaster-of-Paris jacket (J) for nine months or to ambulatory treatment without any support (No J). All patients recieved chemotherapy with PAS with isoniazid for eighteen months, either supplemented with streptomycin for the first three months (SPH) or without this supplement (PH), by random allocation. The main analysis of this report concerns 299 patients (eighty-three IP, eighty-three OP, sixty-three J, seventy No J; 143 SPH, 156 PH). Pre-treatment factors were similar in both centres except that the patients in Pusan had, on average, less extensive lesions although in a greater proportion the disease was radiographically active. One patient (J/SPH) died with active spinal disease and three (all No J/SPH) with paraplegia. A fifth patient (IP/PH) who died from cardio respiratory failure also had pulmonary tuberculosis. Twenty-three patients required operation and/or additional chemotherapy for the spinal lesion. A sinus or clinically evident abscess was either present initially or developed during treatment in 41 per cent of patients. Residual lesions persisted in ten patients (four IP, two OP, one J, three No J; six SPH, four PH) at five years. Thirty-two patients had paraparesis on admission or developing later. Complete resolution occurred in twenty on the allocated regimen and in eight after operation or additional chemotherapy or both. Of the remaining four atients, all of whom had operation and additional chemotherapy, three died and one still had paraparesis at five years. Of 295 patients assessed at five years 89 per cent had a favourable status. The proportions of the patients responding favourably were similar in the IP (91 per cent) and OP (89 per cent) series, in the J (90 per cent) and No J (84 per cent) series and in the SPH (86 per cent) and PH (92 per cent) series

Streptomycin and the newer antibiotics have already belied the pessimistic agnosticism of 1947. In certain instances, notably in disease of the knee and hip and in some cases with draining sinuses, it appears that they are sufficient to produce a quiescence which may be a cure. For the rest it remains to map out in detail what has in part been explored. In particular it is essential to confirm how far antibiotics enable surgeons to treat tuberculosis upon the basic principles applicable to other infections of bone without fear of secondary infection: where there is diseased bone, to remove it: where there is pus, to relieve the tension and evacuate it. The surgeon fears not so much the infection itself as the inability of the tuberculous soil ordinarily to deal with secondary infection. With the control of the diseased soil the risk should be no greater than that of any other surgery of bone.

The early case and the advanced case; age and site of disease; these and other variables must subdivide basic method. What is the best application of the new "combined operation" to a child of three with thoracic Pott's disease and a globular abscess? What is the wisest plan for a man of forty with old disease in his lumbar vertebrae and discharging sinuses? We begin to see what we could do. At the present the question still remains: What should we do?

We studied 51 patients with osteo-articular tuberculosis who were divided into two groups. Group I comprised 31 newly-diagnosed patients who were given first-line antituberculous treatment consisting of isoniazid, rifampicin, ethambutol and pyrazinamide. Group II (non-responders) consisted of 20 patients with a history of clinical non-responsiveness to supervised uninterrupted antituberculous treatment for a minimum of three months or a recurrence of a previous lesion which on clinical observation had healed. No patient in either group was HIV-positive. Group II were treated with an immunomodulation regime of intradermal BCG, oral levamisole and intramuscular diphtheria and tetanus vaccines as an adjunct for eight weeks in addition to antituberculous treatment. We gave antituberculous treatment for a total of 12 to 18 months in both groups and they were followed up for a mean of 30.2 months (24 to 49). A series of 20 healthy blood donors served as a control group.

Twenty-nine (93.6%) of the 31 patients in group I and 14 of the 20 (70%) in group II had a clinicoradiological healing response to treatment by five months.

The CD4 cell count in both groups was depressed at the time of enrolment, with a greater degree of depression in the group-II patients (686 cells/mm³ (sd 261) and 545 cells/mm³ (sd 137), respectively; p < 0.05). After treatment for three months both groups showed significant elevation of the CD4 cell count, reaching a level comparable with the control group. However, the mean CD4 cell count of group II (945 cells/mm³ (sd 343)) still remained lower than that of group I (1071 cells/mm³ (sd 290)), but the difference was not significant. Our study has shown encouraging results after immunomodulation and antituberculous treatment in non-responsive patients. The pattern of change in the CD4 cell count in response to treatment may be a reliable clinical indicator.

Two hundred and eighty-three patients with tuberculosis of the thoracic and/or lumbar spine have been followed for 10 years from the start of treatment. All patients received PAS plus isoniazid daily for 18 months, either with streptomycin for the first three months (SPH) or no streptomycin (PH), by random allocation. There was also a second random allocation for all patients: in Masan to inpatient rest in bed (IP) for six months followed by outpatient treatment or to ambulatory outpatient treatment from the start (OP), and in Pusan to outpatient treatment with a plaster-of-Paris jacket (J) for nine months or to ambulatory treatment without any support (No J). A favourable status was achieved on their allocated regimen by 88% of patients at 10 years. Some of the remaining patients also attained a favourable status after additional chemotherapy and/or operation, and if these are included the proportion achieving such a status increases to 96%. There were five patients whose deaths were attributed to their spinal disease. A sinus or clinically evident abscess was present on at least one occasion in the 10-year period in 42% of the patients. Residual sinuses persisted at 10 years in two patients, at death at seven years in a third and at default in the seventh year in a fourth. Thirty-five patients had paraparesis at some time during the 10-year period, including two who died with paraplegia before five years. Complete resolution occurred in 26 patients (in six after additional chemotherapy and/or surgery). At 10 years two patients had severe paraplegia and one a moderate paraparesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Streptomycin and iso-nicotinic acid hydrazide are two powerful drugs lethal to tubercle bacilli, when access to the infected tissues is free. For early disease, before ischaemia and necrosis become established, they are curative: afterwards they are not. In this paper the use of surgery to augment their action has been discussed. The development of such methods may well revolutionise the treatment of skeletal tuberculosis. Therein lies a danger because attempts to cure the patient by exterminating the tubercle bacilli in his lesion may lead to a precarious recovery: treatment directed against the bacilli may greatly facilitate a real cure if constitutional treatment is also applied to make the patient immune. Revolutionary though the change may become, it will not be so great as the revolution which occurred thirty years ago when open-air hospitals were first provided for patients with skeletal tuberculosis. The first patient ever seen on a surgical ward by the author, when he was a student, suffices still as an example. A child with tuberculosis of the cervical spine was admitted from out-patients with multiple discharging sinuses from the neck which was supported in a sodden plaster jacket. "Whoever," said the house surgeon dramatically, "removes that plaster, will kill that child." Most unfortunately his words were true. Many other such patients could, in those days, be seen in the wards of city hospitals. It was largely due to the work of Sir Robert Jones, friend of children, that the value of constitutional treatment became recognised. With the combination of the old knowledge and the development of the new, a new chapter in the treatment of skeletal tuberculosis has opened and rapid restoration of function and permanent cure can now take the place of long and sometimes crippling illness.

