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Abstract Bone sarcomas are malignant tumors of mesenchymal origin. Complete surgical resection is the cornerstone of multidisciplinary treatment. However, advanced, unresectable forms remain incurable. A crucial step towards addressing this challenge involves comprehending the molecular mechanisms underpinning tumor progression and metastasis, laying the groundwork for innovative precision medicine-based interventions. We previously showed that tyrosine kinase receptor Ephrin Type-A Receptor 2 (EphA2) is overexpressed in bone sarcomas. EphA2 is a key oncofetal protein implicated in metastasis, self-renewal, and chemoresistance. Molecular, genetic, biochemical, and pharmacological approaches have been developed to target EphA2 and its signaling pathway aiming to interfere with its tumor-promoting effects or as a carrier for drug delivery. This review synthesizes the main functions of EphA2 and their relevance in bone sarcomas, providing strategies devised to leverage this receptor for diagnostic and therapeutic purposes, with a focus on its applicability in the three most common bone sarcoma histotypes: osteosarcoma, chondrosarcoma, and Ewing sarcoma.

Bone sarcomas are malignant tumors of mesenchymal origin. Complete surgical resection is the cornerstone of multidisciplinary treatment. However, advanced, unresectable forms remain incurable. A crucial step towards addressing this challenge involves comprehending the molecular mechanisms underpinning tumor progression and metastasis, laying the groundwork for innovative precision medicine-based interventions. We previously showed that tyrosine kinase receptor Ephrin Type-A Receptor 2 (EphA2) is overexpressed in bone sarcomas. EphA2 is a key oncofetal protein implicated in metastasis, self-renewal, and chemoresistance. Molecular, genetic, biochemical, and pharmacological approaches have been developed to target EphA2 and its signaling pathway aiming to interfere with its tumor-promoting effects or as a carrier for drug delivery. This review synthesizes the main functions of EphA2 and their relevance in bone sarcomas, providing strategies devised to leverage this receptor for diagnostic and therapeutic purposes, with a focus on its applicability in the three most common bone sarcoma histotypes: osteosarcoma, chondrosarcoma, and Ewing sarcoma. [ABSTRACT FROM AUTHOR]

Sarcomas comprise between 10-15% of all pediatric malignancies. Osteosarcoma and Ewing sarcoma are the two most common pediatric bone tumors diagnosed in children and young adults. These tumors are commonly treated with surgery and/or radiation therapy and combination chemotherapy. However, there is a strong need for the development and utilization of targeted therapeutic methods to improve patient outcomes. Towards accomplishing this goal, pre-clinical models for these unique malignancies are of particular importance to design and test experimental therapeutic strategies prior to being introduced to patients due to their origination site and propensity to metastasize. Pre-clinical models offer several advantages for the study of pediatric sarcomas with unique benefits and shortcomings dependent on the type of model. This review addresses the types of pre-clinical models available for the study of pediatric solid tumors, with special attention to the bone sarcomas osteosarcoma and Ewing sarcoma. [ABSTRACT FROM AUTHOR]

Aims: We endeavored to introduce a novel scoring system (Lumbar Functional Index, LFI) capable of evaluating lumbar function in pelvic bone sarcoma patients who underwent surgical resection and spinal pelvic fixation, while simultaneously identifying the incidence, outcomes, and risk factors of lumbar function impairment among these populations. Patients and Methods: A cohort of 304 primary bone sarcoma patients were recruited. The LFI was created based on the Oswestry Dysfunction Index (ODI) and Japanese Orthopaedic Association (JOA) scores. Lumbar function impairment was defined as LFI score ≥ 18 points, which was identified as high LFI. Demographic data, clinical characteristics, and oncological outcomes were analyzed. Results: The cohort included chondrosarcoma (39.8%), osteosarcoma (29.9%), Ewing sarcoma (8.6%), bone‐derived undifferentiated pleomorphic sarcoma (7.2%), giant cell tumor of bone (7.2%), chordoma (2.3%), and other bone sarcomas (5.0%). The LFI score exhibited significant negative correlation with common scoring systems of bone sarcoma. The incidence of high LFI was 23.0%. Patients with high LFI demonstrated a higher prevalence of type I + II + III + IV pelvic tumor, more sacrificed nerve roots and bilateral lumbar spine fixation during surgery, while lower percentage of R0 resection and local control of pelvic tumor. Decreased median overall survival (30 vs. 52 months, p < 0.001) and recurrence‐free survival (14 vs. 24 months, p < 0.001) time were observed in these patients. Type I + II + III + IV pelvic tumor and sacrificed nerve roots≥2 were identified as risk factors for high LFI, while R0 resection and local control were identified as protective factors. Conclusion: The LFI scoring system exhibited a significant negative correlation to current scoring systems. High LFI patients had worse prognosis and distinct characteristics. The risk factors of high LFI included type I + II + III + IV pelvic tumor and sacrificed nerve roots≥2, and the protective factors included R0 resection and local control. [ABSTRACT FROM AUTHOR]

Sarcomas comprise between 10–15% of all pediatric malignancies. Osteosarcoma and Ewing sarcoma are the two most common pediatric bone tumors diagnosed in children and young adults. These tumors are commonly treated with surgery and/or radiation therapy and combination chemotherapy. However, there is a strong need for the development and utilization of targeted therapeutic methods to improve patient outcomes. Towards accomplishing this goal, pre-clinical models for these unique malignancies are of particular importance to design and test experimental therapeutic strategies prior to being introduced to patients due to their origination site and propensity to metastasize. Pre-clinical models offer several advantages for the study of pediatric sarcomas with unique benefits and shortcomings dependent on the type of model. This review addresses the types of pre-clinical models available for the study of pediatric solid tumors, with special attention to the bone sarcomas osteosarcoma and Ewing sarcoma.

