Bone tumors can be classified as primary or metastatic. Primary tumors are divided into benign and malignant. Benign lesions include developmental abnormalities such as fibrous dysplasia and osteochondroma, categorized as pseudotumors. Osteoblastoma is a rare primary benign bone tumor that is categorized as a true neoplasia. Benign tumors rarely metastasize, but they may be locally very destructive, as in the case of giant cell tumors. Aggressive benign tumors may require radical surgery.
Skeletal tissue is composed of tissues of mesodermal origin including bone, cartilage fibrous tissue and bone marrow. Any of these tissues can produce a malignant tumor. Primary malignant bone tumors are known as sarcomas and they are classified by cell type.1Metastatic tumors are the most common type of tumor affecting the bone and frequently arise from the lung, breast, kidneys, prostate or thyroid.2
Primary bone tumors can occur spontaneously and in the majority of cases, the etiology is unknown.3 However, known risk factors for primary bone tumors include inherited conditions such as retinoblastoma, Li-Fraumeni syndrome, Rothmund-Thomas syndrome and Werner syndrome. Underlying abnormalities or benign precursor lesions such as Paget’s disease, fibrous dysplasia, previous radiation exposure, bone infarction, chronic osteomyelitis and Ollier disease are also known risk factors for development of primary bone tumors.1,2,4
Epidemiology including risk factors and primary prevention
Because most benign tumors are asymptomatic, the real incidence is unknown. Primary malignant bone tumors represent 0.2% of all cancers in the United States, with estimated incidence of 3,610 cases in 2021.The three most common tumors in order of frequency are osteogenic sarcoma, chondrosarcoma, and Ewing’s sarcoma. The incidence of primary bone tumors is most common in patients less than 20 years old. However, age range of diagnosis depends of the type of malignant tumor.5
Osteogenic and Ewing’s sarcomas occur most frequently in children and young adults, although a second peak incidence of osteogenic sarcomas occurs in patients over 60 years of age. There is an increased prevalence in males. Pediatric osteosarcomas affects most predominantly black population, while adult osteosarcomas affect most commonly white population.6 These sarcomas commonly occur secondary to radiation therapy and Paget’s disease.1
Chrondrosarcoma is more prevalent in the middle-aged population and older adults over 40 years, and its risk increases with advancing age. These tumors begin in cartilaginous tissues at the epiphysis of bones and joint lines and usually grow insidiously. They affect primarily the proximal femur and flat bones.
Chordomas are very rare tumors that form in the bones of the spine, especially at the sacrum or at the base of the skull. They occur most frequently in older adult men.7
Typically, primary bone tumors are classified based on histology, as this allows for prediction of their biological behavior and provides guidance for treatment.8Tumor grading is based on nuclear size, staining pattern, mitotic activity and degree of cellularity evaluated on histologic examination:
- Low grade tumors- have limited capacity for local recurrence
- Intermediate grade tumors include:
- Locally aggressive- often recur locally and are associated with infiltrative and locally destructive growth pattern
- Rarely metastasizing – tumors are locally aggressive but could give rise to distant metastasis
- High grade or malignant tumors- have significant risk for distant metastasis
Sarcomas arise from transformed mesenchymal cells that differentiate into osteoblasts. The majority of osteogenic sarcomas occur in the metaphysis of the long bones. They are categorized into low and high grades. More than half of these tumors occur in the distal femur, the proximal tibia and the proximal humerus.2 Osteogenic sarcomas often grow fast and may spread to other parts of the body, including the lungs.6
Chondrosarcomas are a group of tumors that have in common the production of a cartilaginous matrix. They are categorized into low, intermediate, high grade and de-differentiated. Ninety percent of these tumors are low grade, including the atypical cartilaginous tumors (ACT) which involve the appendicular skeleton and grade 1 chondrosarcomas, that affect the axial skeleton and flat bones (the pelvis, scapula and skull base). They may arise primarily, without a precursor lesion (most common), or can be preceded by a benign precursor cartilaginous lesion, either osteochondromas or enchondromas. Osteochondromas are associated with mutation in one of the tumor suppressor genes Exostosin Glycosyltransferase (EXT1 or EXT2). Enchondromas are associated with somatic mosaic mutations in the Isocitrate Dehydrogenase genes (IDH1 or IDH2), seen in Ollier disease and Maffucci syndrome.3
