Cartilage lesions vary in the spectrum from benign enchondromas to highly malignant dedifferentiated chondrosarcomas. From the treatment perspective, enchondromas are observed, Grade 1 chondrosarcomas are curetted like aggressive benign tumors, and rest are resected like other sarcomas. Although biopsy for tissue diagnosis is the gold standard for diagnosis and grade determination in chondrosarcoma, tumor heterogeneity limits the grading in patients following a biopsy. In the absence of definite pre-treatment grading, a surgeon is therefore often in a dilemma when deciding the best treatment option. Radiology has identified aggressive features and aggressiveness scores have been used to try and grade these tumors based on the imaging characteristics but there have been very few published reports with a uniform group and large number of cases to derive a consistent scoring and correlation. The authors asked these study questions :(1) Does Radiology Aggressiveness and its Score correlate with the grade of chondrosarcoma? (2) Can a cut off Radiology Agressiveness Score value be used to guide the clinician and add value to needle biopsy information in offering histological grade dependent management? A retrospective analysis of patients with long bone extremity intraosseous primary chondrosarcomas were correlated with the final histology grade for the operated patients and Radiological parameters with 9 parameters identified a priori and from published literature (radiology aggressiveness scores - RAS) were evaluated and tabulated. 137 patients were identified and 2 patients were eliminated for prior surgical intervention. All patients had tissue diagnosis available and pre-treatment local radiology investigations (radiographs and/or CT scans and MRI scans) to define the RAS parameters. Spearman correlation has indicated that there was a significant positive association between RAS and final histology grading of long bone primary intraosseous chondrosarcomas. We expect higher RAS values will provide grading information in patients with inconclusive pre-surgery biopsy to tumor grades and aid in correct grade dependant surgical management of the lesion. Prediction of dedifferentiated chondrosarcoma from higher RAS will be attempted and a correlation to obtain a RAS cut off, although this may be challenging to achieve due to the overlap of features across the intermediate grade, high grade and dedifferentiated grades. Radiology Aggressiveness correlates with the histologic grade in long bone extremity primary chondrosarcomas and the correlation of radiology and biopsy can aid in treatment planning by guiding us towards a low-grade neoplasm which may be dealt with intralesional extended curettage or high-grade lesion which need to be resected. Standalone RAS may not solve the grading dilemma of primary long bone intraosseous chondrosarcomas as the need for tissue diagnosis for confirming atypical cartilaginous neoplasm cannot be eliminated, however in the event of a needle biopsy grade or inconclusive open biopsy it may guide us towards a correlational diagnosis along with radiology and pathology for grade based management of the chondrosarcoma.
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.
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.
Novel immersive virtual reality (IVR) technologies are revolutionizing medical education. Virtual anatomy education using head-mounted displays allows users to interact with virtual anatomical objects, move within the virtual rooms, and interact with other virtual users. While IVR has been shown to be more effective than textbook learning and 3D computer models presented in 2D screens, the effectiveness of IVR compared to cadaveric models in anatomy education is currently unknown. In this study, we aim to compare the effectiveness of IVR with direct cadaveric bone models in teaching upper and lower limb anatomy for first-year medical students. A randomized, double-blind crossover non-inferiority trial was conducted. Participants were first-year medical students from a single University. Exclusion criteria included students who undertook prior undergraduate or graduate degrees in anatomy. In the first stage of the study, students were randomized in a 1:1 ratio to IVR or cadaveric bone groups studying upper limb skeletal anatomy. All students were then crossed over and used cadaveric bone or IVR to study lower limb skeletal anatomy. All students in both groups completed a pre-and post-intervention knowledge test. The educational content was based on the University of Toronto Medical Anatomy Curriculum. The Oculus Quest 2 Headsets (Meta Technologies) and PrecisionOS Anatomy application (PrecisionOS Technology) were utilized for the virtual reality component. The primary endpoint of the study was student performance on the pre-and post-intervention knowledge tests. We hypothesized that student performance in the IVR groups would be comparable to the cadaveric bone group. 50 first-year medical students met inclusion criteria and were computer randomized (1:1 ratio) to IVR and cadaveric bone group for upper limb skeletal anatomy education. Forty-six students attended the study, 21 completed the upper limb modules, and 19 completed the lower limb modules. Among all students, average score on the pre-intervention knowledge test was 14.6% (Standard Deviation (SD)=18.2%) and 25.0% (SD=17%) for upper and lower limbs, respectively. Percentage increase in students’ scores between pre-and post-intervention knowledge test, in the upper limb for IVR, was 15 % and 16.7% for cadaveric bones (p = 0. 2861), and for the lower limb score increase was 22.6% in the IVR and 22.5% in the cadaveric bone group (p = 0.9356). In this non-inferiority crossover randomized controlled trial, we found no significant difference between student performance in knowledge tests after using IVR or cadaveric bones. Immersive virtual reality and cadaveric bones were equally effective in skeletal anatomy education. Going forward, with advances in VR technologies and anatomy applications, we can expect to see further improvements in the effectiveness of these technologies in anatomy and surgical education. These findings have implications for medical schools having challenges in acquiring cadavers and cadaveric parts.
