Myxoid or Myxoid Round Cell liposarcoma (MLS) is a mesenchymal malignancy with adipocyte differentiation accounting for 15–20% of liposarcomas and 5% of all adult soft tissue sarcomas (STS). Like other STS, treatment of MLS is generally by wide surgical resection in conjunction with radiotherapy and this approach is associated with low rates of local recurrence [1]. However, most MLS are located between muscles so wide local excision(WLE) can be quite morbid with adverse functional results. MLS are known to be extremely sensitive to radiotherapy which has led to development of treatment protocols utilizing neoadjuvant radiation. Given the radiosensitivity of MLS, we hypothesize that resection with marginal margins (1mm) does not result in higher rates of local recurrence or disease-free survival if performed following pre-operative radiotherapy. We identified all patients with localized MLS who underwent preoperative radiation and surgical resection between January 2000 and January 2018 from a prospectively collected sarcoma database. We calculated the ellipsoid tumour volume(ETV=h x w x d x ()) at diagnosis and after radiation, and documented the necrosis percentage of the tumour and margin status following resection based on histological analysis [2]. Marginal resection was identified by the operative report describing no or only very minimal resection of muscle surrounding the tumour, and a negative surgical margin 0.1cm/1mm as defined histologically. In comparison, WLE was defined if the operative note described an attempt to remove the tumour with a cuff of surrounding muscle, and the final histology reported a negative margin 0.1cm/1mm which included skeletal muscle. The third group for analysis included patients with positive resection margins. There were 91 patients with MLS of mean age 48 years (range 18–88) with 69% male and 31% female. The mean pre-radiotherapy ETV was 507cm. 3. (16.1cm. 3. to 6961cm. 3. ) and decreased to 361cm. 3. (8.7cm. 3. to 5695cm. 3. ) following radiation, with an average percentage reduction in ETV of −45%(+129%to-99%). Mean patient follow-up was 7.3 years (0.2–18) with no differences between margin groups(p=0.284). Only 10(11%) patients had positive margins, of which 43(47%) underwent marginal resection and 38(42%) WLE. Overall the mean necrosis as measured histologically following preoperative radiation was 69% (range 0–100%) with no differences between the 3 resection groups(p-0.151). Similarly, there was no significant difference in reduction in mean ETV between the three resection groups(p=0.311), there was no significant difference between the three treatment groups in 5-year LR-free survival (p=0.469), metastasis-free survival (p=0.841) or overall survival (p=0.873). Most patients with MLS experienced significant reduction in tumour size and necrosis following preoperative radiation. We found no differences in the risk of local recurrence or survival based on the type of surgical approach for patients with MLS. Based on these results, we conclude that MLS can be safely removed by marginal resection following preoperative radiotherapy with high rates of local tumour control. Even following a positive margin resection, local recurrence remains uncommon after preoperative radiation. A marginal surgical approach for patients with MLS reduces the need for major muscle resection and is associated with improved functional outcomes with less complications

Between 1966 and 2001, 1254 patients underwent excision of a bone tumour with endoprosthetic replacement. All patients who had radiotherapy were identified. Their clinical details were retrieved from their records. A total of 63 patients (5%) had received adjunctive radiotherapy, 29 pre-operatively and 34 post-operatively. The mean post-operative Musculoskeletal Tumor Society scores of irradiated patients were significantly lower (log-rank test, p = 0.009). The infection rate in the group who had not been irradiated was 9.8% (117 of 1191), compared with 20.7% (6 of 29) in those who had pre-operative radiotherapy and 35.3% (12 of 34) in those who radiotherapy post-operatively. The infection-free survival rate at ten years was 85.5% for patients without radiotherapy, 74.1% for those who had pre-operative radiotherapy and 44.8% for those who had post-operative radiotherapy (log-rank test, p < 0.001). The ten-year limb salvage rate was 89% for those who did not have radiotherapy and 76% for those who did (log-rank test, p = 0.02). Radiotherapy increased the risk of revision (log-rank test, p = 0.015). A total of ten amputations were necessary to control infection, of which nine were successful. Radiotherapy may be necessary for the treatment of a bone sarcoma but increases the risk of deep infection for which amputation may be the only solution

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.”

Optimising post-operative joint function is challenging when treating periarticular soft tissue sarcoma (STS). Radiotherapy reduces local recurrence rates but periarticular fibrosis may adversely affect joint function. Neo-adjuvant radiotherapy requires lower doses and smaller treatment volumes and therefore has potential benefits for the management of periarticular STS, but may lead to an increased risk of post-operative wound complications. This study assesses initial outcome and complications after treatment with neo-adjuvant radiotherapy and surgery for patients with periarticular STS. 17 patients treated with neo-adjuvant radiotherapy and surgery were identified. 3D conformal radiotherapy was delivered at a single centre with a dose of 50Gy in 25 fractions over 5 weeks. Patients were assessed weekly for adverse effects. Resection was planned 4–6 weeks after radiotherapy. Median follow-up was 13 months (range 5–44 months). No patients had significant adverse effects during radiotherapy. One patient had surgery delayed due to local skin reaction. Minor complications in five patients (three superficial infections, one seroma, one neuropraxia). One patient required further surgery due to incomplete margins. TESS scores for upper and lower limb patients were 86.1 and 78.1 respectively. No cases of local recurrence have occurred to date. Two patients have developed distant metastatic disease. The early results for periarticular STS managed with neo-adjuvant radiotherapy and surgery are excellent. There does not appear to be a significant increase in post-operative complication rates. With neo-adjuvant radiotherapy. Long term follow-up is required to demonstrate final functional outcome and local control rates

