Delay in Diagnosis and Treatment of Primary Bone Tumors.

BACKGROUND: Delay in the diagnosis and treatment of bone tumors continues to be a common problem. Prolonged diagnosis can significantly reduce the chances of successful treatment of the disease. Accordingly, the aim of this study was to assess the delay in the diagnosis of primary bone tumors, identify the most common symptoms and analyze the course of the diagnostic and therapeutic path. MATERIAL AND METHODS: Thirty-two (K=18; M=14) patients treated surgically for primary bone tumors were included in the retrospective study. Patient records were analyzed. Delay in diagnosis was defined as the time from the onset of symptoms to the initial diagnosis and referral to an orthopedic oncology center. RESULTS: The median delay in diagnosis was 7 (3-12) months. For tumors located in the pelvis, the delay was 10 months, compared to 5 months for the upper limb and 7 months for the lower limb (p=0.2312). The delay was 6 months In patients with osteosarcoma, and 8 months in chondrosarcoma patients (p=0.1786). At the first office visit, an x-ray was ordered in 19 cases (59.4%), of whom 9 patients (47.4%) were referred on to the oncology center. The most common symptoms were pain in the affected area (90.6%), limited mobility (28.1%) and pathological fracture (25%). After admission to an orthopedic department, a biopsy was performed after 5.5 (3-8.2) days. The histology results were ready after another 14 (8-18) days, and surgical treatment was performed after 95 (76-100) days. CONCLUSIONS: 1. Although patients show typical symptoms of bone tumors, only a small proportion are referred directly to an oncology center. After a primary bone tumor is suspected, further diagnostic and therapeutic activities proceed efficiently, in accordance with the current guidelines.

Diagnostics and Treatment of Extrameningeal Solitary Fibrous Tumors.

Solitary fibrous tumors (SFT) are rare mesenchymal neoplasms that account for less than 2% of all soft tissue masses. In the latest WHO 2020 Classification of Soft Tissue Tumors, extrameningeal SFT was listed as intermediate (rarely metastasizing) or malignant neoplasms. Due to the lack of characteristic clinical features, their diagnosis and treatment remain challenging. The pathogenesis of SFT is often associated with the presence of fusions of the NAB2-STAT6 gene on the 12q13 chromosome. Cytoplasmic CD34 positive staining is considerably characteristic for most SFTs; less frequently, factor XII, vimentin, bcl-2, and CD99 are present. A key factor in the diagnosis is the prevalent nuclear location of STAT6 expression. Radical resection is the mainstay of localized SFTs. In the case of unresectable disease, only radiotherapy or radio-chemotherapy may significantly ensure long-term local control of primary and metastatic lesions. To date, no practical guidelines have been published for the treatment of advanced or metastatic disease. Classical anthracycline-based chemotherapy is applicable. The latest studies suggest that antiangiogenic therapies should be considered after first-line treatment. Other drugs, such as imatinib, figitumumab, axitinib, and eribulin, are also being tested. Definitive radiotherapy appears to be a promising therapeutic modality. Since standards for the treatment of advanced and metastatic diseases are not available, further investigation of novel agents is necessary.

Mesenchymal Chondrosarcoma from Diagnosis to Clinical Trials.

Mesenchymal chondrosarcoma (MCS) is a rare subtype of chondrosarcoma with a poor prognosis. Although these tumors are sensitive to radiotherapy/chemotherapy, the standard treatment for localized MCS is only surgical resection, and there are no established treatment guidelines for patients with advanced and metastatic MCS. Due to the low incidence of MCS, the pathology of these tumors is still unknown, and other therapeutic options are lacking. Some studies show the potential role of the PDGF/PPI3K/AKT, PKC/RAF/MEK/ERK, and pRB pathways, and BCL2 overexpression in the pathogenesis of MCS. These findings provide an opportunity to use protein kinases and BCL2 inhibitors as potential therapy in MCS. In this review, we summarize the current knowledge about MCS diagnosis and treatment options. We show the immunological and molecular biomarkers used in the diagnosis of MCS. In addition, we discuss the known prognostic and predictive factors in MCS. Finally, we present the novel trends, including targeted therapies and ongoing clinical trials using protein kinase inhibitors and the death receptor 5 (DR5) agonist, which may be the focus of future MCS treatment studies.