Abstract Despite technical and fundamental progress in conventional cancer treatment methods, there still exists a vital need for more effective methods to address the current limitations in treatment. Combinational therapies are strategies suggested to enhance the chance of recurrence‐free and disease‐free survival in sarcomas. Among them magnetic hyperthermia has been attracting more and more attention for use in multimodal bone sarcoma treatment. The magnetic hyperthermia supposed to be non‐invasive, more tissue‐specific, and more effective in deep tissues. Magnetic nanoparticles and other active agents can be delivered through various drug delivery administrations to the tumor site and be heated remotely via alternating magnetic fields. Designing favorable drug delivery platforms that contain magnetic particles besides other anti‐tumor agents is a vital key in hyperthermia combinational therapies. Nanomaterials and nanotechnology have been widely engaged for designing efficient platforms in multimodal treatments. The purpose of this review is to discuss the latest designed magnetic nanoparticle platforms in hyperthermia combinational treatment in bone sarcoma.

Simple Summary: Soft tissue and bone sarcomas belong to a group of rare and malignant tumors. The treatment of these tumors is very complex and depends on their specific subtypes. Therefore, there is a great need to develop novel therapeutic options for patients with sarcomas. One such option may be to target tumor-associated macrophages (TAMs), which are involved in immunosuppression during tumor growth. High levels of TAMs are widely recognized as a poor prognostic factor in many tumors, including sarcomas, making them a promising target for future targeted therapies. In this review, we highlight the role of TAMs in the microenvironment of sarcomas, along with their clinical relevance, potential targetable markers on their surface, and the molecular pathways involved. We also discuss currently ongoing clinical trials with TAMs. Sarcomas are a heterogeneous group of malignant mesenchymal tumors, including soft tissue and bone sarcomas. Macrophages in the tumor microenvironment, involved in immunosuppression and leading to tumor development, are called tumor-associated macrophages (TAMs). TAMs are very important in modulating the microenvironment of sarcomas by expressing specific markers and secreting factors that influence immune and tumor cells. They are involved in many signaling pathways, such as p-STAT3/p-Erk1/2, PI3K/Akt, JAK/MAPK, and JAK/STAT3. TAMs also significantly impact the clinical outcomes of patients suffering from sarcomas and are mainly related to poor overall survival rates among bone and soft tissue sarcomas, for example, chondrosarcoma, osteosarcoma, liposarcoma, synovial sarcoma, and undifferentiated pleomorphic sarcoma. This review summarizes the current knowledge on TAMs in sarcomas, focusing on specific markers on sarcoma cells, cell–cell interactions, and the possibly involved molecular pathways. Furthermore, we discuss the clinical significance of macrophages in sarcomas as a potential target for new therapies, presenting clinical relevance, possible new treatment options, and ongoing clinical trials using TAMs in sarcoma treatment. [ABSTRACT FROM AUTHOR]

Despite technical and fundamental progress in conventional cancer treatment methods, there still exists a vital need for more effective methods to address the current limitations in treatment. Combinational therapies are strategies suggested to enhance the chance of recurrence‐free and disease‐free survival in sarcomas. Among them magnetic hyperthermia has been attracting more and more attention for use in multimodal bone sarcoma treatment. The magnetic hyperthermia supposed to be non‐invasive, more tissue‐specific, and more effective in deep tissues. Magnetic nanoparticles and other active agents can be delivered through various drug delivery administrations to the tumor site and be heated remotely via alternating magnetic fields. Designing favorable drug delivery platforms that contain magnetic particles besides other anti‐tumor agents is a vital key in hyperthermia combinational therapies. Nanomaterials and nanotechnology have been widely engaged for designing efficient platforms in multimodal treatments. The purpose of this review is to discuss the latest designed magnetic nanoparticle platforms in hyperthermia combinational treatment in bone sarcoma. [ABSTRACT FROM AUTHOR]

Background: Diagnosis of a bone or soft tissue sarcomas is uncommon, and the odds of being present during pregnancy are rare. Hence, the management of sarcoma during pregnancy is more complicated, and to date, no single guideline suits all. Method: Patients diagnosed with either bone or soft-tissue sarcomas or metastatic sarcoma progression during pregnancy were identified retrospectively between 1983 and 2021 from our orthopaedic oncology database. Demographic and relevant information regarding their management was collected, including maternal and neonatal outcomes, metastatic progression, and survival rates. Results: A sum of 30 patients diagnosed with sarcoma during pregnancy were included; 16 (53.33%) with bone sarcoma and nine (30%) with soft-tissue sarcoma. Five (16.67%) had metastatic progression of their bone or soft-tissue sarcoma during pregnancy. The median age at diagnosis is 31 years old, youngest at 18 and eldest at 38 years old. Detailed discussions between the sarcoma multidisciplinary team (MDT) and obstetric teams took place throughout each patient's pregnancy follow-up. Seven underwent termination of pregnancy, and six underwent surgical treatment during pregnancy with no maternal or neonatal complications reported. Eight were induced early and four underwent early caesarean section to allow for staging and definitive management without any neonatal complications. Maternal one-year and five-year survival rates for bone sarcomas were 100% and 73.68%, respectively, and 100% and 70%, respectively, for soft-tissue sarcomas. One survived more than five years in the metastatic progression group but succumbed at 7th year due to cerebral metastasis. Conclusion: The management of bone and soft-tissue sarcomas during pregnancy by sarcoma MDT with collective knowledge and expertise led to good neonatal or maternal outcomes comparable to maternal survival rates of the non-pregnant population. The treatment plan should be based on individual expectations from the patient depending on the gestational period of the pregnancy, the type of pathology, and the location of the sarcoma.