One hundred and fifty patients in Hong Kong with a diagnosis of tuberculosis of the thoracic, thoracolumbar or lumbar spine were allocated a random to the "Hong Kong" radical resection of the lesion and the insertion of autologous bone grafts (Rad. series) or to debridement of the spinal focus without bone grafting (Deb. series). All patients received daily chemotherapy with para-aminosalicylic acid (PAS) plus isoniazid for 18 months, with streptomycin for the first three months. After exclusions, the main analyses of this report concern 119 patients (58 Rad., 61 Deb.) followed up for 10 years. During the first five years the allocated regimen was modified because of the spinal lesion in 14 patients, but there were no further modifications between five and 10 years. No patient developed a sinus or clinically evident abscess or a neurological abnormality between five and 10 years. Bony fusion occurred earlier and in a higher proportion of patients in the Rad, series but at five and 10 years there was vary little difference between the series. Over the period of 10 years there was a mean increase in vertebral loss of 0.05 of a vertebral body in the Rad. series and 0.23 in the Deb. series. In both series most of this loss occurred in the first 18 months, with very little subsequent change in the next eight and a half years. Over the 10 years there was a mean reduction in the angle of kyphosis in the Rad. series of 1.4 degrees for patients with thoracic and thoracolumbar lesions and 0.5 degrees for those with lumbar lesions. By contrast, in the Deb. series there were mean increases in the angle of 9.8 degrees and 7.6 degrees respectively. In both series most of the changes had occurred early, and persisted subsequently. At 10 years 57 of 58 Rad. and all 61 Deb. patients had a favourable status, 50 (86 per cent) and 54 (89 per cent) respectively on the allocated regimen without modification

Background: Infection remains the single most devastating complication of joint arthroplasty. In cases of established prosthetic infection, where implant retention is not feasible, there is limited consensus on an optimum management protocol.

Aim: To assess the outcome of revision for infected hip prostheses using a novel treatment regimen.

Materials and Methods: Retrospective study of a consecutive case series of 40 patients with late chronic hip joint prosthetic infection treated by a single surgeon over a 4 year period. The mean interval between index arthroplasty and revision for infection was 40 months, with patients having prior symptoms of infection for a mean of 22 months.

The treatment protocol consisted of a two stage exchange with removal of infected components via a posterior approach incorporating an extended trochanteric osteotomy, insertion of an interim antibiotic eluting cement spacer and re-implantation of an extensively coated uncemented prosthesis on the femoral side. Systemic antibiotic treatment following each stage consisted of an abridged course of 5 days post operative intravenous administration followed by complete cessation of anti-microbial therapy. The mean interval between implant removal and re-implantation was 111 days.

Results: At a mean follow up of 29.6 months (minimum 12 months), there were 2 cases of recurrent prosthetic infection. Dislocation following the second stage occurred in 7 patients. There was one mortality and one case of post operative sciatic nerve palsy. The Harris hip score increased from a pre-operative mean of 43.8 to a post operative mean of 83.9. At follow up, no patient had required revision for aseptic loosening or mechanical instability on the femoral side

Conclusion: The combination of effective staged surgical joint debridement, a shortened post operative course of systemic antibiotic treatment and an adequate latent period before re-implantation has led to encouraging early results in this series of revised chronic hip joint prosthetic infections.

Aims. The aim of this study was to determine the rate of indocyanine green (ICG) staining of bone and soft-tissue tumours, as well as the stability and accuracy of ICG fluorescence imaging in detecting tumour residuals during surgery for bone and soft-tissue tumours. Methods. ICG fluorescence imaging was performed during surgery in 34 patients with bone and soft-tissue tumours. ICG was administered intravenously at a dose of 2 mg/kg over a period of 60 minutes on the day prior to surgery. The tumour stain rate and signal-to-background ratio of each tumour were post hoc analyzed. After tumour resection, the tumour bed was scanned to locate sites with fluorescence residuals, which were subsequently inspected and biopsied. Results. The overall tumour stain rate was 88% (30/34 patients), and specific stain rates included 90% for osteosarcomas and 92% for giant cell tumours. For malignant tumours, the overall stain rate was 94%, while it was 82% for benign tumours. The ICG tumour stain was not influenced by different pathologies, such as malignant versus benign pathology, the reception (or lack thereof) of neoadjuvant chemotherapies, the length of time between drug administration and surgery, the number of doses of denosumab for patients with giant cell tumours, or the tumour response to neoadjuvant chemotherapy. The overall accuracy rate of successfully predicting tumour residuals using fluorescence was 49% (23/47 pieces of tissue). The accuracy rate after en bloc resection was significantly lower than that after piecemeal resection (16% vs 71%; p < 0.001). Conclusion. A high percentage of bone and soft-tissue tumours can be stained by ICG and the tumour staining with ICG was stable. This approach can be used in both benign and malignant tumours, regardless of whether neoadjuvant chemotherapy is adopted. The technique is also useful to detect tumour residuals in the wound, especially in patients undergoing piecemeal resection. Cite this article: Bone Joint J 2023;105-B(5):551–558

Aims. The aim of this study was to report the long-term prognosis of patients with multiple Langerhans cell histiocytosis (LCH) involving the spine, and to analyze the risk factors for progression-free survival (PFS). Methods. We included 28 patients with multiple LCH involving the spine treated between January 2009 and August 2021. Kaplan-Meier methods were applied to estimate overall survival (OS) and PFS. Univariate Cox regression analysis was used to identify variables associated with PFS. Results. Patients with multiple LCH involving the spine accounted for 15.4% (28/182 cases) of all cases of spinal LCH: their lesions primarily involved the thoracic and lumbar spines. The most common symptom was pain, followed by neurological dysfunction. All patients presented with osteolytic bone destruction, and 23 cases were accompanied by a paravertebral soft-tissue mass. The incidence of vertebra plana was low, whereas the oversleeve-like sign was a more common finding. The alkaline phosphatase was significantly higher in patients with single-system multifocal bone LCH than in patients with multisystem LCH. At final follow-up, one patient had been lost to follow-up, two patients had died, three patients had local recurrence, six patients had distant involvement, and 17 patients were alive with disease. The median PFS and OS were 50.5 months (interquartile range (IQR) 23.5 to 63.1) and 60.5 months (IQR 38.0 to 73.3), respectively. Stage (hazard ratio (HR) 4.324; p < 0.001) and chemotherapy (HR 0.203; p < 0.001) were prognostic factors for PFS. Conclusion. Pain is primarily due to segmental instability of the spine from its destruction by LCH. Chemotherapy can significantly improve PFS, and radiotherapy has achieved good results in local control. The LCH lesions in some patients will continue to progress. It may initially appear as an isolated or single-system LCH, but will gradually involve multiple sites or systems. Therefore, long-term follow-up and timely intervention are important for patients with spinal LCH. Cite this article: Bone Joint J 2023;105-B(6):679–687

Aims. For paediatric and adolescent patients with growth potential, preservation of the physiological joint by transepiphyseal resection (TER) of the femur confers definite advantages over arthroplasty procedures. We hypothesized that the extent of the tumour and changes in its extent after neoadjuvant chemotherapy are essential factors in the selection of this procedure, and can be assessed with MRI. The oncological and functional outcomes of the procedure were reviewed to confirm its safety and efficacy. Methods. We retrospectively reviewed 16 patients (seven male and nine female, mean age 12.2 years (7 to 16)) with osteosarcoma of the knee who had been treated by TER. We evaluated the MRI scans before and after neoadjuvant chemotherapy for all patients to assess the extent of the disease and the response to treatment. Results. The mean follow-up period was 64.3 months (25 to 148) after surgery and no patients were lost to follow-up. On MRI evaluation, 13 tumours were near but not in contact with the physes and three tumours were partially in contact with the physes before neoadjuvant chemotherapy. Bone oedema in the epiphysis was observed in eight patients. After neoadjuvant chemotherapy, bone oedema in the epiphysis disappeared in all patients. In total, 11 tumours were not in contact and five tumours were in partial contact with the physes. The postoperative pathological margin was negative in all patients. At the last follow-up, 12 patients were continuously disease-free and three had no evidence of disease. One patient died due to the disease. Functionally, the patients with retained allograft or recycled autograft had a mean knee range of flexion of 126° (90° to 150°). The mean Musculoskeletal Tumor Society functional score was 27.6 (23 to 30). Conclusion. TER is an effective limb-salvage technique for treating malignant metaphyseal bone tumours in paediatric and young osteosarcoma patients with open physes when a good response to chemotherapy and no progression of the tumour to the epiphysis have been confirmed by MRI. Cite this article: Bone Joint J 2020;102-B(6):772–778

