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Cytotoxic T lymphocyte antigen 4 (CTLA-4) genetic polymorphisms are implicated to be associated with susceptibility to bone sarcomas, but published studies have reported inconclusive results. The objective of our study was to conduct a meta-analysis investigating the associations between CTLA-4 gene polymorphisms and risk of bone sarcomas. PubMed and Embase databases were searched for all articles published up to June 2, 2013. Odds ratio (OR) with a 95 % confidence interval (95 % CI) was used to assess the association. Finally, 11 individual studies with a total of 2,951 cases with bone sarcomas and 3,396 controls were included in the meta-analysis. There were four studies on the CTLA-4 49G/A polymorphism, three studies on CTLA-4 318C/T polymorphism, two studies on CTLA-4 1661A/G polymorphism, and two studies on CTLA-4 60A/G polymorphism. Overall, CTLA-4 49G/A polymorphism was obviously associated with risk of bone sarcomas (A vs. G: OR = 1.36, 95 % CI = 1.20-1.54; AA vs. GG: OR = 2.24, 95 % CI = 1.67-2.99; AA vs. AG/GG: OR = 2.00, 95 % CI = 1.53-2.62; AA/GA vs. GG: OR = 1.35, 95 % CI = 1.14-1.61). However, CTLA-4 318C/T, 1661A/G, and 60A/G polymorphisms were not associated with risk of bone sarcomas. The current meta-analysis suggests that CTLA-4 49G/A polymorphism is obviously associated with risk of bone sarcomas. More studies are needed to further evaluate the associations between CTLA-4 polymorphisms and risk of bone sarcomas. [ABSTRACT FROM AUTHOR]

Abstract: The role of imaging in planning oncologic treatment and follow-up of patients with bone sarcomas is discussed in the present article. Tumor staging and radiographic assessment of response to chemotherapy in bone sarcomas may be of difficult interpretation. In particular, the use of the criterion of tumor shrinkage to measure response to chemotherapy is not always applicable in bone tumors where higher calcification rather than reduction in size is frequently observed. New techniques such as (18)F-FDG PET/CT, dynamic contrast-enhanced computed tomography or magnetic resonance are now available allowing a more accurate staging of patients and adding information for the evaluation of tumor response. Innovative approaches aiming to evaluate vascular and metabolic response rather than mono- or bi-dimensional changes may be more informative and require further investigations. [Copyright &y& Elsevier]

Abstract: Sarcomas are a heterogeneous group of malignant neoplasms arising from mesenchymal cells which encompass dozens of histological types and can occur in virtually any anatomic site. They form one of the principal groups of rare cancers in Europe as defined in the RARECARE project. We analysed 45,568 incident cases diagnosed during 1995–2002 and registered by 76 population-based cancer registries. Total crude incidence was 5.6 per 100,000 per year with an estimated 27,908 new cases per year in the EU27 countries, of which 84% were soft tissue sarcomas and 14% were bone sarcomas. Gastrointestinal stromal tumours (GIST) were only widely recognised as an entity in the late 1990s and consequently were under-registered. Their true incidence is believed to be about 1.5 per 100,000. Age-standardised incidence of soft tissue sarcomas ranged from 3.3 per 100,000 in Eastern Europe to 4.7 per 100,000 in Northern Europe. About 280,000 persons were estimated to be alive at the beginning of 2003 with a past diagnosis of sarcoma, of which 83% were soft tissue sarcomas and 16% were bone sarcomas. Five-year relative survival for 2000–2002 by the period was 58% for soft tissue sarcomas and 62% for bone sarcomas. The diversity and rarity of sarcomas combined with the quite large number of people affected by them mean that they provide a classic example of the importance of networking in diagnosis, therapy and research for rare cancers. [Copyright &y& Elsevier]

Abstract: Bone remodelling is related to coordinated phases of bone resorption and bone apposition allowing the maintenance of bone integrity, the phosphocalcic homoeostasis all along the life and consequently the bone adaptation to mechanical constraints or/and to endocrine fluctuations. Unfortunately, bone is a frequent site of tumour development originated from bone cell lineages (primary bone tumours: bone sarcomas) or from nonosseous origins (bone metastases: carcinomas). These tumour cells disrupt the balance between osteoblast and osteoclast activities resulting in a disturbed bone remodelling weakening the bone tissue, in a strongly altered bone microenvironment and consequently facilitating the tumour growth. At the early stage of tumour development, osteoclast differentiation and recruitment of mature osteoclasts are strongly activated resulting in a strong bone matrix degradation and release of numerous growth factors initially stored into this organic/calcified matrix. In turn these soluble factors stimulate the proliferation of tumour cells and exacerbate their migration and their ability to initiate metastases. Because Receptor Activator of NFκB Ligand (RANKL) is absolutely required for in vivo osteoclastogenesis, its role in the bone tumour growth has been immediately pointed out and has consequently allowed the development of new targeted therapies of these malignant diseases. The present review summarises the role of RANKL in the bone tumour microenvironment, the most recent pre-clinical and clinical evidences of its targeting in bone metastases and bone sarcomas. The following sections position RANKL targeted therapy among the other anti-resorptive therapies available and underline the future directions which are currently under investigations. [Copyright &y& Elsevier]

