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Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_3 | Pages 76 - 76
1 Mar 2021
Malik A Alexander J Khan S Scharschmidt T
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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


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 101 - 101
1 Dec 2022
Abbott A Kendal J Moorman S Wajda B Schneider P Puloski S Monument M
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The presence of metastatic bone disease (MBD) often necessitates major orthopaedic surgery. Patients will enter surgical care either through emergent or electively scheduled care pathways. Patients in a pain crisis or with an acute fracture are generally admitted via emergent care pathways whereas patients with identified high-risk bone lesions are often booked for urgent yet scheduled elective procedures. The purpose of this study is to compare the post-operative outcomes of patients who present through emergent or electively scheduled care pathways in patients in a Canadian health care system. We have conducted a retrospective, multicenter cohort study of all patients presenting for surgery for MBD of the femur, humerus, tibia or pelvis in southern Alberta between 2006 and 2021. Patients were identified by a search query of all patients with a diagnosis of metastatic cancer who underwent surgery for an impending or actual pathologic fracture in the Calgary, South and Central Alberta Zones. Subsequent chart reviews were performed. Emergent surgeries were defined by patients admitted to hospital via urgent care mechanisms and managed via unscheduled surgical bookings (“on call list”). Elective surgeries were defined by patients seen by an orthopaedic surgeon at least once prior to surgery, and booked for a scheduled urgent, yet elective procedure. Outcomes include overall survival from the time of surgery, hospital length of stay, and 30-day hospital readmission rate. We have identified 402 patients to date for inclusion. 273 patients (67.9%) underwent surgery through emergent pathways and 129 patients (32.1%) were treated through urgent, electively scheduled pathways. Lung, prostate, renal cell, and breast cancer were the most common primary malignancies and there was no significant difference in these primaries amongst the groups (p=0.06). Not surprisingly, emergent patients were more likely to be treated for a pathologic fracture (p<0.001) whereas elective patients were more likely to be treated for an impending fracture (p<0.001). Overall survival was significantly shorter in the emergent group (5.0 months, 95%CI: 4.0-6.1) compared to the elective group (14.9 months 95%CI: 10.4-24.6) [p<0.001]. Hospital length of stay was significantly longer in the emergent group (13 days, 95%CI: 12-16 versus 5 days, 95%CI: 5-7 days). There was a significantly greater rate of 30-day hospital readmission in the emergent group (13.3% versus 7.8%) [p=0.01]. Electively managed MBD has multiple benefits including longer post-operative survival, shorter length of hospital stay, and a lower rate of 30-day hospital readmission. These findings from a Canadian healthcare system demonstrate clinical value in providing elective orthopaedic care when possible for patients with MBD. Furthermore, care delivery interventions capable of decreasing the footprint of emergent surgery through enhanced screening or follow-up of patients with MBD has the potential to significantly improve clinical outcomes in this population. This is an ongoing study that will justify refinements to the current surgical care pathways for MBD in order to identify patients prior to emergent presentation. Future directions will evaluate the costs associated with each care delivery method to provide opportunity for health economic efficiencies


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_3 | Pages 71 - 71
1 Mar 2021
Ibe I Perera J Aoude A Griffin A Wunder J Ferguson P Tsoi K
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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.”


