Bone Sarcomas Research Articles

Leveraging homologous recombination deficiency for sarcoma

Abstract Background Homologous recombination deficiency (HRD) in tumors correlates with poor prognosis and metastases development. Determining HRD is of major clinical relevance as it can be treated with PARP inhibitors (PARPi). HRD remains poorly investigated in sarcoma, a rare and heterogeneous cancer of mesenchymal origin. Objective We aimed (i) to investigate predictive biomarkers of HRD in several independent sarcoma cohorts using a cross-functional strategy by combining genomic, transcriptomic and phenotypic approaches and (ii) to evaluate the therapeutic potential of PARPi and DNA damage response (DDR)-based therapies ex vivo. Materials and methods We performed a comprehensive genomic and transcriptomic characterization of sarcoma using datasets from The Cancer Genome Atlas (TCGA) and Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and our own bone and soft tissue sarcoma cohorts. We evaluated PARP1/2 and WEE1 inhibition ex vivo in patient-derived sarcoma cell models as monotherapy and in combination with chemotherapeutic agents to identify synergistic effects. Results Firstly, we identified genomic traits of HRD in a subset of sarcomas associated with molecular alterations in homologous recombination repair (HRR) pathway genes and high chromosomal instability. Secondly, we identified and validated distinct SARC-HRD transcriptional signatures that predicted sensitivity to PARPi. Finally, we showed functional defects in HRR in sarcoma cells that were associated with functional dependency towards PARPi and WEE1i and support the clinical use of RAD51 as a predictive biomarker for PARPi sensitivity. Conclusion We provide a personalized oncological approach to potentially improve the treatment of sarcoma patients. We encourage the evaluation of gene expression signatures to enhance the identification of patients who might benefit from DDR-based therapies.

Is intercalary frozen autograft augmented with intramedullary cement and bridging plates fixation a durable reconstruction?

AimsWe analysed the survival, complications, and function of frozen autograft augmented with intramedullary cement and bridging plates fixation for intercalary bone defect reconstruction in primary bone sarcomas.Patients and MethodsA retrospective cohort study was conducted on 72 patients with primary bone sarcomas (34 males, 38 females) between January 2016 and June 2023. The average age was 22.0 ± 13.6 years (6 to 61 years) and the pathological type included osteosarcoma (55), followed by adamantinoma (5), Ewing’s sarcoma (4), undifferentiated pleomorphic sarcoma (4), chondrosarcoma (3), and malignant tenosynovial giant cell tumor (1). The oncological outcomes included local control, metastasis, progression-free survival and overall survival. The functional outcomes were evaluated by the Musculoskeletal Tumor Society Score (MSTS-93), the Toronto Extremity Salvage Score (TESS), and the motion of the joint.ResultsThe mean follow-up time was 50.0 ± 27.4 months (12 to 99 months). 10 patients died of the disease, 9 patients were alive with disease and 53 patients were alive with no evidence of disease. The average 5-year overall survival of autograft was 85.8% (95% CI, 72.1-93.1%). The average MSTS-93 score was 96% ( 67–100%) and the average TESS score was 98% (74–100%). Twenty-four patients (33.3%) had at least one complication in the follow-up period. The most common complications were nonunion (9.7%, 7/72) and local recurrence (9.7%, 7/72), followed by leg length discrepancy (6.9%, 5/72), infection (5.6%, 4/72), implant failure (4.2%, 3/72), delayed union (2.8%, 2/72), and graft fractures (1.4%, 1/72). Tumor site was an independent risk factor for bone nonunion (OR, 22.23; p = 0.006).ConclusionsWe presented a large technique series for preventing autograft-related complications (especially for autograft fractures) of intercalary frozen autograft reconstruction. This method showed promising functional outcomes and provided durable reconstruction.Level of evidencelevel IV therapeutic study.