Dedifferentiated Chondrosarcoma from Molecular Pathology to Current Treatment and Clinical Trials.

Dedifferentiated chondrosarcoma (DDCS) is a rare subtype of chondrosarcoma, a primary cartilaginous malignant neoplasm. It accounts for up to 1-2% of all chondrosarcomas and is generally associated with one of the poorest prognoses among all chondrosarcomas with the highest risk of metastasis. The 5-year survival rates range from 7% to 24%. DDCS may develop at any age, but the average presentation age is over 50. The most common locations are the femur, pelvis humerus, scapula, rib, and tibia. The standard treatment for localised disease is surgical resection. Most patients are diagnosed in unresectable and advanced stages, and chemotherapy for localised and metastatic dedifferentiated DDCS follows protocols used for osteosarcoma.

Denosumab in Giant Cell Tumor of Bone: Multidisciplinary Medical Management Based on Pathophysiological Mechanisms and Real-World Evidence.

(1) Despite the benign nature of the giant cell tumor of bone (GCTB), it shows a local recurrence rate of up to 50% and a chance of malignant transformation. The widely accepted local therapy in extremity GCTB is surgery, in the form of extended intralesional curettage with adequate disease clearance and retention of the limb, wherever possible. Denosumab, a human monoclonal antibody directed against the RANKL and associated inhibition of the RANKL pathway, is a relevant therapy option for advanced GCTB, to benefit tumor response and surgical down-staging. (2) The literature review of patients with GCTB treated with denosumab is performed via PubMed, using suitable keywords from January 2009 to January 2021. (3) Current indications for denosumab use are not definitively clear and unambiguous. Most GCTB patients with localized disease can be successfully treated with surgical curettage, and the role of denosumab in preoperative therapy in this patient population remains unclear. (4) However, patients with primary unresectable lesions or metastases may experience long-term clinical and radiological remission and pain control with denosumab treatment, and in this clinical situation, denosumab is currently the treatment of choice.

Diagnostic Utility of Genetic and Immunohistochemical H3-3A Mutation Analysis in Giant Cell Tumour of Bone.

To validate the reliability and implementation of an objective diagnostic method for giant cell tumour of bone (GCTB). H3-3A gene mutation testing was performed using two different methods, Sanger sequencing and immunohistochemical (IHC) assays. A total of 214 patients, including 120 with GCTB and 94 with other giant cell-rich bone lesions, participated in the study. Sanger sequencing and IHC with anti-histone H3.3 G34W and G34V antibodies were performed on formalin-fixed, paraffin-embedded tissues, which were previously decalcified in EDTA if needed. The sensitivity and specificity of the molecular method was 100% (95% CI: 96.97-100%) and 100% (95% CI: 96.15-100%), respectively. The sensitivity and specificity of IHC was 94.32% (95% CI: 87.24-98.13%) and 100% (95% CI: 93.94-100.0%), respectively. P.G35 mutations were discovered in 2/9 (22.2%) secondary malignant GCTBs and 9/13 (69.2%) GCTB after denosumab treatment. We confirmed in a large series of patients that evaluation of H3-3A mutational status using direct sequencing is a reliable tool for diagnosing GCTB, and it should be incorporated into the diagnostic algorithm. Additionally, we discovered IHC can be used as a screening tool. Proper tissue processing and decalcification are necessary. The presence of the H3-3A mutation did not exclude malignant GCTB. Denosumab did not eradicate the neoplastic cell population of GCTB.

Chondrosarcoma-from Molecular Pathology to Novel Therapies.

Chondrosarcoma (CHS) is the second most common primary malignant bone sarcoma. Overall survival and prognosis of this tumor are various and often extreme, depending on histological grade and tumor subtype. CHS treatment is difficult, and surgery remains still the gold standard due to the resistance of this tumor to other therapeutic options. Considering the role of differentiation of CHS subtypes and the need to develop new treatment strategies, in this review, we introduced a multidisciplinary characterization of CHS from its pathology to therapies. We described the morphology of each subtype with the role of immunohistochemical markers in diagnostics of CHS. We also summarized the most frequently mutated genes and genome regions with altered pathways involved in the pathology of this tumor. Subsequently, we discussed imaging methods and the role of currently used therapies, including surgery and the limitations of chemo and radiotherapy. Finally, in this review, we presented novel targeted therapies, including those at ongoing clinical trials, which can be a potential future target in designing new therapeutics for patients with CHS.