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_3 | Pages 69 - 69
1 Mar 2021
Bozzo A Seow H Pond G Ghert M
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Population-based studies from the United States have reported that sarcoma patients living in rural areas or belonging to lower socioeconomic classes experience worse overall survival; however, the evidence is not clear for universal healthcare systems where financial resources should theoretically not affect access to standard of care. The purpose of this study was to determine the survival outcomes of soft-tissue sarcoma (STS) patients treated in Ontario, Canada over 23 years and determine if the patient's geographic location or income quintile are associated with survival. We performed a population-based cohort study using linked administrative databases of patients diagnosed with STS between 1993 – 2015. The Kaplan-Meier method was used to estimate 2, 5, 10, 15 and 20-year survival stratified by age, stage and location of tumor. We estimated survival outcomes based on the patient's geographic location and income quintile. The Log-Rank test was used to detect significant differences between groups. If groups were significantly different, a Cox proportional hazards model was used to test for interaction effects with other patient variables. We identified 8,896 patients with biopsy-confirmed STS during the 23-year study period. Overall survival following STS diagnosis was 70% at 2 years, 59% at 5 years, 50% at 10 years, 43% at 15 years, and 38% at 20 years. Living in a rural location (p=0.0028) and belonging to the lowest income quintile (p<0.0001) were independently associated with lower overall survival following STS diagnosis. These findings were robust to tests of interaction with each other, age, gender, location of tumor and stage of disease. This population-based cohort study of 8,896 STS patients treated in Ontario, Canada over 23 years reveals that patients living in a rural area and belonging to the lowest income quintile are at risk for decreased survival following STS diagnosis. We extend previous STS survival reporting by providing 15 and 20-year survival outcomes stratified by age, stage, and tumor location


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_3 | Pages 62 - 62
1 Mar 2021
Lee J Perera J Trottier ER Tsoi K Hopyan S
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Paediatric bone sarcomas around the knee are often amenable to either endoprosthetic reconstruction or rotationplasty. Cosmesis and durability dramatically distinguish these two options, although patient-reported functional satisfaction has been similar among survivors. However, the impact on oncological and surgical outcomes for these approaches has not been directly compared. We retrospectively reviewed all wide resections for bone sarcoma of the distal femur or proximal tibia that were reconstructed either with an endoprosthesis or by rotationplasty at our institution between June 2004 and December 2014 with a minimum two year follow-up. Pertinent demographic information, surgical and oncological outcomes were reviewed. Survival analysis was performed using the Kaplan-Meier method with statistical significance set at p<0.05. Thirty eight patients with primary sarcomas around the knee underwent wide resection and either endoprosthetic reconstruction (n=19) or rotationplasty (n=19). Groups were comparable in terms of demographic parameters and systemic tumour burden at presentation. We found that selection of endoprosthetic reconstruction versus rotationplasty did not impact overall survival for the entire patient cohort but was significant in subgroup analysis. Two-year overall survival was 86.7% and 85.6% in the endoprosthesis and rotationplasty groups, respectively (p=0.33). When only patients with greater than 90% chemotherapy-induced necrosis were considered, overall survival was significantly better in the rotationplasty versus endoprosthesis groups (100% vs. 72.9% at two years, p=0.013). Similarly, while event-free survival was not affected by reconstruction method (60.2% vs. 73.3% at two years for endoprosthesis vs rotationplasty, p=0.27), there was a trend towards lower local recurrence in rotationplasty patients (p=0.07). When surgical outcomes were considered, a higher complication rate was seen in patients that received an endoprosthesis compared to those who underwent rotationplasty. Including all reasons for re-operation, 78.9% (n=15) of the endoprosthesis patients required a minimum of one additional surgery compared with only 26.3% (n=5) among rotationplasty patients (p=0.003). The most common reasons for re-operation in endoprosthesis patients were wound breakdown/infection (n=6), limb length discrepancy (n=6) and periprosthetic fracture (n=2). Excluding limb length equalisation procedures, the average time to re-operation in this patient population was 5.6 months (range 1 week to 23 months). Similarly, the most common reason for a secondary procedure in rotationplasty patients was wound breakdown/infection, although only two patients experienced this complication. Average time to re-operation in this group was 23.8 months (range 5 to 49 months). Endoprosthetic reconstruction and rotationplasty are both viable limb-salvage options following wide resection of high-grade bony sarcomas located around the knee in the paediatric population. Endoprosthetic reconstruction is associated with a higher complication rate and may negatively impact local recurrence. Study of a larger number of patients is needed to determine whether the reconstructive choice affects survival


