Mesenchymal chondrosarcoma: prognostic factors and outcome in 113 patients. A European Musculoskeletal Oncology Society study

BACKGROUND: Mesenchymal chondrosarcoma (MCS) is a distinct, very rare sarcoma with little evidence supporting treatment recommendations. PATIENTS AND METHODS: Specialist centres collaborated to report prognostic factors and outcome for 113 patients. RESULTS: Median age was 30 years (range: 11-80), male/female ratio 1.1. Primary sites were extremities (40%), trunk (47%) and head and neck (13%), 41 arising primarily in soft tissue. Seventeen patients had metastases at diagnosis. Mean follow-up was 14.9 years (range: 1-34), median overall survival (OS) 17 years (95% confidence interval (CI): 10.3-28.6). Ninety-five of 96 patients with localised disease underwent surgery, 54 additionally received combination chemotherapy. Sixty-five of 95 patients are alive and 45 progression-free (5 local recurrence, 34 distant metastases, 11 combined). Median progression-free survival (PFS) and OS were 7 (95% CI: 3.03-10.96) and 20 (95% CI: 12.63-27.36) years respectively. Chemotherapy administration in patients with localised disease was associated with reduced risk of recurrence (P=0.046; hazard ratio (HR)=0.482 95% CI: 0.213-0.996) and death (P=0.004; HR=0.445 95% CI: 0.256-0.774). Clear resection margins predicted less frequent local recurrence (2% versus 27%; P=0.002). Primary site and origin did not influence survival. The absence of metastases at diagnosis was associated with a significantly better outcome (P<0.0001). Data on radiotherapy indications, dose and fractionation were insufficiently complete, to allow comment of its impact on outcomes. Median OS for patients with metastases at presentation was 3 years (95% CI: 0-4.25). CONCLUSIONS: Prognosis in MCS varies considerably. Metastatic disease at diagnosis has the strongest impact on survival. Complete resection and adjuvant chemotherapy should be considered as standard of care for localised disease

FOS Expression in Osteoid Osteoma and Osteoblastoma: A Valuable Ancillary Diagnostic Tool

Osteoblastoma and osteoid osteoma together are the most frequent benign bone-forming tumor, arbitrarily separated by size. In some instances, it can be difficult to differentiate osteoblastoma from osteosarcoma. Following our recent description of FOS gene rearrangement in these tumors, the aim of this study is to evaluate the value of immunohistochemistry in osteoid osteoma, osteoblastoma, and osteosarcoma for diagnostic purposes. A total of 337 cases were tested with antibodies against c-FOS: 84 osteoblastomas, 33 osteoid osteomas, 215 osteosarcomas, and 5 samples of reactive new bone formation. In all, 83% of osteoblastomas and 73% of osteoid osteoma showed significant expression of c-FOS in the osteoblastic tumor cell component. Of the osteosarcomas, 14% showed c-FOS expression, usually focal, and in areas with severe morphologic atypia which were unequivocally malignant: 4% showed more conspicuous expression, but these were negative for FOS gene rearrangement. We conclude that c-FOS immunoreactivity is present in the vast majority of osteoblastoma/osteoid osteoma, whereas its expression is usually focal or patchy, in no more than 14% of osteosarcoma biopsies. Therefore, any bone-forming tumor cases with worrying histologic features would benefit from fluorescence in situ hybridization analysis for FOS gene rearrangement. Our findings highlight the importance of undertaking a thorough assessment of expression patterns of antibodies in the light of morphologic, clinical, and radiologic features

Survival of massive allografts in segmental oncological bone defect reconstructions

Reconstructions of large segmental bone defects after resection of bone tumours with massive structural allografts have a high number of reported complications including fracture, infection and non-union. Our goal is to report the survival and complications of massive allografts in our patients. A total of 32 patients were evaluated for fracture, infection, non-union rate and survival of their massive allograft reconstructions. The average follow-up for this group was five years and three months. The total fracture rate was 13% with a total infection rate of 16%. We found a low union rate of 25%. The total survival of the allografts was 80.8% (± 18.7%) after five years. We found a five-year allograft survival of 80.8% which is comparable with other studies

The landscape of functional outcome measures used in patients with bone sarcoma of the lower extremity or pelvis: a systematic review

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

Isolated Limb Perfusion and External Beam Radiotherapy for Soft Tissue Sarcomas of the Extremity: Long-Term Effects on Normal Tissue According to the LENT-SOMA Scoring System

