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The Bone & Joint Journal
Vol. 104-B, Issue 9 | Pages 1011 - 1016
1 Sep 2022
Acem I van de Sande MAJ

Prediction tools are instruments which are commonly used to estimate the prognosis in oncology and facilitate clinical decision-making in a more personalized manner. Their popularity is shown by the increasing numbers of prediction tools, which have been described in the medical literature. Many of these tools have been shown to be useful in the field of soft-tissue sarcoma of the extremities (eSTS). In this annotation, we aim to provide an overview of the available prediction tools for eSTS, provide an approach for clinicians to evaluate the performance and usefulness of the available tools for their own patients, and discuss their possible applications in the management of patients with an eSTS. Cite this article: Bone Joint J 2022;104-B(9):1011–1016


Bone & Joint Research
Vol. 5, Issue 6 | Pages 232 - 238
1 Jun 2016
Tanaka A Yoshimura Y Aoki K Kito M Okamoto M Suzuki S Momose T Kato H

Objectives. Our objective was to predict the knee extension strength and post-operative function in quadriceps resection for soft-tissue sarcoma of the thigh. Methods. A total of 18 patients (14 men, four women) underwent total or partial quadriceps resection for soft-tissue sarcoma of the thigh between 2002 and 2014. The number of resected quadriceps was surveyed, knee extension strength was measured with the Biodex isokinetic dynamometer system (affected side/unaffected side) and relationships between these were examined. The Musculoskeletal Tumor Society (MSTS) score, Toronto Extremity Salvage Score (TESS), European Quality of Life-5 Dimensions (EQ-5D) score and the Short Form 8 were used to evaluate post-operative function and examine correlations with extension strength. The cutoff value for extension strength to expect good post-operative function was also calculated using a receiver operating characteristic (ROC) curve and Fisher’s exact test. Results. Extension strength decreased when the number of resected quadriceps increased (p < 0.001), and was associated with lower MSTS score, TESS and EQ-5D (p = 0.004, p = 0.005, p = 0.006, respectively). Based on the functional evaluation scales, the cutoff value of extension strength was 56.2%, the equivalent to muscle strength with resection of up to two muscles. Conclusion. Good post-operative results can be expected if at least two quadriceps muscles are preserved. Cite this article: A. Tanaka, Y. Yoshimura, K. Aoki, M. Kito, M. Okamoto, S. Suzuki, T. Momose, H. Kato. Knee extension strength and post-operative functional prediction in quadriceps resection for soft-tissue sarcoma of the thigh. Bone Joint Res 2016;5:232–238. DOI: 10.1302/2046-3758.56.2000631


Bone & Joint Research
Vol. 10, Issue 9 | Pages 602 - 610
24 Sep 2021
Tsoi KM Gokgoz N Darville-O'Quinn P Prochazka P Malekoltojari A Griffin AM Ferguson PC Wunder JS Andrulis IL

Aims. Cell-free DNA (cfDNA) and circulating tumour DNA (ctDNA) are used for prognostication and monitoring in patients with carcinomas, but their utility is unclear in sarcomas. The objectives of this pilot study were to explore the prognostic significance of cfDNA and investigate whether tumour-specific alterations can be detected in the circulation of sarcoma patients. Methods. Matched tumour and blood were collected from 64 sarcoma patients (n = 70 samples) prior to resection of the primary tumour (n = 57) or disease recurrence (n = 7). DNA was isolated from plasma, quantified, and analyzed for cfDNA. A subset of cases (n = 6) underwent whole exome sequencing to identify tumour-specific alterations used to detect ctDNA using digital droplet polymerase chain reaction (ddPCR). Results. Cell-free was present in 69 of 70 samples above 0.5 ng/ml. Improved disease-free survival was found for patients with lower cfDNA levels (90% vs 48% at one-year for ≤ 6 ng/ml and > 6 ng/ml, respectively; p = 0.005). Digital droplet PCR was performed as a pilot study and mutant alleles were detectable at 0.5% to 2.5% of the wild type genome, and at a level of 0.25 ng tumour DNA. Tumour-specific alterations (ctDNA) were found in five of six cases. Conclusion. This work demonstrates the feasibility and potential utility of cfDNA and ctDNA as biomarkers for bone and soft-tissue sarcomas, despite the lack of recurrent genomic alterations. A larger study is required to validate these findings. Cite this article: Bone Joint Res 2021;10(9):602–610