Introduction. Sacro-coccygeal chordomas pose a difficult diagnostic and therapeutic problem due to late presentation, large size, soft-tisue extension, difficulties in obtaining adequate resection margins, higher local recurrence rate and uncertain effectiveness of adjuvant treatment. We present a series of 21 patients of sacral chordomas obtained from Scottish Bone Tumour Registry to analyse predictors of local control and survival. Patients and methods. The clinical and morphologic features, type of treatment and follow-up of 21 consecutive patients with sacral chordoma were retrospectively reviewed and analysed. Results. The average age at time of the biopsy was 59 years (range, 12 to 82 years): twelve patients were male and nine were female. Pain was the presenting symptom in all patients. Two had intralesional (both recurred), 9 marginal (4 recurred) and 3 wide resections (1 recurred). Fifteen of the twenty-one patients were treated with adjuvant radiation therapy. In seven patients, the chordoma was inoperable and all but one were treated with adjuvant radiotherapy. Local recurrence and metastases occurred in 7 (50%) and 5 (23.8%) patients. The 5-year and 10-year survival were 38% and 14.2%, respectively. Conclusion. Excision of the lesion combined with adjuvant radiation therapy provided satisfactory results. Local recurrence presents a major problem in the management of sacral chordomas (50%). Intralesional resection should be avoided as it is associated with 100% local recurrence in our series

Purpose. The optimal sequencing of radiotherapy (RT) with surgery in soft-tissue sarcomas (STS) remains undefined. We assessed the impact of RT sequencing on overall survival (OS), cause-specific survival (CSS), local failure, and distant failure. Methods. A retrospective analysis was conducted using the National Oncology Database, a proprietary database of aggregated tumour registries owned by Impac. (r). Medical Systems (Sunnyvale, CA). Eligible sites were soft tissues of the head/neck, thorax, abdomen, pelvis, extremities, trunk, and peritoneum. Only patients with known stage and grade were included. Prognostic factors were identified with multivariate analysis (MVA) using the Cox proportional hazards model. Survival was calculated using the Kaplan-Meier method, and compared for statistical significance (p< 0.05) using the log-rank test. Results. A total of 821 patients met the inclusion criteria. The median follow-up time for living patients was 62 months. The 5-year CSS was 69%. MVA identified the following independent predictors for CSS (p< 0.01): age, stage, grade, histology, surgery, RT sequence, and tumour size. CSS was significantly improved with pre-op RT versus post-op RT [hazard ratio (HR) 0.7, 95% confidence interval (CI) 0.51-0.94, p< 0.05], with a 5-year CSS of 81% and 73%, respectively (log-rank, p< 0.01). Pre-op RT improved CSS in patients with lower extremity tumours, leiomyosarcoma, and synovial sarcoma (p< 0.05). OS was not significantly improved with pre-op RT. Pre-op RT also resulted in significantly reduced local and distant relapse rates than post-op RT. Adverse prognostic factors were balanced between both groups. Conclusion. Pre-operative RT has a significant benefit in reducing cancer-specific mortality compared to post-operative RT in STS

