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

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

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

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

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

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

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

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

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

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

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.