Traditional staging systems for high grade osteosarcoma (Enneking, MSTS) are based largely on gross surgical margins and were developed before the widespread use of neoadjuvant chemotherapy. It is now well known that both microscopic margins and chemotherapy are predictors of local recurrence. However, neither of these variables are used in the traditional surgical staging and the precise safe margin distance is debated. Recently, a novel staging system utilizing a 2mm margin cutoff and incorporating precent necrosis was proposed and demonstrated improved prognostic value for local recurrence free survival (LRFS) when compared to the MSTS staging system. This staging system has not been validated beyond the original patient cohort. We propose to analyze this staging system in a cohort of patients with high-grade osteosarcoma, as well as evaluate the ability of additional variables to predict the risk of local recurrence and overall survival. A retrospective review of a prospectively collected database of all sarcoma patients between 1985 and 2020 at a tertiary sarcoma care center was performed. All patients with high-grade osteosarcoma receiving neo-adjuvant chemotherapy and with no evidence of metastatic disease on presentation were isolated and analyzed. A minimum of two year follow up was used for surviving patients. A total of 225 patients were identified meeting these criteria. Univariate analysis was performed to evaluate variable that were associated with LRFS. Multivariate analysis is used to further analyze factors associated with LRFS on univariate analysis. There were 20 patients (8.9%) who had locally recurrent disease. Five-year LRFS was significantly different for patients with surgical margins 2mm or less (77.6% v. 93.3%; p=0.006) and those with a central tumor location (67.9 v. 94.4; <0.001). A four-tiered staging system using 2mm surgical margins and a percent necrosis of 90% of greater was also a significant predictor of 5-year LRFS (p=0.019) in this cohort. Notably, percent necrosis in isolation was not a predictor of LRFS in this cohort (p=0.875). Tumor size, gender, and type of surgery (amputation v. limb salvage) were also analyzed and not associated with LRFS. The MSTS surgical margin staging system did not significantly stratify groups (0.066). A 2mm surgical margin cutoff was predictive of 5-year LRFS in this cohort of patients with localized high-grade osteosarcoma and a combination of a 2mm margin and percent necrosis outperformed the prognostic value of the traditional MSTS staging system. Utilization of this system may improve the ability of surgeons to stage thier patients. Additional variables may increase the value of this system and further validation is required

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?

Chondrosarcoma is the second most common surgically treated primary bone sarcoma. Despite a large number of scientific papers in the literature, there is still significant controversy about diagnostics, treatment of the primary tumour, subtypes, and complications. Therefore, consensus on its day-to-day treatment decisions is needed. In January 2024, the Birmingham Orthopaedic Oncology Meeting (BOOM) attempted to gain global consensus from 300 delegates from over 50 countries. The meeting focused on these critical areas and aimed to generate consensus statements based on evidence amalgamation and expert opinion from diverse geographical regions. In parallel, periprosthetic joint infection (PJI) in oncological reconstructions poses unique challenges due to factors such as adjuvant treatments, large exposures, and the complexity of surgery. The meeting debated two-stage revisions, antibiotic prophylaxis, managing acute PJI in patients undergoing chemotherapy, and defining the best strategies for wound management and allograft reconstruction. The objectives of the meeting extended beyond resolving immediate controversies. It sought to foster global collaboration among specialists attending the meeting, and to encourage future research projects to address unsolved dilemmas. By highlighting areas of disagreement and promoting collaborative research endeavours, this initiative aims to enhance treatment standards and potentially improve outcomes for patients globally. This paper sets out some of the controversies and questions that were debated in the meeting. Cite this article: Bone Joint J 2024;106-B(5):425–429

The December 2022 Oncology Roundup. 360. looks at: Is high-dose radiation therapy associated with early revision with a cemented endoprosthesis?; Neoadjuvant chemotherapy and endoprosthetic reconstruction for lower extremity sarcomas: does timing impact complication rates?; Late amputation after treatment for lower extremity sarcoma; Osteosarcoma prediagnosed as another tumour: a report from the Cooperative Osteosarcoma Study Group; The influence of site on the incidence and diagnosis of solitary central cartilage tumours of the femur: a 21st century perspective

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

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

Aims. The purpose of this study was to clarify the clinical behaviour, prognosis, and optimum treatment of dedifferentiated low-grade osteosarcoma (DLOS) diagnosed based on molecular pathology. Patients and Methods. We retrospectively reviewed 13 DLOS patients (six men, seven women; median age 32 years (interquartile range (IQR) 27 to 38)) diagnosed using the following criteria: the histological coexistence of low-grade and high-grade osteosarcoma components in the lesion, and positive immunohistochemistry of mouse double minute 2 homolog (MDM2) and cyclin-dependent kinase 4 (CDK4) associated with MDM2 amplification. These patients were then compared with 51 age-matched consecutive conventional osteosarcoma (COS) patients (33 men, 18 women; median age 25 years (IQR 20 to 38)) regarding their clinicopathological features. Results. The five-year overall survival (OAS) rates in the DLOS and COS patients were 85.7% and 77.1% (p = 0.728), respectively, and the five-year progression-free survival (PFS) rates were 57.7% and 44.9% (p = 0.368), respectively. A total of 12 DLOS patients received chemotherapy largely according to regimens for COS. Among the nine cases with a histological evaluation after chemotherapy, eight showed a poor response, and seven of these had a necrosis rate of < 50%. One DLOS patient developed local recurrence and five developed distant metastases. Conclusion. Based on our study of 13 DLOS cases that were strictly defined by histological and molecular means, DLOS showed a poorer response to a standard chemotherapy regimen than COS, while the clinical outcomes were not markedly different. Cite this article: Bone Joint J 2019;101-B:745–752

Aims. The aim of this study was to analyse a group of patients with non-metastatic Ewing’s sarcoma at presentation and identify prognostic factors affecting the development of local recurrence, in order to assess the role of radiotherapy. Patients and Methods. A retrospective review of all patients with a Ewing’s sarcoma treated between 1980 and 2012 was carried out. Only those treated with chemotherapy followed by surgery and/or radiotherapy were included. Patients were grouped according to site (central or limb) for further analysis of the prognostic factors. Results. A total of 388 patients were included in the study. Of these, 60 (15%) developed local recurrence at a mean median of 27 months (. sd. 24, range 7 to 150) and the five-year local recurrence-free survival (5yrLRFS) was 83%. For central tumours, the size of the tumour and histological response to chemotherapy were found to be significant factors for local recurrence. For limb tumours, local recurrence was affected by intralesional and marginal resections, but not by the histological response to chemotherapy. Radiotherapy in those with a marginal resection reduced the risk of local recurrence (5yrLRFS: 96% versus 81%, p = 0.044). Conclusion. Local recurrence significantly affects the overall survival in patients with a Ewing’s sarcoma. For those with a tumour in a limb, radiotherapy reduced the risk of local recurrence, especially in those with a marginal margin of excision, but the effect in central tumours was less clear. Radiotherapy for those who have had a wide margin of resection does not reduce the risk of local recurrence, regardless of the histological response to chemotherapy. Cite this article: Bone Joint J 2018;100-B: 247–55