BACKGROUND: With the combined treatment procedure of isolated limb perfusion (ILP), delayed surgical resection and external beam radiotherapy (EBRT) for locally advanced soft tissue sarcomas (STS) of the extremities, limb salvage rates of more than 80% can be achieved. However, long-term damage to the healthy surrounding tissue cannot be prevented. We studied the late effects on the normal tissue using the LENT-SOMA scoring system. PATIENTS AND METHODS: A total of 32 patients-median age 47 (range 14-71) years-were treated for a locally advanced STS with ILP, surgical resection and often adjuvant 60-70 Gy EBRT. After a median follow-up of 88 (range 17-159) months, the patients were scored, using the LENT-SOMA scales, for the following late tissue damage: muscle/soft tissue, peripheral nerves, skin/subcutaneous tissue and vessels. RESULTS: According to the individual SOM parameters of the LENT-SOMA scales, 20 patients (63%) scored grade-3 toxicity on one or more separate items, reflecting severe symptoms with a negative impact on daily activities. Of these patients, 3 (9%) even scored grade-4 toxicity on some of the parameters, denoting irreversible functional damage necessitating major therapeutic intervention. CONCLUSIONS: In evaluating long-term morbidity after a combined treatment procedure for STS of the extremity, using modified LENT-SOMA scores, two-thirds of patients were found to have experienced serious late toxic effects

Targeting metastasis in paediatric bone sarcomas

Paediatric bone sarcomas (e.g. Ewing sarcoma, osteosarcoma) comprise significant biological and clinical heterogeneity. This extreme heterogeneity affects response to systemic therapy, facilitates inherent and acquired drug resistance and possibly underpins the origins of metastatic disease, a key component implicit in cancer related death. Across all cancers, metastatic models have offered competing accounts on when dissemination occurs, either early or late during tumorigenesis, whether metastases at different foci arise independently and directly from the primary tumour or give rise to each other, i.e. metastases-to-metastases dissemination, and whether cell exchange occurs between synchronously growing lesions. Although it is probable that all the above mechanisms can lead to metastatic disease, clinical observations indicate that distinct modes of metastasis might predominate in different cancers. Around 70% of patients with bone sarcoma experience metastasis during their disease course but the fundamental molecular and cell mechanisms underlying spread are equivocal. Newer therapies such as tyrosine kinase inhibitors have shown promise in reducing metastatic relapse in trials, nonetheless, not all patients respond and 5-year overall survival remains at ~ 50%. Better understanding of potential bone sarcoma biological subgroups, the role of the tumour immune microenvironment, factors that promote metastasis and clinical biomarkers of prognosis and drug response are required to make progress. In this review, we provide a comprehensive overview of the approaches to manage paediatric patients with metastatic Ewing sarcoma and osteosarcoma. We describe the molecular basis of the tumour immune microenvironment, cell plasticity, circulating tumour cells and the development of the pre-metastatic niche, all required for successful distant colonisation. Finally, we discuss ongoing and upcoming patient clinical trials, biomarkers and gene regulatory networks amenable to the development of anti-metastasis medicines

Biological Sample Collection to Advance Research and Treatment: A Fight Osteosarcoma Through European Research and Euro Ewing Consortium Statement

Osteosarcoma and Ewing sarcoma are bone tumors mostly diagnosed in children, adolescents, and young adults. Despite multimodal therapy, morbidity is high and survival rates remain low, especially in the metastatic disease setting. Trials investigating targeted therapies and immunotherapies have not been groundbreaking. Better understanding of biological subgroups, the role of the tumor immune microenvironment, factors that promote metastasis, and clinical biomarkers of prognosis and drug response are required to make progress. A prerequisite to achieve desired success is a thorough, systematic, and clinically linked biological analysis of patient samples, but disease rarity and tissue processing challenges such as logistics and infrastructure have contributed to a lack of relevant samples for clinical care and research. There is a need for a Europe-wide framework to be implemented for the adequate and minimal sampling, processing, storage, and analysis of patient samples. Two international panels of scientists, clinicians, and patient and parent advocates have formed the Fight Osteosarcoma Through European Research consortium and the Euro Ewing Consortium. The consortia shared their expertise and institutional practices to formulate new guidelines. We report new reference standards for adequate and minimally required sampling (time points, diagnostic samples, and liquid biopsy tubes), handling, and biobanking to enable advanced biological studies in bone sarcoma. We describe standards for analysis and annotation to drive collaboration and data harmonization with practical, legal, and ethical considerations. This position paper provides comprehensive guidelines that should become the new standards of care that will accelerate scientific progress, promote collaboration, and improve outcomes