Objective Currently, there is a lack of good clinical tools for evaluating the effect of chemotherapy preoperatively on primary high‐grade bone sarcomas. Our goal was to investigate the predictive value of the clinical findings and establish a scoring system to predict chemotherapy response. Methods We conducted a retrospective multicenter cohort study and reviewed 322 patients with primary high‐grade bone sarcomas. Patients who routinely received neoadjuvant chemotherapy and underwent primary tumor resection with an assessment of tumor necrosis rate (TNR) were enrolled in this study. The medical records of patients were collected from November 1, 2011, to March 1, 2018, at Peking University People's Hospital (PKUPH) and Peking University Shougang Hospital (PKUSH). The mean age of the patients was 16.2 years (range 3–52 years), of whom 65.5% were male. The clinical data collected before and after neoadjuvant chemotherapy included the degree of pain, laboratory inspection, X‐ray, CT, contrast‐enhanced magnetic resonance (MR), and positron emission tomography‐computed tomography (PET‐CT). Several machine learning models, including logistic regression, decision trees, support vector machines, and neural networks, were used to classify the chemotherapy responses. Area under the curve (AUC) of the scoring system to predict chemotherapy response is the primary outcome measure. Results For patients without events, a minimum follow‐up of 24 months was achieved. The median follow‐up time was 43.3 months, and it ranged from 24 to 84 months. The 5 years progression‐free survival (PFS) of the included patients was 54.1%. The 5 years PFS rate was 39.7% for poor responders and 74.9% for good responders. Features such as longest diameter reduction ratio (up to three points), clear bone boundary formation (up to two points), tumor necrosis measured by magnetic resonance (up to two points), maximum standard uptake value (SUVmax) decrease (up to three points), and significant alkaline phosphatase decrease (up to 1 point) were identified as significant predictors of good histological response and constituted the scoring system. A score ≥4 predicts a good response to chemotherapy. The scoring system based on the above factors performed well, achieving an AUC of 0.893. For nonmeasurable lesions (classified by the revised Response Evaluation Criteria in Solid Tumors [RECIST 1.1]), the AUC was 0.901. Conclusion We first devised a well‐performing comprehensive scoring system to predict the response to neoadjuvant chemotherapy in primary high‐grade bone sarcomas.

Malignant giant-cell tumors are extremely rare bone sarcomas that transform from conventional giant-cell tumors during long periods of treatment. Owing to their rarity, no further analysis of their molecular pathogenesis exists, and thus, no standard treatment has been established. Recently, organoid culture methods have been highlighted for recapturing the tumor microenvironment, and we have applied the culture methods and succeeded in establishing patient-derived organoids (PDO) of rare sarcomas. This study aimed to investigate the genomic characteristics of our established novel organoids from human malignant giant-cell tumors. At our institute, we treated a patient with malignant giant-cell tumor. The remaining sarcoma specimens after surgical resection were cultured according to the air–liquid interface organoid-culture method. Organoids were xenografted into NOD-scid IL2Rgnull mice. The developed tumors were histologically and genomically analyzed to compare their characteristics with those of the original tumors. Genetic changes over time throughout treatment were analyzed, and the genomic status of the established organoid was confirmed. Organoids from malignant giant-cell tumors could be serially maintained using air–liquid interface organoid-culture methods. The tumors developed in xenografted NOD-scid IL2Rgnull mice. After several repetitions of the process, a patient-derived organoid line from the malignant giant-cell tumor was established. Immunohistochemical analyses and next-generation sequencing revealed that the established organoids lacked the H3-3A G34W mutation. The xenografted organoids of the malignant giant-cell tumor had phenotypes histologically and genetically similar to those of the original tumor. The established organoids were confirmed to be derived from human malignant giant-cell tumors. In summary, the present study demonstrated a novel organoid model of a malignant giant-cell tumor that was genetically confirmed to be a malignant transformed tumor. Our organoid model could be used to elucidate the molecular pathogenesis of a malignant giant-cell tumor and develop novel treatment modalities.

Aims: Socioeconomic and racial disparities have been recognized as impacting the care of patients with cancer, however there are a lack of data examining the impact of these disparities on patients with bone sarcoma. The purpose of this study was to examine socioeconomic and racial disparities that impact the oncological outcomes of patients with bone sarcoma. Methods: We reviewed 4,739 patients diagnosed with primary bone sarcomas from the Surveillance, Epidemiology and End Results (SEER) registry between 2007 and 2015. We examined the impact of race and insurance status associated with the presence of metastatic disease at diagnosis, treatment outcome, and overall survival (OS). Results: Patients with Medicaid (odds ratio (OR) 1.41; 95% confidence interval (CI) 1.15 to 1.72) and uninsured patients (OR 1.90; 95% CI 1.26 to 2.86) had higher risks of metastatic disease at diagnosis compared to patients with health insurance. Compared to White patients, Black (OR 0.63, 95% CI 0.47 to 0.85) and Asian/Pacific Islander (OR 0.65, 95% CI 0.46 to 0.91) were less likely to undergo surgery. In addition, Black patients were less likely to receive chemotherapy (OR 0.67, 95% CI 0.49 to 0.91) compared to White patients. In patients with chondrosarcoma, those with Medicaid had worse OS compared to patients with insurance (hazard ratio (HR) 1.65, 95% CI 1.06 to 2.56). Conclusion: In patients with a bone sarcoma, the cancer stage at diagnosis varied based on insurance status, and racial disparities were identified in treatment. Further studies are needed to identify modifiable factors which can mitigate socioeconomic and racial disparities found in patients with bone sarcomas. Cite this article: Bone Joint Res 2022;11(5):278–291.