The concomitant of non-classical stereotactic body radiotherapy with tislelizumab based on multidisciplinary modalities for leiomyosarcoma: A case report

Background: Stereotactic body radiotherapy (SBRT) and immune checkpoint inhibitors (ICIs) could obtain a certain synergistic effect on bone and soft tissue sarcoma (BSTS). Given its low radiosensitivity, BSTS usually require an irradiation dose >65 Gy to achieve local control. Herein, we developed a non-classical SBRT technique called “onion-shaped simultaneous boost (OSB),” and reported a patient with prostatic leiomyosarcoma which received non-classical SBRT and other systemic treatments. Methods: In the case, a 49-year-old male patient was diagnosed with prostatic leiomyosarcoma in November 2018. In the radiotherapy plans, the maximum doses of the targets were more than 65 Gy, while the doses of the organs at risk (OARs) were strictly limited. Results: After receiving radiotherapy, ICI, and other multidisciplinary modalities, the patient achieved partial response (PR). Conclusion: In this clinical case, we have observed that the OSB technique, which employs an increased per-fraction radiotherapy dose without the need to match the single-fraction doses typical of conventional SBRT, effectively enhances the therapeutic impact on leiomyosarcoma without an increase in radiotherapy-related side effects. By integrating the OSB technique with a multidisciplinary array of antineoplastic strategies, we can more effectively manage sarcomas in clinical practice.

Dysregulation of miRNAs in Soft Tissue Sarcomas

MicroRNAs (miRNAs) are pivotal regulators of gene expression, influencing key cellular processes such as proliferation, differentiation, apoptosis, and metastasis. In the realm of sarcomas—a diverse group of malignant tumors affecting soft tissues and bone sarcomas—miRNAs have emerged as crucial players in tumorigenesis and tumor progression. This review delves into the intricate roles of miRNAs across various soft tissue sarcoma subtypes, including rhabdomyosarcoma, liposarcoma, leiomyosarcoma, synovial sarcoma, fibrosarcoma, angiosarcoma, undifferentiated pleomorphic sarcoma (UPS), and malignant peripheral nerve sheath tumor (MPNST). We explore how dysregulated miRNAs function as oncogenes or tumor suppressors, modulating critical pathways that define the aggressive nature of these cancers. Furthermore, we discuss the diagnostic and prognostic potential of specific miRNAs and highlight their promise as therapeutic targets. By understanding the miRNA-mediated regulatory networks, this review aims to provide a comprehensive overview of current research while pointing towards future directions for miRNA-based therapies. Our findings underscore the potential of miRNAs to transform the landscape of sarcoma treatment, offering hope for more precise, personalized, and effective therapeutic strategies.

COMPARATIVE ANALYSIS OF THE DIAGNOSTIC ACCURACY OF ENDOSTATIN AND VEGF SERUM LEVELS IN PATIENTS WITH BONE SARCOMAS

Introduction. Angiogenesis regulators are of particular interest as new serum markers in cancer patients, since they reflect the intensity of tumor growth and metastasis. Currently, many works are dedicated to the study of vascular endothelial growth factor (VEGF), which activates angiogenesis, and endostatin, which inhibits it. However, a comparative study of the diagnostic accuracy of serum levels of these two markers in patients with bone sarcomas has not been conducted yet. Аim. A comparative analysis of the diagnostic accuracy indicators and prognostic significance of VEGF and endostatin in the blood serum of patients with primary malignant bone tumors. Methods. During the study, the levels of endostatin and VEGF in blood serum samples from 123 patients with a newly diagnosed and morphologically verified bone sarcoma were measured. Patients were examined at the Federal State Budgetary Institution “National Medical Research Center of Oncology named after N.N. Blokhin” of the Russian Ministry of Health from July 2001 to December 2022. Sixty age- and gender-matched healthy donors were included in the control group. Results. Median serum concentrations of endostatin and VEGF in the patient group were statistically significantly increased compared to the control group by 1.3 and 1.4 times, respectively (p < 0.01). Statistically significant differences in the serum concentrations of VEGF and endostatin depending on the T category and the tumor grade and stage were not identified. The cut-off value of VEGF was 279 pg/ml, and the cut-off value of endostatin was 121 ng/ml. With the same sensitivity of 75.6%, endostatin is characterized by higher specificity than VEGF (73.0 and 67.6%, respectively). The proportional hazards model characterizing the effect of serum VEGF and endostatin levels on overall and survival was not statistically significant. Conclusion. Endostatin in the blood serum of patients with bone tumors is more informative compared to VEGF; however, both markers are not predictors of overall and survival.