Ewing’s sarcoma typically occurs in the diaphysis of long bones, but it is not uncommon in the pelvis. It is always categorized as high grade.7 Chromosomal translocation (11; 22) is used by pathologists in the diagnosis of Ewing’s Sarcoma.1
The World Health Organization (WHO) Classification of Tumors, updated in 2020, reclassified some bone tumors based on molecular genetic alterations and immunohistochemistry, as there are innovative therapies available to target specific mutations. Some chondrosarcomas present aberrant mutations related to IDH1 and IDH2, and inactivating mutations of Cyclin-Dependent Kinase Inhibitor (CDKN2A) and Collagen Type II Alpha (COL2A) genes. Low grade osteosarcomas have been associated with Mouse Double Minute homolog gene (2MDM2) and Cyclin Dependent Kinase 4 (CDK4) amplification mutations.3
Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)
Metastatic disease is the most important prognostic factor in malignant bone tumors. Patients who present with metastatic disease have an overall survival of 20% to 30% compared with 70% to 80% in non-metastatic disease after completion of treatments.5 Metastases are more common with high grade tumors. Metastatic lesions usually disseminate through the blood, most commonly to the lung, followed by bone. Skip metastases are found in high grade sarcomas, where tumor embolizes via marrow sinusoids, forming a lesion that is discontinuous from the primary tumor, but in the same bone.1 Transarticular spread across a joint may occur as well.2Patients with lung metastasis have better prognosis than those with metastatic disease in the bones.
Another important prognostic factor is response to chemotherapy. When the tumor is resected after neoadjuvant chemotherapy, if the specimen has at least 90% necrosis, it suggests an improved overall survival compared to patients who present lower histologic response to chemotherapy. Axial tumors and older age are factors associated with poorer survival. 9
Specific secondary or associated conditions and complications
Pain and lack of cortical integrity are major indicators of impending fracture in primary malignant bone tumors. Making the diagnosis of impending fracture is a challenge in primary malignant bone tumors just as it is in metastatic bone tumors. The guidelines set forth in the Mirels scoring system and the criteria proposed by Harrington for prophylactic internal fixation are not applicable as they pertain only to metastatic lesions. 10, 11 In addition, there have been studies where risk of impending fracture has been evaluated through computed tomography (CT) scan imaging, based on axial cortical and circumferential involvement of the lesion.12 These studies have been focused on metastatic disease as well. No proven clinical guidelines exist to predict fracture risk with benign tumors of the bone. CT-based analysis of bone rigidity in affected bone and homologous healthy bone has demonstrated high specificity for predicting fracture risk in benign tumors; however, its use is limited secondary to the excessive radiation exposure. 13
Essentials of Assessment
Pain, especially night pain, is the hallmark of primary bone tumors. Pain could be described as waxing and waning as seen in osteogenic sarcomas. In cases of Ewing’s sarcoma, pain has been reported as localized and associated with joint swelling. The presentation of chondrosarcoma has been described as a gradual limitation in range of motion of the extremity over months. Other symptoms reported by patients with diagnosis of primary bone tumors is a palpable mass and history of soft tissue swelling that may be associated with a prior injury. Unexplained fever is rare in bone tumors and may suggest disseminated disease.7In the benign bone lesion osteoid osteoma, instant relief of pain on taking NSAIDs is diagnostic. Osteochondromas on the other hand, typically present as a painless lump.7One needs to ask about prior cancer history, radiation exposure, Paget’s disease, and fracture history. The latter may be important on reviewing imaging.