Reconstruction with a Custom made Prosthetic Wrist Arthrodesis after Bone Tumor Resections of the Distal Radius. Single Centre Experience.

Objective The present study aimed at analyzing the clinical, radiological and functional results of the reconstruction of the distal radius after tumor resection with a custom-made metal arthrodesis implant and compare them with other types of distal radius reconstruction, as presented in the literature. To our best knowledge, this is the first article describing this particular type of implant and patient functionality. Methods Functional outcomes of reconstruction of the distal radius were assessed in a series of 4 patients. Three of the patients having had resection of giant cell tumors (GCTs), one patient having had resection of osteosarcoma. Results There were no major implant-related complications like infection, nonunion or loosening. Two patients had to undergo further surgery for protruding metalwork. Overall function was good according to the Musculoskeletal Tumor Society MSTS and Disabilities of the Arm, Shoulder, and Hand (DASH) scores. Conclusion The present study shows that custom-made metal arthrodesis implant benefits from the fact that it can be used as a salvage option when other treatments have failed, or it can be used as a primary option in cases in which there is limited bone stock after distal radius tumor resection.

Reconstruction with a Custom made Prosthetic Wrist Arthrodesis after Bone Tumor Resections of the Distal Radius. Single Centre Experience / Reconstrução com implante metálico personalizado de artrodese após ressecções de tumor ósseo do rádio distal. Experiência em um único centro

Abstract Objective The present study aimed at analyzing the clinical, radiological and functional results of the reconstruction of the distal radius after tumor resection with a custom-made metal arthrodesis implant and compare them with other types of distal radius reconstruction, as presented in the literature. To our best knowledge, this is the first article describing this particular type of implant and patient functionality. Methods Functional outcomes of reconstruction of the distal radius were assessed in a series of 4 patients. Three of the patients having had resection of giant cell tumors (GCTs), one patient having had resection of osteosarcoma. Results There were no major implant-related complications like infection, nonunion or loosening. Two patients had to undergo further surgery for protruding metalwork. Overall function was good according to the Musculoskeletal Tumor Society MSTS and Disabilities of the Arm, Shoulder, and Hand (DASH) scores. Conclusion The present study shows that custom-made metal arthrodesis implant benefits from the fact that it can be used as a salvage option when other treatments have failed, or it can be used as a primary option in cases in which there is limited bone stock after distal radius tumor resection.

Resumo Objetivo O presente estudo teve como objetivo analisar os resultados clínicos, radiológicos e funcionais da reconstrução do rádio distal após a ressecção do tumor com implante metálico personalizado de artrodese e compará-los com outros tipos de reconstrução do rádio distal, conforme apresentado na literatura. Pelo que conhecemos, este é o primeiro artigo descrevendo esse tipo particular de implante e funcionalidade no paciente. Métodos Os desfechos funcionais de reconstrução do rádio distal foram avaliados em uma série de 4 pacientes. Três dos pacientes tiveram ressecção de tumores de células gigantes (TCGs), sendo um paciente com ressecção de osteossarcoma. Resultados Não houve complicações relacionadas ao implante, como infecção, não sindicalidade ou afrouxamento. Dois pacientes tiveram que passar por uma nova cirurgia para a protusão da prótese metálica. A função geral foi boa de acordo com as pontuações da Musculoskeletal Tumor Society (MSTS) e Disabilities of the Arm, Shoulder, and Hand (DASH). Conclusão O estudo mostra que o implante metálico personalizado de artrodese se beneficia do fato de que pode ser usado como opção de salvamento quando outros tratamentos falharam, ou pode ser usado como opção primária nos casos em que há estoque ósseo limitado após a ressecção do tumor do rádio distal.

Functional outcome of surgical treatment of adults with extremity osteosarcoma after megaprosthetic reconstruction-single-center experience.