Comparative analysis of bone and soft tissue vs. visceral synovial sarcoma: Demographic, clinical, and survival outcomes; a retrospective population-based study

BackgroundSynovial sarcoma (SS) is typically diagnoses in young adults and usually appears in the extremities and soft tissues. However, it can sometimes arise in visceral organs. This study examines the differences in patient demographics, clinical features, and survival rates between soft tissue and visceral synovial sarcoma. MethodsWe analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database spanning 2000–2018. ANOVA (analysis of variance) was used to identify significant factors for multivariate analysis. Cox regression modeling was used to determine independent risk factors for survival. ResultsOf the 2,776 SS patients included, the median age was 39.0 years, predominating male (53.0 %) and white (81.3 %). Bone and soft tissue sarcomas were more common, accounting for 86.4 % of cases (p-value<0.001), while the rest were diagnosed as visceral sarcomas. Visceral SS patients were typically older (p-value<0.001), male (56.8 %), and white (84.8 %). They also presented more frequently with distant metastasis (HR 3.8, 95 % CI, 2.4-6.1), had larger tumors on average (HR for tumors >10 cm: 2.9, 95 % CI, 2.0-4.1), and were less likely to undergo surgery (HR 0.4, 95 % CI, 0.3-0.6). Despite receiving multimodal treatments, including surgery, radiation, and/or chemotherapy, visceral SS patients exhibited poorer overall survival compared to their bone and soft tissue SS counterparts (p-value<0.001). ConclusionVisceral SS often presents in older patients with advanced-stage and larger tumor size as compared to bone and soft tissue SS, which likely contributes to poorer survival. Advanced age, regional spread, and larger tumor size were all found to worsen outcomes, while surgery and radiation were found to be protective factors.

Enhanced immune responses are accompanied by increased MAGEA expression in osteosarcoma metastases

ObjectiveOsteosarcoma is the most common primary bone sarcoma. About 50% of patients develop metastatic disease and their 5-year survival lingers at around 20%–30%. T cell checkpoint blockade immunotherapies have revolutionised cancer treatment in the last decade, but their impact remains limited in osteosarcoma.Methods and analysisIn order to reveal potentially novel immunotherapeutic strategies for advanced osteosarcoma, we conducted an immunogenomic characterisation of a unique sample set comprising 30 osteosarcoma samples from seven patients, collected throughout disease progression. We performed RNA-sequencing and imaging mass cytometry analysis on these samples to reveal the immunological landscape during osteosarcoma progression.ResultsTranscriptional and phenotypical hallmarks of cytotoxic T cell-driven anticancer immunity were enriched in metastatic lesions as compared with primary tumours. Spatial analysis showed T cells infiltrating central regions of osteosarcoma metastases, indicating the absence of an immune excluded environment. In parallel, we found a pronounced increase in the expression of cancer testis antigens, particularly melanoma antigen family A (MAGEA)-related antigens, in osteosarcoma metastases, which was validated in an independent cohort (N=91). In addition, we demonstrated the presentation of MAGE-derived peptides in three out of four osteosarcoma cell lines.ConclusionThese findings indicate a concurrent augmentation of cytotoxic antitumour immune responses and expression of MAGEA antigens from primary to metastatic osteosarcoma. This observation suggests the exploration of MAGEA antigens as potential targets for immunotherapy in the treatment of advanced osteosarcoma.

Roles and Applications of Circulating Tumor-Derived RNAs in Sarcoma Patients: A Systematic Review

Sarcomas are a heterogeneous group of malignancies with a high mortality rate. Detection of circulating tumor-derived material, such as circulating RNA in the peripheral blood of patients, has shown to be useful in diagnosis, prediction of prognosis and disease monitoring in several malignancies. This systematic review aims to probe the existing methods for detecting circulating tumor-derived RNAs from patients affected by sarcoma and their possible clinical application. A systematic review of the literature indexed in PubMed was performed. Each article had to analyze circulating RNA in human specimens obtained from liquid biopsies of patients affected by sarcoma. A total of 26 articles were included. We evaluated 1381 patients; 72% were affected by bone sarcoma and 28% by soft tissue sarcoma. By PCR-based methods, all the studies investigated circulating tumor RNA, mostly in the peripheral blood. Nearly half of the authors investigated the tumor expression and/or release of miRNA (42%). Several authors pointed out that circulating tumor-derived RNA has proven to have potential application in a clinical setting for sarcomas. To the best of our knowledge, this is the first review in the literature to attempt to put together data specifically on ctRNA in patients affected by sarcoma.