Objective: Currently, there is a lack of good clinical tools for evaluating the effect of chemotherapy preoperatively on primary high‐grade bone sarcomas. Our goal was to investigate the predictive value of the clinical findings and establish a scoring system to predict chemotherapy response. Methods: We conducted a retrospective multicenter cohort study and reviewed 322 patients with primary high‐grade bone sarcomas. Patients who routinely received neoadjuvant chemotherapy and underwent primary tumor resection with an assessment of tumor necrosis rate (TNR) were enrolled in this study. The medical records of patients were collected from November 1, 2011, to March 1, 2018, at Peking University People's Hospital (PKUPH) and Peking University Shougang Hospital (PKUSH). The mean age of the patients was 16.2 years (range 3–52 years), of whom 65.5% were male. The clinical data collected before and after neoadjuvant chemotherapy included the degree of pain, laboratory inspection, X‐ray, CT, contrast‐enhanced magnetic resonance (MR), and positron emission tomography‐computed tomography (PET‐CT). Several machine learning models, including logistic regression, decision trees, support vector machines, and neural networks, were used to classify the chemotherapy responses. Area under the curve (AUC) of the scoring system to predict chemotherapy response is the primary outcome measure. Results: For patients without events, a minimum follow‐up of 24 months was achieved. The median follow‐up time was 43.3 months, and it ranged from 24 to 84 months. The 5 years progression‐free survival (PFS) of the included patients was 54.1%. The 5 years PFS rate was 39.7% for poor responders and 74.9% for good responders. Features such as longest diameter reduction ratio (up to three points), clear bone boundary formation (up to two points), tumor necrosis measured by magnetic resonance (up to two points), maximum standard uptake value (SUVmax) decrease (up to three points), and significant alkaline phosphatase decrease (up to 1 point) were identified as significant predictors of good histological response and constituted the scoring system. A score ≥4 predicts a good response to chemotherapy. The scoring system based on the above factors performed well, achieving an AUC of 0.893. For nonmeasurable lesions (classified by the revised Response Evaluation Criteria in Solid Tumors [RECIST 1.1]), the AUC was 0.901. Conclusion: We first devised a well‐performing comprehensive scoring system to predict the response to neoadjuvant chemotherapy in primary high‐grade bone sarcomas. [ABSTRACT FROM AUTHOR]

Highlights New role of EVs in cell–cell communication in bone sarcoma. New clinical practicality and future application prospects of EVs. EVs can be use as biomarker vehicles for diagnosis and prognosis in bone sarcomas. Bone sarcomas cells derived EVs may influence angiogenesis, osteoclastogenesis, immunomodulation, drug resistance, invasion, and migration processes.

Abstract We reviewed the recent literature related to primary musculoskeletal tumors and metastatic bone tumors. With regard to primary bone tumors, computer navigation systems and three-dimensional-printed prostheses seem to be new treatment options, especially in challenging anatomical locations, such as the sacrum and pelvis. Regarding the treatment of giant cell tumor of bone, recent studies have suggested that denosumab administration is related to a higher local recurrence rate following curettage, but a lower local recurrence rate following en bloc resection. In addition, there was no difference in the local recurrence rate at five years after surgery between short-term and long-term denosumab therapy. With regard to soft tissue tumors, percutaneous cryoablation appears to be a new treatment option for extra-abdominal desmoid tumors, with encouraging results. Regarding soft tissue sarcomas, a negative surgical margin of

Primary bone cancers, also called bone sarcomas, can arise anywhere in the body. Less than 1% of cancers are identified as primary bone cancers annually, and they are correlated with high rates of morbidity and death. Twenty to twenty-seven percent of primary malignant osseous neoplasms are chondrosarcomas, the rarest subtype of bone sarcomas. The incidence of chondrosarcomas in Saudi Arabia was less common than globally discovered chondrosarcomas, and only a few cases have been recorded. The most common presentation of the primary chondrosarcoma (CS) is to encompass the bony skeleton of the long bones of the lower extremities and the axial skeleton. Detecting primary CS in the anterior chest wall and the rib cage is rare. To our knowledge, chondrosarcomas of the ribs encroaching on the anterior chest are rare and have never been documented in Saudi Arabian or Middle East medical or surgical literature. We describe a case of a 32-year-old female with chondrosarcoma of the left anterior seventh rib, with no other medical or surgical histories. Further work-up at the tertiary care center, including computed tomography-scan, magnetic resonance imaging, and detailed triple bone scan (nuclear scan) imaging and histological biopsy, revealed features of chondrosarcoma arising from the ribs and involving the surrounding soft tissue. The patient underwent en masse surgical resection with a 4 cm margin, including the sixth rib and partial resection of the left hemidiaphragm and a small piece of the diaphragm. The patient was discharged without any inauspicious consequences. In the current work, we comprehensively discussed a scarce case of the anterior chest wall chondrosarcoma affecting the rib. This case highlights the importance of early detection of a rare tumor using a toolkit diagnostic approach to provide successful management and caring of the patient. Consequently, this will guarantee encouraging outcomes and thus stress the fruitful role of the surgery as the best curative modality in chondrosarcoma patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objectives: 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., Methods: 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., Results: 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., Conclusions: 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., (© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.)

The acronym for the CCN family was recently revised to represent "cellular communication network". These six, small, cysteine-enriched and evolutionarily conserved proteins are secreted matricellular proteins, that convey and modulate intercellular communication by interacting with structural proteins, signalling factors and cell surface receptors. Their role in the development and physiology of musculoskeletal system, constituted by connective tissues where cells are interspersed in the cellular matrix, has been broadly studied. Previous research has highlighted a crucial balance of CCN proteins in mesenchymal stem cell commitment and a pivotal role for CCN1, CCN2 and their alter ego CCN3 in chondrogenesis and osteogenesis; CCN4 plays a minor role and the role of CCN5 and CCN6 is still unclear. CCN proteins also participate in osteoclastogenesis and myogenesis. In adult life, CCN proteins serve as mechanosensory proteins in the musculoskeletal system providing a steady response to environmental stimuli and participating in fracture healing. Substantial evidence also supports the involvement of CCN proteins in inflammatory pathologies, such as osteoarthritis and rheumatoid arthritis, as well as in cancers affecting the musculoskeletal system and bone metastasis. These matricellular proteins indeed show involvement in inflammation and cancer, thus representing intriguing therapeutic targets. This review discusses the current understanding of CCN proteins in the musculoskeletal system as well as the controversies and challenges associated with their multiple and complex roles, and it aims to link the dispersed knowledge in an effort to stimulate and guide readers to an area that the writers consider to have significant impact and relevant potentialities. [ABSTRACT FROM AUTHOR]