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_2 | Pages 1 - 1
10 Feb 2023
Sundaram A Perianayagam G Hong A Mar J Lo H Lawless A Carey Smith R
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The Australia and New Zealand Sarcoma Association established the Sarcoma Guidelines Working Party to develop national guidelines for the management of Sarcoma. We asked whether surgery at a specialised centre improves outcomes. A systematic review was performed of all available evidence pertaining to paediatric or adult patients treated for bone or soft tissue sarcoma at a specialised centre compared with non-specialised centres. Outcomes assessed included local control, limb salvage rate, 30-day and 90-day surgical mortality, and overall survival. Definitive surgical management at a specialised sarcoma centre improves local control as defined by margin negative surgery, local or locoregional recurrence, and local recurrence free survival. Limb conservation rates are higher at specialised centres, due in part to the depth of surgical experience and immediate availability of multidisciplinary and multimodal therapy. A statistically significant correlation did not exist for 30-day and 90-day mortality between specialised centres and non-specialised centres. The literature is consistent with improved survival when definitive surgical treatment is performed at a specialised sarcoma centre. Evidence-based recommendation: Patients with suspected sarcoma to be referred to a specialised sarcoma centre for surgical management to reduce the risk of local recurrence, surgical complication, and to improve limb conservation and survival. Practice point: Patients with suspected sarcoma should be referred to a specialised sarcoma centre early for management including planned biopsy


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_3 | Pages 63 - 63
1 Mar 2021
Bozzo A Deng J Bhasin R Deodat M Abbas U Wariach S Axelrod D Masrouha K Wilson D Ghert M
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Lung cancer is the most common cancer diagnosed, the leading cause of cancer-related deaths, and bone metastases occurs in 20–40% of lung cancer patients. They often present symptomatically with pain or skeletal related events (SREs), which are independently associated with decreased survival. Bone modifying agents (BMAs) such as Denosumab or bisphosphonates are routinely used, however no specific guidelines exist from the National Comprehensive Cancer Center or the European Society of Medical Oncologists. Perhaps preventing the formation of guidelines is the lack of a high-quality quantitative synthesis of randomized controlled trial (RCT) data to determine the optimal treatment for the patient important outcomes of 1) Overall survival (OS), 2) Time to SRE, 3) SRE incidence, and 4) Pain Resolution. The objective of this study was to perform the first systematic review and network meta-analysis (NMA) to assess the best BMA for treatment of metastatic lung cancer to bone. We conducted our study in accordance to the PRISMA protocol. We performed a librarian assisted search of MEDLINE, PubMed, EMBASE, and Cochrane Library and Chinese databases including CNKI and Wanfang Data. We included studies that are RCTs reporting outcomes specifically for lung cancer patients treated with a bisphosphonate or Denosumab. Screening, data extraction, risk of bias and GRADE were performed in duplicate. The NMA was performed using a Bayesian probability model with R. Results are reported as relative risks, odds ratios or mean differences, and the I2 value is reported for heterogeneity. We assessed all included articles for risk of bias and applied the novel GRADE framework for NMAs to rate the quality of evidence supporting each outcome. We included 132 RCTs comprising 11,161 patients with skeletal metastases from lung cancer. For OS, denosumab was ranked above zoledronic acid (ZA) and estimated to confer an average of 3.7 months (95%CI: −0.5 – 7.6) increased survival compared to untreated patients. For time to SRE, denosumab was ranked first with an average of 9.1 additional SRE-free months (95%CI: 4.0 – 14.0) compared to untreated patients, while ZA conferred an additional 4.8 SRE-free months (2.4 – 7.0). Patients treated with the combination of Ibandronate and systemic therapy were 2.3 times (95%CI: 1.7 – 3.2) more likely to obtain successful pain resolution, compared to untreated. Meta-regression showed no effect of heterogeneity length of follow-up or pain scales on the observed treatment effects. Heterogeneity in the network was considered moderate for overall survival and time to SRE, mild for SRE incidence, and low for pain resolution. While a generally high risk of bias was observed across studies, whether they were from Western or Chinese databases. The overall GRADE for the evidence underlying our results is High for Pain control and SRE incidence, and Moderate for OS and time to SRE. This study represents the most comprehensive synthesis of the best available evidence guiding pharmacological treatment of bone metastases from lung cancer. Denosumab is ranked above ZA for both overall survival and time to SRE, but both treatments are superior to no treatment. ZA was first among all bisphosphonates assessed for odds of reducing SRE incidence, while the combination of Ibandronate and radionuclide therapy was most effective at significantly reducing pain from metastases. Clinicians and policy makers may use this synthesis of all available RCT data as support for the use of a BMA in MBD for lung cancer