A Century of Surgical Quality: Origins, Evolution, and Future Directions.

Over a century has passed since Ernst A. Codman's pioneering call for surgeons to take open responsibility for patient care, a concept integral to the emergence and leadership of the American College of Surgeons (ACS). Codman's End Result Idea, originating in the early 20th century, laid the groundwork for professional responsibility and accountability in surgical practice, catalyzing the formation of the ACS. His innovative use of the "end result" technique at Massachusetts General Hospital highlighted significant variability in surgical outcomes, spurring debates on specialization and accountability. The ACS, under John Bowman's leadership, aimed to ensure optimal care through defined standards and verification mechanisms. Codman's Bone Sarcoma Registry, initiated in 1920, marked an early attempt at quality assessment and improvement through data collection. Despite facing resistance, Codman's vision laid the foundation for modern quality initiatives in surgical care. ACS programs, spanning trauma care to cancer treatment and beyond, have significantly enhanced patient outcomes while reducing costs. Looking forward, advancing surgical quality requires measuring quality, leveraging trusted data, embracing change management, fostering collaboration, and empowering specialists. The future of surgical care depends on collective efforts to uphold standards that ensure optimal care for all.

Assessment of Artificial Intelligence Chatbot Responses to Common Patient Questions on Bone Sarcoma.

The potential impacts of artificial intelligence (AI) chatbots on care for patients with bone sarcoma is poorly understood. Elucidating potential risks and benefits would allow surgeons to define appropriate roles for these tools in clinical care. Eleven questions on bone sarcoma diagnosis, treatment, and recovery were inputted into three AI chatbots. Answers were assessed on a 5-point Likert scale for five clinical accuracy metrics: relevance to the question, balance and lack of bias, basis on established data, factual accuracy, and completeness in scope. Responses were quantitatively assessed for empathy and readability. The Patient Education Materials Assessment Tool (PEMAT) was assessed for understandability and actionability. Chatbots scored highly on relevance (4.24) and balance/lack of bias (4.09) but lower on basing responses on established data (3.77), completeness (3.68), and factual accuracy (3.66). Responses generally scored well on understandability (84.30%), while actionability scores were low for questions on treatment (64.58%) and recovery (60.64%). GPT-4 exhibited the highest empathy (4.12). Readability scores averaged between 10.28 for diagnosis questions to 11.65 for recovery questions. While AI chatbots are promising tools, current limitations in factual accuracy and completeness, as well as concerns of inaccessibility to populations with lower health literacy, may significantly limit their clinical utility.

Association of MRI findings with intra-articular tumour extension.

Treatment of high-grade limb bone sarcoma that invades a joint requires en bloc extra-articular excision. MRI can demonstrate joint invasion but is frequently inconclusive, and its predictive value is unknown. We evaluated the diagnostic accuracy of direct and indirect radiological signs of intra-articular tumour extension and the performance characteristics of MRI findings of intra-articular tumour extension. We performed a retrospective case-control study of patients who underwent extra-articular excision for sarcoma of the knee, hip, or shoulder from 1 June 2000 to 1 November 2020. Radiologists blinded to the pathology results evaluated preoperative MRI for three direct signs of joint invasion (capsular disruption, cortical breach, cartilage invasion) and indirect signs (e.g. joint effusion, synovial thickening). The discriminatory ability of MRI to detect intra-articular tumour extension was determined by receiver operating characteristic analysis. Overall, 49 patients underwent extra-articular excision. The area under the curve (AUC) ranged from 0.65 to 0.76 for direct signs of joint invasion, and was 0.83 for all three combined. In all, 26 patients had only one to two direct signs of invasion, representing an equivocal result. In these patients, the AUC was 0.63 for joint effusion and 0.85 for synovial thickening. When direct signs and synovial thickening were combined, the AUC was 0.89. MRI provides excellent discrimination for determining intra-articular tumour extension when multiple direct signs of invasion are present. When MRI results are equivocal, assessment of synovial thickening increases MRI's discriminatory ability to predict intra-articular joint extension. These results should be interpreted in the context of the study's limitations. The inclusion of only extra-articular excisions enriched the sample for true positive cases. Direct signs likely varied with tumour histology and location. A larger, prospective study of periarticular bone sarcomas with spatial correlation of histological and radiological findings is needed to validate these results before their adoption in clinical practice.