Primary bone sarcomas are rare tumors and surgical resection in combination with chemo and radiation therapy is the mainstay of treatment. Some specific anatomical sites still represent a reconstructive challenge due to their complex three-dimensional anatomy. In recent years, patient specific instruments along with 3D printing technology has come to represent innovative techniques in orthopaedic oncology. We retrospectively reviewed 23 patients affected by primary bone sarcoma treated with patient-specific instruments and 3D printing custom made prostheses. At follow up after approximately two years, the infection rate was 26%, mechanical complication rate 13%, and local recurrence rate 13% (with a five-years implant survival rate of 74%). Based on our experience, patient-specific instruments and 3D custom-made prostheses represents a reliable and safe technique for improving the accuracy of resection of primary bone tumour, with a particular use in pelvic surgery ameliorating functional results. [ABSTRACT FROM AUTHOR]

While distant metastases in primary bone sarcomas have been extensively studied, the impact of isolated regional lymph node (LN) metastasis on survival remains unknown. In patients with primary bone sarcomas, we sought to assess the prevalence of isolated regional LN metastasis and the survival of this population. A total of 6651 patients with histologically-confirmed high-grade osteosarcoma, Ewing sarcoma, or chondrosarcoma were retrieved from the SEER database. We defined four subgroups for our analysis: localized disease (N0 M0), isolated regional LN metastasis (N1 M0), isolated distant metastasis (N0 M1), and combined regional LN and distant metastasis (N1 M1). Disease-specific survival (DSS) was assessed using the Kaplan-Meier method. Prevalence of isolated regional LN metastasis (N1 M0) was highest in Ewing sarcoma (27/1097; 3.3 %), followed by chondrosarcoma (18/1702; 1.4 %) and osteosarcoma (26/3740; 0.9 %). In all three histologies, patients with isolated regional LN metastasis had a worse 2-year, 5-year, and 10-year DSS than those with localized disease. Chondrosarcoma patients with isolated regional LN (N1 M0) metastasis had a significantly higher DSS in comparison to those with only distant metastasis (N0 M1) at the 5- and 10-year marks; for osteosarcoma and Ewing sarcoma, only a pattern towards higher survival was seen. Risk factors for presenting isolated regional LN metastasis included tumor location in lower-limb (OR = 2.01) or pelvis (OR = 2.49), diagnosis of Ewing sarcoma (OR = 2.98), and tumor >10 cm (OR = 1.96). Isolated regional LN metastases in primary bone sarcomas is an infrequent presentation associated with worse survival than localized disease. III. [ABSTRACT FROM AUTHOR]

We reviewed the recent literature related to primary musculoskeletal tumors and metastatic bone tumors. With regard to primary bone tumors, computer navigation systems and three-dimensional-printed prostheses seem to be new treatment options, especially in challenging anatomical locations, such as the sacrum and pelvis. Regarding the treatment of giant cell tumor of bone, recent studies have suggested that denosumab administration is related to a higher local recurrence rate following curettage, but a lower local recurrence rate following en bloc resection. In addition, there was no difference in the local recurrence rate at five years after surgery between short-term and long-term denosumab therapy. With regard to soft tissue tumors, percutaneous cryoablation appears to be a new treatment option for extra-abdominal desmoid tumors, with encouraging results. Regarding soft tissue sarcomas, a negative surgical margin of < 1 mm is sufficient to control local recurrence. Pexidartinib seems to be a promising systemic therapy for the treatment of tenosynovial giant cell tumors for which surgery is not expected to improve the function of the affected limb. Finally, the life expectancy of patients is the most important factor in determining the optimal surgical procedure for patients with impending or pathological fractures of the long bone due to metastatic bone tumors. Elevated C-reactive protein level was found to be an independent poor prognostic factor at 1 year after surgery for long bone metastases. [ABSTRACT FROM AUTHOR]

Background. Solid tumors in children are one of the most common childhood malignancy, second only to hemoblastosis. Among solid tumours, about 5% are bone sarcomas: osteosarcoma (3%) and Ewing's sarcoma (2%). Atypicality of the these diseases course makes an early diagnosis a real challenge.Case Reports. The article presents six clinical observations of patients with bone sarcomas. We demonstrate the difficulties in diagnosing of this disease group which is associated with the absence of both specific symptoms and distinct clinical picture.Conclusion. Pediatricians and pediatric surgeons should take into account the possibility of atypical course of bone sarcomas in children. Low cancer alertness is the reason for a significant delay in establishing the correct diagnosis which contributes to the tumour process generalization and reduces the chances of achieving remission while increasing the cost of treating such patients.

to review a group of patients with primary bone tumors treated with intraoperative navigation and analyze: (1) The technical problems; (2) Indications for Computer Assisted Surgery (CAS); (3) Oncological results; (4) Non oncological complications. All patients from a single institution who had preoperative virtual planned for an oncological primary bone resection assisted with navigation between May 2010 and July 2017 were enrolled in the study (203 patients). The use of computer-assisted surgery (CAS) was classified according to the oncologic procedure performed: (1) intralesional resections, (2) en-block resections, and (3) en-block resections + navigated allograft reconstructions. Four patients (4/203, 2%) of the series presented technical problems which came from 2 software and 2 hardware crashes. Eight (4%) procedures were intralesional resections and no local recurrences or complications were reported in this group. Ninety-eight surgeries (49%) were pure en block resection. The pelvis and sacrum were the main location in this group (57%). All bone margins were defined negative but 2 patients presented a positive resection in the soft tissues. Infection was the most prevalent complication (16/23). Ninety-three procedures were done for en block resections + allograft reconstruction (all extremities tumor). All margins were free of tumor and non oncological rate for this group was 28%. The main indications for CAS were malignant bone tumors resection. The technical failures precluded navigation use in 2%. CAS for pure en-block resections were mainly indicated in pelvic and sacrum tumors while en-block resection + allograft reconstruction assisted with navigation were only indicated in extremities tumors. IV. [ABSTRACT FROM AUTHOR]