Physical examination typically demonstrates a firm, fixed mass along the involved bone. In some cases, the mass can be pulsatile with associated increased vascularity. The affected area may be warm and tender to palpation. In cases of metastatic disease, the patient may have a fever, lymphadenopathy, dyspnea and fatigue.
Functional goals are extremely important for these patients. However, they are typically considered after initial treatment is started. In a study performed by Corr et al, it was found that pre-habilitation in pediatric patients with diagnosis of lower extremity sarcoma receiving chemotherapy resulted in decreased functional deficits compared to the control group.14 In post-surgical patients, it is important to perform a comprehensive evaluation that includes skin inspection, signs of neuropathic or phantom limb pain and any dysfunction that may occur secondary to leg length discrepancy or alterations in the gait pattern. There are two questionnaires being used to evaluate outcome measures that could aid when planning rehabilitation care: Musculoskeletal Tumor Society (MSTS) scoring and Toronto Extremity Salvage Score (TESS).15
Lower extremity osteosarcoma survivors have 50% increased risk of limitations for performing moderate intensity activities such as climbing stairs and walking one block after receiving treatment. Survivors of upper extremity sarcomas have 10% increased risk of not finishing college education.16 In prospective studies of patients with osteosarcoma who underwent major joint arthroplasty, it was found that participation of early rehabilitation as soon as the first post-operative day helped patients to achieve functional gains in a short time. In addition, these patients had reduced hospital length of stay, without increasing post-operative complications.17Cognitive or behavioral deficits are not usually seen.18
Serum alkaline phosphatase levels (ALP) are elevated in the majority of patients with osteogenic sarcoma and is a poor prognostic sign.7 ALP is frequently elevated in Paget’s disease and extremely high levels are found in Paget’s sarcoma. Serial alkaline phosphatase analysis may be used to assess the response to chemotherapy in osteogenic sarcoma. Serum lactate dehydrogenase is of prognostic significance in Ewing’s sarcoma and in some cases of osteogenic sarcoma.1,5 Erythrocyte sedimentation rate and C-reactive protein tend to be elevated and is a poor prognostic indicator in Ewing’s sarcoma.
In primary malignant bone tumors, initial plain radiographs may reveal a combination of characteristics including cortical destruction, areas of radiolucency, extraosseous extension and permeating destruction with poorly defined borders. Specifically, Ewing sarcoma tumors appear as mottled bone on imaging studies, and has a typical appearance of periosteal reaction also known as “onion skin”.2 Destruction of the bone cortex, scattered calcifications and loss of medullary bone trabeculations are described in central chondrosarcomas.19
In patients younger than 40 years, symptomatic lesions suggest high risk for malignancy, for which orthopedic referral is recommended prior to considering further workup. In patients older than 40 years of age and older with X rays unequivocal for a specific diagnosis, further imaging studies are recommended, including chest, abdominopelvic CT scan with contrast, PET (Positron Emission Tomography) and MDP (Methylene Diphosphonate) total body bone scans, used for tumor staging and identification of bone or lung metastasis respectively.7 In addition, whole body MRI is useful to define the tumor prior to resection and allows identification of skeletal metastasis.20
Supplemental assessment tools
The definitive histological diagnosis is made on biopsy, that could be performed as an open (incisional) procedure or closed (percutaneous-CT guided procedure) procedure in the form of fine needle aspiration or core needle biopsy. Surgical staging systems, one based on the Enneking Staging System (modified by the Musculoskeletal Tumor Society [MSTS]) and the other by the American Joint Commission on Cancer, are used in staging patients with primary bone tumors. 21, 22
Early predictions of outcomes
Poor prognostic indicators include metastases at presentation, tumors arising from the axial skeleton, large tumor volume (size > 10 cm), increased alkaline phosphatase or lactate dehydrogenase levels, poor response to preoperative chemotherapy, skip metastases, discontinuous tumors in bone, and lymph node involvement.4
