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Physiological Reviews Jul 2021Skeletal metastases are frequent complications of many cancers, causing bone complications (fractures, bone pain, disability) that negatively affect the patient's... (Review)
Review
Skeletal metastases are frequent complications of many cancers, causing bone complications (fractures, bone pain, disability) that negatively affect the patient's quality of life. Here, we first discuss the burden of skeletal complications in cancer bone metastasis. We then describe the pathophysiology of bone metastasis. Bone metastasis is a multistage process: long before the development of clinically detectable metastases, circulating tumor cells settle and enter a dormant state in normal vascular and endosteal niches present in the bone marrow, which provide immediate attachment and shelter, and only become active years later as they proliferate and alter the functions of bone-resorbing (osteoclasts) and bone-forming (osteoblasts) cells, promoting skeletal destruction. The molecular mechanisms involved in mediating each of these steps are described, and we also explain how tumor cells interact with a myriad of interconnected cell populations in the bone marrow, including a rich vascular network, immune cells, adipocytes, and nerves. We discuss metabolic programs that tumor cells could engage with to specifically grow in bone. We also describe the progress and future directions of existing bone-targeted agents and report emerging therapies that have arisen from recent advances in our understanding of the pathophysiology of bone metastases. Finally, we discuss the value of bone turnover biomarkers in detection and monitoring of progression and therapeutic effects in patients with bone metastasis.
Topics: Animals; Biomarkers; Bone Density Conservation Agents; Bone Neoplasms; Bone and Bones; Denosumab; Humans
PubMed: 33356915
DOI: 10.1152/physrev.00012.2019 -
Nature Reviews. Disease Primers Oct 2020Bone is the most frequent site for metastasis for many cancers, notably for tumours originating in the breast and the prostate. Tumour cells can escape from the primary... (Review)
Review
Bone is the most frequent site for metastasis for many cancers, notably for tumours originating in the breast and the prostate. Tumour cells can escape from the primary tumour site and colonize the bone microenvironment. Within the bone, these disseminated tumour cells, as well as those arising in the context of multiple myeloma, may assume a state of dormancy, remaining quiescent for years before resuming proliferation and causing overt metastasis, which causes bone destruction via activation of osteoclast-mediated osteolysis. This structural damage can lead to considerable morbidity, including pain, fractures and impaired quality of life. Although treatment of bone metastases and myeloma bone disease is rarely curative, disease control is often possible for many years through the use of systemic anticancer treatments on a background of multidisciplinary supportive care. This care should include bone-targeted agents to inhibit tumour-associated osteolysis and prevent skeletal morbidity as well as use of appropriate local treatments such as radiation therapy, orthopaedic surgery and specialist palliative care to minimize the impact of metastatic bone disease on physical functioning. In this Primer, we provide an overview of the clinical features, the pathophysiology and the specific treatment approaches to prevent and treat bone metastases from solid tumours as well as myeloma bone disease.
Topics: Bone Neoplasms; Humans; Neoplasm Metastasis; Neoplasms
PubMed: 33060614
DOI: 10.1038/s41572-020-00216-3 -
Advances in Anatomic Pathology May 2021Bone tumors are a rare and heterogeneous group of neoplasms that occur in the bone. The diversity and considerable morphologic overlap of bone tumors with other... (Review)
Review
Bone tumors are a rare and heterogeneous group of neoplasms that occur in the bone. The diversity and considerable morphologic overlap of bone tumors with other mesenchymal and nonmesenchymal bone lesions can complicate diagnosis. Accurate histologic diagnosis is crucial for appropriate management and prognostication. Since the publication of the fourth edition of the World Health Organization (WHO) classification of tumors of soft tissue and bone in 2013, significant advances have been made in our understanding of bone tumor molecular biology, classification, prognostication, and treatment. Detection of tumor-specific molecular alterations can facilitate the accurate diagnosis of histologically challenging cases. The fifth edition of the 2020 WHO classification of tumors of soft tissue and bone tumors provides an updated classification scheme and essential diagnostic criteria for bone tumors. Herein, we summarize these updates, focusing on major changes in each category of bone tumor, the newly described tumor entities and subtypes of existing tumor types, and newly described molecular and genetic data.
Topics: Bone Neoplasms; Chondrosarcoma; Humans; World Health Organization
PubMed: 33480599
DOI: 10.1097/PAP.0000000000000293 -
British Journal of Pharmacology Jan 2022Osteosarcoma is one of the most common primary tumours of the bone, with a 5-year survival rate of less than 20% after the development of metastases. Osteosarcoma is... (Review)
Review
Osteosarcoma is one of the most common primary tumours of the bone, with a 5-year survival rate of less than 20% after the development of metastases. Osteosarcoma is highly predisposed in Paget's disease of the bone, and both have common characteristic skeletal features due to rapid bone remodelling. Osteosarcoma prognosis is location dependent, which further emphasizes the likely contribution of the bone microenvironment in its pathogenesis. Mechanobiology describes the processes involved when mechanical cues from the changing physical microenvironment of the bone are transduced to biological pathways through mechanosensitive cellular components. Mechanobiology-driven therapies have been used to curb tumour progression by direct alteration of the physical microenvironment or inhibition of metastasis-associated mechanosensitive proteins. This review emphasizes the contribution of mechanobiology to the progression of osteosarcoma and sheds light on current mechanobiology-based therapies and potential new targets for improving disease management. Additionally, the many different 3D models currently used to study osteosarcoma mechanobiology are summarized.