The reconstruction of peri-acetabular defects after severe bone loss or pelvic resection for tumor is among the most challenging surgical intervention. The Lumic® prosthesis (Implantcast, Buxtehude, Germany) was first introduced in 2008 in an effort to reduce the mechanical complications encountered with the classic peri-acetabular reconstruction techniques and to improve functional outcomes. Few have evaluated the results associated with the use of this recent implant. A retrospective study from five Orthopedic Oncology Canadian centers was conducted. Every patient in whom a Lumic® endoprosthesis was used for reconstruction after peri-acetabular resection or severe bone loss with a minimal follow-up of three months was included. The charts were reviewed and data concerning patients’ demographics, peri-operative characteristics and post-operative complications was collected. Surgical and functional outcomes were also assessed. Sixteen patients, 11 males and five females, were included and were followed for 28 months [3 – 60]. Mean age was 55 [17–86], and mean BMI reached 28 [19.6 – 44]. Twelve patients (75%) had a Lumic® after a resection of a primary sarcoma, two following pelvic metastasis, one for a benign tumor and one after a comminuted acetabular fracture with bone loss. Twelve patients (75%) had their surgery performed in one stage whereas four had a planned two-stage procedure. Mean surgical time was 555 minutes [173-1230] and blood loss averaged 2100 mL [500-5000]. MSTS score mean was 60.3 preoperatively [37.1 – 97] and 54.3 postoperatively [17.1-88.6]. Five patients (31.3%) had a cemented Lumic® stem. All patients got the dual mobility bearing, and 10 patients (62.5%) had the largest acetabular cup implanted (60 mm). In seven of these 10 patients the silver coated implant was used to minimize risk of infection. Five patients (31.3%) underwent capsular reconstruction using a synthetic fabric aiming to reduce the dislocation risk. Five patients had per-operative complications (31.3%), four were minor and one was serious (comminuted iliac bone fracture requiring internal fixation). Four patients dislocated within a month post-operatively and one additional patient sustained a dislocation one year post-operatively. Eight patients (50%) had a post-operative surgical site infection. All four patients who had a two-stage surgery had an infection. Ten patients (62.5%) needed a reoperation (two for fabric insertion, five for wash-outs, and three for implant exchange/removal). One patient (6.3%) had a septic loosening three years after surgery. At the time of data collection, 13 patients (81.3%) were alive with nine free of disease. Silver coating was not found to reduce infection risk (p=0.2) and capsuloplasty did not prevent dislocation (p=1). These results are comparable to the sparse data published. Lumic® endoprosthesis is therefore shown to provide good functional outcomes and low rates of loosening on short to medium term follow-up. Infection and dislocation are common complications but we were unable to show benefits of capsuloplasty and of the use of silver coated implants. Larger series and longer follow-ups are needed.
