Osteosarcoma

  1. Overview and Epidemiology
  2. Pathophysiology and Cell of Origin
  3. Genetic Risk Factors
  4. Clinical Presentation
  5. Imaging and Staging
  6. Biopsy and Diagnosis
  7. Chemotherapy (Neoadjuvant and Adjuvant)
  8. Surgical Treatment and Limb Salvage
  9. Histologic Response and Prognosis
  10. Metastatic and Recurrent Disease
  11. Key Research Papers
  12. PubMed Topic Searches
  13. Connections
  14. Featured Videos

Overview and Epidemiology

Osteosarcoma is the most common primary malignant tumor of bone, accounting for approximately 20% of all primary bone sarcomas. In the United States, roughly 800 new cases are diagnosed each year, with a global incidence of 3–4 cases per million population annually. Despite its relative rarity, osteosarcoma carries substantial morbidity and, when metastatic, significant mortality — making it one of the most intensively studied bone tumors in pediatric and adolescent oncology.

The age distribution is bimodal. The first and dominant peak occurs in adolescents and young adults between ages 10 and 20, tightly correlated with the pubertal growth spurt. During rapid longitudinal bone growth, the proliferating metaphyseal cells are at highest risk for the replication errors and oncogenic mutations that initiate osteosarcoma. Patients diagnosed during this peak tend to be statistically taller than their unaffected peers — a compelling epidemiologic signal that rapid skeletal growth itself is a permissive factor. A second, smaller peak occurs in adults over age 60, most often in the setting of Paget's disease of bone, prior radiation therapy, or other preexisting bone pathology. The male-to-female ratio is approximately 1.4:1, most pronounced in the adolescent peak and attributable in part to the longer duration of male pubertal bone growth.

Anatomically, osteosarcoma shows a strong predilection for the metaphysis of long bones — the flared end of the shaft adjacent to the growth plate where remodeling activity is highest. The distal femur is the single most common site, accounting for approximately 40% of cases. The proximal tibia accounts for roughly 20%, and the proximal humerus for about 10%. Together these three locations account for 70% of all extremity osteosarcomas. Less commonly, osteosarcoma arises in the pelvis, proximal femur, jaw (craniofacial osteosarcoma), or axial skeleton; these locations carry a worse prognosis due to surgical access limitations. Approximately 10% of patients present with overt metastatic disease at diagnosis; of these metastases, 80–85% involve the lungs, 10–15% involve other bones, and a small fraction involve regional lymph nodes.

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Pathophysiology and Cell of Origin

Osteosarcoma arises from primitive mesenchymal cells that retain the capacity to produce malignant osteoid — the unmineralized organic matrix of bone. The defining histologic criterion is the production of osteoid or immature woven bone directly by malignant spindle cells, distinguishing osteosarcoma from other bone sarcomas that lack this matrix-producing capacity. This osteoid production occurs even in variants classified as "lytic," "blastic," or "mixed" on plain radiography, reflecting differences in the ratio of matrix synthesis to mineralization rather than a fundamental change in the cell of origin.

The World Health Organization classifies osteosarcoma into several histologic subtypes. Conventional high-grade central osteosarcoma — the most common form — is further divided into osteoblastic (~50%), chondroblastic (~25%), and fibroblastic (~25%) subtypes based on the predominant matrix produced. These subtypes do not strongly influence treatment but affect radiographic appearance and biopsy interpretation. Telangiectatic osteosarcoma is a blood-filled cystic variant that can mimic aneurysmal bone cyst on imaging; it behaves as aggressive high-grade osteosarcoma. Small cell osteosarcoma resembles Ewing sarcoma histologically and may require molecular testing to distinguish. Low-grade central osteosarcoma and parosteal osteosarcoma (arising on the bone surface) are low-grade variants with a markedly better prognosis; they are treated surgically without chemotherapy in most cases. Periosteal osteosarcoma is an intermediate-grade surface variant.