Social role and social support system
Recognizing and overcoming environmental barriers such as political, familial, structural, and economic factors can be instrumental in lessening the degree of disability in patients treated for primary bone tumors. Studies examining quality of life of patients who have had limb salvage surgery and amputations vary widely in terms of their definitions of quality of life, however, both types of patients report poor quality of life. Amputees, however, do report improvements in quality of life when a proper fitting prosthesis is received. 18,6
There is no difference in long-term survival or local tumor control for patients treated with amputation versus limb salvage plus adjuvant therapy for extremity sarcoma.18 Limb salvage has emerged as the treatment of choice in this population as the functional outcomes appears to be similar to amputation, although rotationplasty may be functionally desirable in select patients.18 However, some studies have concluded that patients who would like to pursue more physically intense activities after treatment, amputation could be considered over limb sparing surgery as precautions for the latter include avoiding running and jumping.15
Rehabilitation Management and Treatments
Available or current treatment guidelines
Until the late 1970s, amputation was the treatment of choice for most bone sarcomas. The introduction of systemic chemotherapy has had a significant effects on survival rates for osteogenic and Ewing’s sarcoma. The five-year survival rate for patients presenting with non-metastatic osteogenic and Ewing’s sarcoma is now 74% and 81%, respectively. 23, 24
Patients with osteogenic and Ewing’s sarcoma receive two to three months of neo-adjuvant chemotherapy, followed by wide surgical resection. Depending on whether the surgical margins are negative or positive, further treatment with chemotherapy, radiotherapy or a combination of both will follow.20 The preferred chemotherapy regimen for Ewing’s sarcoma includes Vincristine, Doxorubicin and Cyclophosphamide alternating with Ifosfamide and Etoposide (VDC/IE).20 Agents preferred for Osteosarcoma include Cisplatin and Doxorubicin or high dose Methotrexate, Cisplatin and Doxorubicin. Chemotherapy-induced toxicity, including cardiomyopathy, neuropathy, nephropathy and late leukemias have been reported.
With advances in imaging and adjuvant therapies, wide resections resulting in limb salvage have replaced amputation as the mainstay of treatment. Today, close to 90% of patients receive limb salvage. Amputation is considered when the tumor surrounds neurovascular structures, the patient is at immature skeletal age, there are large ulcerated infected masses or displaced pathologic fractures.15 Young patients who are skeletally immature and present with lower limb tumors, can be managed with Van Ness rotationplasty as there is potential for limb growth.25 Studies have shown that in properly selected patients, functional outcome is superior in limb salvage procedures, while survival rates are equivalent to those receiving amputation. Patients with painful lytic lesions should be considered at risk of fracture and should be managed with protected weight-bearing, casts and braces as indicated. In a minority of cases with gross bony destruction, definitive limb salvage surgery may be required prior to completion of neoadjuvant chemotherapy in order to prevent a fracture.
Radiation in combination with surgery is superior to surgery alone for local control of soft tissue sarcomas. The timing of preoperative versus post-operative radiation in soft tissue sarcoma treatment remains arguable with each having benefits and risks. Preoperative radiation is known to reduce local disease recurrence; however, it carries a risk of wound complications of 25-35% in addition to other toxicities that impair quality of life. Post-operative radiation allows for histological examination of the tumor but carries the risk of greater long term radiation toxicity. Radiation complications include skin fibrosis with associated limited joint range of motion, dry skin, skin blisters, lymphedema and fatigue. 26 In addition, long term skin changes, physical deformities and pain may increase psychological distress in these patients.