The reconstruction of peri-acetabular defects after severe bone loss or pelvic resection for tumor is among the most challenging surgical intervention. The Lumic® prosthesis (Implantcast, Buxtehude, Germany) was first introduced in 2008 in an effort to reduce the mechanical complications encountered with the classic peri-acetabular reconstruction techniques and to improve functional outcomes. Few have evaluated the results associated with the use of this recent implant. A retrospective study from five Orthopedic Oncology Canadian centers was conducted. Every patient in whom a Lumic® endoprosthesis was used for reconstruction after peri-acetabular resection or severe bone loss with a minimal follow-up of three months was included. The charts were reviewed and data concerning patients’ demographics, peri-operative characteristics and post-operative complications was collected. Surgical and functional outcomes were also assessed. Sixteen patients, 11 males and five females, were included and were followed for 28 months [3 – 60]. Mean age was 55 [17-86], and mean BMI reached 28 [19.6 – 44]. Twelve patients (75%) had a Lumic® after a resection of a primary sarcoma, two following pelvic metastasis, one for a benign tumor and one after a comminuted acetabular fracture with bone loss. Twelve patients (75%) had their surgery performed in one stage whereas four had a planned two-stage procedure. Mean surgical time was 555 minutes [173-1230] and blood loss averaged 2100 mL [500-5000]. MSTS score mean was 60.3 preoperatively [37.1 – 97] and 54.3 postoperatively [17.1-88.6]. Five patients (31.3%) had a cemented Lumic® stem. All patients got the dual mobility bearing, and 10 patients (62.5%) had the largest acetabular cup implanted (60 mm). In seven of these 10 patients the silver coated implant was used to minimize risk of infection. Five patients (31.3%) underwent capsular reconstruction using a synthetic fabric aiming to reduce the dislocation risk. Five patients had per-operative complications (31.3%), four were minor and one was serious (comminuted iliac bone fracture requiring internal fixation). Four patients dislocated within a month post-operatively and one additional patient sustained a dislocation one year post-operatively. Eight patients (50%) had a post-operative surgical site infection. All four patients who had a two-stage surgery had an infection. Ten patients (62.5%) needed a reoperation (two for fabric insertion, five for wash-outs, and three for implant exchange/removal). One patient (6.3%) had a septic loosening three years after surgery. At the time of data collection, 13 patients (81.3%) were alive with nine free of disease. Silver coating was not found to reduce infection risk (p=0.2) and capsuloplasty did not prevent dislocation (p=1). These results are comparable to the sparse data published. Lumic® endoprosthesis is therefore shown to provide good functional outcomes and low rates of loosening on short to medium term follow-up. Infection and dislocation are common complications but we were unable to show benefits of capsuloplasty and of the use of silver coated implants. Larger series and longer follow-ups are needed.
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.
Novel immersive virtual reality (IVR) technologies are revolutionizing medical education. Virtual anatomy education using head-mounted displays allows users to interact with virtual anatomical objects, move within the virtual rooms, and interact with other virtual users. While IVR has been shown to be more effective than textbook learning and 3D computer models presented in 2D screens, the effectiveness of IVR compared to cadaveric models in anatomy education is currently unknown. In this study, we aim to compare the effectiveness of IVR with direct cadaveric bone models in teaching upper and lower limb anatomy for first-year medical students. A randomized, double-blind crossover non-inferiority trial was conducted. Participants were first-year medical students from a single University. Exclusion criteria included students who undertook prior undergraduate or graduate degrees in anatomy. In the first stage of the study, students were randomized in a 1:1 ratio to IVR or cadaveric bone groups studying upper limb skeletal anatomy. All students were then crossed over and used cadaveric bone or IVR to study lower limb skeletal anatomy. All students in both groups completed a pre-and post-intervention knowledge test. The educational content was based on the University of Toronto Medical Anatomy Curriculum. The Oculus Quest 2 Headsets (Meta Technologies) and PrecisionOS Anatomy application (PrecisionOS Technology) were utilized for the virtual reality component. The primary endpoint of the study was student performance on the pre-and post-intervention knowledge tests. We hypothesized that student performance in the IVR groups would be comparable to the cadaveric bone group. 50 first-year medical students met inclusion criteria and were computer randomized (1:1 ratio) to IVR and cadaveric bone group for upper limb skeletal anatomy education. Forty-six students attended the study, 21 completed the upper limb modules, and 19 completed the lower limb modules. Among all students, average score on the pre-intervention knowledge test was 14.6% (Standard Deviation (SD)=18.2%) and 25.0% (SD=17%) for upper and lower limbs, respectively. Percentage increase in students’ scores between pre-and post-intervention knowledge test, in the upper limb for IVR, was 15 % and 16.7% for cadaveric bones (p = 0. 2861), and for the lower limb score increase was 22.6% in the IVR and 22.5% in the cadaveric bone group (p = 0.9356). In this non-inferiority crossover randomized controlled trial, we found no significant difference between student performance in knowledge tests after using IVR or cadaveric bones. Immersive virtual reality and cadaveric bones were equally effective in skeletal anatomy education. Going forward, with advances in VR technologies and anatomy applications, we can expect to see further improvements in the effectiveness of these technologies in anatomy and surgical education. These findings have implications for medical schools having challenges in acquiring cadavers and cadaveric parts.