Background/Aim: Ewing sarcoma (ES) and osteosarcomas (OSA) are the most common bone tumor types in adolescents and young adults (AYA). Therapy management of these tumors consists of preoperative chemotherapy, operation, and postoperative chemotherapy. The aim of this study was to evaluate the efficacy and tolerability of EURAMOS-A and EURO E.W.I.N.G. protocols. Patients and Methods: We retrospectively evaluated 31 patients between 18 and 39 years of age with ES and OSA treated at the Department of Medicine I, Clinical Division of Oncology. Patients with ES were treated according the EURO E.W.I.N.G protocol, whereas patients with OSA according to the EURAMOS-1 protocol. Results: Most frequent tumor sites for ES were thorax and pelvis, each 33%. Eight patients had initially localized disease (67%). A median of 3 cycles of full dose chemotherapy could be administered. Nine patients had a dose reduction (75%). Most common reason for dose reduction was prolonged aplasia (67%). Overall response rate (ORR) was 33%. For OSA patients, the most frequent tumor site was the lower extremity (58%). Sixteen patients (84%) had initially localized disease. A median of only 9 cycles of EURAMOS-1 in full dose could be administered. Most common reason for dose reduction was elevated methotrexate level (53%) and ORR was 90%. Conclusion: The two studied protocols were well-tolerated in the AYA patients included in this study. Dose reductions instead of dose delays should be considered when side effects occur. [ABSTRACT FROM AUTHOR]

Chondrosarcomas constitute the 3rd most common primary bone malignancy. These tumours grow slowly and rarely metastasize, usually having a good prognosis after surgery. Among patients registered and treated at the Brazilian National Institute of Traumatology and Orthopedics, an uncommon case of chondrosarcoma was identified in a 63-year-old man, who was diagnosed with multicentric chondrosarcoma of the appendicular skeleton. This example is atypical in the medical literature because multicentric tumours are different from metastatic events, and their frequency in chondrosarcoma is rare. This article therefore provides a rare case report alongside a review of additional cases in the medical literature. [ABSTRACT FROM AUTHOR]

Primary bone sarcomas are rare tumors and surgical resection in combination with chemo and radiation therapy is the mainstay of treatment. Some specific anatomical sites still represent a reconstructive challenge due to their complex three-dimensional anatomy. In recent years, patient specific instruments along with 3D printing technology has come to represent innovative techniques in orthopaedic oncology. We retrospectively reviewed 23 patients affected by primary bone sarcoma treated with patient-specific instruments and 3D printing custom made prostheses. At follow up after approximately two years, the infection rate was 26%, mechanical complication rate 13%, and local recurrence rate 13% (with a five-years implant survival rate of 74%). Based on our experience, patient-specific instruments and 3D custom-made prostheses represents a reliable and safe technique for improving the accuracy of resection of primary bone tumour, with a particular use in pelvic surgery ameliorating functional results.

Bone or soft tissue sarcomas are rarely diagnosed during pregnancy. Until today 137 well documented cases have been reported in the English literature between 1963 and 2014. Thirty-eight pregnant mothers were diagnosed with osteosarcoma, Ewing’s sarcoma or chondrosarcoma, whereas 95 other cases of soft tissue sarcomas of various types have been documented. We present the clinical picture and therapeutic management of this coexistence.

Capabilities of 199Tl-chloride and 99mTc-MIBI scintigraphy in the non-nonspecific indications of bone and soft tissue sarcomas in overall 31 patients (34 lesions) were studied. Sensitivity of these methods in the detections of neoplasms reached 96.0 % and 100.0 %, respectively. It described positive, negative and mixed types of sarcomas visualizations on the both 199Tl-chloride and 99mTc-MIBI scintigraphy. There are preconditions for the 199Tl-chloride scintigraphy in the successful differentiations between bone and soft tissue sarcomas and benign tumors or non-tumor diseases, primarily inflammations.

Bone sarcomas are rare tumors, approximating 0.2% of all cancers, with osteosarcoma (OGS), chondrosarcoma, and Ewing sarcoma being the most common cancers in this subset. The formation of disease management groups/clinics focused on sarcomas has resulted in better understanding and management of these uncommon tumors. Multiple large-scale retrospective data from Tata Memorial Hospital (TMH) and All India Institute of Medical Sciences have reported outcomes comparable to Western data in the field of OGS and Ewing sarcoma, with interesting prognostic factors identified for further evaluation. Soft tissue sarcomas are a rare heterogeneous group of tumors, more than 50 different tumor entities. The common subtypes identified in India include Ewing sarcoma and synovial sarcoma. Valuable work regarding brachytherapy has been done by radiation oncologists from the TMH, especially in pediatric patients.