Purpose. Mesenchymal stromal cells (MSCs) are an attractive choice for regenerative medicine. We previously showed that MSCs enhance wound healing in animals after radiotherapy. The effect of MSCs on tumor growth is not well understood. The potential use of MSCs to enhance wound healing after radiotherapy (RT) and resection of soft tissue sarcoma (STS) is dependent on a satisfactory safety profile to ensure that tumor proliferation does not occur and recurrence is not increased. Method. Primary cell lines (human myxofibrosarcoma and undifferentiated sarcoma) derived from sarcoma bearing patients and a commercialized human fibrosarcoma cell line (HT1080) were used. Cell line proliferation assay after co-culture with MSCs was done using flow cytometry (CFSE) and bioluminescence emission (BLI) (using eGFP/Fluc transduced cell lines). Five xenograft models were developed with NOD/SCID gc-null mice (n=164) harbouring primary tissue lines obtained from patients biopsies (myxofibrosarcoma and three pleomorphic undifferentiated sarcoma [PUS A, B and C]) and a a fibrosarcoma cell line previously transduced with eGFP/Fluc. Tumors were passaged to three mouse generations before a tissue line was established and the model was then used. For the fibrosarcoma model, eGFP/Fluc HT1080 were injected under the dorsal skin. When tumors reached 1cm in diameter, they received localized RT and 48hr later were resected. MSCs (n=82) or medium alone (n=82) was injected subcutaneously adjacent to the wound after tumor resection. Histological and in vivo BLI analysis were performed 3 and 12 weeks after surgery. Results. In Vitro Proliferation Assay. For the flow cytometric proliferation assay, there was an increase in the doubling time after five days in the myxofibrosarcoma-MSCs co-culture system (140.4h) compared with controls (55.4 h, p<0.001). No significant differences were found in other cells lines. Lower BLI emission was found in co-cultured myxofibrosarcoma cells at the 3rd and 4th day compared with controls (p<0.01 and p<0.05 respectively). In Vivo Recurrence Assay. For mice bearing the fibrosarcoma cell line, in vivo BLI performed 3 weeks after surgery showed similar emission intensity in MSC-treated mice and controls while histological recurrence was significantly lower in MSC-treated animals (40%) than control (72%, p=0.045). For mice bearing the myxofibrosarcoma tissue line, histological recurrence at 12 weeks was similar in MSCs-treated animals and controls (p=0.44). Mice xenografted with pleomorphic undifferentiated sarcoma A and B did not develop local tumor recurrence after histological analysis, while pleomorphic undifferentiated sarcoma C showed similar recurrence in MSC and medium treated mice (p=0.46). Conclusion. We showed that MSCs decrease the proliferation rate of the myxofibrosarcoma cell line in vitro and have no effect, or even decrease, local recurrence of different STS tissue lines in vivo after RT and resection. Clinical investigation of this approach is warranted

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

Metastatic bone disease (MBD) is a significant contributor to diminished quality of life in cancer patients, often leading to pathologic fractures, hypercalcaemia, intractable bone pain, and reduced functional independence. Standard of care management for MBD patients undergoing orthopaedic surgery is multi-disciplinary, includes regular surgical follow-up, case by case assessment for use of bone protective medications, and post-operative radiation therapy to the operative site. The number of patients in southern Alberta receiving standard of care post-operative management is currently unclear. Our aim is to develop a database of all patients in southern Alberta undergoing orthopaedic surgery for MBD and to assess for deficiencies and opportunities to ensure standard of care for this complex patient population. Patients were identified for database inclusion by a search query of the Alberta Cancer Registry of all patients with a diagnosis of metastatic cancer who underwent surgery for an impending or pathologic fracture in the Calgary, South and Central Alberta Zones. Demographic information, primary cancer history, previous local and systemic treatments, anatomical location of MBD event(s), surgical fixation techniques, and post-operative care details were collected. The rate of standard of care post-operative treatment was evaluated. A comparison of outcomes between tertiary urban centres and rural centres was also completed. Survival was calculated from time of first operation to date of death. Univariate and multivariate analyses were performed to identify the impact of post-operative care variables on survival amongst patients surviving longer than one month. We identified 402 patients who have undergone surgical treatment for MBD in southern Alberta from 2006-2018. Median age at time of surgery was 66.3 years and 52.7% of patients were female. Breast, lung, prostate, renal cell and multiple myeloma were the most common primary malignancies (n=328, 81.6%). Median post-operative survival was 6.8 months (95%CI: 5.7-8.3). 203 patients (52.5%) were treated with post-operative radiotherapy and 159 patients (50.8%) had post-operative surgical follow-up. Only 39 patients (11.3%) received bone protective agents in the peri-operative period. On multivariate survival analysis, post-operative surgical follow-up was associated with improved survival (p<0.001). Patients were treated at nine hospitals across southern Alberta with most patients treated in an urban center (65.9%). Post-operative survival was significantly longer amongst patients treated in an urban center (9.0 months, 95%CI: 6.9-12.3 versus 4.3 months, 95%CI: 3.4-5.6, p<0.001). The burden of MBD is significant and increasing. With treatment occurring at multiple provincial sites, there is a need for standardized, primary disease-specific peri- and post-operative protocols to ensure quality and efficacious patient care. To provide evidence informed treatment recommendations, we have developed a database of all patients in southern Alberta undergoing orthopaedic surgery for MBD. Our results demonstrate that many patients were not treated according to post-operative standard of care recommendations. Notably, half of the included patients did not have documented surgical follow-up, post-operative radiation treatment was low and only 11% were actively treated with bone protective agents. This data justifies the need for established surgical MBD care pathways and provides reference data to benchmark prospective QA and QI outcomes in this patient population