Summary: Pathological fractures in patients with primary bone sarcomas should not be considered an absolute indication for amputation. Initial fracture management should include cast immobilisation or external fixation avoiding tumour-cell dissemination. The extent of fracture displacement and the type of fracture stabilisation may affect the outcome of patients with primary bone sarcomas presenting with pathological fractures. Patients with high-grade primary bone sarcomas should be treated by neo-adjuvant chemotherapy, and limb-salvage surgery. Pathological fractures in chemo-resistant primary bone sarcomas are a relative contraindication for limb salvage surgery. [Copyright &y& Elsevier]

Background: The prognosis of patients with advanced sarcoma remains poor. Whether high-dose chemotherapy with stem cell support improves the long-term outcome for these patients or not is controversial. Methods: We present a large institutional experience of sarcoma patients treated with this therapy option. Thirty-eight patients with bone (n = 17) and soft tissue sarcomas (n = 21) were included. Apart from haematological complications, no WHO grade III–IV complications were observed. One patient died due to cardiac arrest after transplantation. Results: Following chemotherapy and/or surgery, but prior to high-dose chemotherapy, diagnoses were made of: no evidence of disease (NED; n = 12), partial remission (n = 17), stable disease (n = 3) and progressive disease (PD; n = 6). Six patients died within 8 months due to PD, in 18 patients disease recurred and led to death and 13 patients are alive with/without disease. Median progression-free survival was 19.1 months (range: 0–121) for all patients, and 48.8 months (range: 3–121) for 12 patients with NED. Conclusion: A subgroup of patients with NED before high-dose chemotherapy gained survival benefit. Therefore, we emphasize the value of high-dose chemotherapy as a treatment option for younger patients with a good performance status in partial or complete remission. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Copyright of Medicina Oral (16656024) is the property of Colegio Nacional de Cirujanos Dentistas Militares A.C. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Sarcomas represent a rare and heterogeneous disease, and the prognosis of patients with unresectable or advanced metastatic bone and especially soft-tissue sarcomas remains poor, with a disease-free survival of less than 10% at 5 years. Only few chemotherapeutic agents have been identified to be active, with reported response rates for doxorubicin, epirubicin and ifosfamide above 20%. Although combination therapy with different chemotherapeutic substances results in higher response rates, superiority against single-agent chemotherapy in terms of survival has not been demonstrated yet. Regarding anthracyclines, and ifosfamide in particular, a dose-response relationship has been shown, and high-dose chemotherapy with stem cell support has also been evaluated by several investigators. However, all studies comprised small patient cohorts and included very heterogeneous histological subtypes of soft-tissue sarcoma. Moreover, randomized trials are missing. Nevertheless, higher doses of chemotherapy result in higher response rates possibly correlating with longer survival. Finally, well-designed randomized trials should be performed, preferably in younger patients and in the context of an interdisciplinary treatment approach. In this review, we provide an overview of the literature concerning high-dose chemotherapy with hematopoietic stem cell support in the treatment of bone and soft-tissue sarcomas. On the basis of our own data, we would like to emphasize the importance of high-dose chemotherapy in the treatment of sarcomas. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The aim of our study was to determine whether or not the tyrosine kinase receptor, HER2 (also known as ErbB2/Her2/neu), is overexpressed in human osteosarcomas (OS). We studied 15 biopsy and 18 resection specimens at the mRNA and protein levels. HER2 status in the OS specimens was assessed by immunohistochemistry (IHC) and quantitative Real-Time Polymerase chain reaction (PCR). In moderately immunopositive cases fluorescent in situ hybridisation (FISH) analysis was used in order to identify any possible gene amplification. 27 samples were evaluable for IHC and only 1 case showed a moderately positive membrane staining. The remaining samples showed no staining or focal cytoplasmic staining (2 samples). In the moderately positive case, FISH analysis showed no HER-2 gene amplification. There was also no overexpression of HER2 mRNA suggesting this sample was a false-positive immunostain. HER2 mRNA expression was present in all samples at a similar level to that in the breast cancer cell line, MCF7, which does not overexpress HER2 and was used as a negative control. In conclusion, this study shows that HER2 mRNA or membranous HER2 protein overexpression is absent in human OS. We noted various inconsistencies in previous published studies, with regard to methodology and the interpretation of the results based on poor methodology. We therefore conclude that the positive data with regard to HER2 overexpression reported in these previous studies is not reliable. Our results suggest that the monoclonal antibody trastuzumab (Herceptin®), directed against the HER2-receptor, is not likely to be an effective therapeutic agent in OS. [Copyright &y& Elsevier]