RANK/RANKL/OPG ligand-receptor system is a key player in bone homeostasis regulation directly regulating osteoclast differentiation and osteolysis. Disbalance of bone homeostasis associated with malfunctioning of RANK/RANKL/OPG system underlies such oncological processes as the destruction of bone, metastasis development, tumor progression. Involvement of RANK/RANKL/OPG system in the development of metastasis from various tumors is practically confirmed, but its influence on the development and progression of primary bone tumors still needs thorough evaluation. , In this paper experimental and clinical-laboratory data on the role of RANK/RANKL/OPG system in primary bone tumors pathogenesis available in modern literature are summarized with special attention,paid to giant-cell bone tumor (GCBT) that is already treated with RANK/RANKL interaction inhibitor denosumab. Results of authors study of the levels of RANK/RANKL/OPG system,s components in blood serum of 101 malignant bone tumor (37 – osteosarcoma, 41 – chondrosarcoma, 12 – chordoma, 7 – Ewing sarcoma, 2 – pleomorhic undifferentiated sarcoma, 2 – fibrosarcoma), 32 borderline GCBT, and 30 benign bone tumor patients are also presented. The disturbances in the balance of osteolysis activators and inhibitors in patients with primary bone tumor depending both on the character of neoplasm (malignant, borderline or benign), and histological structure of malignant tumors were demonstrated. The most striking changes in RANK/ RANKL/OPG system manifesting itself in an increase of serum concentrations of all its components and strengthening of association between the levels of soluble receptor and its natural inhibitor OPG were revealed in giant-cell bone tumor patients.The study of the role of RANK/RANKL/OPG system in primary bone neoplasms is a topical goal for clinical investigations; it is also a promising tool for development of new diagnostic methods and for targeted application of specific drugs inhibiting its activity.

Primary malignant bone tumors are uncommon and heterogeneous malignancies. This document is a guideline developed by the Spanish Group for Research on Sarcoma with the participation of different specialists involved in the diagnosis and treatment of bone sarcomas. The aim is to provide practical recommendations with the intention of helping in the clinical decision-making process. The diagnosis and treatment of bone tumors requires a multidisciplinary approach, involving as a minimum pathologists, radiologists, surgeons, and radiation and medical oncologists. Early referral to a specialist center could improve patients' survival. The multidisciplinary management of osteosarcoma, chondrosarcoma, chordoma, giant cell tumor of bone and other rare bone tumors is reviewed in this guideline. Ewing's sarcoma will be the focus of a separate guideline because of its specific biological, clinical and therapeutic features. Each statement has been accompanied by the level of evidence and grade of recommendation on the basis of the available data. Surgical excision is the mainstay of treatment of a localized bone tumor, with various techniques available depending on the histologic type, grade and location of the tumor. Chemotherapy plays an important role in some chemosensitive subtypes (such as high-grade osteosarcoma). In other subtypes, historically considered chemoresistant (such as chordoma or giant cell tumor of bone), new targeted therapies have emerged recently, with a very significant efficacy in the case of denosumab. Radiation therapy is usually necessary in the treatment of chordoma and sometimes of other bone tumors. [ABSTRACT FROM AUTHOR]

• We investigated the genomic characteristics of our established novel organoids from human MGCTs. • Our novel organoid model was genetically confirmed to be a malignant transformed tumor. • Our organoid model could be used to elucidate the molecular pathogenesis of a MGCT and develop novel treatment modalities. Malignant giant-cell tumors are extremely rare bone sarcomas that transform from conventional giant-cell tumors during long periods of treatment. Owing to their rarity, no further analysis of their molecular pathogenesis exists, and thus, no standard treatment has been established. Recently, organoid culture methods have been highlighted for recapturing the tumor microenvironment, and we have applied the culture methods and succeeded in establishing patient-derived organoids (PDO) of rare sarcomas. This study aimed to investigate the genomic characteristics of our established novel organoids from human malignant giant-cell tumors. At our institute, we treated a patient with malignant giant-cell tumor. The remaining sarcoma specimens after surgical resection were cultured according to the air–liquid interface organoid-culture method. Organoids were xenografted into NOD-scid IL2Rgnull mice. The developed tumors were histologically and genomically analyzed to compare their characteristics with those of the original tumors. Genetic changes over time throughout treatment were analyzed, and the genomic status of the established organoid was confirmed. Organoids from malignant giant-cell tumors could be serially maintained using air–liquid interface organoid-culture methods. The tumors developed in xenografted NOD-scid IL2Rgnull mice. After several repetitions of the process, a patient-derived organoid line from the malignant giant-cell tumor was established. Immunohistochemical analyses and next-generation sequencing revealed that the established organoids lacked the H3-3A G34W mutation. The xenografted organoids of the malignant giant-cell tumor had phenotypes histologically and genetically similar to those of the original tumor. The established organoids were confirmed to be derived from human malignant giant-cell tumors. In summary, the present study demonstrated a novel organoid model of a malignant giant-cell tumor that was genetically confirmed to be a malignant transformed tumor. Our organoid model could be used to elucidate the molecular pathogenesis of a malignant giant-cell tumor and develop novel treatment modalities. [ABSTRACT FROM AUTHOR]

Background: The aim of this retrospective study was to define clinical and pathologic features and prognostic factors among children and adolescents diagnosed with high-grade osteosarcoma of the extremities. Methods: A total of 73 patients younger than 18 years old diagnosed with primary osteosarcoma of the extremities between January 1998 and December 2013 were retrospectively evaluated. Prognostic factors such as age, gender, primary tumor site, alkaline phosphatase and lactate dehydrogenase levels, metastatic disease, pathological fracture, histological response and surgery type were analyzed to evaluate their effects on overall (OS) and event free survival (EFS). Results: At a median follow-up of 30 months (1.5-152), OS and EFS at 5 years was 64.5±8.1% and 48.5±8.7% for patients with localized disease; and 16.2±7.9% and 14.4±7.3% for patients with initial metastatic disease, respectively. In patients with localized disease, conservative surgery was performed on 22 of 46 patients (43.5%), and there was no significant difference in survival rates among patients who had conservative vs radical surgery (p=0.65). Although tumor size (>12cm) was significant prognostic factor in univariate analysis; multivariate analysis identified elevated levels of alkaline phosphatase (p=0.033) and poor response to neoadjuvant chemotherapy (p