Topics: Biophysics; Bone Neoplasms; Humans; Osteitis Deformans; Osteosarcoma; Tumor Microenvironment
PubMed: 34679192
DOI: 10.1111/bph.15713 -
Frontiers in Immunology 2019Immunotherapy is often perceived as a relatively recent advance. In reality, however, one should be looking for the beginnings of cancer immunotherapy under different... (Review)
Review
Immunotherapy is often perceived as a relatively recent advance. In reality, however, one should be looking for the beginnings of cancer immunotherapy under different names as far as in the Antiquity. The first scientific attempts to modulate patients' immune systems to cure cancer can be attributed to two German physicians, Fehleisen and Busch, who independently noticed significant tumor regression after erysipelas infection. The next significant advances came from William Bradley Coley who is known today as the Father of Immunotherapy. It was Coley who first attempted to harness the immune system for treating bone cancer in 1891. His achievements were largely unnoticed for over fifty years, and several seminal discoveries in the field of Immunology, such as the existence of T cells and their crucial role in immunity in 1967, stepped up the research toward cancer immunotherapy known today. The following paper tracks cancer immunotherapy from its known beginnings up until recent events, including the 2018 Nobel Prize award to James Allison and Tasuku Honjo for their meticulous work on checkpoint molecules as potential therapeutic targets. That work has led to the successful development of new checkpoint inhibitors, CAR T-cells and oncolytic viruses and the pace of such advances brings the highest hope for the future of cancer treatment.
Topics: Bone Neoplasms; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Immunotherapy
PubMed: 31921205
DOI: 10.3389/fimmu.2019.02965 -
Medical Oncology (Northwood, London,... Nov 2020Stereotactic Body Radiotherapy (SBRT) is a technique for delivering high doses of radiation to tumors while preserving the normal tissues located around this area. Bone... (Review)
Review
Stereotactic Body Radiotherapy (SBRT) is a technique for delivering high doses of radiation to tumors while preserving the normal tissues located around this area. Bone metastases are frequent in cancer patients. They can be distressingly painful or may cause pathological fractures. Radiation therapy is a fundamental aspect of treatment for bone metastases. The objective of this study is to analyze the literature on non-spine bone metastasis treated with SBRT, including immobilization, volume delineation, dose and fractionation, local control, side effects, and assessment of response after treatment. Full-text articles written in English language and published in the last 10 years were included in this review and were accessible on PubMed and MEDLINE. We examined 78 articles. A total of 40 studies were included in this review. Most were retrospective studies. The articles included were evaluated for content and validation. The immobilization systems and imaging tests used for tumor delimitation were variable between studies. The use of CTV (Clinical Target Volume) has not been defined. Doses and fractions were variable from 15 to 24 Gy/1 fraction to 24-50 Gy in 3-5 fractions, with local control being around 90% with a low rate of side effects. We review state of the art in SBRT non-spine metastases. SBRT can result in better local control and pain management in non-spine bone metastases patients. We need more research in volume delineation determining whether or not to use CTV and the role of MRI in volume contouring, optimal doses, and fractionation according to histology and a reliable response assessment tool. Studies that compare SBRT to conventional radiotherapy in local control and pain control are needed.
Topics: Bone Neoplasms; Humans; Magnetic Resonance Imaging; Radiosurgery; Tomography, X-Ray Computed
PubMed: 33221952
DOI: 10.1007/s12032-020-01442-1 -
Surgical Pathology Clinics Dec 2021Although uncommon in many pathology practices, cartilage-forming tumors represent some of the most frequent primary bone tumors. Diagnosis can be challenging given their... (Review)
Review
Although uncommon in many pathology practices, cartilage-forming tumors represent some of the most frequent primary bone tumors. Diagnosis can be challenging given their variable histologic spectrum and the presence of overlapping morphologic, immunohistochemical, and genetic features between benign and malignant entities, particularly low-grade malignancies. Correlation with clinical findings and radiographic features is crucial for achieving an accurate diagnosis and appropriate clinical management, ranging from observation to excision. Tumors can be characterized broadly by their location in relation to the bone (surface or intramedullary). In specific instances, ancillary testing may help.