Soft tissue and bone sarcomas represent a group of aggressive neoplasms often accompanied by dismal patient prognosis, especially when distant metastases are present. Moreover, effective treatment can pose a challenge, as recurrences are frequent and almost half of patients present with advanced disease. Researchers have unveiled the molecular abnormalities implicated in sarcomas' carcinogenesis, paving the way for novel treatment strategies based on each individual tumor's characteristics. Therefore, the development of new techniques aiding in early disease detection and tumor molecular profiling is imperative. Liquid biopsy refers to the sampling and analysis of patients' fluids, such as blood, to identify tumor biomarkers, through a variety of methods, including qRT-PCR, qPCR, droplet digital PCR, magnetic microbeads and digital PCR. Assessment of circulating tumor cells (CTCs), circulating free DNA (ctDNA), micro RNAs (miRs), long non-coding RNAs (lncRNAs), exosomes and exosome–associated proteins can yield a plethora of information on tumor molecular signature, histologic type and disease stage. In addition, the minimal invasiveness of the procedure renders possible its wide application in the clinical setting, and, therefore, the early detection of the presence of tumors. In this review of the literature, we gathered information on biomarkers assessed through liquid biopsy in soft tissue and bone sarcoma patients and we present the information they can yield for each individual tumor type. [ABSTRACT FROM AUTHOR]

Copyright of Langenbecks Archiv fuer Chirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Epidemiology data from population-based cancer registries (PBCR) can be very valuable in the development of health policy and for improving the quality of cancer control strategies., Methods: This study analyzed the incidence of bone sarcomas in Thailand during 2001 - 2015 by analyzing data obtained from 5 PBCRs across country. Incidence rates per million person-years by sex, histological subtype, primary site and 5-year age group were calculated. Age-standardized incidence rates (ASR) were adjusted using the WHO's World Standard Population and comparisons between populations were done using standardized rate ratios (SRR). Incidence trends were evaluated using Joinpoint Trend Analysis. Survival rates were analyzed using STATA., Results: The ASR of bone sarcomas in Thailand was 5.1/10 6 person-years, with an estimated 328 newly diagnosed bone sarcomas per year for the country overall. Osteosarcoma (52.5%), chondrosarcoma (18%), Ewing's sarcoma (11.6%), giant cell tumor (4.8%) and chordoma (4.7%) were the most common malignant bone tumors, representing 91.5% of all bone sarcomas. Bone sarcoma has a predilection for males (1.29:1) and an age-specific bimodal rate pattern closely related to the major histological subtypes, osteosarcoma. One- and five-year survival rates of Thai patients with bone sarcoma were 74% and 52%, respectively. Survival rates of bone sarcomas, particularly osteosarcoma, were lower than the rates reported from the United States, Europe and Japan., Conclusion: The lower overall survival rate of bone sarcoma represented the gap of bone sarcoma control program in Thailand. That indicates the need for improvement in health promotion, treatment process and chemotherapy for bone sarcoma patients in the future., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Bone sarcomas, although rare, are associated with significant morbidity and mortality. The most frequent primary bone cancers include osteosarcoma, chondrosarcoma and Ewing sarcoma. The treatment approaches are heterogeneous and mainly chosen based on precise tumour staging. Unfortunately, clinical outcome has not changed significantly in over 30 years and tumour grade is still the best prognosticator of metastatic disease and survival. An option to improve this scenario is to identify molecular biomarkers in the early stage of the disease, or even before the disease onset. Blood-based liquid biopsies are a promising, non-invasive way to achieve this goal and there are an increasing number of studies which investigate their potential application in bone cancer diagnosis, prognosis and personalised therapy. This review summarises the interplay between clinical and molecular aspects of the three main bone sarcomas, alongside biomarker discovery and promising applications of liquid biopsy in each tumour context. [ABSTRACT FROM AUTHOR]