Bone & Joint Research
Vol. 4, Issue 3 | Pages 45 - 49
1 Mar 2015
Thompson MJ Ross J Domson G Foster W

Objectives. The clinical utility of routine cross sectional imaging of the abdomen and pelvis in the screening and surveillance of patients with primary soft-tissue sarcoma of the extremities for metastatic disease is controversial, based on its questionable yield paired with concerns regarding the risks of radiation exposure, cost, and morbidity resulting from false positive findings. Methods. Through retrospective review of 140 patients of all ages (mean 53 years; 2 to 88) diagnosed with soft-tissue sarcoma of the extremity with a mean follow-up of 33 months (0 to 291), we sought to determine the overall incidence of isolated abdominopelvic metastases, their temporal relationship to chest involvement, the rate of false positives, and to identify disparate rates of metastases based on sarcoma subtype. Results. A total of four patients (2.9%) exhibited isolated abdominopelvic metastatic disease during the surveillance period. In all cases of concomitant chest and abdominopelvic disease, chest involvement preceded abominopelvic involvement. There was a significant false positive rate requiring invasive workup. Conclusions. In the setting of a relative paucity of evidence concerning a rare disease process and in difference to recently published investigations, we add a clinical cohort not supportive of routine cross sectional imaging of the abdomen and pelvis. Cite this article: Bone Joint Res 2015;4:45–9


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_2 | Pages 114 - 114
10 Feb 2023
Rosser K Ryu J Deo S Flint M
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The NZ Standards of Service Provision for Sarcoma patients were developed by the NZ Sarcoma working group and published by the Ministry of Health (MOH) in 2013. Although not formally enacted by the MOH we aimed to determine the impact of these published standards and referral pathways on disease-specific survival of patients with soft-tissue sarcoma in NZ. The Middlemore Musculoskeletal Tumour Unit database was searched. Patients referred for treatment in our centre with a diagnosis of soft tissue sarcoma in the five-year period before (n=115) and after (n=155) were included. We excluded patients with bone sarcomas and retroperitoneal soft tissue sarcomas. The rate of referral after inappropriate treatment reduced after implementation of the Standards (24% vs 12%, p=0.010). The number of patients referred with tumours larger than 50mm decreased (74.8% vs 72.3%, p=0.021) and fewer had metastases at diagnosis (11.3% vs 3.2%, p=0.017). Mortality was lower in the group after introduction of the Standards (45% vs 30%, p=0.017). The estimated disease-specific survival curve between the two groups shows a trend towards increased survival in the post-standards group, although not reaching statistical significance. Local recurrence rate and metastasis rate after definitive treatment were similar between the two groups. Patients had a shorter duration of symptoms before referral in the post-Standards group although this was not statistically significant. Since implementation of the Standards, patients have been referred more promptly, with fewer inappropriate treatments. The time to mortality curve indicates a trend towards improved disease-specific survival. We conclude that the pathway for investigation and referral for this condition has become clearer, supporting the ongoing use of the Sarcoma Standards, and that these should be formally implemented by the MOH


Bone & Joint Open
Vol. 2, Issue 12 | Pages 1049 - 1056
1 Dec 2021
Shields DW Razii N Doonan J Mahendra A Gupta S

Aims. The primary objective of this study was to compare the postoperative infection rate between negative pressure wound therapy (NPWT) and conventional dressings for closed incisions following soft-tissue sarcoma (STS) surgery. Secondary objectives were to compare rates of adverse wound events and functional scores. Methods. In this prospective, single-centre, randomized controlled trial (RCT), patients were randomized to either NPWT or conventional sterile occlusive dressings. A total of 17 patients, with a mean age of 54 years (21 to 81), were successfully recruited and none were lost to follow-up. Wound reviews were undertaken to identify any surgical site infection (SSI) or adverse wound events within 30 days. The Toronto Extremity Salvage Score (TESS) and Musculoskeletal Tumor Society (MSTS) score were recorded as patient-reported outcome measures (PROMs). Results. There were two out of seven patients in the control group (28.6%), and two out of ten patients in the intervention group (20%) who were diagnosed with a SSI (p > 0.999), while one additional adverse wound event was identified in the control group (p = 0.593). No significant differences in PROMs were identified between the groups at either 30 days (TESS, p = 0.987; MSTS, p = 0.951) or six-month (TESS, p = 0.400) follow-up. However, neoadjuvant radiotherapy was significantly associated with a SSI within 30 days of surgery, across all patients (p = 0.029). The mean preoperative modified Glasgow Prognostic Score (mGPS) was also significantly higher among patients who developed a postoperative adverse wound event (p = 0.028), including a SSI (p = 0.008), across both groups. Conclusion. This is the first RCT comparing NPWT with conventional dressings following musculoskeletal tumour surgery. Postoperative wound complications are common in this group of patients and we observed an overall SSI rate of 23.5%. We propose proceeding to a multicentre trial, which will help more clearly define the role of closed incision NPWT in STS surgery. Cite this article: Bone Jt Open 2021;2(12):1049–1056