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_8 | Pages 38 - 38
1 Aug 2020
Mattei J Alshaygy I Basile G Griffin A Wunder JS Ferguson P
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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


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 97 - 97
1 Dec 2022
Burke Z Lazarides A Gundavda M Griffin A Tsoi K Ferguson P Wunder JS
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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


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 94 - 94
1 Dec 2022
Lazarides A Novak R Burke Z Gundavda M Ghert M Rose P Houdek M Wunder JS Ferguson P Griffin A Tsoi K
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Radiation induced sarcoma of bone is a rare but challenging disease process associated with a poor prognosis. To date, series are limited by small patient numbers; data to inform prognosis and the optimal management for these patients is needed. We hypothesized that patients with radiation-induced pelvic bone sarcomas would have worse surgical, oncologic, and functional outcomes than patients diagnosed with primary pelvic bone sarcomas. This was a multi-institution, comparative cohort analysis. A retrospective chart review was performed of all patients diagnosed with a radiation-induced pelvic and sacral bone sarcoma between January 1st, 1985 and January 1st, 2020 (defined as a histologically confirmed bone sarcoma of the pelvis in a previously irradiated field with a minimum 3-year interval between radiation and sarcoma diagnosis). We also identified a comparison group including all patients diagnosed with a primary pelvic osteosarcoma/spindle cell sarcoma of bone (i.e. eligible for osteosarcoma-type chemotherapy) during the same time interval. The primary outcome measure was disease-free and overall survival. We identified 85 patients with primary osteosarcoma of the pelvis (POP) and 39 patients with confirmed radiation induced sarcoma of the bony pelvis (RISB) undergoing surgical resection. Patients with RISB were older than patients with POP (50.5 years vs. 36.5 years, p67.7% of patients with POP underwent limb salvage as compared to 77% of patients with RISB; the type of surgery was not different between groups (p=.0.24). There was no difference in the rate of margin positive surgery for RISB vs. POP (21.1% vs. 14.1%, p=0.16). For patients undergoing surgical resection, the rate of surgical complications was high, with more RISB patients experiencing complications (79.5%) than POP patients (64.7%); this approached statistical significance (p=0.09). 15.4% of patients with RISB died perioperative period (within 90 days of surgery) as compared to 3.5% of patients with POP (p= 0.02). For patients undergoing surgical resection, 5-year OS was significantly worse for patients with RISB vs. POP (27.3% vs. 47.7%, p=0.02). When considering only patients without metastatic disease at presentation, a significant difference in 5-year survival remains for patients with RISB vs. POP (28.6% vs. 50%, p=0.03) was a trend towards poorer 5-year DFS for patients with RISB vs. POP (30% vs. 47.5%), though this did not achieve statistical significance (p=0.09). POP and RISB represent challenging disease processes and the oncologic outcomes are similarly poor between the two; however, the disease course for patients with RISB appears to be worse overall. While surgery can result in a favorable outcome for a small subset of patients, surgical treatment is fraught with complications