Aims. The purpose of this study was to review a large cohort of patients and further assess the correlation between the histological response to chemotherapy in patients with Ewing’s sarcoma with the overall (OS) and event-free survival (EFS). Patients and Methods. All patients treated for Ewing’s sarcoma between 1980 and 2012 were reviewed. Of these, 293 patients without metastases at the time of diagnosis and treated with chemotherapy and surgery were included. Patients were grouped according to the percentage of necrosis after chemotherapy: Group I: 0% to 50%, Group II: 51% to 99% and Group III: 100%. Results. The mean age at diagnosis was 16 years (1 to 62) and the mean follow-up was 9.1 years (six months to 32.6 years). The OS and EFS for the series were 75% and 65% at five years. There were significant differences in survival between the groups of necrosis: 0% to 50% (OS: 49% and EFS: 45% at five years, respectively) compared with 51% to 99% (OS: 72% and EFS: 59% at five years, respectively) and 100% (OS: 94% and EFS: 81% at five years, respectively) (p <  0.001). There were no significant differences in survival between patients treated between 1980 and 1989 compared with those treated between 1990 and 1999, and those treated between 2000 and 2012 (p = 0.55). Conclusion. Only patients with 100% necrosis after chemotherapy should be classified as having a good response to chemotherapy because they have significantly better rates of survival compared with those with any viable tumour in the surgical specimen. Cite this article: Bone Joint J 2016;98-B:1138–44

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

Introduction. Patients with metastatic spinal cord compression (MSCC) or unstable spinal lesions warrant early surgical consultation. In multiple myeloma, chemotherapy and radiotherapy have the potential to decompress the spinal canal effectively in the presence of epidural lesions. Mechanical stability conferred by bracing may potentiate intraosseous and extraosseous bone formation, thus increasing spinal stability. This study aims to review the role of non-operative management in myeloma patients with a high degree of spinal instability, in a specialist tertiary centre. Methods. Retrospective analysis of a prospectively collected database of 83 patients with unstable myelomatous lesions of the spine, defined by a Spinal Instability Neoplastic Score (SINS) of 13–18. Data collected include patient demographics, systemic treatment, neurological status, radiological presence of cord compression, most unstable vertebral level and presence of intraosseous and extraosseous bone formation. Post-treatment scores were calculated based on follow-up imaging which was carried out at 2 weeks for cord compression and 12 weeks for spinal instability. A paired t-test was used to identify any significant difference between pre- and post-treatment SINS and linear regression was used to assess the association between variables and the change in SINS. Results. A significant reduction in SINS was observed from a pre-treatment average score of 14 to a score of 9, following treatment for myeloma (p<0.001). A higher initial score and a younger age were associated with a larger overall reduction in SINS (p<0.001 and p=0.02 respectively). No single variable (bisphosphates, chemotherapy, radiotherapy and steroids) had a significant association with SINS reduction. 25 (30%) patients had spinal cord compression, all of which showed radiological resolution of cord compression at 2 weeks. No patients developed neurological deterioration during treatment and all patients had an improvement in their pain scores. 64 (77%) patients had evidence of intraosseous and/or extraosseous bone formation on their follow-up scan. Conclusion. Non-operative management in the form of bracing and systemic therapy is a safe and effective treatment for spinal instability and spinal cord compression in myeloma. Treatment of unstable myelomatous lesions of the spine with or without cord compression should not follow traditional guidelines for MSCC. The decision to adopt a non-operative approach in this cohort of patients should ideally be made in a tertiary centre with expertise in multiple myeloma and in a multidisciplinary setting

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. Extracorporeal radiation therapy (ECRT) has been reported as an oncologically safe and effective reconstruction technique for limb salvage in diaphyseal sarcomas with promising functional results. Factors affecting the ECRT graft-host bone incorporation have not been fully investigated. Methods. In our series of 51 patients of primary bone tumors treated with ECRT, we improvised this technique by using a modified V-shaped osteotomy, additional plates and intra-medullary fibula across the diaphyseal osteotomy in an attempt to increase the stability of fixation, augment graft strength and enhance union at the osteotomy sites. We analyzed our patients for various factors that affected union time and union rate at the osteotomy sites. Results. On univariate analysis, age <20 years, metaphyseal osteotomy site, V-shaped diaphyseal osteotomy, extramedullary plate fixation and use of additional plate at diaphyseal ostetomy had a significantly faster time to union while gender, tumor type, resection length, chemotherapy and use of intra-medullary fibula did not influence union time. In multivariate analysis, metaphyseal ostoeotomy, V-shaped diaphyseal osteotomy and use of additional plate at diaphyseal ostetomy were the independent factors with favourable time to union. Although the rate of union was higher with V-shaped diaphyseal osteotomy and use of additional plate and intra-medullary fibula at diaphyseal ostetomy, this difference could not be established statistically. None of the analyzed factors apparently affected the union rate in univariate analysis. Conclusion. Judicious choice of osteosynthesis and augmentation of ECRT graft can enhance incorporation with reduced complications and good functional outcome

Aim. Deep infection following endoprosthetic replacement (EPR) of long bones is a devastating complication occurring in 15% of musculoskeletal tumour patients. The recently published PARITY Trial demonstrated that extending antibiotic prophylaxis from 24 hours to 5 days does not reduce infection rates. However, questions remain about the optimal antibiotic choice and dose. Method. A 23-question multiple-choice questionnaire was designed and piloted through an iterative feedback process until the final version was agreed by all authors. Open and closed-ended questions were used to gather information on practice and Likert-type scale responses were used to grade responses to ascertain surgeon perceptions and preferences. The online survey was sent to all surgeon delegates of the 34th Annual Meeting of the European Musculo-Skeletal Oncology Society in London in October 2022. Results. Amongst 61 respondents, 43 were based in Europe and 18 outside of Europe. The majority (48/61) had been in clinical practice over 11 years. Antibiotic choice. 1st or 2nd generation cephalosporins were the first line choice practiced among 49 (80.3%) of respondents. Of these, 39 responded had a 2nd line protocol for beta-lactam allergy which was most commonly clindamycin (18), vancomycin (11) or a combination of a glycopeptide or clindamycin plus gentamicin (4). Respondents changed their first line regimen for radiotherapy in 6/61, chemotherapy in 8/61 and tumour site in 20/61. Re-dosing. Intraoperative re-dosing intervals of 1st and 2nd generation cephalosporins ranged from 2 to 8 hourly. Re-dosing for blood loss ranged from never to when 2 litres was lost. Of the 47 respondents, 24 said intraoperative re-dosing is always reliably administered. Duration. Six (10%) of 61 respondent routinely cover the intraoperative period only, whereas 30 (49%) give 24 hours, 16 (give 48 hours or longer and 8 continue until surgical drains are removed. 31 of 61 change duration depending on clinical situation. The most common reasons for changing were patient risk factors, soft tissue status and previous radiotherapy. 57/61 surgeons were aware of the PARITY Trial. When these respondents were asked whether they had changed practice based on PARITY, 12 said yes, 24 said no and 21 said they always give 24 hours anyway. Conclusions. Amongst an international cohort of orthopaedic oncology surgeons there was a wide variation in practice. Further research should focus on the optimum choice and re-dosing strategy, which have not been defined