At the molecular level, conventional high-grade osteosarcoma is characterized by genomic instability of extraordinary degree — complex structural rearrangements, chromothripsis events, and whole-genome duplication are common. Mutational burden varies widely. Unlike many carcinomas driven by single oncogenic driver mutations (e.g., KRAS in pancreatic cancer), osteosarcoma is defined by the loss of key tumor suppressors — particularly TP53 and RB1 — rather than by activating oncogene mutations. Elevated alkaline phosphatase (ALP) is the most consistent serum biomarker, reflecting increased osteoblastic activity, and correlates with tumor bulk. Lactate dehydrogenase (LDH) elevation correlates with tumor necrosis and high proliferative rate and independently predicts worse outcome.

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Genetic Risk Factors

The vast majority of osteosarcoma cases are sporadic, arising from somatic mutations in dividing metaphyseal cells without a heritable predisposition. However, several germline syndromes confer dramatically elevated risk, providing critical insights into the molecular pathogenesis of the disease.

Hereditary retinoblastoma is the strongest known predisposition syndrome for osteosarcoma. Germline loss-of-function mutations in RB1 — the gene encoding the retinoblastoma protein, a master regulator of the G1/S cell cycle checkpoint — confer approximately a 500-fold increase in osteosarcoma risk, particularly in patients who received radiation therapy to the orbit. Even without radiation, the cumulative lifetime risk of osteosarcoma in bilateral retinoblastoma survivors is approximately 13%. This association established RB1 as a critical osteosarcoma suppressor gene, and somatic loss of RB pathway function is now recognized in ~70% of all osteosarcomas through various mechanisms including deletion, mutation, and promoter methylation.

Li-Fraumeni syndrome, caused by germline TP53 mutations, is the second major predisposition syndrome. TP53 encodes p53, the "guardian of the genome" that orchestrates DNA damage responses, apoptosis, and senescence. Li-Fraumeni families are at elevated risk for osteosarcoma, soft-tissue sarcoma, breast cancer, brain tumors, and adrenocortical carcinoma, often at young ages. Osteosarcoma accounts for approximately 12% of cancers in Li-Fraumeni kindreds. Somatic TP53 mutations or deletions occur in 30–50% of sporadic osteosarcomas, and the two tumor suppressors — p53 and Rb — cooperate to restrain osteoblastic proliferation; loss of both is highly oncogenic in mouse models.

Rothmund-Thomson syndrome (RTS type 2) and Werner syndrome are caused by mutations in RECQL4 and WRN, respectively — members of the RecQ DNA helicase family. These proteins maintain genomic stability during DNA replication and repair. RTS type 2 patients have a 30–40% lifetime osteosarcoma risk. Werner syndrome patients have premature aging and approximately 10% osteosarcoma risk. Both syndromes illustrate how replication stress and DNA repair deficiency drive the chromosomal catastrophe characteristic of osteosarcoma.

Hereditary multiple osteochondromatosis (mutations in EXT1/EXT2) predisposes primarily to chondrosarcoma but carries a small osteosarcoma risk. Paget's disease of bone (predominantly SQSTM1 mutations) causes pathologically disordered bone remodeling; approximately 1% of patients develop secondary osteosarcoma, most commonly in the femur, humerus, or pelvis. Fibrous dysplasia and sites of prior therapeutic radiation (typically appearing 10–20 years after radiation with a latency inversely related to dose) are additional secondary osteosarcoma risk factors in adults.

Genome-wide association studies have identified susceptibility loci on chromosomes 6p21.3 (near GRM4) and 2p25.2 that modestly increase population-level osteosarcoma risk, though these associations explain only a small fraction of sporadic cases.