BACKGROUND: Osteosarcoma is the most common primary malignant bone tumor in adults and is usually located in the long bones. Standard treatment consists of perioperative chemotherapy and radical surgical resection. Limb-sparing surgery using a variety of reconstructive techniques remains the gold standard. METHODS: In our study, we retrospectively analyzed 90 adult patients operated at our institution between 2000 and 2017 for extremity osteosarcoma that underwent limb-sparing reconstruction with the megaprosthesis. Sixty-one patients underwent resection and reconstruction of the distal femur, 9 patients-proximal femur, 7 patients-proximal tibia, 5 patients-total femoral resection and reconstruction, 5 patients-proximal humeral resection, and 3 patients-other types of resection with endoprosthetic reconstruction. The median follow-up time was 41 months, median overall survival was 86 months (3-225 months), and progression-free survival was 81 months (1-86 months). Functional assessment was made on 48 out of 56 living patients, after endoprosthetic reconstruction. The assessment was made according to MSTS functional scale. RESULTS: In 14 cases (15%), the endoprosthesis had to be explanted, or amputation was performed for local recurrence or septic complication. Due to a mechanical failure of the implant, we had to perform a revision in 5 patients (5%). Eighteen out of 74 patients with endoprosthesis died of the disease. The median MSTS score was 84% (53-100%), and the best result of 85% was achieved in patients after distal femoral resection with endoprosthetic reconstruction. CONCLUSION: Careful planning of the treatment of patients with extremity osteosarcoma that is performed at the referral centers gives the possibility of long-term survival with a good and excellent functional result.

Long-term follow-up in adults with extremity osteosarcoma: comparison of different surgical procedures - single-center experience.

INTRODUCTION: Osteosarcoma is the most common primary malignant bone tumor in adults and is usually located in long bones. Standard treatment consists of perioperative chemotherapy and radical surgical resection. In the case of the extremity location, the gold standard is limb-sparing surgery (LSS) using a variety of reconstructive techniques. AIM OF THE STUDY: To assess long-term results of adults patients treated for limb osteosarcoma in our referral center depending on the method of surgical treatment. MATERIAL AND METHODS: In our study, we analyzed 175 adult patients with localized disease (American Joint Committee on Cancer [AJCC] stage I-III) treated for extremity osteosarcoma at our institution between 2000 and 2017. The median observation time was 41 months (3-225 months). 111 patients were treated with LSS (80 patients had tumor resection followed by endoprosthetic reconstruction, 31 patients had local resection without reconstruction) and 64 patients underwent amputation. RESULTS: 5-year overall survival (OS) and progression-free survival (PFS) in the study group were 62% and 52% and the life expectancy was on average 136 months. In the group of patients treated with LSS, 5-year OS and PFS were 66% and 59%, respectively, and life expectancy was 147 months, while in the group of patients undergoing amputation 5-year OS, PFS and life expectancy were 55%, 42% and 117 months. CONCLUSIONS: The best results in the treatment of extremity osteosarcoma were achieved in a group of patients without distant metastases at the time of diagnosis, treated with perioperative chemotherapy and radical resection followed by endoprosthetic reconstruction.

Atypical Fractures of the Femur Associated with Chronic Treatment with Bisphosphonates.

BACKGROUND: The problem of atypical fractures, such as subtrochanteric or diaphyseal femoral fractures, associated with long-term treatment with bisphosphonates (BPs) has recently been given increasingly more attention. These fractures develop as stress fractures and are characterised by diaphyseal cortical thickening and a transverse or slightly oblique fracture line. The use of bisphosphonates has been documented to reduce the risk of osteoporotic fractures. However, an increasing number of papers verify the safety and benefits of the administration of these drugs over more than 3-5 years. MATERIAL AND METHODS: This paper presents 13 cases of atypical femoral fractures in 11 patients of the Department of Orthopaedics and Traumatology of the Musculoskeletal System of the Warsaw Medical University. RESULTS: All patients had been taking BPs for a mean period of over 13 years (between 2 and 25 years) before the fracture. CONCLUSIONS: 1. The authors stress that these fractures differ from "classic" osteoporotic fractures. 2. The authors indicate surgical treatment of these fractures (even incomplete ones) as a method of choice. 3. The authors suggest that the need for further BP therapy should be assessed after 3-5 years of treatment.