Benign aggressive tumors are common and can be debilitating for patients especially if they are in peri-articular regions or cause pathological fracture as is common for giant cell tumor of bone (GCT). Although GCT rarely metastasize, the literature reports many series with high rates of local recurrence, and evidence about which risk factors influence recurrence is lacking. This study aims to evaluate the recurrence rate and identify local recurrence risk factors by reviewing patient data from a single high-volume orthopedic oncology center. A retrospective analysis of all patients treated for GCT at a tertiary orthopedic oncology center was conducted. In total 413 patients were treated for GCT between 1989 and 2017. Multiple patient and tumour characteristics were analysed to determine if they influenced local recurrence including: age, gender, anatomical site, Campanacci stage, soft tissue extension, presence of metastasis, pathologic fractures, and prior local recurrence. Additional variables that were analysed included type of treatment (en bloc resection or aggressive intralesional curettage) and use of local adjuvants. The main outcome parameters were local recurrence- free survival, metastasis-free survival and complications. Patients treated with Denosumab were excluded from analysis given its recently documented association with high rates of local recurrence. “There were 63/413 local recurrences (15.3%) at a mean follow-up of 30.5 months. The metastatic rate was 2.2% at a mean 50.6 months follow-up and did not vary based on type of treatment. Overall complication rate of 14.3% was not related to treatment modality. Local recurrence was higher (p=0.019) following curettage (55/310; 17.7%) compared to resection (8/103; 7.8%) however, joint salvage was possible in 87% of patients (270/310) in the curettage group. Use of adjuvant therapy including liquid nitrogen, peroxide, phenol, water versus none did not show any effect on local recurrence rates (p= 0.104). Pathological fracture did not affect local recurrence rates regardless of treatment modality (p= 0.260). Local recurrence at presentation was present in 16.3% (58/356) patients and did not show any significance for further local recurrence (p= 0.396). Gender was not associated with local recurrence (p=0.508) but younger patient age, below 20 years (p = 0.047) or below 30 years (p = 0.015) was associated with higher local recurrence rates. GCT in distal radius demonstrated the highest rate of local recurrence at 31.6% compared to other sites, although this was not significant (p=0.098). In addition, Campanacci stage and soft tissue extension were not risk factors for recurrence. The overall GCT local recurrence rate was 15.3%, but varied based on the type of resection: 17.7% following joint sparing curettage compared to 7.8% following resection. Local recurrence was also higher with younger patient age (30 years or less) and in distal radius lesions. In addition, neither Campanacci stage, soft tissue extension or presence of a pathologic fracture affected local recurrence. Most patients with GCT can undergo successful curettage and joint sparing, while only a minority require resection +/− prosthetic reconstruction. Even in the presence of soft tissue extension or a pathologic fracture, most joints can be salvaged with curettage.
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.
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 507cm3(16.1cm3 to 6961cm3) and decreased to 361cm3(8.7cm3 to 5695cm3) 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.
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.”
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.
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.
Dermatofibrosarcoma protuberans (DFSP) is a rare, monoclonal dermal neoplasm. DFSP is known to be locally aggressive and infiltrative, but with a very low systemic recurrence risk. It is reported to be associated with high local recurrence rates following surgical excision. Positive or marginal resection margins can lead to a high risk of local recurrence. The objective was to determine the oncologic outcome for DFSP treated at our institution. We reviewed our prospectively collected database for all DFSP treated at our unit between 1990 and 2016. Patients were included whether or not they had excision prior to referral (“whoops” procedure). Those with fibrosarcomatous degeneration at presentation to our unit or less than 1 year of follow-up were excluded. The goal of surgery was a negative margin with a minimum margin of 2 cm where possible. Patients were followed up after surgery to monitor complications, recurrence, transformation and/or metastasis. 139 patients with a mean age of 42.7 (SD=14.1) were included. Mean follow-up was 56 months.101 patients had prior “whoops” surgery before referral. 14 patients were also treated with radiotherapy (13 preoperatively, 1 postoperatively). Following surgery, 6 patients had positive margins, 4 underwent radiation treatment while the other 2 had no further treatment. One patient who presented to our unit with a local recurrence developed a further local recurrence, which demonstrated fibrosarcomatous degeneration at the time of resection (1/139, 0.7%). 1 other patient developed a lesion at another site. The recurrence rate in our DFSP cohort is significantly lower than previous reports. Wide margin resection following oncologic principles can result in a very low recurrence rate. After the initial recovery phase, these patients do not require ongoing, frequent follow-up. Future studies should look at if closer margins can also produce similar treatment outcome.