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. 102-B, Issue SUPP_7 | Pages 77 - 77
1 Jul 2020
Goulding K Turcotte R Tsimicalis A Košir U Mate K Freeman C
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This study explored psychological functioning and coping styles in adult patients with localized and metastatic extremity soft-tissue sarcoma (STS) from diagnosis through survivorship in a single expert sarcoma center in Canada. Our analyses were driven by three main goals: 1) to develop a better understanding of the affective responses and coping mechanisms in patients who face this rare illness, 2) to identify areas of psychological functioning in which patients with STS experience most difficulties, and 3) to describe how these areas could be best addressed in clinical settings. This descriptive qualitative study is a part of a larger mixed-methods study on health related quality of life (HRQoL) in adult patients with soft-tissue sarcoma treated between 2003 and 2018. Purposive sampling based on demographic and disease variables from all patients within a prospective database was utilized to ensure a representative patient population. Three formats of data collection were conducted in French and English, 2 online focus groups (total n=12), 2 in-person focus groups (total n=12), as well as individual semi-structured interviews (n=4). Data was analyzed using inductive thematic networks approach using the qualitative software N-Vivo 12. Codes were generated by 2 independent qualitative experts that captured key concepts referring to psychological functioning and coping mechanisms. Basic themes were clustered into organizing themes, which were later merged into a global theme. Attention was paid to deviant cases, and within-group dynamics during focus group discussion analysis. Any discrepancies or inconsistencies in coding were resolved in a consensus meeting. The final sample size was determined when data saturation was reached, and no new themes emerged. Our analyses of psychological well-being and functioning revealed three main themes, mood, anxiety, and body image concerns. Feelings of depression and low mood were prominent, coinciding with physical symptoms and limitations especially during the phase of treatment and recovery. Women were more likely to report emotional volatility, while men tended to report more preoccupation. Loss of control and independence, anxiety related to illness recurrence, uncertainty about the future and facing one's mortality significantly impacted quality of life. Furthermore, while patients were more concerned with limb functionality, disfigurement and self-consciousness featured prominently in the narrative. Four adaptive coping styles were observed, positive reframing and optimism, finding a purpose, being proactive, and using humor. Among the maladaptive strategies, we noted passive acceptance, and avoidance and denial. Psychological well-being is an important domain in the HRQoL of adult patients with extremity STS. Physicians and medical workers should encourage adaptive coping mechanisms such as positive reframing and optimism. Patients endorsing higher levels of psychological distress and maladaptive coping styles should be monitored for their well-being and multidisciplinary strategies employed to optimize psychological function and HRQoL


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXI | Pages 16 - 16
1 May 2012
R. LR S. S Y. H D. S T. S J. W
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Purpose. The optimal sequencing of radiotherapy (RT) with surgery in soft-tissue sarcomas (STS) remains undefined. We assessed the impact of RT sequencing on overall survival (OS), cause-specific survival (CSS), local failure, and distant failure. Methods. A retrospective analysis was conducted using the National Oncology Database, a proprietary database of aggregated tumour registries owned by Impac. (r). Medical Systems (Sunnyvale, CA). Eligible sites were soft tissues of the head/neck, thorax, abdomen, pelvis, extremities, trunk, and peritoneum. Only patients with known stage and grade were included. Prognostic factors were identified with multivariate analysis (MVA) using the Cox proportional hazards model. Survival was calculated using the Kaplan-Meier method, and compared for statistical significance (p< 0.05) using the log-rank test. Results. A total of 821 patients met the inclusion criteria. The median follow-up time for living patients was 62 months. The 5-year CSS was 69%. MVA identified the following independent predictors for CSS (p< 0.01): age, stage, grade, histology, surgery, RT sequence, and tumour size. CSS was significantly improved with pre-op RT versus post-op RT [hazard ratio (HR) 0.7, 95% confidence interval (CI) 0.51-0.94, p< 0.05], with a 5-year CSS of 81% and 73%, respectively (log-rank, p< 0.01). Pre-op RT improved CSS in patients with lower extremity tumours, leiomyosarcoma, and synovial sarcoma (p< 0.05). OS was not significantly improved with pre-op RT. Pre-op RT also resulted in significantly reduced local and distant relapse rates than post-op RT. Adverse prognostic factors were balanced between both groups. Conclusion. Pre-operative RT has a significant benefit in reducing cancer-specific mortality compared to post-operative RT in STS