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Clinical Presentation

The most common presenting symptom is progressive, worsening pain at the involved site. Early in the course, pain is often intermittent and activity-related, easily dismissed as sports injury or "growing pains" — a misattribution that is extremely common in the adolescent peak age group. As the tumor enlarges, pain becomes continuous, nocturnal, and eventually severe enough to disrupt sleep. The median delay from symptom onset to diagnosis is 3–4 months, partly because the initial presentation is indistinguishable from much more common benign conditions (patellar tendinopathy, Osgood-Schlatter disease, muscular strain).

On examination, there is typically a palpable soft tissue or bony mass with local warmth and tenderness over the metaphysis. The overlying skin may appear stretched or have prominent superficial veins due to the increased vascularity of the tumor. Range of motion of the adjacent joint may be restricted. Pathological fracture occurs at presentation in approximately 10% of cases, most often in lytic or telangiectatic variants; it significantly complicates surgical planning because fracture hematoma can contaminate tissue planes and potentially convert a limb-salvageable case to amputation.

Constitutional symptoms — fever, night sweats, and unintentional weight loss — are present in a minority of osteosarcoma patients, in contrast to Ewing sarcoma where they are more prominent. Fever occurs more often in advanced or necrotic tumors. Elevated alkaline phosphatase is found in approximately 50% of patients and often correlates with tumor volume and osteoblastic activity; it normalizes with successful treatment and may re-elevate at relapse. Elevated LDH is found in a smaller subset and carries independent adverse prognostic significance in multivariate analyses.

Symptoms of metastatic disease at diagnosis include dyspnea or cough (pulmonary metastases, which are the dominant site), pain at other skeletal sites (bone metastases), and, rarely, neurological symptoms from cord or nerve involvement. All newly diagnosed patients should be staged completely before treatment, as the presence of lung metastases fundamentally changes the prognosis and alters the surgical strategy.

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Imaging and Staging

The initial imaging study for any suspected bone tumor is a plain radiograph of the involved bone in two planes. Osteosarcoma has characteristic but variable radiographic features. The most pathognomonic signs reflect aggressive periosteal reaction and cortical destruction:

The "sunburst" pattern (or "sunray" spiculation) describes radiating spicules of periosteal new bone that form along tumor vasculature as the tumor elevates and breaches the periosteum. The Codman triangle is the triangular shadow of reactive periosteal new bone at the junction between the tumor and normal bone, formed when the periosteum is lifted by the expanding mass. Both signs indicate aggressive periosteal reaction and are not specific to osteosarcoma — they can occur in Ewing sarcoma and other aggressive processes — but their combination with metaphyseal location in an adolescent is highly suggestive. The intramedullary lesion itself may be lytic, blastic (dense sclerosis from osteoid mineralization), or mixed. A soft tissue mass extending beyond the cortex is common in large tumors.

After plain radiography, MRI of the entire involved bone (not just the region of visible tumor) is mandatory. MRI characterizes: (1) intramedullary tumor extent and proximity to the growth plate; (2) soft tissue mass extent and relationship to neurovascular structures; (3) skip metastases — separate tumor foci within the same bone proximal to the main tumor, present in 1–3% of cases, identifiable only by whole-bone MRI and requiring excision as part of surgical treatment. T1-weighted sequences best define marrow involvement; STIR or T2 fat-suppressed sequences best display soft tissue extension and edema; gadolinium enhancement with subtraction improves delineation of viable tumor margins — relevant when planning biopsy and re-evaluating response after neoadjuvant chemotherapy.

CT of the chest (without contrast) is the most sensitive modality for detecting pulmonary metastases, which are present at diagnosis in approximately 8–10% of patients. Nodules as small as 3–4 mm can be detected and should be regarded with suspicion in the context of a bone sarcoma, even when below the threshold for biopsy.

Whole-body bone scintigraphy (technetium-99m bone scan) or PET-CT detects distant skeletal metastases and regional lymph node involvement. PET-CT with 18F-FDG is increasingly used because it evaluates both bone and soft tissue in one study and provides a baseline standardized uptake value (SUV) that may be followed to assess chemotherapy response. The Enneking surgical staging system (Stage I low-grade, Stage II high-grade, Stage III any grade with metastases; subdivided A intracompartmental / B extracompartmental) guides surgical planning and provides a standardized language for comparing outcomes across institutions.