Bone turnover and the accumulation of microdamage are impacted by the presence of skeletal metastases which can contribute to increased fracture risk. Treatments for metastatic disease may further impact bone quality. The present study aims to establish a preliminary understanding of microdamage accumulation and load to failure in osteolytic vertebrae following stereotactic body radiotherapy (SBRT), zoledronic acid (ZA), or docetaxel (DTX) treatment. Twenty-two six-week old athymic female rats (Hsd:RH-Foxn1rnu, Envigo, USA) were inoculated with HeLa cervical cancer cells through intracardiac injection (day 0). Institutional approval was obtained for this work and the ARRIVE guidelines were followed. Animals were randomly assigned to four groups: untreated (n=6), spine stereotactic body radiotherapy (SBRT) administered on day 14 (n=6), zoledronic acid (ZA) administered on day 7 (n=5), and docetaxel (DTX) administered on day 14 (n=5). Animals were euthanized on day 21. T13-L3 vertebral segments were collected immediately after sacrifice and stored in −20°C wrapped in saline soaked gauze until testing. µCT scans (µCT100, Scanco, Switzerland) of the T13-L3 segment confirmed tumour burden in all T13 and L2 vertebrae prior to testing. T13 was stained with BaSO. 4. to label microdamage. High resolution µCT scans were obtained (90kVp, 44uA, 4W, 4.9µm voxel size) to visualize stain location and volume. Segmentations of bone and BaSO. 4. were created using intensity thresholding at 3000HU (~736mgHA/cm. 3. ) and 10000HU (~2420mgHA/cm. 3. ), respectively. Non-specific BaSO. 4. was removed from the outer edge of the cortical shell by shrinking the segmentation by 105mm in 3D. Stain volume fraction was calculated as the ratio of BaSO. 4. volume to the sum of BaSO. 4. and bone volume. The L1-L3 motion segments were loaded under axial compression to failure using a µCT compatible loading device (Scanco) and force-displacement data was recorded. µCT scans were acquired unloaded, at 1500µm displacement and post-failure. Stereological analysis was performed on the L2 vertebrae in the unloaded µCT scans. Differences in mean stain volume fraction, mean load to failure, and mean bone volume/total volume (BV/TV) were compared between treatment groups using one-way ANOVAs. Pearson's correlation between stain volume fraction and load to failure by treatment was calculated using an adjusted load to failure divided by BV/TV. Stained damage fraction was significantly different between treatment groups (p=0.0029). Tukey post-hoc analysis showed untreated samples to have higher stain volume fraction (16.25±2.54%) than all treatment groups (p<0.05). The ZA group had the highest mean load to failure (195.60±84.49N), followed by untreated (142.33±53.08N), DTX (126.60±48.75N), and SBRT (95.50±44.96N), but differences did not reach significance (p=0.075). BV/TV was significantly higher in the ZA group (49.28±3.56%) compared to all others. The SBRT group had significantly lower BV/TV than the untreated group (p=0.018). Load divided by BV/TV was not significantly different between groups (p=0.24), but relative load to failure results were consistent (ZA>Untreated>DTX>SBRT). No correlations were found between stain volume fraction and load to failure. Focal and systemic cancer treatments effect microdamage accumulation and load to failure in osteolytic vertebrae. Current testing of healthy controls will help to further separate the effects of the tumour and cancer treatments on bone quality

Bone turnover and the accumulation of microdamage are impacted by the presence of skeletal metastases which can contribute to increased fracture risk. Treatments for metastatic disease may further impact bone quality. The present study aims to establish a preliminary understanding of microdamage accumulation and load to failure in osteolytic vertebrae following stereotactic body radiotherapy (SBRT), zoledronic acid (ZA), or docetaxel (DTX) treatment. Twenty-two six-week old athymic female rats (Hsd:RH-Foxn1rnu, Envigo, USA) were inoculated with HeLa cervical cancer cells through intracardiac injection (day 0). Institutional approval was obtained for this work and the ARRIVE guidelines were followed. Animals were randomly assigned to four groups: untreated (n=6), spine stereotactic body radiotherapy (SBRT) administered on day 14 (n=6), zoledronic acid (ZA) administered on day 7 (n=5), and docetaxel (DTX) administered on day 14 (n=5). Animals were euthanized on day 21. T13-L3 vertebral segments were collected immediately after sacrifice and stored in −20°C wrapped in saline soaked gauze until testing. µCT scans (µCT100, Scanco, Switzerland) of the T13-L3 segment confirmed tumour burden in all T13 and L2 vertebrae prior to testing. T13 was stained with BaSO. 4. to label microdamage. High resolution µCT scans were obtained (90kVp, 44uA, 4W, 4.9µm voxel size) to visualize stain location and volume. Segmentations of bone and BaSO. 4. were created using intensity thresholding at 3000HU (~736mgHA/cm. 3. ) and 10000HU (~2420mgHA/cm. 3. ), respectively. Non-specific BaSO. 4. was removed from the outer edge of the cortical shell by shrinking the segmentation by 105mm in 3D. Stain volume fraction was calculated as the ratio of BaSO. 4. volume to the sum of BaSO. 4. and bone volume. The L1-L3 motion segments were loaded under axial compression to failure using a µCT compatible loading device (Scanco) and force-displacement data was recorded. µCT scans were acquired unloaded, at 1500µm displacement and post-failure. Stereological analysis was performed on the L2 vertebrae in the unloaded µCT scans. Differences in mean stain volume fraction, mean load to failure, and mean bone volume/total volume (BV/TV) were compared between treatment groups using one-way ANOVAs. Pearson's correlation between stain volume fraction and load to failure by treatment was calculated using an adjusted load to failure divided by BV/TV. Stained damage fraction was significantly different between treatment groups (p=0.0029). Tukey post-hoc analysis showed untreated samples to have higher stain volume fraction (16.25±2.54%) than all treatment groups (p<0.05). The ZA group had the highest mean load to failure (195.60±84.49N), followed by untreated (142.33±53.08N), DTX (126.60±48.75N), and SBRT (95.50±44.96N), but differences did not reach significance (p=0.075). BV/TV was significantly higher in the ZA group (49.28±3.56%) compared to all others. The SBRT group had significantly lower BV/TV than the untreated group (p=0.018). Load divided by BV/TV was not significantly different between groups (p=0.24), but relative load to failure results were consistent (ZA>Untreated>DTX>SBRT). No correlations were found between stain volume fraction and load to failure. Focal and systemic cancer treatments effect microdamage accumulation and load to failure in osteolytic vertebrae. Current testing of healthy controls will help to further separate the effects of the tumour and cancer treatments on bone quality