Aims. The aim of this study was to assess orthopaedic oncologic patient morbidity resulting from COVID-19 related institutional delays and surgical shutdowns during the first wave of the pandemic in New York, USA. Methods. A single-centre retrospective observational study was conducted of all orthopaedic oncologic patients undergoing surgical evaluation from March to June 2020. Patients were prioritized as level 0-IV, 0 being elective and IV being emergent. Only priority levels 0 to III were included. Delay duration was measured in days and resulting morbidities were categorized into seven groups: prolonged pain/disability; unplanned preoperative radiation and/or chemotherapy; local tumour progression; increased systemic disease; missed opportunity for surgery due to progression of disease/lost to follow up; delay in diagnosis; and no morbidity. Results. Overall, 25 patients met inclusion criteria. There were eight benign tumours, seven metastatic, seven primary sarcomas, one multiple myeloma, and two patients without a biopsy proven diagnosis. There was no priority level 0, two priority level I, six priority level II, and 17 priority level III cases. The mean duration of delay for priority level I was 114 days (84 to 143), priority level II was 88 days (63 to 133), and priority level III was 77 days (35 to 269). Prolonged pain/disability and delay in diagnosis, affecting 52% and 40%,respectively, represented the two most frequent morbidities. Local tumour progression and increased systemic disease affected 32% and 24% respectively. No patients tested positive for COVID-19. Conclusion. COVID-19 related delays in surgical management led to major morbidity in this studied orthopaedic oncologic patient population. By understanding these morbidities through clearer hindsight, a thoughtful approach can be developed to balance the risk of COVID-19 exposure versus delay in treatment, ensuring optimal care for orthopedic oncologic patients as the pandemic continues with intermittent calls for halting surgery. Cite this article: Bone Jt Open 2021;2(4):236–242

Aims. Tocilizumab, an interleukin-6 (IL-6) receptor (IL-6R) targeting antibody, enhances the anti-tumour effect of conventional chemotherapy in preclinical models of cancer. We investigated the anti-tumour effect of tocilizumab in osteosarcoma (OS) cell lines. Methods. We used the 143B, HOS, and Saos-2 human OS cell lines. We first analyzed the IL-6 gene expression and IL-6Rα protein expression in OS cells using reverse transcription real time quantitative-polymerase chain reaction (RT-qPCR) analysis and western blotting, respectively. We also assessed the effect of tocilizumab on OS cells using proliferation and invasion assay. Results. The OS cell lines 143B, HOS, and Saos-2 expressed IL-6R. Recombinant human IL-6 treatment increased proliferation of 143B and HOS cells. Tocilizumab treatment decreased proliferation and invasion of 143B, HOS, and Saos-2. Conclusion. In conclusion, we confirmed the production of IL-6 and the expression of IL-6R in OS cells and demonstrated that tocilizumab inhibits proliferation and invasion in OS cells. Cite this article: Bone Joint Res 2020;9(11):821–826

A poor response to chemotherapy (≤ 90% necrosis) for osteosarcomas leads to poorer survival and an increased risk of local recurrence, particularly if there is a close margin of excision. We evaluated whether amputation confers any survival benefit over limb salvage surgery (LSS) with narrow margins in patients who respond poorly to chemotherapy. We only analysed patients with an osteosarcoma of the limb, a poor response to chemotherapy and close margins on LSS (marginal/intralesional) or primary amputation: 360 patients (36 LSS (intralesional margins), 197 LSS (marginal margins) and 127 amputations) were included. Local recurrence developed in 13 (36%) following LSS with intralesional margins, and 39 (20%) following LSS with marginal margins. There was no local recurrence in patients who underwent amputation. The five-year survival for all patients was 41% (95% confidence interval (CI) 35 to 46), but for those treated by LSS with marginal margins was 46.2% (95% CI 38 to 53), 36.3% (95% CI 27 to 45) for those treated by amputation, and 28% (95 CI 14 to 44) for those treated by LSS with intralesional margins. Patients who had LSS and then developed local recurrence as a first event had the same survival as those who had primary amputation without local recurrence. Prophylactic adjuvant radiotherapy was used in 40 patients but had no discernible effect in preventing local recurrence. Although amputation offered better local control, it conferred no clear survival benefit over LSS with marginal margins in these patients with a poor overall prognosis. Cite this article: Bone Joint J 2015;97-B:115–20

Aims. Malignancy and surgery are risk factors for venous thromboembolism (VTE). We undertook a systematic review of the literature concerning the prophylactic management of VTE in orthopaedic oncology patients. Methods. MEDLINE (PubMed), EMBASE (Ovid), Cochrane, and CINAHL databases were searched focusing on VTE, deep vein thrombosis (DVT), pulmonary embolism (PE), bleeding, or wound complication rates. Results. In all, 17 studies published from 1998 to 2018 met the inclusion criteria for the systematic review. The mean incidence of all VTE events in orthopaedic oncology patients was 10.7% (1.1% to 27.7%). The rate of PE was 2.4% (0.1% to 10.6%) while the rate of lethal PE was 0.6% (0.0% to 4.3%). The overall rate of DVT was 8.8% (1.1% to 22.3%) and the rate of symptomatic DVT was 2.9% (0.0% to 6.2%). From the studies that screened all patients prior to hospital discharge, the rate of asymptomatic DVT was 10.9% (2.0% to 20.2%). The most common risk factors identified for VTE were endoprosthetic replacements, hip and pelvic resections, presence of metastases, surgical procedures taking longer than three hours, and patients having chemotherapy. Mean incidence of VTE with and without chemical prophylaxis was 7.9% (1.1% to 21.8%) and 8.7% (2.0% to 23.4%; p = 0.11), respectively. No difference in the incidence of bleeding or wound complications between prophylaxis groups was reported. Conclusion. Current evidence is limited to guide clinicians. It is our consensus opinion, based upon logic and deduction, that all patients be considered for both mechanical and chemical VTE prophylaxis, particularly in high-risk patients (pelvic or hip resections, prosthetic reconstruction, malignant diagnosis, presence of metastases, or surgical procedures longer than three hours). Additionally, the surgeon must determine, in each patient, if the risk of haemorrhage outweighs the risk of VTE. No individual pharmacological agent has been identified as being superior in the prevention of VTE events. Cite this article: Bone Joint J 2020;102-B(12)1743:–1751

Breast cancer is generally managed surgically with adjuvant agents which include hormone therapy, chemotherapy, radiotherapy and bisphosphonate therapy. However, some of these adjuvant therapies may cause adverse events, including wound infection, neutropenia, bone marrow suppression and fever. The simultaneous presentation of osteonecrosis and osteomyelitis has not previously been described in patients with breast cancer undergoing hormone therapy and chemotherapy. We report a patient with breast cancer who developed bone infarcts in both legs as well as osteomyelitis in the right distal tibia after treatment which included a modified radical mastectomy, hormone therapy and chemotherapy. Simultaneous osteonecrosis and osteomyelitis should be considered in patients with breast cancer who are receiving chemotherapy and hormone therapy who present with severe bone pain, especially if there have been infective episodes during treatment

Between 1986 and 2002, 42 patients with synchronous multifocal osteosarcoma were treated with two different protocols of neoadjuvant chemotherapy. When feasible, the primary and secondary tumours were excised as a combined procedure. After initial chemotherapy 26 patients were excluded from simultaneous excision of all their secondary bone lesions as their disease was too advanced. In 12 patients only isolated excision of the primary lesion was possible. For 16 patients simultaneous operations were conducted to excise the primary and secondary lesions. This involved two supplementary sites in 15 patients and four additional sites in one patient. Of these, 15 attained remission but 12 relapsed and died (11 within two years). Three patients remained disease-free at five, six and 17 years. The histological response to pre-operative chemotherapy of the primary and secondary lesions was concordant in 13 of the 16 patients who underwent simultaneous operations at more than one site. The prognosis for synchronous multifocal osteosarcoma remains poor despite combined chemotherapy and surgery. The homogeneous histological responses in a large proportion of the primary and secondary lesions implies that synchronous multifocal osteosarcoma tumours are not multicentric in origin, but probably represent bone-to-bone metastases from a single tumour