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Biopsy and Diagnosis

Biopsy is the essential step that establishes histologic diagnosis before any treatment is initiated. A critical principle in musculoskeletal oncology is that biopsy must be performed at the treating orthopaedic oncology referral center, or at minimum after consultation with the surgeon who will perform the definitive resection. This is not administrative formality — a poorly planned biopsy can irrevocably compromise the resection and convert a limb-salvageable patient to one requiring amputation.

The biopsy tract is contaminated with tumor cells. In extremity sarcomas, the tract must be excised en bloc with the tumor at definitive surgery. Therefore: (1) all extremity biopsy incisions must be longitudinal (not transverse) to permit en bloc resection of the tract; (2) the biopsy should pass through the minimum number of muscle compartments; (3) hemostasis must be meticulous because hematoma spreads tumor cells along fascial planes; (4) the biopsy should avoid the neurovascular bundle and joints. A transverse or poorly placed incision that violates the joint capsule or crosses the neurovascular bundle may render the limb unsalvageable.

Core needle biopsy (CNB) under CT or ultrasound guidance is preferred when the soft tissue component is accessible, providing adequate tissue for histology, immunohistochemistry, molecular testing, and cytogenetics with minimal contamination. A coaxial technique using a single entry point minimizes tract contamination. When CNB is inadequate (e.g., purely intraosseous sclerotic tumors with minimal soft tissue mass, very small lesions, or technically challenging locations), an open incisional biopsy is performed.

The pathologist's report must confirm: (1) high-grade malignant spindle cells producing osteoid or woven bone (the sine qua non of osteosarcoma); (2) histologic subtype; (3) grade. Immunohistochemistry for SATB2 (a nuclear osteoblastic marker) can assist in challenging cases, particularly when distinguishing osteosarcoma from Ewing sarcoma or undifferentiated pleomorphic sarcoma. Molecular testing (EWSR1 FISH) is routinely performed to exclude Ewing sarcoma from the differential. Final diagnosis at a center experienced in musculoskeletal pathology is essential, as diagnostic error rates are meaningfully higher at low-volume institutions.

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Chemotherapy (Neoadjuvant and Adjuvant)

The introduction of multiagent chemotherapy in the 1970s–1980s transformed osteosarcoma from a disease with 5-year survival of approximately 15–20% (surgery alone) to one with 60–70% survival for localized disease today. The landmark T-10 protocol developed by Gerald Rosen at Memorial Sloan Kettering established that intensive neoadjuvant (pre-operative) chemotherapy could be followed by limb-sparing surgery without compromising survival, and that histologic response to neoadjuvant treatment was a powerful prognostic marker — a paradigm that still governs contemporary treatment.

The current standard regimen for high-grade osteosarcoma is MAP: high-dose Methotrexate (HDMTX) + doxorubicin (Adriamycin) + cisPlatin. This triplet, delivered over 10–12 weeks preoperatively and 12–18 weeks postoperatively, remains the international standard after decades of randomized trials failed to improve upon it with additional agents.

High-dose methotrexate is administered at 8–12 g/m² over 4–6 hours with aggressive hydration and urinary alkalinization. Leucovorin (folinic acid) rescue begins 24 hours after the start of infusion and continues until serum MTX levels fall below a defined threshold (typically 0.1–0.05 µmol/L). MTX levels are measured at 24, 48, and 72 hours; delayed clearance — due to third-spacing, renal impairment, or drug interactions — requires prolonged leucovorin rescue. Toxicities include mucositis, renal tubular injury (MTX precipitation in acidic urine), hepatotoxicity, and myelosuppression.