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_12 | Pages 51 - 51
1 Dec 2022
Gazendam A Bali K Tushinski D Petruccelli D Winemaker MJ de Beer J Wood T
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During total knee arthroplasty (TKA), a tourniquet is often used intraoperatively. There are proposed benefits of tourniquet use including shorter duration of surgery, improved surgical field visualization and increased cement penetration which may improve implant longevity. However, there are also cited side effects that include increased post-operative pain, slowed recovery, skin bruising, neurovascular injury and quadriceps weakness. Randomized controlled trials have demonstrated no differences in implant longevity, however they are limited by short follow-up and small sample sizes. The objective of the current study was to evaluate the rates of revision surgery among patients undergoing cemented TKA with or without an intraoperative tourniquet and to understand the causes and risk factors for failure. A retrospective cohort study was undertaken of all patients who received a primary, cemented TKA at a high-volume arthroplasty centre from January 1999 to December 2010. Patients who underwent surgery without the use of a tourniquet and those who had a tourniquet inflated for the entirety of the case were included. The causes and timing of revision surgery were recorded and cross referenced with the Canadian Institute of Health Information Discharge Abstract Database to reduce the loss to follow-up. Survivorship analysis was performed with the use of Kaplan-Meier curves to determine overall survival rates at final follow-up. A Cox proportional hazards model was utilized to evaluate independent predictors of revision surgery. Data from 3939 cases of primary cemented TKA were available for analysis. There were 2276 (58%) cases in which a tourniquet was used for the duration of the surgery and 1663 (42%) cases in which a tourniquet was not utilized. Mean time from the primary TKA was 14.7 years (range 0 days - 22.8 years) when censored by death or revision surgery. There were 150 recorded revisions in the entire cohort, with periprosthetic joint infection (n=50) and aseptic loosening (n=41) being the most common causes for revision. The cumulative survival at final follow-up for the tourniquetless group was 93.8% at final follow-up while the cumulative survival at final follow-up for the tourniquet group was 96.9% at final follow-up. Tourniquetless surgery was an independent predictor for all-cause revision with an HR of 1.53 (95% CI 1.1, 2.1, p=0.011). Younger age and male sex were also independent factors for all cause revision. The results of the current study demonstrate higher all-cause revision rates with tourniquetless surgery in a large cohort of patients undergoing primary cemented TKA. The available literature consists of short-term trials and registry data, which have inherent limitations. Potential causes for increased revision rates in the tourniquetless group include reduced cement penetration, increased intraoperative blood loss and longer surgical. The results of the current study should be taken into consideration, alongside the known risks and benefits of tourniquet use, when considering intraoperative tourniquet use in cemented TKA


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_20 | Pages 40 - 40
1 Nov 2016
Laflamme C Mottard S Dionne J Isler M Ahmad I
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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


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_3 | Pages 54 - 54
23 Feb 2023
Boyle R Stalley P Franks D Guzman M Maher A Scholes C
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We present the indications and outcomes of a series of custom 3D printed titanium acetabular implants used over a 9 year period at our institution (Sydney, Australia), in the setting of revision total hip arthroplasty. Individualised image-based case planning with additive manufacturing of pelvic components was combined with screw fixation and off-the-shelf femoral components to treat patients presenting with failed hip arthroplasty involving acetabular bone loss. Retrospective chart review was performed on the practices of three contributing surgeons, with an initial search by item number of the Medicare Benefits Scheme linked to a case list maintained by the manufacturer. An analysis of indications, patient demographics and clinical outcome was performed. The cohort comprised 65.2% female with a median age of 70 years (interquartile range 61–77) and a median follow up of 32.9 months (IQR 13.1 - 49.7). The indications for surgery were infection (12.5%); aseptic loosening (78.1%) and fracture (9.4%), with 65.7% of cases undergoing previous revision hip arthroplasty. A tumour prosthesis was implanted into the proximal femur in 21.9% of cases. Complications were observed in 31.3% of cases, with four cases requiring revision procedures and no deaths reported in this series. Kaplan-Meier analysis of all-cause revision revealed an overall procedure survival of 88.7% at two years (95%confidence interval 69 - 96.2) and 83.8% (95%CI 62 - 93.7) at five years, with pelvic implant-specific survival of 98% (95%CI 86.6 - 99.7) at two and five year follow up. We conclude that an individualised planning approach for custom 3D printed titanium acetabular implants can provide high overall and implant-specific survival at up to five years follow up in complex cases of failed hip arthroplasty and acetabular bone loss


