Publications by authors named "Jay Wunder"

Aims: Soft-tissue sarcomas (STSs) are rare cancers with centralized care advocated to consolidate resources and expertise. However, geographical challenges, particularly in countries like Canada, can increase travel distances for patients. The impact of travel distance on sarcoma presentation and outcomes remains unclear, particularly in single-payer healthcare systems with centralized care.

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Background: Socioeconomic status and community marginalization can impact overall survival and functional outcome in patients with cancer. However, this association has not been determined in patients with soft tissue sarcoma (STS) within Canada. The primary aim of this study was to determine the impact of marginalization on STS 5-year overall survival.

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Background: Differentiation of benign myxomas and malignant myxoid sarcomas can be difficult with an overlapping spectrum of morphologic MR findings.

Purpose: To assess the diagnostic utility of MRI radiomics in the differentiation of musculoskeletal myxomas and myxoid sarcomas.

Study Type: Retrospective.

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Background: Peritumoral edema on staging magnetic resonance imaging (MRI) is associated with higher local recurrence in soft tissue sarcoma (STS). This may relate to the presence of satellite malignant cells that are difficult to distinguish from benign atypia, leading to over- or undertreatment. This study evaluated a novel targeted molecular approach to identify malignancy in STS peritumoral planes as a means to improve personalized care.

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Introduction: Approximately 40-50 % of sarcoma patients will develop lung metastasis, but only 10 % will develop bone metastasis. The survival benefit of surgery for solitary bone metastasis remains unclear.

Methods: From 1987 to 2019, 47 patients who underwent curative-intent treatment for localized bone or soft tissue sarcoma in the extremities or trunk wall developed solitary bone metastases as the first distant recurrence.

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: Sarcomas are a heterogeneous group of cancers, many with high rates of recurrence and metastasis, leading to significant morbidity and mortality. Due to a lack of early diagnostic biomarkers, by the time recurrent disease can be clinically detected, it is often extensive and difficult to treat. Here, we sought to investigate methods of detecting ctDNA in sarcoma patient plasma to potentially monitor disease recurrence, progression, and response to treatment.

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Article Synopsis
  • Solitary fibrous tumor (SFT) is a rare type of tumor that can occur in various body parts and is often linked to specific genetic fusions, with 10-30% of cases becoming metastatic.
  • A study involving DNA methylation analysis of 79 SFTs revealed distinct epigenetic changes linked to their primary sites, identifying key genes such as EGFR and TBX15 that showed differing levels of expression based on the tumor's location and genetic fusion type.
  • TBX15 emerged as a significant marker, with changes in its methylation and expression strongly correlating to the tumor's tissue of origin, suggesting it could help differentiate between new tumors and metastases without needing extensive genomic analysis.
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Background: Despite the goal of an acceptable functional result, the surgical treatment of soft-tissue sarcoma can portend a prolonged course of recovery. More comprehensive data on the expected course of recovery following extremity sarcoma surgery are needed to help to inform physicians and patients. The purpose of the present study was to describe the typical course of functional recovery following limb-salvage resection of a soft-tissue sarcoma and to identify factors associated with a delayed postoperative course of recovery.

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Background And Objectives: Intraoperative frozen section analysis is commonly used to evaluate marrow margins during extremity bone sarcoma resections, but its efficacy in the era of magnetic resonance imaging is debated. This study aimed to compare the accuracy of intraoperative frozen section assessment with final pathology, assess its correlation with gross intraoperative margin assessment, and evaluate its impact on surgical decision making.

Methods: Consecutive patients undergoing extremity bone sarcoma resections from 2010 to 2022 at a single sarcoma center were included.

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Introduction: Perioperative bleeding increases morbidity and mortality in sarcoma patients. Tranexamic acid (TXA), an antifibrinolytic, is widely utilized in non-sarcoma orthopaedic surgeries, but its adoption in sarcoma surgery is hindered by concerns about thrombotic events.

Methods: Searches in Ovid MEDLINE, EMBASE, and CENTRAL were performed without date restrictions.

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Background: Joint-sparing resection of periarticular bone tumors can be challenging because of complex geometry. Successful reconstruction of periarticular bone defects after tumor resection is often performed with structural allografts to allow for joint preservation. However, achieving a size-matched allograft to fill the defect can be challenging because allograft sizes vary, they do not always match a patient's anatomy, and cutting the allograft to perfectly fit the defect is demanding.

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Synovial sarcoma (SyS) is an aggressive soft-tissue malignancy characterized by a pathognomonic chromosomal translocation leading to the formation of the SS18::SSX fusion oncoprotein. SS18::SSX associates with mammalian BAF complexes suggesting deregulation of chromatin architecture as the oncogenic driver in this tumour type. To examine the epigenomic state of SyS we performed comprehensive multi-omics analysis on 52 primary pre-treatment human SyS tumours.