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

The management of primary malignant bone tumors with metastatic disease at presentation remains a challenge. While surgical resection has been shown to improve overall survival among patients with non-metastatic malignant bone tumors, current evidence regarding the utility of surgery in improving overall survival in metastatic patients remains limited. The 2004–2016 National Cancer Database (NCDB) was queried using International Classification of Diseases 3rd Edition (ICD-O-3) topographical codes to identify patients with primary malignant bone tumors of the extremities (C40.0-C40.3, C40.8 and C40.9) and/or pelvis (C41.4). Patients with malignant bone tumors of the axial skeleton (head/skull, trunk and spinal column) were excluded, as these cases are not routinely encountered and/or managed by orthopaedic oncologists. Histological codes were used to categorize the tumors into the following groups - osteosarcomas, chondrosarcomas, and Ewing sarcomas. Patients who were classified as stage I, II or III, based on American Joint Commission of Cancer (AJCC) guidelines, were excluded. Only patients with metastatic disease at presentation were included in the final study sample. The study sample was divided into two distinct groups – those who underwent surgical resection of the primary tumors vs. those who did not receive any surgery of the primary tumor. Kaplan-Meier survival analysis was used to report unadjusted 5-year overall survival rates between patients who underwent surgical resection of the primary tumor, compared to those who did not. Multi-variate Cox regression analyses were used to assess whether undergoing surgical resection of the primary tumor was associated with improved overall survival, after controlling for differences in baseline demographics, tumor characteristics (grade, location, histological type and tumor size), and treatment patterns (underwent metastatectomy of distal and/or regional sites, positive vs. negative surgical margins, use of radiation therapy and/or chemotherapy). Additional sensitivity analyses, stratified by histologic type for osteosarcomas, chondrosarcomas and Ewing sarcomas, were used to assess prognostic factors for overall survival. A total of 2,288 primary malignant bone tumors (1,121 osteosarcomas, 345 chondrosarcomas, and 822 Ewing sarcomas) with metastatic disease at presentation were included – out of which 1,066 (46.0%) underwent a surgical resection of the primary site. Overall 5-year survival rates, on unadjusted Kaplan-Meier log-rank analysis, were significantly better for individuals who underwent surgical resection vs. those who did not receive any surgery (31.7% vs. 17.3%; p<0.001). After controlling for differences in baseline demographics, tumor characteristics and treatment patterns, undergoing surgical resection of primary site was associated with a reduced overall mortality (HR 0.42 [95% CI 0.36–0.49]; p<0.001). Undergoing metastectomy (HR 0.92 [95% CI 0.81–1.05]; p=0.235) was not associated with a significant improvement in overall survival. On stratified analysis, radiation therapy was associated with improved overall survival for Ewing Sarcoma (HR 0.71 [95% CI 0.57–0.88]; p=0.002), but not for osteosarcoma (HR 1.14 [95% CI 0.91–1.43]; p=0.643) or chondrosarcoma (HR 1.08 [95 % CI 0.78–1.50]; p=0.643). Chemotherapy was associated with improved overall survival for osteosarcoma (HR 0.50 [95% CI 0.39–0.64]; p<0.001) and chondrosarcoma (HR 0.62 [95% CI 0.45–0.85]; p=0.003), but not Ewing sarcoma (HR 0.79 [95% CI 0.46–1.35]; p=0.385). Surgical resection of the primary site significantly improves overall survival for primary malignant bone tumors with metastatic disease at presentation. Physicians should strongly consider surgical resection of the primary tumor, with adjunct systemic and/or radiation therapy (dependent on tumor histology), in patients presenting with metastatic disease at presentation