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 42 - 42
1 Oct 2022
Goosen J Weegen WVD Rijnen W Eck JV Liu W
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Aim. To date, the value of culture results after a debridement, antibiotics and implant retention (DAIR) for early (suspected) prosthetic joint infection (PJI) as risk indicators in terms of prosthesis retention is not clear. At one year follow-up, the relative risk of prosthesis removal was determined for culture-positive and culture-negative DAIRs after primary total hip or knee arthroplasty. The secondary aim was to explore differences in patient characteristics, infection characteristics and outcomes between these two groups. Methods. A retrospective regional registry study was performed in a group of 359 patients (positive cultures: n = 299, negative cultures n = 60) undergoing DAIR for high suspicion of early PJI in the period from 2014 to 2019. Differences in patient characteristics, deceased patients and number of subsequent DAIRs between the positive and negative DAIR groups were analyzed using independent t-tests, Mann-Whitney, Pearson's Chi-square tests and Fisher's Exact tests. Results. Overall implant survival rate following DAIR was 89%. The relative risk for prosthesis removal was 7.4 times higher (95% confidence interval (CI) 1.0–53.1) in the positive DAIR group (37/299, 12.4%) compared to the negative DAIR group (1/60, 1.7%). The positive group had a higher body mass index (p = 0.034), rate of wound leakage of >10 days (p = 0.016) and more subsequent DAIRs (p = 0.006). Conclusion. Since implant survival results after DAIR are favorable, the threshold to perform a DAIR procedure in early PJI should be low in order to retain the prosthesis. A DAIR procedure in case of negative cultures does not seem to have unfavorable results in terms of prosthesis retention


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_3 | Pages 73 - 73
1 Mar 2021
Lazarides A Somarelli J Altunel E Rao S Hoskinson S Cheng S Eward C Hsu D Eward W
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Osteosarcoma (OSA) is a rare, but disproportionately lethal cancer that predominantly affects children. Sadly, discovery of new therapies for OSA has largely been unsuccessful in the past 30 years; there is an urgent need to identify new treatments for OSA. Pet dogs with naturally-occurring OSA represent a unique comparative “model” to discover new treatments for OSA. Unlike humans, in which fewer than 1,000 cases of OSA occur each year, there are nearly 50,000 new cases each year of OSA in dogs. In addition, dogs have an intact immune system, a shared environment with humans, and more rapid progression of disease. Together these factors make dogs an important comparative model for new therapies for OSA. The purpose of this study was: 1) to validate this mouse-dog-human pipeline for drug discovery and 2) to validate CRM1 as a novel target for ostesoarcoma treatment. We developed patient-derived cell lines and xenografts of OSA from both dogs and humans and applied these models to identify new therapies for OSA using high-throughput drug screens in vitro followed by in vivo validation. Whole exome sequencing was performed on the patient-derived models and original tumors to identify potential driver mutations. A high-throughput screen in both dog and human OSA identified CRM1 inhibitors as effective at killing dog and human OSA patient-derived cell lines in vitro. In vivo, CRM1 inhibition led to significant tumor growth inhibition in patient-derived xenografts from dogs and humans. Western blotting demonstrated increased levels of CRM1 protein expression across nine different dog and human OSA cell lines compared to non-transformed human osteoblasts. CRM1 upregulation in OSA cells was further verified by immunofluorescence staining. Increased CRM1 expression was prognostic for poorer metastasis-free survival and poorer overall survival. Our cross-species personalized medicine pipeline identified CRM1 as a potential therapeutic target to treat OSA in both dogs and humans. Future studies are focused on testing CRM1 inhibitors in canine clinical trials


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_3 | Pages 65 - 65
1 Mar 2021
Perera J Ibe I Aoude A Griffin A Ferguson P Wunder J Tsoi K
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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