Topics: Bone Neoplasms; Cartilage; Chondroma; Diagnosis, Differential; Humans
PubMed: 34742482
DOI: 10.1016/j.path.2021.06.004 -
Practical Radiation Oncology 2020Stereotactic body radiation therapy (SBRT) is increasingly used for nonspine bone metastases (NSBM); however, there are limited data informing treatment planning. We...
PURPOSE
Stereotactic body radiation therapy (SBRT) is increasingly used for nonspine bone metastases (NSBM); however, there are limited data informing treatment planning. We surveyed international experts to better understand worldwide practice patterns in delivering NSBM-SBRT.
METHODS AND MATERIALS
Nine international radiation oncologists were invited to participate based on demonstrated expertise with NSBM-SBRT. Experts were sent gross tumor volume contours and planning computed tomography and magnetic resonance images for 11 NSBM cases that covered a range of bony sites, including metastases to long bones (femur, humerus), pelvic bones (ilium, ischium, acetabulum, pubic symphysis), and thoracic bones (rib, sternum, scapula, clavicle). Experts were surveyed regarding treatment planning decisions and dose-fractionation selection. Descriptive analysis was conducted on the survey data.
RESULTS
All experts participated and completed the survey. Most (56%) routinely fused magnetic resonance imaging with planning computed tomography imaging for target delineation. Dose fractionation schedules included single-fraction (18-24 Gy/1), 2 fractions (24 Gy/2), 3 fractions (28-30 Gy/3), 5 fractions (30-50 Gy/5), and 10 fractions (42-50 Gy/10). Although doses varied considerably, all had a biological equivalent dose of ≤100 Gy. Five-fraction schedules were most common, specifically 35 Gy/5, with 56% opting for this dose-fractionation in at least 1 case. Other dose-fractionation schedules used by at least 3 experts were 20 Gy/1, 30 Gy/3, and 30 Gy/5. Three experts prescribed 2 dose volumes using a simultaneous integrated boost. The 2 dose volumes were either the gross tumor volume and clinical target volume (CTV) or a smaller CTV (CTV1) encompassed within a larger CTV (CTV2) (eg, 30 Gy/3 to gross tumor volume or CTV1 and 15-24 Gy/3 to CTV or CTV2). Dose de-escalation was recommended by all experts in the setting of previous SBRT and by most in the context of previous convevoltherapy or in weight-bearing bones, especially if moderate-to-severe cortical erosion was present.
CONCLUSIONS
Significant heterogeneity exists worldwide in radiation technique and dose-fractionation for NSBM-SBRT, which supports the need for consensus guidelines to inform practice and trial design. Nonetheless, these data demonstrate expert agreement on selecting dose schedules with a biologically effective dose ≤100 Gy, reasons for dose de-escalation, and in determining acceptable dose schedules based on bony site.
Topics: Bone Neoplasms; Dose Fractionation, Radiation; Humans; Magnetic Resonance Imaging; Radiosurgery; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted
PubMed: 32171852
DOI: 10.1016/j.prro.2020.02.011 -
Surgical Pathology Clinics Dec 2021Benign bone-forming tumors comprise osteomas, osteoid osteomas, and osteoblastomas. Osteomas affect a wide age range and are usually discovered incidentally. They occur... (Review)
Review
Benign bone-forming tumors comprise osteomas, osteoid osteomas, and osteoblastomas. Osteomas affect a wide age range and are usually discovered incidentally. They occur predominantly in the craniofacial skeleton and are classically composed of compact bone. Osteoid osteomas and osteoblastomas are painful lesions occurring in young patients. They are morphologically similar and characterized by FOS gene rearrangement and c-FOS expression at a protein level. Osteoid osteomas are usually smaller than 2 cm in maximum dimension with limited growth potential; osteoblastomas are larger than 2 cm and may be locally aggressive. Histologically both are composed of anastomosing trabeculae of woven bone.
Topics: Bone Neoplasms; Gene Rearrangement; Humans; Osteoblastoma; Osteoma, Osteoid; Soft Tissue Neoplasms
PubMed: 34742480
DOI: 10.1016/j.path.2021.06.002 -
Histopathology Apr 2021The fifth edition of the World Health Organization (WHO) classification of soft tissue and bone tumours was published in May 2020. This 'Blue Book', which is also...
The fifth edition of the World Health Organization (WHO) classification of soft tissue and bone tumours was published in May 2020. This 'Blue Book', which is also available digitally for the first time, incorporates an array of new information on these tumours, amassed in the 7 years since the previous edition. Major advances in molecular characterisation have driven further refinements in classification and the development of ancillary diagnostic tests, and have improved our understanding of disease pathogenesis. Several new entities are also included. This review summarises the main changes introduced in the 2020 WHO classification for each subcategory of soft tissue and bone tumours.
Topics: Bone Neoplasms; History, 21st Century; Humans; Soft Tissue Neoplasms; World Health Organization
PubMed: 33438273
DOI: 10.1111/his.14265