Some cancer treatments may be toxic to the palms and soles, causing “hand-foot syndrome” or erythrodysesthesias, which is a painful condition of the hands and feet that may limit patient’s mobility and activities of daily living. The use of specialized and innovative techniques such as intensive-modulated radiotherapy, particle beam radiotherapy or stereotactic radiotherapy allow delivering high doses of radiation maximizing normal tissues sparing.20
Radiation therapy is often employed as a local treatment for Ewing’s sarcoma. Osteogenic sarcoma and chondrosarcoma are resistant to traditional radiation therapy. However, proton and/or photon beam radiation may be useful for patients with tumors in unfavorable locations not amenable to resection, for example the skull base and axial skeleton.20 Radiation may be used as a palliative measure in inoperable forms of chondrosarcomas. In addition to being radio-resistant, chondrosarcoma does not respond to chemotherapy; therefore, surgery is the only definitive and curative treatment in this disease.
For metastatic chondrosarcoma, a comprehensive assessment of the genetic profile is recommended to determine candidacy for clinical trials and targeted therapies.20 Selected patients with widespread chondrosarcoma may benefit from off label immunotherapy for bone sarcoma such as Pembrolizumab (if deficient mismatch repair or microsatellite instability-high), or kinase inhibitors Dasatinib and Pazopanib. The role of targeted therapies for osteosarcoma is being studied, with particular attention to Rearranged during Transfection proto-oncogene (RET) and Vascular Endothelial Growth Factor Receptor (VEGFR).27 Ivosidenib, an isocitrate dehydrogenase-1 (IDH1) inhibitor could be favorable for patients with IDH1-mutant advanced chondrosarcoma.20 In addition, innovative therapies are under study for Ewing’s sarcoma, particularly agents with high affinity to adenosine triphosphate (ATP) binding sites to overcome drug resistant mutations that have been reported.28
Exercise is an important aspect in the treatment of primary bone tumors. An exercise routine has a positive impact in osteosarcoma survivors including psychosocial benefits, physical functioning and quality of life. Moreover, there is a potential improvement in therapeutic efficacy, decreased mortality and recurrence when exercise is combined with cancer treatment.15,29
Coordination of care
Primary tumors of the bone usually require coordination with multiple physicians, including a primary oncologist, surgeon, pathologist, and physiatrist. Following treatment, services for survivors should include rehabilitation with physical and occupational therapy. Survivorship care should also include psychological support, social worker, sexual health services and expert pain management.30
Patient & family education
Patient and family education prior to limb salvage surgery, amputation, or Van Ness rotationplasty are important to manage expectations for post-operative care and function. In addition, providing information on the possible secondary complications of surgery and chemotherapy are imperative. Response to amputation in children varies; the surgery was better accepted when the tumor was causing pain and/or functional loss.31
Studies examining functional outcomes in patients who have undergone limb salvage versus amputation have varied.1 Currently there is no consensus that lower extremity limb salvage improves functional outcomes in comparison to amputation, especially in those patients with proximal limb lesions. Despite this, there appears to be a trend towards increased disability and handicap in those patients who have undergone amputation.18
The National Comprehensive Cancer Network (NCCN) general guidelines for bone cancers recommend local control by either limb-sparing surgery or amputation. Amputation may be necessary in certain cases to achieve local control. When possible, limb-sparing surgery is preferred if reasonable functional outcome can be achieved.20
Limb sparing surgery along with radiation is promising in treating sarcomas of the hands and feet with reduced morbidity.32
Cutting Edge/ Emerging and Unique Concepts and Practice
Genetic targets continue to be studied including the role of tyrosine kinase inhibitors and PARP inhibitors combined with conventional cytotoxic agents for treatment of Ewing’s and Osteogenic sarcomas. In addition, multiple active studies aim to develop and/or test the efficacy of therapies to reprogram the immune system, including Interleukins-6 (IL-6) receptor antibodies, Programmed cell death-1 (PD-1) receptor blockers, and T-cell immunotherapies, among others. Finally, inoculation of attenuated oncolytic viruses in the form of vaccines are under study as well. Results of these potential therapies have been mostly anecdotal, for which additional studies of tumor microenvironment are warranted to better understand therapeutic responses.33, 34
Gaps in the Evidence-Based Knowledge
- DeVita VT, Lawrence TS, Rosenberg SA. Cancer, principles & practice of oncology. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2011. 1578-609.