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_8 | Pages 4 - 4
1 Aug 2020
Basile G Alshaygy I Mattei J Griffin A Ferguson P Wunder JS
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Lymph node metastasis are a rare occurrence in soft tissue sarcomas of the extremity, arising in less than 5% of patients. Few studies have evaluated the prognosis and survival of patients with a lymph node metastasis. Early reports compared lymph node involvement to lung metastasis, while others suggested a slightly better outcome. The purpose of this study was to evaluate the impact of lymph node metastasis on patient survival and to investigate the histologic and clinical features associated with lymph node involvement. A retrospective review was done of the prospectively collected soft tissue sarcoma database at our institution. Two thousand forty-five patients had surgery for soft tissue sarcoma of an extremity between January 1986 and August 2017. Included patients either presented with a synchronous lymph node metastasis or were diagnosed with a lymph node metastasis after their initial treatment. Demographic, treatment, and outcome data for patients with lymph node involvement were obtained from the clinical and radiographic records. Lymph node metastases were identified as palpable adenopathy by physical examination and were further characterized on cross-sectional imaging by computed tomography (CT) or magnetic resonance imaging (MRI) scans. All cases were confirmed by pathologic examination of biopsy specimens. A pathologist with expertise in sarcoma determined the histologic type and graded tumors as 1, 2, or 3. One hundred eighteen patients with a mean age of 55.7 (SD=18.9) were included in our study. Seventy-two (61.3%) out of 119 patients were male. Thirty six patients (57.1%) had lymph node involvement at diagnosis. The mean follow-up from the date of the first surgery was 56.3 months. The most common histological diagnoses were Malignant fibrous histiocytoma (35) and liposarcoma (12). Ninety eight patients (89%) underwent surgical treatment of the lymph node metastasis while 21 (17.6%) were treated with chemotherapy and/or radiation therapy. The mean survival was 52.6 months (range 1–307). Our results suggest that patients with a lymph node metastasis have a better prognosis than previously described. Their overall survival is superior to patients diagnosed with lung metastasis. A signifant proportion of patients may expect long term survival after surgical excision of lymph node metastasis. Furthermore, our study also indicates that different histological subtypes such as liposarcoma or malignant peripheral nerve sheath tumor (MPNST) may also be responsible for lymph node metastasis. Additional studies to further improve the treatment of soft tissue sarcoma nodal metastasis are warranted


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_1 | Pages 37 - 37
1 Feb 2020
Veettil M Tsuda Y Abudu A Tillman R
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Aim. We present the long-term surgical outcomes, complications, implant survival and causes of implant failure in patients treated with the modified Harrington procedure using antegrade large diameter pins. Patients and Methods. A cohort of 50 consecutive patients who underwent the modified Harrington procedure along with cemented THA for peri-acetabular metastasis or haematological malignancy between 1990 and April 2018 were studied. The median follow-up time for all patients was 14 years (interquartile range, 9 – 16 years). Results. The 5-year overall survival rate was 33% for all the patients. However, implant survival rates were 100% and 46% at 5 and 10 years respectively. Eight patients survived beyond 5 years. There was no immediate peri-operative mortality or complications. Fifteen late complications occurred in 11 patients (22%). Five (10%) patients required additional surgeries to treat complications. The most frequent complication was pin breakage without evidence of acetabular loosening (6%). Two patients (4%) underwent revision for aseptic loosening at 6.5 and 8.9 years after surgery. Ambulatory status improved in 83%. Conclusions. The modified Harrington procedure for acetabular destruction showed low complication rates, good functional outcome and improved pain relief in selected patients. Long-term results are acceptable in this high risk group of patients. The described procedure using antegrade fully threaded large diameter pins combined with standard arthroplasty showed low rates of complications in this high risk cohort of patients with significant improvement in mobility and pain. This method of reconstruction remains robust for at least 5 years in appropriately selected group of patients