Aim. Extraspinal osteoarticular tuberculosis (TOA-ER) is a rare form of extra-pulmonary tuberculosis. It remains a topical problem not only in underdeveloped countries but also in developed countries due to cases of immune deficiency. Through a study of 40 cases, we specify the current diagnostic aspects of TOA-ER and detail their therapeutic and evolutionary modalities. Method. The mean age of our patients was 40 years with a clear predominance of females observed (SR = 0.66). 76.31% of the cases were from a rural setting. The impairment was single-focal in 72.5%. Associated tuberculosis location was found in 59% of cases. Pain and swelling were the main clinical symptoms. Signs of tuberculous impregnation were found in less than half of the cases. The IDR was positive in 67%. All patients underwent an appropriate radiological exploration consisting of a standard x-ray (30 cases), CT (21 cases) and MRI (23 cases). technetium-99m bone scintigraphy, performed in 15 cases, detected 5 infra-clinical osteoarticular locations. 77.5% of patients had formal pathological and / or bacteriological confirmation of the diagnosis. All patients had adequate anti-tuberculosis chemotherapy with a mean duration of 18 months. 67% of patients had a surgical debridement procedure. Results. After a mean follow-up of 5 years, the outcome was favourable in 75.2% of cases. A microbiological cure at the cost of serious functional sequelae was noted in 12.8% of cases. The outcome was unfavourable with relapse observed in 4.8% of cases and death in 7.2% of cases. Conclusions. Extraspinal osteoarticular tuberculosis is a fairly common condition in our country. Its insidious clinical course is the cause of diagnostic and therapeutic delay. Its treatment is mainly medical. The surgery keeps some indications. Good therapeutic adherence and early diagnosis are the best guarantees of good therapeutic results

The February 2015 Oncology Roundup. 360 . looks at: Achieving global collaboration; A new standard for limb salvage; Inoperable chondrosarcoma and chemotherapy; Soft-tissue sarcoma and adjuvant chemotherapy; Missed diagnoses and malpractice in sarcoma; Radiofrequency and cartilage tumours

Sarcomas generally metastasize to the lung, while extra-pulmonary metastases are rare. However, they may occur more frequently in certain histological sub-types. Bone metastases from bone and soft tissue sarcomas account for a significant number of extra-pulmonary disease. Resection of lung metastases is widely accepted as therapeutic option to improve the survival of oligometastatic patients but there is currently no literature supporting curative surgical management of sarcoma bone metastases. Most are treated on a case-by-case basis, following multidisciplinary tumour boards recommendations. One study reported some success in controlling bone metastases using radiofrequency ablation. Our goal was to assess the impact of curative resection of bone metastases from soft tissue and bone sarcomas on oncologic outcomes. Extensive review of literature was done to evaluate epidemiological and outcomes of bone metastases in sarcoma. We examined our prospective database for all cases of bone metastases from sarcoma treated with surgical resection between 1990 and 2016. Epidemiology, pathology, metastatic status upon diagnosis, type of secondary relapses and their treatments were recorded. Overall survival and disease-free survival were calculated and compared to literature. Thirty-five patients were included (18 men, 17 women) with a mean age of 46 years. Fifteen were soft tissue (STS) and 20 were bone (BS) sarcomas. Most STS were fibrosarcomas, leiomyosarcomas or UPS while chondrosarcomas and osteosarcomas were the most frequent BS. Nine (60%) STS were grade 3, 4 (27%) grade 2 and one grade 1 (3%). Eight (23%) were metastatic upon diagnosis (6 lungs, 3 bone). Treatment of the primary tumour included wide excision with reconstruction and (neo)-adjuvant therapies as required. Margins were negative in 32 cases and micro-positive in 3 cases. Amputation occurred in 6 (17%) cases. Primary lung metastases were treated by thoracotomy and primary bone metastases by wide excision. First relapse occurred in bone in 19 cases (54%), lungs and bone in 7 cases, 5 in lungs and 4 in soft-tissues. Lung metastases were treated by thoracotomy and chemotherapy in 3 cases, chemotherapy alone in the remaining cases. Bone metastases were treated by wide resection-reconstruction in 24 cases, extensive curettage in 4. Soft tissue relapses were re-excised in 4 patients. Two amputations were required. All margins were negative except for the 4 treated by curettage. Fourteen second relapses occurred in bone, 7 were radically-excised and 2 curetted. At last follow-up, 6 patients were alive (overall survival of 17%), with a mean survival of 57 months, a median overall survival of 42.5 months and a median disease-free survival (DFS) of 17 months. Overall survival was 17%, compared to an 11% 10-year survival previously reported in metastatic sarcomas. Median disease-free survival was better in this study, compared to 10 months in literature, so as median OS (42.5 months vs 15). Three patients were alive with no evidence of disease. DFS, OS and median survival seemed to be improved by bone metastases wide excision and even if several recurrences occur, curative surgery with adjuvant therapies should be considered

The aim of this study was to evaluate the prognostic and therapeutic factors which influence the oncological outcome of parosteal osteosarcoma. A total of 80 patients with a primary parosteal osteosarcoma were included in this retrospective study. There were 51 females and 29 males with a mean age of 29.9 years (11 to 78). The mean follow-up was 11.2 years (1 to 40). Overall survival was 91.8% at five years and 87.8% at ten years. Local recurrence occurred in 14 (17.5%) patients and was associated with intralesional surgery and a large volume of tumour. On histological examination, 80% of the local recurrences were dedifferentiated high-grade tumours. A total of 12 (14.8%) patients developed pulmonary metastases, of whom half had either a dedifferentiated tumour or a local recurrence. Female gender and young age were good prognostic factors. Local recurrence was a poor prognostic factor for survival. Medullary involvement or the use of chemotherapy had no impact on survival. The main goal in treating a parosteal osteosarcoma must be to achieve a wide surgical margin, as inadequate margins are associated with local recurrence. Local recurrence has a significant negative effect on survival, as 80% of the local recurrences are high-grade dedifferentiated tumours, and half of these patients develop metastases. The role of chemotherapy in the treatment of parosteal osteosarcoma is not as obvious as it is in the treatment of conventional osteosarcoma. The mainstay of treatment is wide local excision. Cite this article: Bone Joint J 2015;97-B:1698–1703

Aim. Many aspects of the surgical treatment of patients with tuberculosis (TB) of the spine, including the use of instrumentation and the types of graft, remain controversial. Our aim was to report the outcome of a single-stage posterior procedure, with or without posterior decompression, in this group of patients. Patients and Methods. Between 2001 and 2010, 51 patients with a mean age of 62.5 years (39 to 86) underwent long posterior instrumentation and short posterior or posterolateral fusion for TB of the thoracic and lumbar spines, followed by anti-TB chemotherapy for 12 months. No anterior debridement of the necrotic tissue was undertaken. Posterior decompression with laminectomy was carried out for the 30 patients with a neurological deficit. Results. The mean kyphotic angle improved from 26.1° (- 1.8° to 62°) to 15.2° (-25° to 51°) immediately after the operation. At a mean follow-up of 68.8 months (30 to 144) the mean kyphotic angle was 16.9° (-22° to 54°), with a mean loss of correction of 1.6° (0° to 10°). There was a mean improvement in neurological status of 1.2 Frankel grades in those with a neurological deficit. Bony union was achieved in all patients, without recurrent infection. Conclusions. Long posterior instrumentation with short posterior or posterolateral fusion is effective in the treatment of TB spine. It controls infection, corrects the kyphosis, and maintains correction and neurological improvement over time. . Take home message: With effective anti-TB chemotherapy, a posterior only procedure without debridement of anterior lesion is effective in the treatment of TB spondylitis, and an anterior procedure can be reserved for those patients who have not improved after posterior surgery. Cite this article: Bone Joint J 2016;98-B:834–9