- Ferguson JL, Turner SP. Bone Cancer: Diagnosis and Treatment Principles. Am Fam Physician. 2018;98(4):205-213.
- Choi JH, Ro JY. The 2020 WHO Classification of Tumors of Bone: An Updated Review. Adv Anat Pathol. 2021;28(3):119-138. doi:10.1097/PAP.0000000000000293
- Hameed M, Dorfman H. Primary malignant bone tumors–recent developments. Seminars in diagnostic pathology 2011;28(1):86-101.
- SEER Cancer Statistics Factsheets: Bone and Joint Cancer. National Cancer Institute. Bethesda, MD. Available at: http://seer.cancer.gov/statfacts/html/bones.html. Accessed August 31, 2021
- Osteosarcoma and Undifferentiated Pleomorphic Sarcoma of Bone Treatment (PDQ®)–Health Professional Version. National Cancer Institute. Bethesda, MD. Available at: https://www.cancer.gov/types/bone/hp/osteosarcoma-treatment-pdq#_21 Accessed August 31, 2021
- Grimer RJ, Hogendoorn PCW, Vanel D. Tumors of Bone: Introduction. In: Who Classification of Tumours of Soft Tissue and Bone. Vol 5. 4th ed. Lyon: International agency for research on cancer (IARC) Press; 2013:244-247.
- Franchi A. Epidemiology and classification of bone tumors. Clin Cases Miner Bone Metab. 2012;9(2):92-95.
- Anderson ME. Update on Survival in Osteosarcoma. Orthop Clin North Am. 2016;47(1):283-292. doi:10.1016/j.ocl.2015.08.022
- Mirels H. Metastatic disease in long bones. A proposed scoring system for diagnosing impending pathologic fractures. Clinical Orthopedics & Related Research 1989(249):256-64.
- Harrington KD. Impending pathologic fractures from metastatic malignancy: evaluation and management. Instr Course Lect. 1986;35:357-81
- Tatar Z, Soubrier M, Dillies AF, Verrelle P, Boisgard S, Lapeyre M. Assessment of the risk factors for impending fractures following radiotherapy for long bone metastases using CT scan-based virtual simulation: a retrospective study. Radiat Oncol. 2014;9:227. Published 2014 Oct 16. doi:10.1186/s13014-014-0227-1
- Leong NL, Anderson ME, Gebhardt MC, et al. Computed tomography-based structural analysis for predicting fracture risk in children with benign skeletal neoplasms: comparison of specificity with that of plain radiographs. Journal of Bone & Joint Surgery. 2010 Aug 4;92(9):1827-33.
- Corr AM, Liu W, Bishop M, et al. Feasibility and functional outcomes of children and adolescents undergoing preoperative chemotherapy prior to a limb-sparing procedure or amputation. Rehabil Oncol. 2017;35(1):38-45
- Smith SR. Rehabilitation Strategies and Outcomes of the Sarcoma Patient. Phys Med Rehabil Clin N Am. 2017;28(1):171-180. doi:10.1016/j.pmr.2016.08.008
- Marina N, Hudson MM, Jones KE, et al. Changes in health status among aging survivors of pediatric upper and lower extremity sarcoma: a report from the childhood cancer survivor study. Arch Phys Med Rehabil. 2013;94(6):1062-1073. doi:10.1016/j.apmr.2013.01.013
- Grushina TI, Teplyakov VV. Physiotherapy in early rehabilitation of patients with bone sarcomas after arthroplasty of large bones and joints. Vopr Kurortol Fizioter Lech Fiz Kult. 2020;97(3):53-59. doi:10.17116/kurort20209703153
- Custodio CM. Barriers to rehabilitation of patients with extremity sarcomas. Journal of Surgical Oncology 2007;95(5):393-9.