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.
Hindquarter amputations for bone or soft tissue sarcoma cause a high degree of disability in patients and are associated with high morbidity rates. The goal of this study is to determine prognostic factors for outcome and analyse quality of life after resection, in order to better select patients who are more likely to benefit from a hindquarter amputation. Our prospectively collected database was searched for all patients treated with a hindquarter amputation between 1989 and 2015. Clinical and histopathological features were analysed for their prognostic value using Kaplan-Meier and Cox proportional hazard analysis. Endpoints were set at recurrent disease and death. Also, functional and social outcome as well as pain was assessed from the hospital charts in the patients that are still alive. 82 patients underwent a hindquarter resection in the given time frame. Of these patients, 63 were treated with a curative intent. The median hospital stay was 25 days, and 49% of the patients had wound complications. The in-hospital mortality was 6%. The 5-year overall survival in the whole group was 31%, while disease free survival was 26%. As expected, patients with metastases at presentation had a significantly worse outcome, while patients with locally recurrent sarcoma had the same outcome as patients with primary sarcoma. For those patients treated with curative intent, younger age was correlated with better survival, while higher histological grade was correlated with worse disease free survival. The functional and social outcome for patients who survived more then one year varied widely, with about 50% of the patients living an acceptable social life with reasonable pain levels and mobility status. Hindquarter amputations for sarcoma patients are still indicated for a select group of patients. Younger patients and/or patients with low grade sarcomas are more likely to benefit form this resection in terms of survival and long term function. However, for patients with less favourable prognostic factors a hindquarter operation might be an unreasonable palliative option.
Due to the aging population, an increasing proportion of elderly patients with soft tissue sarcoma are presenting to cancer centers. This population appears to have a worse prognosis but the reasons for this has not been studied in depth. The purpose of this study is to examine the effect of age on the outcome of patients with extremity and trunk soft tissue sarcoma. This is a multicenter study including 2071 patients with median age at operation of 57 years (1st quartile–3rd quartile: 42–70). The endpoints considered were local recurrence and metastasis with death as a competing event. Cox proportional hazards models were used to estimate hazard ratios across the age ranges with and without adjustment for known confounding factors.Purpose
Method
Ewings sarcoma (EWS) is the second most common primary malignancy of bone. Five-year survival ranges between 50 and 70% for patients who present with localized disease. EWS occurs in both axial and appendicular locations. The prognostic importance of anatomic location (axial vs. appendicular) is unclear. The purpose of this study is to report a single institution experience in the management of patients with EWS, and to investigate anatomic location as a prognostic factor. After ethics board approval, we searched our prospective sarcoma database for all EWS patients treated between 1989 and 2007. Sixty-seven patients with adequate follow-up were identified and records were reviewed. Axial bone EWS was defined as originating from the spine, sacrum, pelvis, scapula, clavicle, or rib cage. Appendicular bone EWS was defined as disease from any bone in the extremities. Axial soft tissue EWS was defined as originating in the head, neck, or torso. Appendicular soft tissue EWS originated from the extremeties. Sixty-six (99%) patients received chemotherapy. Definitive local treatment was by surgical resection whenever possible (n=44). Radiation therapy (RT) was used for unresectable lesions (n=10) or to treat positive margins (n=10). The primary outcome measure was overall survival (OS) measured from the date of diagnosis to the date of death or last follow-up and estimated using the Kaplan-Meier method. Univariate and multivariate analyses were performed. Besides anatomic location, the variables of tumor size, metastases at diagnosis, treatment with radiation, and surgical margins were studied.Purpose
Method
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. 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.Purpose
Method