The Critical Role of Stereotactic Body Radiation Therapy in Multimodal Treatment of Lung Metastasis from Bone and Soft Tissue Sarcomas

Background: Stereotactic body radiotherapy (SBRT) is increasingly used to treat lung metastasis (LM) in patients with soft tissue sarcoma (STS) and bone sarcoma (BS). Methods: This retrospective study evaluated the outcomes of patients with BS and STS treated with SBRT for LM between 2010 and 2023. Results: We enrolled 102 patients (51 each with STS and BS), of whom 71 were males and 31 were females (median age, 40 years; range, 11–81 years). At diagnosis, 76 and 26 patients had localized and metastatic disease, respectively, with a median of 4 recurrences (range, 1–12). Before SBRT, 75 patients received chemotherapy and 52 underwent surgery for LM, with 276 nodules treated with SBRT (median dose, 48 Gy; range, 40–52). Local control of irradiated LM was 86% at 1 year and 78% at 2 years. By 31 December 2023 (median follow-up, 4.8 years), 60 patients had died and 42 survived (20 without ongoing disease). From the first LM relapse, the median overall survival (OS) was 4.8 years and the 5-year OS was 49% (95% confidence interval, 39–60%), with no difference between STS and BS; the median OS was 2.9 years and the 5-year OS was 36% after SBRT. Chemotherapy before SBRT was a negative prognostic factor by multivariate analysis. Conclusions: Long-term follow-up shows that SBRT as part of a multimodal treatment approach has reasonable survival rates in patients with LM due to sarcoma. Compared with historical results using only surgery and chemotherapy, SBRT has improved the 5-year OS.

ANGIOGENIC FACTORS AS PREDICTORS OF SURVIVAL IN PATIENTS WITH BONE SARCOMAS

Introduction. Primary bone sarcomas are relatively rare neoplasms. They occur predominantly in adolescents and young adults, are characterized by an aggressive clinical course and a high metastatic potential, have a poor prognosis. In this regard, the problem of stratifying the risk of metastasis and death in order to select the optimal treatment tactics always remains relevant. The study of such markers as endostatin, vascular endothelial growth factor (VEGF), insulin-like growth factors IGF-1, IGF-2 as potentially informative predictors of survival in patients with bone sarcomas is pathogenetically determined by their involvement in the processes of tumor growth and metastasis. Aim – to analyze the relationship between pre-treatment serum levels of endostatin, VEGF, IGF-1 and IGF-2 with overall survival rates in patients with bone sarcomas. Material and methods. An analysis of overall survival rates was carried out in 134 patients with malignant bone tumors aged from 1 to 73 years (Me=27.0 years; Q1–Q3: 18.0 – 43.0 years), among them 87 men (64.9%) and 47 women (35.1%). All patients comprised 4 groups: osteosarcoma (n=58), undifferentiated pleomorphic sarcoma (n=5), Ewing sarcoma (n=29), chondrosarcoma (n=42). In all of them, before the start of specific antitumor treatment, the levels of endostatin, VEGF, IGF-1, and IGF-2 in the blood serum were determined using enzyme immunoassay. The follow-up period ranged from 1 to 229 months (Me=23.0 months; Q1–Q3: 10.0–121.0 months). To analyze overall survival, life tables and Kaplan–Meier curves were constructed. The effect of the studied serum markers on survival rates was assessed using the logrank test and Cox proportional hazards regression model. Results. During observation, death occurred in 51 patients (38.1%). In the group of deceased patients, serum levels of endostatin and IGF-2 were statistically significantly increased compared to the group of surviving patients (p 0.001 and p=0.011, respectively). Kaplan-Meier survival analysis using the logrank test revealed statistically significant differences in overall survival between the four groups of patients with different serum levels of endostatin, IGF-1 and IGF-2. The Cox regression method established the prognostic significance of endostatin as a predictor of overall survival (HR=1.012; p=0.013). Conclusion. Endostatin, IGF-1, IGF-2 can serve as predictors of overall survival of patients with bone sarcomas.

Histology-specific clinical trial of lenvatinib and pembrolizumab in patients with sarcoma.