Bone & Joint Open
Vol. 4, Issue 6 | Pages 442 - 446
12 Jun 2023
Toda Y Iwata S Kobayashi E Ogura K Osaki S Fukushima S Mawatari M Kawai A

Aims. The risk of postoperative complications after resection of soft-tissue sarcoma in the medial thigh is higher than in other locations. This study investigated whether a vessel sealing system (VSS) could help reduce the risk of postoperative complications after wide resection of soft-tissue sarcoma in the medial thigh. Methods. Of 285 patients who underwent wide resection for soft-tissue sarcoma between 2014 and 2021 at our institution, 78 patients with tumours in the medial thigh were extracted from our database. Information on clinicopathological characteristics, preoperative treatment, surgical treatment (use of VSS, blood loss volume, operating time), and postoperative course (complications, postoperative haemoglobin changes, total drainage volume, and drainage and hospitalization durations) were obtained from medical records. We statistically compared clinical outcomes between patients whose surgery did or did not use VSS (VSS and non-VSS groups, respectively). Results. There were 24 patients in the VSS group and 54 in the non-VSS group. There were no significant differences between the two groups in terms of clinicopathological background. The total drainage volume in the VSS group was significantly less than that in the non-VSS group (1,176 ml vs 3,114 ml; p = 0.018). Moreover, the drainage and hospitalization durations were significantly shorter in the VSS group compared to the non-VSS group (p = 0.017 and p = 0.024, respectively). Conclusion. Our results suggest that use of VSS can help reduce the risk of postoperative complications after wide resection of soft-tissue sarcoma in the medial thigh. Cite this article: Bone Jt Open 2023;4(6):442–446


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 439 - 439
1 Jul 2010
Bruns J
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Clear cell sarcoma (CCS) is a rare and highly malignant soft-tissue sarcoma (STS) constituting 1% of all STS. It most often appears in the soft tissue closely assocíated with tendons, aponeuroses or fascial tissue of the distal extremities. It shares features of melanomas, hence is dubbed as a soft-tissue melanoma or clear cell sarcoma of the tendons and aponeuroses (CCSTA). CCS differs from the more common STS by its more aggressive growth and greater propensity to metastasise to lymph nodes, bones and lung. On a molecular basis, CCS is characterised by the chromosomal translocation. Clinically, the tumor is firm, slowly growing and painless in half of the cases, thus rarely awakening suspicion of a STS. Thus, the diagnosis is difficult. Furthermore, on an MRI the tumor exhibits mostly a homogenous mass with a higher signal intensity as compared to muscle on T1-weighted images and implies a benign tumor. The most important treatment is a wide resection to ensure local control. Little is known about neo- and/or adjuvant chemotherapy or radiation. Regarding chemotherapy different substances (doxorubicin, ifosfamide, cisplatin, mesna, dacarbazine, cyclophosphamide) have been administered under different conditions (single or combined substances, different doses, neo- or adjuvant). There are also some reports displaying the advantages of caffeine-assisted chemotherapy. Under similar different circumstances radiation therapy was applied. Most important prognostic factors are the presence of tumor necroses, size and regional lymph node metastases, local recurrence and distant metastases. The reported 5-year survival ranges from 48% to 68%, the 10-year survival from 36% to 41%. Summarising all reports there is a need at least for a retrospective study to gather information about more patients