Objective. Primary malignant bone tumors are rare and heterogeneous, and the diagnosis and multimodal treatment require a multidisciplinary approach in specialized centers, involving pathologists, radiologists, surgeons, and radiation and medical oncologists. The early referral to a specialist center that provides a multidisciplinary diagnosis and therapeutic approach and manages a high number of cases annually could improve the survival for these young patients. Materials and method. The multidisciplinary management of osteosarcoma, chordoma and Ewing’s sarcoma includes surgery, radiotherapy and systemic treatment, which are reviewed in this case series presentation. Surgical excision is the primary treatment for localized bone tumor. Radiation therapy is usually necessary, but chemotherapy plays an important role in some chemosensitive subtypes (high­grade osteosarcoma). In other subtypes, considered chemoresistant (such as chordoma), new targeted therapies have showed improvement in the disease management. Results. The cases presented included chordoma, osteosarcoma and Ewing’s sarcoma patients from our clinical department. The first case is a 58­year­old male patient, with multiple comorbidities, diagnosed with sacrococcygeal chondroid chordoma in 2019. Our patient’s tumor was inoperable and local recurrence was observed after radiotherapy. Targeted therapy was an option and the patient started imatinib 800 mg/day, with clinical and imagistic response. The second case is a 37­year­old female patient diagnosed with right knee high­grade osteosarcoma. The imagistic work­up (MRI, PET­CT) confirmed the local disease. The patient started MAP­EURAMOS protocol, with reversible hepatic severe toxicity, but with clinical benefit (remission of pain syndrome, without functional impotence – impact on quality of life). Surgery was indicated due to good response to neoadjuvant treatment. The third case is a 27­year­old patient diagnosed with spine Ewing’s sarcoma in 2009, amendable to surgery with adjuvant chemotherapy and radiotherapy. In 2020, pleural and pulmonary progression was diagnosed, associated with pain syndrome by the invasion of the costal grid. Chemotherapy was started – Ewing VDC/IE protocol, well tolerated, with hematological grade I/II toxicity, with complete response and indication for bone marrow transplant. Conclusions. Given the diagnosis at a young age, the unfavorable prognosis, the effects and the adverse events of multimodal treatments in the short and long run, the diagnosis, treatment and followup of these patients should be performed in specialized reference centers, with case studies and access to clinical trials. [ABSTRACT FROM AUTHOR]

The high complexity of multimodality treatment frequently results in undertreatment of elderly sarcoma patients, and this may be one of the factors that influence their prognosis. We describe the real-life approach to a population of patients aged over 70 with both soft tissue (STS) and bone sarcomas (BS) followed by our Sarcoma Disease Management Team from 2012 to 2017. One-hundred and twenty-three patients with a median age of 77 years (range: 70–92) were identified. STS were the most common histological subtypes (94%) and the grade was high in 79/123 patients (64%). At diagnosis, 88% of patients had localized disease (LD) and 12% were metastatic (MD). Overall, 96% of patients with LD underwent surgery, 46/54 (85%) with high grade STS patients underwent complementary radiotherapy, and 10/54 (19%) received adjuvant treatments. Twelve out of 33 patients who relapsed (36%) underwent local therapies. Seventeen (52%) and eight (24%) patients were treated with first-line and second-line medical treatments, respectively. Tolerability to systemic treatments was fairly good. Overall, 21% of the patients with advanced disease were candidates for best supportive care alone. Our case series of elderly patients with both STS and BS shows that personalized multidisciplinary treatment can nevertheless be offered to this frail population in order to control the evolution of disease. [ABSTRACT FROM AUTHOR]

Myositis ossificans (MO) is a benign bone formation in an extra-skeletal location. The most common subtype of MO, the post-traumatic, usually develops in young males after a traumatic event or sports injury.MO may simulate malignant bone lesions such as extra-skeletal or surface osteosarcomas, or soft tissue sarcomas such as synovial sarcoma or undifferentiated pleomorphic sarcoma. In the early phase the diagnosis of MO is challenging because imaging and histopathological findings may be non-characteristic.Detailed medical history as well as clinical examination, follow-up imaging studies and histological assessment are crucial for a proper diagnosis. Early and accurate differential diagnosis between MO and malignant soft tissue and bone tumours is important to maximize. Cite this article: EFORT Open Rev 2021;6:572-583. DOI: 10.1302/2058-5241.6.210002., Competing Interests: ICMJE Conflict of interest statement: The authors declare no conflict of interest relevant to this work., (© 2021 The author(s).)