Survival of patients with metastatic sarcoma remains poor, and there is pressing need for new therapies. Most sarcoma subtypes are not responsive to immune checkpoint inhibition alone. Lenvatinib, a multi-receptor tyrosine kinase inhibitor targeting tumor vasculature, has immunomodulatory activity that contributes to its antitumor effects. Therefore we hypothesized that combination of lenvatinib and pembrolizumab would lead to improved clinical outcomes in patients with sarcoma. This was an open-label, single-arm study of lenvatinib and pembrolizumab in the following cohorts A: leiomyosarcoma, B: undifferentiated pleomorphic sarcoma (UPS), C: vascular sarcomas (angiosarcoma and epithelioid hemangioendothelioma), D: synovial sarcoma or malignant peripheral nerve sheath tumor (MPNST), and E: bone sarcomas (osteosarcoma and chondrosarcoma). The primary endpoint was best overall response (BOR) rate documented by RECIST v1.1 by 27 weeks in each cohort, with a threshold of ≥2 responses among 10 patients. Secondary endpoints included progression-free survival, overall survival, duration of response and safety. Forty-six patients were evaluable for the primary endpoint which was met in the UPS and MPNST/synovial cohorts (BOR rates by 27 weeks of 25% and 30%,respectively). There were 7 partial responses overall with additional responses noted in angiosarcoma and osteosarcoma. Treatment-related adverse events of any grade, and Grade 3 or higher, occurred in 50/51 (98%) and 29/51 (57%) of patients respectively. We observed durable responses in MPNST, synovial sarcoma and osteosarcoma. Patients with UPS and angiosarcoma also responded. Further exploration of this approach is warranted to confirm activity and determine optimal dosing schedules.

Long-term functional outcome of limb-sparing surgery for paediatric bone sarcoma around the knee.

Surgical limb sparing for knee-bearing paediatric bone sarcoma is considered to have a clinically significant influence on postoperative function due to complications and leg-length discrepancies. However, researchers have not fully evaluated the long-term postoperative functional outcomes. Therefore, in this study, we aimed to elucidate the risk factors and long-term functional prognosis associated with paediatric limb-sparing surgery. We reviewed 40 patients aged under 14 years who underwent limb-sparing surgery for knee bone sarcoma (15 cases in the proximal tibia and 25 in the distal femur) between January 2000 and December 2013, and were followed up for a minimum of five years. A total of 35 patients underwent reconstruction using artificial materials, and five underwent biological reconstruction. We evaluated the patients' postoperative complications, survival rate of reconstruction material, and limb, limb function, and leg-length discrepancy at the final follow-up, as well as the risk factors for each. Complications were observed in 55% (22/40) of patients. The limb survival and reconstruction material rates at five and ten years were 95% and 91%, and 88% and 66%, respectively. Infection was the only risk factor in both survivals (p < 0.001, p = 0.019). In the 35 patients with limb preservation, the median International Society of Limb Salvage (ISOLS) score at the final follow-up was 80 (47% to 97%). Younger age (p = 0.027) and complications (p = 0.005) were poor prognostic factors. A negative correlation was found between age and leg-length discrepancy (R = -0.426; p = 0.011). The ISOLS scores were significantly lower in patients with a leg-length discrepancy of more than 5 cm (p = 0.005). Young age and complications were linked to an unfavourable functional prognosis. Leg-length correction was insufficient, especially in very young children, resulting in decreased function of the affected limb. Limb-sparing surgery for these children remains a considerable challenge.

The Importance of Patient Systemic Health Status in High-Grade Chondrosarcoma Prognosis: A National Multicenter Study