Wide resection, with or without adjuvant therapy, is the mainstay of treatment for soft tissue sarcoma of the extremities. The surgical treatment of soft tissue sarcoma can portend a prolonged course of recovery from a functional perspective. However, data to inform the expected course of recovery following sarcoma surgery is lacking. The purpose of this study was to identify time to maximal functional improvement following sarcoma resection and to identify factors that delay the expected course of recovery. A retrospective chart review was performed of all patients undergoing surgical treatment of a soft tissue sarcoma of the extremities between January 1st, 1985 and November 15, 2020 with a minimum of 1 follow up. The primary outcome measure was time to maximal functional improvement, defined as failure to demonstrate improvement on two consecutive follow up appointments, as defined by the functional outcome measures of Toronto Extremity Salvage Score (TESS) and Musculoskeletal Tumor Society (MSTS) Score or by achieving 90% of maximum outcome score. We identified 1188 patients who underwent surgical resection of a soft tissue sarcoma of the extremities. Patients typically achieved a return to their baseline level of function by 1 year and achieved “maximal” functional recovery by 2 year's time postoperatively. Patient and tumor factors that were associated with worse functional outcome scores and a delayed return to maximal functional improvement included older age (p=0.007), female sex (p-0.004), larger tumor size (p < 0 .001), deep tumor location (p < 0 .001), pelvic location (p < 0 .001), higher tumor grade (p < 0 .001). Treatment factors that were associated with worse functional outcome scores and a delayed return to maximal functional improvement included use of radiation therapy (p < 0 .001), perioperative complications (p < 0 .001), positive margin status (p < 0 .001) and return of disease, locally or systemically (p < 0 .001). Most patients will recover their baseline function by 1 year and achieve “maximal” recovery by 2 years’ time following surgical resection for soft tissue sarcoma of the extremities. Several patient, tumor and treatment factors should be used to counsel patients as to a delayed course of recovery

Myxofibrosarcoma (MFS) is the second most common subtype of soft tissue sarcoma (STS) and is associated with a high rate of local recurrence after resection. These tumours frequently present with peri-lesional edema, termed “tumour tails” on staging MRI scans [1]. Tumour tails(TT) may contain satellite neoplastic cells or can represent benign reactive edema. There are no clear radiological features to distinguish malignant from reactive peri-lesional edema which limits accurate surgical planning, resulting in either high rates of inadvertently positive resection margins and local recurrences or overly-aggressive resections which negatively impact function and increase morbidity [2]. The objective of this pilot study was to prospectively study a cohort of MFS patients with TTs in an attempt to identify radiological features that predict which type of edema is malignant and requires resection together with the main tumour mass. Patients diagnosed with MFS on biopsy at an orthopaedic oncology referral centre between January 1-December 31 2018 who also had TTs on staging MRI scans were prospectively recruited for the study. Tumours were treated with wide surgical excision, including the TTs, and (neo)adjuvant radiotherapy as per institutional protocol. Staging MRI scans were reviewed in a blinded fashion by two musculoskeletal radiologists to distinguish malignant from reactive TTs. The main tumour mass underwent standard histological evaluation while the regions encompassing the TTs were photographed and sectioned into grids. Each tissue section was examined histologically for the presence of satellite neoplastic cells based on morphological criteria. Radiological and histological findings were compared. Six patients met the inclusion criteria and underwent analysis. All tumours were located in the extremities and were deep to fascia. Mean age at presentation was 67 years (range 51 – 85), with a male:female ratio of 4:2. All patients received radiotherapy (50 Gy), either pre- (n=4) or post-operatively (n=2) based on multidisciplinary tumor board discussion or enrolment in a prospective clinical trial. Radiologically, TTs were labelled as malignant in four patients (66.7%) and as benign TTs in two others. The tails were recognised to be malignant due to the differing signal characteristics to reactive edema on mixed MRI sequences. The radiological evaluation correlated exactly with histological analysis, as satellite neoplastic cells were identified microscopically in the same four cases in which the TTs were designated to be malignant by MRI (specificity&sensitivity=100%). Surgical resection margins were microscopically positive in 50% of cases in the TTs themselves, and 75% of cases in which TTs were designated as malignant on staging MRI. “The malignant nature of peri-lesional edema in MFS, also known as the TT, was accurately predicted in this small pilot study based on specific radiological features which correlated exactly with histologic identification of isolated tumor cells. These findings validate development of a larger prospective study to recruit additional patients with tumor tails beyond just MFS, in order to more robustly study the correlation between the MRI appearance and histological distribution of satellite sarcoma cells in peri-lesional edema in STS. We are already recruiting to this expanded radiological-histological investigation including evaluation of additional novel MRI sequences