The treatment of malignant bone tumors, also called bone sarcomas, has changed dramatically over the past 50 years owing to the advances in chemotherapy, immunotherapy, targeted therapy, radiation, prosthetic technology, and surgical advances. There are 3 main primary bone cancers: osteosarcoma, Ewing's sarcoma (or Ewing's family of sarcoma), and chondrosarcoma. Before advances in limb preservation techniques and before the development of prosthetic replacement, the treatment for a malignant bone tumor of the extremity was amputation. This article discusses the progression of surgical treatment of malignant bone cancers., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Osteosarcoma and chondrosarcoma, remain the most common primary bone tumours. Questions have been raised about the prognostic influence of HER-2 in bone sarcomas, but so far the results have been debatable. The her-2 expression is possibly a predictor of chemotherapy response., Aim: In this study, we investigated the extent of HER-2 expression in bone sarcomas, and attempted to correlate it with pertinent variables that will help to provide better treatment options, especially for metastatic ones., Material and Methods: Fifty-two cases of bone sarcomas (32 osteosarcoma cases and 20 chondrosarcoma ones) were studied for HER-2 immunohistochemical expression then correlation with all available clinicopathologic features was done., Results: Most of the osteosarcoma cases exhibited membranous staining (78.1%). Strong staining was observed (score 3+) in 34.4%; while 21.9% showed moderate staining (score 2+); and 21.9% displayed weak staining (score 1+), on the other hand, no staining was detected in 7 out of 32 cases (21.9%) (score 0). As regards chondrosarcoma, the absence of staining in all examined cases was noted. Immunohistochemical HER-2 overexpression correlated significantly with osteosarcoma site with P value = 0.004, with variation relating HER-2 intensity score to the site of osteosarcoma (P = 0.051). A statistically significant negative correlation was detected between HER-2 expression and the presence of metastasis at time of diagnosis (P = 0.006), A significant correlation was also found regarding HER-2 score and presence of metastasis with P value = 0.046 as more than half of cases with no metastasis at diagnosis (17/28 cases, 60.7%) showed positive intensity score. A statistically significant correlation was detected between HER-2 expression and patients' age (P = 0.044). Also, HER-2 expression significantly correlated to histopathological detection of fibrous tissue, with P value = 0.033. Higher scores of HER-2 expression were associated with a significantly better differentiation (P = 0.038) since detection of wide areas of osteoid were associated with higher HER-2 scores., Conclusion: Further research would still be needed to delineate HER-2 role being a new hope for therapeutic targeting in bone sarcoma patients, mainly osteosarcoma in contrast to chondrosarcoma that didn't express HER-2 at all.

Bone sarcomas such as osteosarcoma and chondrosarcoma are frequently refractory to conventional chemotherapy and radiotherapy that exhibit poor prognosis. The Wnt signaling are evolutionarily conserved and implicated in cell proliferation and sarcomagenesis. However, the potential role of the Wnt signaling in bone sarcomas is still unclear. Here we demonstrate aberrant activation of Wnt/β-catenin signaling in bone sarcoma cells, involving an autocrine Wnt signaling loop with upregulation of specific Wnt ligands and receptors. Activation of Wnt/β-catenin signaling with Wnt3a or GSK-3β inhibitor drives the proliferation of bone sarcoma cells, whereas downregulation of activated Wnt signaling with dnTCF4 or siLEF1 suppresses bone sarcoma proliferation and induces cell cycle arrest. Taken together, our findings establish the evidence that aberrant activation of Wnt/β-catenin pathway involving an autocrine Wnt singaling drives the proliferation of bone sarcoma cells, and identify the autocrine activation of the Wnt/β-catenin signaling as a potential novel therapeutic target for bone sarcomas.

Background: The immunomodulatory properties of polyuridylic acid (PolyU) make it a promising agent in cancer immunotherapy. However, there is limited information on its direct effects on tumor cells. Materials and Methods: TLR8 mRNA and protein expression in soft tissue sarcoma (STS) and bone sarcoma (BS) cell lines were determined by PCR and flow cytometry, respectively. Apoptosis and proliferation assays were performed using annexin V staining and BrdU incorporation assays, respectively. A relative cell enumeration was evaluated with WST-1 reagent. Expression levels of apoptotic proteins were evaluated by Western blotting. Results: We demonstrate that PolyU treatment resulted in a significant decrease in STS and BS cell count by inducing apoptosis and inhibition of cell proliferation. All cell lines examined expressed TLR8 and the effect of PolyU was partially mediated through TLR8. Several apoptotic proteins including caspases were activated or increased in STS cells after treatment with PolyU. Administration PolyU resulted in significant growth inhibition of STS without any observable adverse effects in mouse xenograft tumor models. Conclusions: These results elucidate the effect of PolyU in STS and BS cells and demonstrate that PolyU may be a potential therapeutic agent for STS and BS. [ABSTRACT FROM AUTHOR]