Background: Due to the relatively advanced age and high mortality rate of patients with high-grade chondrosarcoma (CS), it is important to holistically assess patient- and tumor characteristics in multidisciplinary team and shared decision-making with regard to treatment options. While current prognostic models include multiple tumor and treatment characteristics, the only patient characteristics that are commonly included are age and gender. Based on clinical experience, we believe that factors related to patient preoperative systemic health status such as the American Society of Anesthesiologists (ASA) score may be equally important prognostic factors for overall survival (OS). Methods: A retrospective nationwide cohort study was identified from four specialized bone sarcoma centers in The Netherlands. Patients with a primary CS grade II, III, and dedifferentiated CS were eligible. Prognostic factors including age at presentation, gender, ASA score, CVD, tobacco use, BMI, histological tumor grade, tumor size, pathological fracture, presentation after unplanned excision, type of surgery and surgical margin were evaluated. The outcome measure was OS at the time of surgery. The Kaplan–Meier methodology was employed to estimate OS; a log-rank test was used to assess the difference in survival. To study the impact of prognostic factors on OS, a multivariate Cox proportional hazard regression model was estimated. Results: In total, 249 patients were eligible for this study, and 89 were deceased at the end of follow-up. In multivariate analysis, histological grade (HR 2.247, 95% CI 1.334–3.783), ASA score III (HR 2.615, 95% CI 1.145–5.976, vs. ASA I), and age per year (HR: 1.025, 95% CI 1.004–1.045) were negatively associated with OS. No association was found between tobacco use, BMI, gender or cardiovascular disease and OS in this cohort. Pathological fracture and tumor size were only associated with OS in univariate analysis. Conclusions: This multicenter study is the first on sarcomas to include ASA in a prognostic model. Results show that ASA score as a proxy for patients’ systemic health status should be included when providing a prognosis for patients with a high-grade primary CS, besides the conventional risk factors such as tumor grade and age. Specifically, severe systemic disease (ASA score III) is a strong negative predictor. Conversely, we found no difference in OS between ASA scores I and II. These findings aid multidisciplinary team and shared decision-making with regard to these complex sarcoma patients that often require life-changing surgeries. Level of Evidence: Prognostic level III. See the instructions for authors for the complete description of levels of evidence.

Surgeon perspectives on a virtual reality platform for preoperative planning in complex bone sarcomas

Background and objectivesTreatment of primary bone and soft tissue sarcomas typically includes complete surgical resection with or without adjunctive modalities. Despite best efforts, for the most challenging clinical scenarios such as axial or pelvic sarcoma, five-year survival rates are reported to be between 27 and 40 %. Since quality of resection is a key determinant of oncologic outcomes, it is critical to preoperatively plan the surgical approach to improve resection accuracy, ensure sufficient surgical margins, and reduce the risk of local or metastatic recurrence. The computer conversion of 2-dimensional (2D) computerized tomography (CT) and magnetic resonance imaging (MRI) to a three-dimensional (3D) virtual reality (VR) avatar image may allow improved preoperative estimation of tumor size, location, adjacent anatomy, and spatial understanding of the tumor without relying on surgeon experience, memory, and imagination. The purpose of this study is to investigate the utility of a virtual reality platform in preoperative planning and surgical approach in a retrospective cohort of pelvic bone sarcoma cases. MethodsThe histopathology database at our institution was queried for all historical cases of bone and soft tissue sarcoma with surgical resection failure, defined as positive gross or microscopic margins. Four cases of pelvic bone sarcoma were chosen for retrospective review by fellowship-trained orthopedic tumor specialists. For each case, participants first studied conventional 2D preoperative CT images and answered a questionnaire pertaining to objective case parameters. Participants then interacted with case-specific 3D models while wearing a VR headset and answered the same questionnaire. The VR ‘avatar’ was created with custom-developed software. After using both modalities, participants completed a Likert-scale survey aiming to evaluate the VR technology's subjective impact on understanding tumor environment, surgical plan confidence, and its ability to improve communication with colleagues and patients. Four attending orthopedic oncologists, one orthopedic oncology fellow, and one senior orthopedic oncology resident participated in the study. ResultsFour cases of failed resection were evaluated by a group of both attending surgeons and a group of trainees composed of both residents and fellows. Tumor borders were clearly delineated in 0 % and 66.6 % cases when evaluating with conventional 2D imaging and VR, respectively. Participants changed adjacent structure involvement grade 22.2 % of the time after assessing involvement grade on the VR technology, with adjacent ligamentous structure grading changed most frequently in 55.5 % of cases. Users reported they would change the surgical approach or margins 44.4 % of the time after reviewing with VR technology. Initial 6 plane resection plans were changed in every user case. Subjective responses indicated that surgeons expressed more confidence in their approach, confidence with obtaining negative margins, and provided more detail regarding structures to be resected in specific planes. ConclusionPelvic tumors present unique surgical challenges due to complex 3D anatomy, the proximity of vital structures, consistency of the tumor, and the need to alter patient position during resection procedures. Using examples of failed pelvic bone sarcoma resections, our study found that VR imaging increased understanding of the tumor environment, characteristics, and ability to communicate with patients and colleagues.