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 103 - 103
1 Dec 2022
Lazarides A Burke Z Gundavda M Griffin A Tsoi K Wunder JS Ferguson P
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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.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_3 | Pages 67 - 67
1 Mar 2021
Perera J Atinga A Ibe I Aoude A White L Howarth D Griffin A Tsoi K Ferguson P Wunder J
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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.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_3 | Pages 66 - 66
1 Mar 2021
Marritt K Hildebrand K Singla A Hildebrand K Yipp B Jirik F Monument M
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Soft tissue sarcomas (STS) are rare, aggressive malignancies derived from connective tissues such as muscle and fat. Undifferentiated pleomorphic sarcoma (UPS) is one of the most common STS in adults. UPS is an aggressive, highly metastatic sarcoma, and is resistant to chemotherapy. New therapies for UPS are desperately needed. STS have an immune desert tumour immune microenvironment (TIME), characterized by a paucity of tumour infiltrating lymphocytes and subsequent resistance to immunotherapies such as immune checkpoint inhibitors. Strategies capable of creating an immune-rich, inflamed TIME may improve immunotherapy efficacies for sarcoma. Activation of the STING (stimulator of interferon genes) receptor can induce potent innate and adaptive immune responses within immunogenic solid tumours. However, this approach has never been attempted in immune-inert sarcomas.

Purpose: To determine the therapeutic anti-tumour effects of STING activation in UPS tumours.

We have developed an inducible, immune-competent mouse model of UPS. We evaluated intra-tumoural injection of the murine STING receptor agonist, DMXAA, into UPS-bearing immune-competent mice. DMXAA was injected into palpable UPS tumours of the hindlimb. Tumour volume and bioluminescence imaging was recorded bi-weekly. DMXAA treated UPS tumours were also evaluated for necrosis and immune infiltration at defined time points.

UPS tumours developed necrosis and lymphocytic infiltration 72 hours after DMXAA treatment. A single intra-tumoural dose of DMXAA into UPS tumours resulted in durable cure in 50% of mice. All survivors rejected a re-challenge of the UPS tumours in both the contralateral hindlimb and lung, suggesting adaptive immunity. The therapeutic effects of DMXAA were mitigated in lymphocyte deficient Rag2 knockout mice.

STING therapy is a promising immunotherapeutic opportunity for immune-inert sarcomas. Our data warrants further preclinical investigations in other sarcoma models and in combination with other immune-based therapies.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_3 | Pages 77 - 77
1 Mar 2021
Lazarides A Saltzman E Visgauss J Mithani S Eward W Brigman B
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For soft tissue sarcoma patients receiving preoperative radiation therapy, wound complications are common and potentially devastating; they may result in multiple subsequent surgeries and significant patient morbidity. The purpose of this study was to assess the feasibility of intraoperative indocyanine green fluorescent angiography (ICGA) as a predictor of wound complications in resections of irradiated soft tissue sarcoma of the extremities.

A consecutive series of patients of patients with soft tissue sarcoma of the extremities or pelvis who received neoadjuvant radiation and a subsequent radical resection received intraoperative ICGA with the SPY PHI device (Stryker Inc, Kalamazoo MI) at the time of closure. Three fellowship trained Orthopaedic Oncologic Surgeons were asked to prospectively predict likelihood of wound complications based on fluorescence. Retrospective analysis of fluorescence signal along multiple points of the wound length was performed and quantified. The primary endpoint was wound complication, defined as delayed wound healing or wound dehiscence, within 3 months of surgery. An a priori power analysis demonstrated that 5 patients were necessary to achieve statistical significance. Univariate and multivariate statistical analyses were performed to identify predictors of wound complications.

14 patients were consecutively imaged. The diagnosis was undifferentiated pleomorphic sarcoma in 9 (64.3%) of patients; 11 (78.6%) tumors were high grade. There were 6 patients with wound complications classified as “aseptic” in 5 cases and secondary to hematoma in 1 case. Using the ICGA, blinded surgeons correctly predicted wound complications in 75% of cases. In the area of wound complication, the mean % of maximal signal for wound complications was 49% during the inflow phase and 48% during the peak phase. The mean % maximal signal for peri-incisional tissue without wound complications was 77% during the inflow phase and 83% during the peak phase (p=0.003 and p<0.001). During the inflow phase, a mean ratio of normal of 0.62 maximized the area under the curve (AUC=0.90) for predicting wound complications with a sensitivity of 100% and specificity of 77.4%. During the peak phase, a mean ratio of normal of 0.55 maximized the area under the curve (AUC=0.95) for predicting wound complications with a sensitivity of 88.9% and a specificity 100%.