Purpose. The focus of current management of soft tissue sarcoma on limb preservation often necessitates that patients undergo multimodal treatment, including both surgery and external beam radiotherapy. Pathologic fracture is a serious, late complication of radiotherapy. In patients who have also undergone wide excision of soft tissue sarcoma, nonunion rates of 80–90% persist despite optimal internal fixationMany sequelae of the treatments for soft tissue sarcoma exhibit the potential to perpetuate failure of bony union. Limb salvage surgery is associated with extensive periosteal excision, disruption of vascular supply and eradication of local osteoprogenitor cells. External beam radiotherapy leads to obliterative endarteritis, decreased osteoblast proliferation and reduction in bone matrix production. We hypothesize that the combination of radiotherapy and surgical periosteal stripping leads to greater impairment in the fracture repair process than either intervention alone will produce. Method. We developed a method for creating a reproducible, low energy, simple femoral fracture in an animal model designed to proceed to nonunion. Female Wistar, retired breeder rats were separated into four treatment groups of 18 animals each: control, radiotherapy, surgery and combination radiotherapy and surgery. Animals were then further randomized to temporal end-points of 21, 28 and 35 days post-fracture. Designated animals first underwent external beam radiotherapy, followed by surgical stripping of the periosteum three weeks later and femoral fracture with fixation after another three weeks. Animals were sacrificed at their randomly assigned end-points. Results. The fracture device was shown to produce simple, transverse or short oblique femoral fractures using x-rays obtained immediately following fracture, validating the reliability of the model. No significant differences were observed in the force required for fracture between treatment groups. Mineralized callus was observed in control animals and those undergoing periosteal stripping alone, but was absent in all animals receiving radiotherapy. Reactive bone formation was observed in animals undergoing periosteal stripping alone, but was absent when preceded by radiotherapyMicroCT analysis confirmed the results visualized on plain x-ray. No callus formation was observed in animals undergoing radiotherapy and significantly less mineralized callus was produced in animals undergoing periosteal stripping when compared to control. Preliminary studies have shown an absence of cellular activity in animals undergoing radiotherapy, suggesting that fracture in these animals will proceed to nonunion. Conclusion. Early results suggest that this pre-clinical model of combined radiation and surgical periosteal stripping prior to controlled fracture reliably results in nonunion. We expect to utilize this model to examine interventions designed to improve fracture healing in this difficult clinical situation

The use of endoprosthesis implants is frequent for tumours involving the proximal third of the femur and not amenable to primary arthroplasty or internal fixation. In this population, these implants are preferentially cemented given poor bone quality associated with systemic diseases and treatments. Loosening is a common complication of these implants that have been linked to poor bone quality, type of implants and importantly cementing technique. Thus, these techniques vary between different surgeons and based mainly on previous experience. One of the most successful cementing techniques in the arthroplasty literature is the French paradox. This technique involves removing the cancellous bone of the proximal femoral metaphysis and selects the largest stem to tightly fit the created cavity delineated by cortical bone. Cementing the implant results in a very thin cement layer that fills the inconsistent gaps between the metal and the bone. To our knowledge, no previous report exists in the literature assessing loosening in proximal femur replacement using the French paradox cementing technique. In this study, we sought to examine (1) rates of loosening in proximal femur replacement, and (2) the oncological outcomes including tumour recurrence and implant related complications. A retrospective study of 42 patients underwent proximal femur replacement between 1990 and 2018 at our institution. Of these, 30 patients met our inclusion criteria. Two independent reviewers have evaluated the preoperative and the most recent postoperative radiographs using the International Society of Limb Salvage (ISOLS) radiographic scoring system and Gruen classification for femoral stem loosening. Additionally, the acetabulum was evaluated for erosion according to the criteria of Baker et al. The mean age of this cohort was 60.5 (19–80), with 60% being males. The primary origin was metastatic in 17 (56.7%) patients, bone sarcoma in 10 (33.3%) patients and soft tissue sarcoma in 3 (10%) patients. Pathological fractures were present in 11 (36.7%) patients. Seven (23.3%) patients had prior intramedullary nailing. Preoperative radiotherapy was used in 8 (26.7%) and postoperative radiotherapy in 17 (56.7%) patients. The mean clinical follow-up was 25.2±26.3 months and the mean radiographical follow-up was 24.8±26 months. The mean ISOLS score for both reviewers was found to be 89±6.5% and 86.5±6.1%, respectively. Additionally, the first reviewer found two patients to be possibly loos (6.7%) compared to one (3.3%) patient for the second reviewer. No components scored as probably or definitely loose and non-required revision for either loosening or metal failure. Furthermore, both reviewers showed no acetabular erosion in 25 (83.3%) and 24 (80%) patients, respectively. On the other hand, the overall rate of complications was 36.6% with 11 complications reported in 30 patients. Local recurrence occurred in five (16.6%) patients. Prosthetic Dislocation was the most frequent complications with eight dislocations in four patients. Despite complications, our results showed no radiographic evidence of stem loosening. Cementing proximal femur prosthesis with a tight canal fit and with a thin cement mantle appears to be a viable option at short and medium term