- Norman A, Sissons HA. Radiographic hallmarks of peripheral chondrosarcoma. Radiology. 1984;151(3):589-596. doi:10.1148/radiology.151.3.6718712
- National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Bone Cancers. Version 1.2022. Available at: NCCN.org Accessed September 8, 2021.
- Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clinical Orthopedics & Related Research 1980(153):106-20.
- AJCC Cancer Staging Manual. 6th ed. Philadelphia, PA: Lippincott Raven; 2002.
- American Society of Clinical Oncology. Ewing Sarcoma – Childhood and Adolescence: Statistics. Alexandria, VA. Available at: https://www.cancer.net/cancer-types/ewing-sarcoma-childhood-and-adolescence/statistics. Accessed September 7, 2021.
- American Society of Clinical Oncology. Osteosarcoma – Childhood and Adolescence: Statistics. Alexandria, VA. Available at: https://www.cancer.net/cancer-types/osteosarcoma-childhood-and-adolescence. Accessed September 7, 2021.
- Merkel KD, Gebhardt M, Springfield DS. Rotationplasty as a reconstructive operation after tumor resection. Clinical Orthopedics & Related Research 1991;(270):231-6.
- Rivard JD, Puloski, SS, Temple WJ. Quality of Life, Functional Outcomes, and Wound Complications in Patients with Soft Tissue Sarcomas Treated with Preoperative Chemoradiation: A Prospective Study. Annals of Surgical Oncology 2015;22(9):2869-2875
- Tian Z, Niu X, Yao W. Receptor Tyrosine Kinases in Osteosarcoma Treatment: Which Is the Key Target?. Front Oncol. 2020;10:1642. Published 2020 Aug 28. doi:10.3389/fonc.2020.01642
- Jin W. The Role of Tyrosine Kinases as a Critical Prognostic Parameter and Its Targeted Therapies in Ewing Sarcoma. Front Cell Dev Biol. 2020;8:613. Published 2020 Jul 9. doi:10.3389/fcell.2020.00613
- Garcia MB, Ness KK, Schadler KL. Exercise and Physical Activity in Patients with Osteosarcoma and Survivors. Adv Exp Med Biol. 2020;1257:193-207. doi:10.1007/978-3-030-43032-0_16
- Kwang TNK, Furtado S, Gerrand C. What do we know about survivorship after treatment for extremity sarcoma? A systemic review. Journal of Cancer Surgery. 2014 March 19; 40:1109-1124
- Clerici CA, Ferrari A, Luksch R, et al. Clinical experience with psychological aspects in pediatric patients amputated for malignancies. Tumori 2004;90(4):399-404.
- Bishop AJ, Zagars GK, Moon BS, et al. Combined Limb Sparing Surgery and Radiation Therapy to Treat Sarcomas of the Hands and Feet: Long-Term Cancer Outcomes and Morbidity. International Jounral of Radiation Oncology 2015;(92)5:1060-1068
- Strauss, S.J., Anninga, J., Baglio, R. et al. Report from the 4th European Bone Sarcoma Networking meeting: focus on osteosarcoma. Clin Sarcoma Res 8, 17 (2018). https://doi.org/10.1186/s13569-018-0103-0
- Heymann MF, Schiavone K, Heymann D. Bone sarcomas in the immunotherapy era. Br J Pharmacol. 2021;178(9):1955-1972. doi:10.1111/bph.14999
Original Version of the Topic:
Michael D. Stubblefield, MD, Marni Hillinger, MD. Primary Bone. 10/30/2012.
Previous Revision(s) of the Topic:
Ritika Oberoi-Jassal, MD, Navdeep Singh Jassal, MD, Jaspreet Singh, MD, Young Chang, MD, Joshua Smith, MD. Primary Bone Tumors. 9/15/2016.
Ady Correa-Mendoza, MD
Nothing to Disclose
Diana Molinares, MD
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Laura Huang, MD
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