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Article Synopsis
  • The study investigates the link between obesity and major wound complications in patients undergoing surgery for pelvic bone sarcoma, using data from surgeries performed between 2005 and 2021.
  • Out of 93 patients reviewed, those with obesity (21 patients) experienced a higher rate of major wound complications (52%) compared to non-obese patients (26%), and also scored lower on functional outcomes after one year.
  • The findings suggest that obesity is a significant independent risk factor for wound complications, emphasizing the need for thorough pre- and postoperative care for obese patients undergoing this type of surgery.
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Background: The Reconstructive Allograft Preparation by Toronto Sarcoma (RAPTORS) protocol is reliable and reproducible without substantially adding to the surgical reconstruction time or cost. Our technique includes clearance of debris, lavage of the medullary canal, pressurized filling of the medullary canal with antibiotic-laden cement for its mechanical and antimicrobial properties, and insertion of cancellous autograft at the allograft-host junctional ends prior to dual-plate compression to fix the allograft into the defect. Our experience with large intercalary allograft reconstruction has demonstrated high rates of long-term success and addresses the most common causes of large allograft failure (infection, fracture, and nonunion), as shown in our long-term outcome study.

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Background: Diffuse-type tenosynovial giant cell tumor (D-TGCT) is a mono-articular, soft-tissue tumor. Although it can behave locally aggressively, D-TGCT is a non-malignant disease. This is the first study describing the natural course of D-TGCT and evaluating active surveillance as possible treatment strategy.

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Aims: The sacroiliac joint (SIJ) is the only mechanical connection between the axial skeleton and lower limbs. Following iliosacral resection, there is debate on whether reconstruction of the joint is necessary. There is a paucity of data comparing the outcomes of patients undergoing reconstruction and those who are not formally reconstructed.

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Article Synopsis
  • Radiation-induced sarcomas (RIS) are rare and aggressive tumors that can complicate treatment decisions due to their unique characteristics and origins in previously irradiated tissues.
  • A retrospective study using the CanSaRCC database analyzed RIS cases from 1996 to 2021, looking specifically at patient demographics, treatment, and outcomes across different sarcoma types.
  • Among the 107 identified RIS tumors, breast angiosarcoma (BAS) was most common and associated with specific clinical trends, including a younger age for osteosarcoma patients and varying time intervals since initial cancer treatment.
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Introduction: Several studies have linked increased risk of osteosarcoma with tall stature, high birthweight, and early puberty, although evidence is inconsistent. We used genetic risk scores (GRS) based on established genetic loci for these traits and evaluated associations between genetically inferred birthweight, height, and puberty timing with osteosarcoma.

Methods: Using genotype data from two genome-wide association studies, totaling 1039 cases and 2923 controls of European ancestry, association analyses were conducted using logistic regression for each study and meta-analyzed to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs).

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  • This study examined how different biopsy methods (open biopsy vs. core needle biopsy) affect surgical outcomes in sarcoma patients.
  • It found that core needle biopsy was the most frequently used method internationally, whereas open biopsy was more common in the U.S. and Canada.
  • Despite open biopsy taking longer and resulting in more tissue removed, both methods showed no significant difference in infection rates or cancer outcomes after one year.
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Aims: The preoperative grading of chondrosarcomas of bone that accurately predicts surgical management is difficult for surgeons, radiologists, and pathologists. There are often discrepancies in grade between the initial biopsy and the final histology. Recent advances in the use of imaging methods have shown promise in the ability to predict the final grade.

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Chondrosarcomas are the most common malignancy of cartilage and are associated with somatic mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 genes. Somatic IDH mutations are also found in its benign precursor lesion, enchondromas, suggesting that IDH mutations are early events in malignant transformation. Human mutant IDH chondrosarcomas and mutant Idh mice that develop enchondromas investigated in our studies display glycogen deposition exclusively in mutant cells from IDH mutant chondrosarcomas and Idh1 mutant murine growth plates.

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  • Giant cell tumour of bone (GCTB) poses a challenge for treatment due to a high rate of local recurrence, with a study of 354 patients revealing a 15% relapse rate, particularly after curettage compared to resection.
  • Factors such as age under 30 and tumour location in the distal radius were linked to higher relapse risks, while other factors like pathological fractures and tumour size showed no significant impact.
  • Despite a notable local recurrence rate, 90% of patients experiencing relapse after curettage successfully underwent repeat procedures, highlighting the importance of joint preservation for long-term functional outcomes.
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Background: Systemic therapy for metastatic clear cell sarcoma (CCS) bearing EWSR1-CREB1/ATF1 fusions remains an unmet clinical need in children, adolescents, and young adults.

Methods: To identify key signaling pathway vulnerabilities in CCS, a multi-pronged approach was taken: (i) genomic and transcriptomic landscape analysis, (ii) integrated chemical biology interrogations, (iii) development of CREB1/ATF1 inhibitors, and (iv) antibody-drug conjugate testing (ADC). The first approach encompassed DNA exome and RNA deep sequencing of the largest human CCS cohort yet reported consisting of 47 patient tumor samples and 8 cell lines.

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Background: Resection of soft-tissue sarcomas from the adductor compartment is associated with significant complications. Free/pedicled flaps often are used for wound closure, but their effect on healing is unclear. We compared wound complications, oncologic, and functional outcomes for patients undergoing flap reconstruction or primary closure following resection of adductor sarcomas.

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