Musculoskeletal sarcomas are rare cancers that as the whole family of sarcomas pose several challenges at different levels, ranging from medical knowledge to clinical research and policymaking. Addressing these challenges, necessarily calls for the inclusion of patient perspective inside the decision-making processes of every area that contributes to treatment improvement, from the provision of high-quality services by healthcare organisations to research issues. Without patient-provided inputs to inform decisions, the current paradigm of patient-centred care makes no sense and sounds at the least irrational if not unethical. Putting PROMs on "centre stage" in cancer research and care, could allow to build a truly Evidence Based Advocacy (EBA) and therefore to empower Evidence Based Medicine (EBM)., Competing Interests: Conflict of Interest Statement The author declares that she has NO affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: A chronic inflammatory cell infiltrate is commonly seen in response to primary malignant tumours of bone. This is known to contain tumour-associated macrophages (TAMs) and lymphocytes; dendritic cells (DCs) and mast cells (MCs) have also been identified but whether these and other inflammatory cells are seen commonly in specific types of bone sarcoma is uncertain. Methods: In this study we determined the nature of the inflammatory cell infiltrate in 56 primary bone sarcomas. Immunohistochemistry using monoclonal antibodies was employed to assess semiquantitatively CD45+ leukocyte infiltration and the extent of the DC, MC, TAM and T and B lymphocyte infiltrate. Results: The extent of the inflammatory infiltrate in individual sarcomas was very variable. A moderate or heavy leukocyte infiltrate was more commonly seen in conventional high-grade osteosarcoma, undifferentiated pleomorphic sarcoma and giant cell tumour of bone (GCTB) than in Ewing sarcoma, chordoma and chondrosarcoma. CD14+/ CD68+ TAMs and CD3+ T lymphocytes were the major components of the inflammatory cell response but (DC-SIGN/ CD11c+) DCs were also commonly noted when there was a significant TAM and T lymphocyte infiltrate. MCs were identified mainly at the periphery of sarcomas, including the osteolytic tumour-bone interface. Discussion: Our findings indicate that, although variable, some malignant bone tumours (e.g. osteosarcoma, GCTB) are more commonly associated with a pronounced inflammatory cell infiltrate than others (e.g. chondrosarcoma. Ewing sarcoma); the infiltrate is composed mainly of TAMs but includes a significant DC, T lymphocyte and MC infiltrate. Conclusion: Tumours that contain a heavy inflammatory cell response, which includes DCs, TAMs and T lymphocytes, may be more amenable to immunomodulatory therapy. MCs are present mainly at the tumour edge and are likely to contribute to osteolysis and tumour invasion. [ABSTRACT FROM AUTHOR]

Bone or soft tissue sarcomas are rarely diagnosed during pregnancy. Until today 137 well documented cases have been reported in the English literature between 1963 and 2014. Thirty-eight pregnant mothers were diagnosed with osteosarcoma, Ewing’s sarcoma or chondrosarcoma, whereas 95 other cases of soft tissue sarcomas of various types have been documented. We present the clinical picture and therapeutic management of this coexistence. [ABSTRACT FROM AUTHOR]

The article focuses on investigating the role of the LINC (linker of nucleoskeleton and cytoskeleton) complex in the differentiation of bone sarcomas, with a particular emphasis on changes in lamin A levels and the interaction between lamins and LINC complex proteins.

Sarcomas comprise 1% of malignant tumors in adults but represent a significant diagnostic and therapeutic challenge. Molecular imaging with ¹¿FDG PET/CT is a powerful modality in oncology. Its use for initial assessment, evaluation of response to therapy and recurrent disease in most tumors is essential for therapeutic decisions. Its indication in sarcomas is still controversial. One of the indications for PET/CT in sarcomas is detection of recurrences. Nowadays magnetic resonance tomography (MRT) has a crucial role in identification of local recurrences in soft tissue and bone sarcoma. ¹¿FDG-PET/CT may serve as a complementary method. Dual time point imaging (DTPI) has been studied for most tumors as a method for differentiating benign from malignant lesions. There is limited data on DTPI in sarcomas. Therefore we studied prospectively patients with suspected local recurrences in the treated area and used DTPI as a method for differentiating benign from malignant tissue.~Background~Background~of this study was to evaluate the ability of dual-time point PET/CT to enhance sensitivity, specificity, PPV, NPV and accuracy of ¹¿FDG PET/CT in high grade and low grade sarcomas.~the Aim~Objective~We conducted a dual-time PET/CT in 15 patients with suspected locally recurrent disease. The delayed scan was conducted on the 120th min in the suspected region. The interpretation of PET/CT was made both upon CT scan and metabolic scans. The percentage change over time per lesion was calculated (%DSUV). The increase in SUVmax with %DSUV > 10% in the late scanning was considered as indicative for malignancy. We assessed the sensitivity, specificity, accuracy, positive and negative predicting value of the interpretation of PET/CT at 60 min and 120 min. All of the patients were followed up for a period of 1-3 years after our examination, either with histologic results, or with an MRT scans.~Material and Methods~Methods~The received sensitivity, specificity and accuracy of ¹¿FDG PET/CT interpretation at 120 min in high grade sarcomas were respectively 100%, 80% and 89%. By comparison, in low grade tumors at 120 min scan, these parameters were 50%, 75% and 66%.~Results~Results~These preliminary data suggests that dual-time imaging in sarcomas improves sensitivity and accuracy in identification of local recurrent disease in high grade sarcomas and have limited role in low grade sarcomas. Further research is necessary to confirm these results.~Conclusion~Conclusions [ABSTRACT FROM AUTHOR]

Osteosarcoma and Ewing sarcoma are themost common bonemalignancies that affect children and adolescents, with an incidence of six new cases/1,000,000 inhabitants/ year, accounting for approximately 7% of cancer diagnoses. They may be defined as neoplastic diseases that involve the bone tissues, the former arising from the mesenchymal bone forming cells and the latter from the neural crest cells. [ABSTRACT FROM AUTHOR]