Socioeconomic disparities in reception of limb-sparing surgery versus amputation for lower extremity sarcoma

BackgroundIn lower extremity sarcoma treatment, limb salvage approaches present superior alternatives to amputation due to reduced postoperative morbidity and improved quality of life. This study provides a novel analysis of socioeconomic disparities that may affect reception of limb-sparing surgery. MethodsPatients with lower extremity bone or soft tissue sarcoma who received either limb-sparing surgery or amputation from 2007 to 2021 were identified in the Surveillance, Epidemiology and End Results (SEER) database. Demographic, socioeconomic, and oncologic variables were collected for each patient. Multivariate binary logistic regression was conducted to assess preoperative demographic and oncologic risk factors for amputation (p < 0.05). ResultsA total of 6465 patients were identified in the final cohort, 586 (9.1%) of whom received amputation. After controlling for tumor size, stage, and neoadjuvant therapy administration, non-Hispanic American Indian/Alaskan Native race/ethnicity predicted the highest odds of amputation (OR: 1.78, 95% CI: 1.12–2.85, p = 0.015). Nonmetropolitan residence (OR: 1.69, 95% CI: 1.43–2.00, p < 0.001) also conferred higher risk of amputation compared with residence in a large metropolitan area. Overall, amputation was associated with a higher risk of ten-year cancer-specific mortality (p < 0.001) even when controlled by sociodemographic and clinical characteristics. ConclusionsThere are significant disparities in limb-sparing surgery and amputation rates in lower extremity sarcoma management, even when accounting for differences in baseline oncologic characteristics. Further study into socioeconomic drivers of these trends will allow the development of initiatives that improve disparities in reconstructive outcomes.

The landscape of Functional Outcome Measures Used in Patients with Bone Sarcoma of the Lower Extremity or Pelvis: A Systematic Review.

This systematic review provides a structured overview of the measurement instruments of functional outcome used in lower extremity and pelvic bone sarcoma patients. We identified 42 unique instruments covering 18 distinct functional outcome constructs with most studies measuring constructs within the activity domain of the International Classification of Functioning, disability, and health. The MusculoSkeletal Tumor Society 1993 and 1987 score, Toronto Extremity Salvage Score, and range of motion instruments were the measurement instruments most commonly used.

Planned and Unplanned Sarcoma Resections: Comparative Analysis of Local Recurrence, Metastasis, and Mortality

Background: Sarcomas, a diverse group of malignant tumors arising from mesenchymal tissues, pose significant diagnostic and therapeutic challenges. This study compares the outcomes of planned resections (PEs) and unplanned resections (UEs) to inform better clinical practices. Methods: Data were analyzed from the Swiss Sarcoma Network (SSN), including patients with soft tissue and bone sarcomas treated at two major hospitals. This study utilized logistic regression and Cox regression models to examine the odds of UEs and their impact on local recurrence-free survival. Results: Among 429 patients registered by SSN members, 323 (75%) underwent PEs and 106 (25%) experienced UEs. PEs were associated with significantly larger tumors (94 mm vs. 47 mm, p &lt; 0.001) and higher-grade tumors (Grade 3: 50.5% vs. 37.4%, p = 0.03). Despite achieving superior resection margins (R0: 78.8% vs. 12.6%, p &lt; 0.001), PEs showed higher metastasis rates at follow-up (31.0% vs. 10.4%, p &lt; 0.001) and greater cancer-specific mortality (16.7% vs. 6.6%, p = 0.01). UEs, while linked to higher local recurrence, did not significantly affect metastasis-free survival (MFS) or overall survival (OS). Conclusions: PEs achieve superior immediate surgical outcomes but are linked to higher metastasis and cancer-specific mortality due to the advanced stage of tumors. UEs, while associated with higher local recurrence rates, do not significantly impact MFS or OS. Early detection, comprehensive diagnostics, and timely referrals to specialized sarcoma hubs are essential to avoid UEs and reduce metastatic risk. Future research should focus on developing diagnostic tools using individual tumor and patient characteristics to improve sarcoma management.