Intraoperative use of indocyanine green fluorescent angiography may help to predict wound complications in patients undergoing resection of preoperatively irradiated soft tissue sarcomas of the extremities and pelvis. Future studies are necessary to validate this technology in a prospective manner and to determine if interventions can be instituted to prevent predicted wound complications.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_20 | Pages 42 - 42
1 Nov 2016
Moore J Mottard S Isler M Barry J
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Major wound complication risk factors following soft tissue sarcoma resection.

Wound-healing complications represent an important source of morbidity in patients treated surgically for soft tissue sarcomas (STS). The purpose of this study was to determine which factors are predictive of major wound complication rates following STS resection, including tumour site, size, grade, and depth, as well as radiotherapy and chemotherapy.

We reviewed 256 cases of STS treated surgically between 2000 and 2011. The primary outcome was occurrence of major wound complications post STS resection.

Major wound complications were more likely to occur post STS resection with larger tumour diameters (p = 0.001), high grade tumours (p = 0.04), location in the proximal lower extremity (p = 0.01), and use of preoperative radiotherapy (p = 0.01). Tumours located in the adductor compartment were at highest risk of complications. We did not demonstrate a significant difference in complications rates based on method of closure. Diabetes, smoking, obesity, tumour diameter, tumour location in the proximal lower extremity, and preoperative radiotherapy were independent predictors on multivariate analysis.

There are multiple predictors for major wound complications post STS resection. A more aggressive resection of irradiated soft tissues, combined with primary reconstruction, should be considered in cases with multiple risk factors.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_3 | Pages 70 - 70
1 Mar 2021
Mate K Goulding K Košir U Tsimicalis A Turcotte R Freeman C Alcindor T Mayo N
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The patient's subjective experience of disease is an increasing focus in health care delivery. Health-related quality of life (HRQoL) is defined as a “functional effect of a medical condition and its consequent treatment”; it is both self-reported and multi-dimensional. While functional outcome is well researched among the soft tissue sarcoma (STS) population, few studies have focused on HRQoL, which gives a broader understanding of the psychological, somatic, social and physical toll of cancer and its treatment from the patient's viewpoint. The biologic and anatomic heterogeneity of sarcomas are considerable, just as the treatments are diverse, we surmise that the indicators of patient HRQoL differ and are not captured in existing generic HRQoL tools for cancer. The study objectives were to explore the domains of HRQoL and functioning in adult patients diagnosed with extremity STS from the patient's perspective from active care through survivorship through qualitative inquiry, so as to form the basis for the development of a patient-derived, sarcoma-specific, preference based HRQoL tool.

Study design is a sequential exploratory mixed methods study of patient experience in localized or metastatic adult extremity STS (2007 and 2017). The study was conducted at a high-volume sarcoma centre. Qualitative descriptive design was grounded in an integrated knowledge translation approach and aimed at identifying HRQoL domains through in-person and electronic focus groups, and individual semi-structured interviews in both English and French (N=28). The interview guide topics were selected based on existing knowledge about PROs and HRQoL life, including (a) impact of diagnosis on employment or acquisition of academic/vocational skills; (b) physical and psychological functioning; (c) symptom burden; (d) treatment preferences; (e) knowledge of and use of existing resources; (f) impact on family time and resources; and (g) overall experience. Data was analyzed using inductive thematic networks approach using the qualitative software N-Vivo 12. Codes were generated by 2 independent qualitative experts capturing key concepts of HRQoL that is impacted by STS. Basic themes were clustered into organizing themes, and merged into global domains. Attention was paid to deviant cases and within-group dynamics during focus group discussion analysis. Discrepancies or inconsistencies in coding were resolved in consensus meetings. Final sample size was determined when data saturation was reached and no new themes emerged. Qualitative reduction of identified items to reach a consensus framework was facilitated by a moderator during multi-disciplinary panel meetings comprised of sarcoma experts, patient partners, allied health staff and other stakeholders.

Twenty-nine patients with biopsy-proven localized or metastatic STS of the extremity participated (69% lower extremity STS; mean age 56 years, 25% with local recurrence, 21% metastatic, 18% amputation). Inductive thematic network analysis revealed five function-related domains HRQoL for patients with STS. The functional domains were mapped to the Wilson & Cleary Model and experience domains were mapped to the Picker Institute's Through Patient's Eyes model.