Aim. Pubic osteomyelitis (PO) is one of less frequent Bone and Joint Infections forms (BJI). Its management is still poorly codified as far as nosological framework is still unclear in medical literature. We aim to describe PO epidemiology and to look for factors associated with management failure. Method. We performed a retrospective cohort study, carried out in two Reference Centres, including patients with PO in 2010–2016. Treatment failure was defined by: (i) persistence of clinical signs despite treatment; (ii) clinical relapse with same microorganisms; (iii) infection recurrence with one or more different microorganism(s);. (iv) new signs of infection (abscess, sinus tract) in same area, without recourse to get microbiological documentation. Factors associated with management failure were determined by univariate Cox analysis (hazard ratio [HR] and 95% confidence interval calculation). Kaplan-Meier curve were compared between groups by log-rank test. Results. Twenty-five patients were included over thirteen years (median age 67 years; 19 men, median ASA score 3). Six (24 %) had a PO from haematogenous origin. Those were all monomicrobial infection, due to S.aureus, mostly identified in young patients without comorbidities, especially in athletes. No surgery was required if no abcess or bone sequestrum were found. Nineteen patients (76 %) had a post-operative chronic PO (developed from 1 month to 11 years after a pelvic surgery); 15 of them had history of pelvic cancer (60%); 12 received radiotherapy at the site of infection (48 %). Infection was polymicrobial in 68 % of cases, including 32 % of cases with multidrug-resistant pathogens. A clinical success was recorded in only 14 patients (56%). Treatment failure was always noticed in chronic post-operative forms. Potential risk factors associated with failure management were: pelvic cancer history (HR 3.8; p=0,089); pelvic radiotherapy history (HR 2.9; p=0.122); clinical sinus tract (HR 5.1; p=0,011); infection with multidrug-resistant bacteria (HR 2.8; p=0,116), and polymicrobial infection (HR 70.5; p=0,090). Conclusions. Our study highlights predominant chronic complex post-operative forms of PO. They are mostly plurimicrobial, sometimes associated with multi-drug resistance, occurring in fragile patients with pelvic cancer. It frequently leads to complex antibiotherapy, with important risk of relapse. Aggressive surgical procedure with large bone resection is frequently required in patients who underwent pelvic radiotherapy

Major wound complication risk factors following soft tissue sarcoma resection. Wound-healing complications represent an important source of morbidity in patients treated surgically for soft tissue sarcomas (STS). The purpose of this study was to determine which factors are predictive of major wound complication rates following STS resection, including tumour site, size, grade, and depth, as well as radiotherapy and chemotherapy. We reviewed 256 cases of STS treated surgically between 2000 and 2011. The primary outcome was occurrence of major wound complications post STS resection. Major wound complications were more likely to occur post STS resection with larger tumour diameters (p = 0.001), high grade tumours (p = 0.04), location in the proximal lower extremity (p = 0.01), and use of preoperative radiotherapy (p = 0.01). Tumours located in the adductor compartment were at highest risk of complications. We did not demonstrate a significant difference in complications rates based on method of closure. Diabetes, smoking, obesity, tumour diameter, tumour location in the proximal lower extremity, and preoperative radiotherapy were independent predictors on multivariate analysis. There are multiple predictors for major wound complications post STS resection. A more aggressive resection of irradiated soft tissues, combined with primary reconstruction, should be considered in cases with multiple risk factors

Solitary plasmacytomas in the appendicular skeleton are rare monoclonal expansions of plasmacytoid cells. They are two main hazards; local destruction of bone with resultant loss of function and possible fracture, and progression to Myeloma. Between February 1988 and July 2005 seven patients (4 male, 3 female) were treated for solitary plasmacytoma with surgical resection and endoprosthetic reconstruction. The median age was 46.7 (35-75). The site was: distal humerus (2), proximal humerus (2) proximal femur (2) proximal tibia (1). Three patients had sustained a pathological fracture. Five patients had received pre-operative radiotherapy and three received post-operative radiotherapy. Mean follow-up is 8.6 years. Two cases became infected at 2 and 5 years post-operatively and have had revisions of their endoprosthesis. Both remain functional at 18 and 15 years. No patient has suffered a local recurrence. Two patients have progressed to multiple Myeloma but no patients have died. Literature review shows that the progression of solitary bone plasmacytoma to Myeloma is around 53% despite radiotherapy, in an average period of 2-4 years. With resection and endoprosthetic reconstruction, the progression in this series has been 28% despite an average follow up of 8.6 years. Although the numbers are small, due to the rarity of the condition, surgical resection and endoprosthetic reconstruction reduces disease progression than radiotherapy alone. This produces far superior results compared to the intramedullary nailing of the long bones for this condition. Endoprosthetic reconstruction after resection should be given consideration in cases of solitary plasmacytoma of the appendicular skeleton when there is extensive bone destruction present. The optimal timing of local radiotherapy to be combined with surgery is still to be established