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_6 | Pages 124 - 124
1 Jul 2020
Woodmass J Wagner E Borque K Chang M Welp K Warner J
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Chronic massive irreparable rotator cuff tears represent a treatment challenge and the optimal surgical technique remains controversial. Superior capsular reconstruction (SCR) has been proposed as a means to provide superior stability to the glenohumeral joint, thus facilitating restoration of shoulder function. However, despite the growing use of SCR there is a paucity of data evaluating the outcomes when performed using a dermal allograft. The purpose of this study was to (1) report the overall survival rate (reoperation and clinical failure) of SCR (2) evaluate for pre-operative factors predicting reoperation and clinical failure. From January 1, 2015 to November 31, 2017, 65 patients were diagnosed with irreparable rotator cuff tears and consented for a superior capsular reconstruction. These surgeries were performed by 6 surgeons, all fellowship trained in either sports or shoulder and elbow fellowships. Outcomes were graded as excellent, satisfactory, or unsatisfactory using the modified Neer scale. An unsatisfactory result was defined as a clinical “failure”. The Kaplan-Meier survival models were created to analyze reoperation-free and failure-free survival for the entire group. The reconstruction was performed using a dermal allograft. There were 31 patients excluded due to insufficient follow-up (< 6 months), leaving 34 included in this study. The mean follow-up was 12 months (range, 6–23). The average number of prior surgeries was 0.91 (range, 0–5), with 52.9% of patients receiving a prior rotator cuff repair and 38.2% of patients with a prior non-rotator cuff arthroscopy procedure. The one and two-year survival-free of surgery was 64% and 44% and the one and two-year survival free of failure was 34% and 16% following SCR, respectively. For the patients that underwent a reoperation, 62.5% (n= 5/8) underwent reverse shoulder replacements, 25% (n= 2/8) latissimus dorsi tendon transfers, and 12.5% (n= 1/8) a diagnostic arthroscopy. The average period between the primary and revision surgery was 10.2 months (range, 2.1–18.5). All but two patients (75%, n= 6/8) had at least one surgery prior to the SCR. There were 14/34 (41.2%) patients who experienced pain, weakness, and restricted range of motion. These patients were defined as clinical failures with an unsatisfactory grading on Neer's criteria. Previous surgery predicted reoperation (80% vs 43%, p = 0.03). Female gender predicted clinical failure (100% vs 43%, p < 0 .01). Superior Capsule Reconstruction performed for large to massive rotator cuff tears has a high rate of persistent pain and limited function leading to clinical failure in 65% (n= 22/34) of patients. The rate of failure is increased in revision cases, female gender and increased Goutallier fatty infiltration of the infraspinatus. Narrowed indications are recommended given the surgical complexity and high rate of early failure


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_20 | Pages 37 - 37
1 Nov 2016
Gupta S Kafchinski L Gundle K Saidi K Griffin A Ferguson P Wunder J
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Biological reconstruction techniques after diaphyseal tumour resection have increased in popularity in recent years. High complication and failure rates have been reported with intercalary allografts, with recent studies questioning their role in limb-salvage surgery. We developed a technique in which large segment allografts are augmented with intramedullary cement and fixed using compression plating. The goal of this study was to evaluate the survivorship, complications and functional outcomes of these intercalary reconstructions. Forty-two patients who had reconstruction with an intercalary allograft following tumour resection between 1989 and 2010 were identified from our prospectively collected database. Allograft survival, local recurrence-free, disease-free and overall survival were assessed using the Kaplan-Meier method. Patient function was assessed using the Musculoskeletal Tumour Society (MSTS) scoring system and the Toronto Extremity Salvage Score (TESS). The 23 women and 19 men had a mean age of 33 years (14–77). The most common diagnoses were osteosarcoma (n=16) and chondrosarcoma (n=9). There were 9 humerus, 18 femur and 15 tibia reconstructions. At a mean follow-up of 95 months (5–288), 31 patients were alive without disease, 10 were dead of disease and 1 was deceased of other causes. There were 4 local recurrences and 11 patients developed metastatic disease. 5-year local recurrence free survival was 92%, 5-year disease-free survival was 70% and overall survival was 75%. Fourteen of 42 patients (33%) experienced complications: 5 wound healing complications, 4 infections, 2 non-unions, 2 fractures and 1 nerve palsy. Four allografts (9.5%) were revised for complications and 2 (5%) for local recurrence. Mean allograft survival was 85 months (4–288). Mean time to union was 8.2 (3–36) months for the proximal osteotomy site and 8.1 (3–23) months for the distal osteotomy site. The mean score for MSTS 87 was 29.4 (+/− 4.4), MSTS 93 was 83.7 (+/−14.8) and TESS was 81.6 (+/−16.9). An intercalary allograft augmented with intramedullary cement and compression plate fixation provides a reliable and durable method of reconstruction after tumour resection. Complication rates are comparable to the literature and are associated with high levels of patient function and satisfaction