Introduction. Spine is a common site for haematological malignancies. Multiple myeloma affects the spine in 70% of cases. New guidelines were published in 2015 to help manage spinal haematological malignancies. Despite neural compression or spinal instability, instrumentation of the spine should be avoided. Surgery carries significant risks of wound complications and more importantly delaying the definitive chemotherapy and radiotherapy. Cement augmentation and bracing for pain and prevention of deformity is key to the new strategies. We aimed to evaluate the different treatment modalities adopted in the spine unit at St George's hospital for spinal haematological malignancies. We compared our practice to the current guidelines published in 2015. Methods. Retrospective review of all spinal haematological malignancy patients who were discussed in the spinal MDT and managed through the spine unit at St George's hospital in the period between April 2019 and February 2021. We analysed the demographics of the patients treated in this period and compared the management modalities adopted in the unit to the current British haematological guidelines. Results. 139 patients were included in this study, 61.9% of them were male. 70 cases came through the MSCC pathway. 15 patients had their spinal involvement in the lumbar spine only below the conus. The Bilsky Grades of the other 124 cases were B0: 35.97 % 1a: 4.31%%, 1b: 7.19%, 1c: 3.59%, 2: 5.75% 3: 32.37%. 43 patients (30.9 %) had neurological deficits on presentation. 70 cases were treated conservatively (50.35%), 21 were treated with brace only (15.1%), 25 had BKP (17.98%) and 23 were treated with instrumentation (16.54%). The number of instrumented cases was small and trending down and cement augmentation and bracing were more frequently chosen for these patients. This comes in accordance to the British haematological guidelines. Conclusion. Utilising BJH 2015 guidelines we have reduced our instrumented operative case load. There is a higher percentage of BKP and Bracing in accordance to the algorithm

The October 2012 Oncology Roundup. 360. looks at: the causes of primary bone tumours; adjuvant chemotherapy in the longer term; vascularised fibular grafts to salvage massive femoral allografts; a new look at old risks; reconstruction with excised irradiated bone; predicting chemosensitivity in osteosarcoma ; and chemotherapy, osteoporosis and the risk of fracture

Osteosarcoma (OS) is a highly malignant primary tumor frequently occurring in children and adolescents. The mainstay of therapy is neoadjuvant chemotherapy and surgical removal of the lesion yielding a 50–70% of 5-year survival rate. Unfortunately, chemotherapy is currently unable to induce complete tumor necrosis leaving residual tumor cells free to metastasize or recidivate, thus resulting in a 30% mortality. The major limitation in those patients is the development of multidrug resistance (MDR) and the low water solubility of drugs such as Paclitaxel (PTX) that is in fact not included in the majority of chemotherapy protocols for OS treatment. We thus hypothesized to prevent the emergence of MDR and obtain significant tumor reduction, by engineering innovative nanoparticles (NPs) able to vehiculate the PTX and induce a dual synergic action: the cytostatic effect of PTX and the cytotoxicity generated by reactive oxygen species produced from light triggered photoactivation (PDT) of Chlorin e6 photosensitizer. To further improve the efficacy and reduce the side effects of NPs systemic administration, Mesenchymal Stromal Cells (MSC) are used as a “Trojan horse” to deliver the NPs directly to tumor cells, taking advantage of MSC ability to selectively recognize and efficiently engraft in OS tumor stroma. HSA were conjugated with photosensitizer Ce6 and the functionalized protein was used to produce PTX loaded nanoparticles through desolvation technique and drug-induced protein self-assembly (PTX-Ce6@HSA NP). Human MSC lines, isolated from the Bone marrow (BM) of different donors, were then loaded with different dosages of nanoparticles and their ability to internalize and transport the NPs, migrate and induce cytotoxic ROS upon light treatment were tested in in vitro cultures. Preliminary results showed that MSC efficiently internalize PTX-Ce6@HSA NPs and the photosensitizer Ce6 remains active inside the cells for at least 3 days after loading. Electron microscopy performed onto loaded MSC showed that NPs internalization take places via clathrin mediated transport, whereas HPLC analysis demonstrated a release kinetics of PTX mediated by exocytosis. Finally, PTX-Ce6@HSA NPs loaded MSC co-cultured with the OS tumor cell line SaOS-2 showed a significant tumor cell growth reduction. So fare, advances in drug delivery have failed to produce specific tool to improve the overall survival of OS patients. However, given our preliminary in vitro data we believe that the proposed multimodal therapy will minimize the side effects of the systemic chemotherapy and enhance the efficacy through the synergic effect of PTX and PDT. In the future, our strategy could be intended as an innovative co-adjuvant approach for OS treatment to be performed right before surgery to eliminate residual tumors cells after tumor mass removal

Congenital fibrosarcoma (CFS) is a rare tumor most often affecting extremities of babies. Considering age, surgery of primary is preferred. Nevertheless amputation rate remains high. Preoperative chemotherapy (CT) role must be emphasised. We present 3 cases receiving preoperative CT. Patients and methods in 1985, we treated a 3 months old girl for CFS of the thigh. To avoid amputation, preoperative CT (3 Ifosfamide- Vincristine- Actinomycine D) was performed leading to complete radiological and histological response. She benefited of conservative surgery She is in first complete remission 23 years later. In September 1999, a 3 ½ y old boy with recurrent l buttock CFS operated elsewhere twice (6 months old, 2 years old), received preoperative chemotherapy with good clinical and radiological response. “En-bloc” extra tumoral resection was performed. Histology showed viable tumoral cells. We completed treatment by chemotherapy. In 01/ 2003 bilateral pulmonary metastases occurred leading to surgery and chemotherapy. In 09/ 2003 a new local recurrence appeared treated by surgery and postoperative chemotherapy. From this time, he received Alpha interferon. He is in complete remission for 6 years. In 12/2005, a 14 y old girl, with local recurrence of CFS, treated elsewhere at the age of 5 months by partial surgery and chemotherapy (remained in remission for 13 years)was admitted. Since this time, she recurred locally despite resections and multiple lines of chemotherapy, but without metastasising. She was amputated in 2008. Conclusion: preoperative chemotherapy is feasible despite low age of the patients, can allow conservative surgery and avoid late metastases

Soft tissue sarcomas (STS) are rare, aggressive malignancies derived from connective tissues such as muscle and fat. Undifferentiated pleomorphic sarcoma (UPS) is one of the most common STS in adults. UPS is an aggressive, highly metastatic sarcoma, and is resistant to chemotherapy. New therapies for UPS are desperately needed. STS have an immune desert tumour immune microenvironment (TIME), characterized by a paucity of tumour infiltrating lymphocytes and subsequent resistance to immunotherapies such as immune checkpoint inhibitors. Strategies capable of creating an immune-rich, inflamed TIME may improve immunotherapy efficacies for sarcoma. Activation of the STING (stimulator of interferon genes) receptor can induce potent innate and adaptive immune responses within immunogenic solid tumours. However, this approach has never been attempted in immune-inert sarcomas. Purpose: To determine the therapeutic anti-tumour effects of STING activation in UPS tumours. We have developed an inducible, immune-competent mouse model of UPS. We evaluated intra-tumoural injection of the murine STING receptor agonist, DMXAA, into UPS-bearing immune-competent mice. DMXAA was injected into palpable UPS tumours of the hindlimb. Tumour volume and bioluminescence imaging was recorded bi-weekly. DMXAA treated UPS tumours were also evaluated for necrosis and immune infiltration at defined time points. UPS tumours developed necrosis and lymphocytic infiltration 72 hours after DMXAA treatment. A single intra-tumoural dose of DMXAA into UPS tumours resulted in durable cure in 50% of mice. All survivors rejected a re-challenge of the UPS tumours in both the contralateral hindlimb and lung, suggesting adaptive immunity. The therapeutic effects of DMXAA were mitigated in lymphocyte deficient Rag2 knockout mice. STING therapy is a promising immunotherapeutic opportunity for immune-inert sarcomas. Our data warrants further preclinical investigations in other sarcoma models and in combination with other immune-based therapies