This is a critical step toward developing disease specific outcome measures. Patient-centered research is crucial to understanding the impact of surgery, adjuvant therapy and the associated complications for patients with extremity STS, and thereby improving the quality of care provision. This study offers a unique perspective on what domains and sub domains are most impactful on HRQoL and provides the basis for our on-going development of a disease-specific, preference-based HRQoL measure.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_18 | Pages 5 - 5
1 Dec 2018
Spence S Alanie O Ong J Findlay H Mahendra A Gupta S
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The modified Glasgow Prognostic Score (mGPS) is a validated prognostic indicator in various carcinomas as demonstrated by several meta-analyses.

The mGPS includes pre-operative CRP and albumin values to calculate a score from 0–2 that correlates with overall outcome. Scores of 2 are associated with a poorer outcome.

Our aim was to assess if the mGPS is reliable as a prognostic indicator for soft tissue sarcoma (STS) patients.

All patients with a STS diagnosed during years 2010–2014 were identified using our prospectively collected MSK oncology database. We performed a retrospective case note review examining demographics, preoperative blood results and outcomes (no recurrence, local recurrence, metastatic disease and death).

94 patients were included. 56% were female and 53% were over 50 years. 91% of tumours were high grade (Trojani 2/3) and 73% were >5cm. 45 patients had an mGPS score of 0, 16 were mGPS 1 and 33 were mGPS 2. On univariate analysis, an mGPS of 0 or 2 was statically significant with regards to outcome (p=0.012 and p=0.005 respectively).

We have demonstrated that pre-treatment mGPS is an important factor in predicting oncological outcome. A score of 0 relates to an improved prognosis whilst a score of 2 relates to an increased risk of developing metastases and death. mGPS as a prognostic indicator was not affected by either the tumour size or grade.

We believe that a pre-operative mGPS should be calculated to help predict oncological outcome and in turn influence management. Further work is being undertaken with a larger cohort.


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. 98-B, Issue SUPP_20 | Pages 44 - 44
1 Nov 2016
Nooh A Turcotte R Goulding K
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Wound complications are common in patients with soft tissue sarcomas (STS) treated with surgical excision. Limited data is available on predictive factors for wound complications beyond the relationship to neo-adjuvant or adjuvant radiotherapy. Likewise, the association between blood transfusion, patient comorbidities and post-operative outcomes is not well described. In the present study we identified the predictive factors for blood transfusion and wound complications in patients undergoing surgical resection of soft tissue sarcoma from a national cohort.

The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was used to identify patients who underwent surgical resection of a STS from 2005 to 2013. Primary malignant soft tissue neoplasms were identified using the following ICD-9 codes: 171.2, 171.3 and 171.6. Patients treated with both wide excision and amputation were identified using the current procedural terminology (CPT) codes. Prolonged operative time was defined as greater than 90th percentile of time required per procedure. A multivariable logistic regression model was used to identify associations between patient factors and post-operative wound complications (superficial and deep surgical site infections (SSI), and wound dehiscence). A similar regression model sought to identify prognostic factors for blood transfusion and associations with post-operative outcomes.

A total of 788 patients met our inclusion criteria. Of theses, 64.2% had tumours in the lower limb, 23.1% patients had tumours in the upper limb, and 12.7% patients had pelvic tumours. Six hundred and forty patients (81.2%) underwent surgical excision; 148 (18.8%) patients had an amputation. Multivariable logistic regression modeling identified American Society of Anaesthesiologist (ASA) class 3 and 4 (OR=2.3, P=0.03; OR=8.3, P=0.001, respectively), amputation (OR=14.0, P<0.001) and prolonged operative time (OR=4.6, P<0.001) as significant predictors of blood transfusion. Radiotherapy (OR=2.6, P=0.01) and amputation (OR=2.6, P=0.01) were identified as predictors of superficial SSI, whereas ASA class 4 (OR=6.2, P=0.03), prolonged operative time (OR=3.9, P=0.012) and return to the operating room (OR=10.5, P<0.001) were associated with deep SSI. Male gender (OR=1.8, P=0.03), diabetes (OR=2.3, P=0.03), ASA class 3 (OR=2.4, P=0.003), amputation (OR=3.8, P<0.001) and steroids (OR=4.5, P=0.03) were identified as predictors for wound dehiscence and open SSI.

A national cohort demonstrates that male gender, diabetes, chronic steroid use, higher ASA score and radiotherapy are associated with an increased incidence of wound complications. One in twenty-three patients undergoing resection of an STS will require a blood transfusion, and this risk is correlated with amputation, prolonged operative time and increased ASA score. Strategies to decrease the risk of blood transfusion and wound complication should be considered for these patient groups.