We aimed to identify the incidence, outcome and prognostic factors associated with spindle cell sarcomas of bone (SCSB). We studied 196 patients with a primary non-metastatic tumour treated with the intent to cure. The results were compared with those of osteosarcoma patients treated at our hospital during the same period. The overall incidence of SCSB was 7.8% of all patients with a primary bone sarcoma. The five- and ten-year survival rates were 67.0% and 60.0%, respectively, which were better than those of patients with osteosarcoma treated over the same period. All histological subtypes had similar outcomes. On univariate analysis, factors that were significantly associated with decreased survival were age > 40 years, size > 8 cm, the presence of a pathological fracture, amputation, involved margins and a poor response to pre-operative chemotherapy. Multivariate analyses showed that age > 65 years, amputation and involved margins were all statistically significant prognostic factors. Involved margins and poor response to pre-operative chemotherapy were associated with an increased risk of local recurrence. SCSB has a better prognosis than osteosarcoma when matched for age. Most prognostic factors for osteosarcoma also seem to apply to SCSB. Patients with SCSB should be treated in the same way as patients of the same age with osteosarcoma

We describe the results of cemented total hip replacement in 23 patients (23 hips) with active tuberculous arthritis of the hip with a mean follow-up of 4.7 years (4 to 7). In two patients the diagnosis was proved by pre-operative biopsy, whereas all others were diagnosed on a clinicoradiological basis with confirmation obtained by histopathological examination and polymerase chain reaction of tissue samples taken at the time of surgery. All patients received chemotherapy for at least three months before surgery and treatment was continued for a total of 18 months. Post-operative dislocation occurred in one patient and was managed successfully by closed reduction. No reactivation of the infection or loosening of the implant was recorded and function of the hip improved in all patients. Total hip replacement in the presence of active tuberculous arthritis of the hip is a safe procedure when pre-operative chemotherapy is commenced and continued for an extended period after operation

Dedifferentiated chondrosarcoma is a rare but highly malignant manifestation that can occasionally arise in patients with cartilage tumours. There remains uncertainty as to the best treatment for this condition and in particular whether chemotherapy may have a role in improving prognosis. Members of EMSOS were invited to contribute data on patients, tumours, treatment and outcomes of patients with dedifferentiated chondrosarcoma. Eight centres contributed data on 317 patients from 7 countries. The mean age was 59 (range 15 to 89) and the most common site was the femur (46%) followed by the pelvis (28%). 25% of patients presented with a pathological fracture and the most common high grade component identified was MFH. 23% had metastases at diagnosis and these patients had a median survival of 5 months. 30% of patients received chemotherapy, with 47% under 60 having chemotherapy compared with 10% over 60. One third of this group had neoadjuvant chemotherapy and the rest had adjuvant reatment. 88% had surgery with limb salvage in 80% of this group. The overall survival was 38% at 2 years and 24% at 5 years but in patients without metastases at diagnosis these figures were 44% and 28% respectively. Poor prognostic factors for survival were: metastases at diagnosis, amputation or no operation, local recurrence, age over 60 and pathological fracture at presentation. We were unable to identify any group in whom chemotherapy appeared to have a survival benefit. Dedifferentiated chondrosarcoma carries a dismal prognosis. Although 30% of patients received chemotherapy in this study we were not able to prove that it improved survival. Early diagnosis and complete surgical excision still offer the best prognosis for this condition

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.”

Background: to study the expression of Bcl-2 gene in osteogen sarcoma of long tubular bones and their effect on the disease prognosis. Study was conducted in 20 patients with osteogen sarcoma of long tubular bones. Of 20 patients studied in 11 patients tumor was localized in femoral bone, in 6 patients in tibia and in 3 patients in fibula. Slices taken from the tumor in open biopsy were the object of research. Immune-hystochemical research was carried out by the standard technique applying antibodies to Bcl-2. The assessment response was made by visual simiquantity method: expression absence was-0, weak-1 (+), moderately expressed-2 (++), intensive-3 (+++). 17 patients were given chemoradiotherapy, 3 patients combined treatment (surgical + adjuvant chemotherapy). 12 got intraarterial chemotherapy (72 hours) by CAP regimen (Cyclophosphamide, Adriamycin, Cisplatin) – 4 cycles with three week interval. Then telegammatherapy, single dose 3.5 Gy up to general dose 60–70 Gy was made, later chemotherapy was completed up to 9 cycles at the same regimen. 8 patients were carried out 4 cycles of intra-arterial chemotherapy by MP regimen (Methotrexate, Cisplatin) with three week interval. Radiotherapy used subsequently (General dose 60–70 Gy) and chemotherapy was reached up to 9 cycles at the same regimen. Research has shown, that in the most of patients 13/20 (65 %) had moderately positive and low positive expression of Bcl-2 gene, in 4/20 (20 %) cases reaction was negative and in 3/20 (15 %) cases it was the expression of the given gene that was high. The assessment of treatment efficiency was carried out by WHO recommendation. The whole effect was obtained in 6 patients (30 %), partial in 11 (55 %) and progressing was in 3 (15 %). Most patients who were given the treatment by specific scheme: chemotherapy + radiotherapy + chemotherapy had good parameters in life expectancy, where 6 of 8 patients (75 %) lived without relapse and metastases more than one year. All patients (3) had numerous lung metastases in operation + chemotherapy group of patients. Aggressive current of tumoral process was characterized with high expression of Bcl-2 gene in tumor tissue. The level of expression Bcl-2 gene can testify the efficiency of conducted treatment

Of 41 consecutive patients with newly diagnosed osteogenic sarcoma admitted to the Children's Orthopedic Hospital and Medical Center in Seattle, Washington, between 1952 and 1977, 19 treated before 1973 did not receive adjunctive chemotherapy (histological group) whereas after 1972 22 have been so treated (chemotherapy group). Chemotherapy consisted primarily of high doses of methotrexate and adriamycin for 16 months after surgical treatment. Patients in the historical group have been observed for a minimum of nine years (six patients) or until death (13 patients). The 13 surviving patients in the chemotherapy group have been followed for a minimum of three years (median five years) and all 12 disease-free patients have been off therapy for between one and a half and five and a half years (median three years). Overall, the chemotherapy group has had a significant increase in both survival (p = 0.03) and disease-free survival (P = 0.02) compared to the historical group. In 35 patients with localised disease at diagnosis, the three-year disease-free survival and the three-year survival rates were 18 per cent and 41 per cent respectively in the historical group, and 67 per cent and 78 per cent (life table estimates) respectively in the chemotherapy group. With adjunctive chemotherapy only one of the seven patients developing pulmonary metastases did so later than nine months after diagnosis. The superior results in the chemotherapy group could not be accounted for by differences in age, sex, presence of metastases at diagnosis, histopathology, location of primary tumour, type of initial or subsequent surgical treatment, or the use of standard or computerised lung tomography. Although the use of historical controls in this study does not exclude other changes as contributing to the observed improvement in outcome, our data support the contention that adjunctive chemotherapy improves both the disease-free survival and the overall survival of patients with osteosarcoma and rarely delays the onset of recurrent or metastatic disease

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