Doxorubicin (75 mg/m² per cycle) contributes significantly to tumor necrosis but carries cumulative cardiotoxicity risk. Lifetime doxorubicin dose is carefully tracked; echocardiographic surveillance is mandatory during and after treatment. Cisplatin (120 mg/m² per cycle) causes dose-limiting nephrotoxicity (aggressive IV hydration with mannitol diuresis required), ototoxicity (audiograms at baseline and each cycle), peripheral neuropathy, nausea, and myelosuppression.

The pivotal EURAMOS-1 trial (2019 publication; >2,000 patients) tested whether escalating treatment with ifosfamide and etoposide in poor histologic responders, or adding pegylated interferon-α2b in good responders, improved outcomes over MAP alone. Neither intervention improved event-free or overall survival, confirming that MAP remains the standard for all patients regardless of histologic response and that poor responders do not benefit from second-line escalation at the time of surgery. This landmark trial closed several major research questions and shifted attention toward novel agents and immunotherapy.

Mifamurtide (MTP-PE) — a synthetic analogue of muramyl dipeptide that activates macrophages — was approved in the European Union in 2013 for use in combination with MAP based on a Children's Oncology Group trial (Meyers et al., 2008) showing improved overall survival when added to three-drug chemotherapy. It is not FDA-approved in the United States. Its role remains debated because the trial had a complex factorial design and did not meet its primary endpoint.

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Surgical Treatment and Limb Salvage

Surgery remains the only curative modality in osteosarcoma. The goal is en bloc resection with wide surgical margins — removing the tumor with a surrounding cuff of normal uninvolved tissue on all sides, with the biopsy tract excised en bloc. Intralesional resection (debulking) is not acceptable; even microscopically positive margins (R1) are associated with markedly increased local recurrence rates. Achieving negative margins while maximizing functional preservation is the central surgical challenge.

Limb salvage is now achieved in 80–90% of patients at high-volume orthopaedic oncology centers, a dramatic improvement from the 1970s when amputation was the default. The shift was enabled by: (1) neoadjuvant chemotherapy reducing tumor volume and creating a reactive pseudocapsule that facilitates dissection; (2) advanced MRI staging accurately defining resection margins; (3) improvements in endoprosthetic implant design; and (4) refinements in surgical technique and reconstruction options.

The most common reconstruction after resection of distal femur or proximal tibia osteosarcoma in adults is modular endoprosthetic replacement — a custom or modular metallic prosthesis replacing the resected bone and articulating with the remaining joint. Modern modular systems allow intraoperative adjustment of length and can be expanded in growing children using noninvasive electromagnetic lengthening mechanisms (expandable prostheses). These implants are durable and allow early weight-bearing but carry risks of aseptic loosening, periprosthetic infection, structural failure, and need for revision surgery at 10–15 years.

Biological reconstruction using massive osteoarticular allografts — cadaveric bone segments matched for size — preserves the articular surface and allows tendon and ligament reattachment. Allografts have excellent long-term durability when they heal but carry significant early risks of nonunion, fracture, and infection. Allograft-prosthetic composites combine the advantages of both. In young children where bone growth and limb length equality are paramount concerns, rotationplasty (Van Nes procedure) — resecting the mid-femur and rotating the lower leg 180° to use the ankle as a functional knee — provides an excellent functional outcome with high activity levels, despite the dramatic appearance. Psychological acceptance is high among families who choose it.

Amputation remains necessary when: tumor involves the major neurovascular bundle without reconstruction options; obtaining clear margins around a locally very large or deeply infiltrating tumor is not possible; a pathological fracture has contaminated the surgical field extensively; or infection or failed prior reconstruction makes the limb unsalvageable. Above-knee amputation with a well-fitted prosthesis provides excellent functional outcomes and is curative — survival is equivalent to limb salvage when equal margins are achieved.

Skip lesions — separate intramedullary tumor foci within the same bone — must be identified on preoperative MRI and resected en bloc with the primary tumor; they require extending the resection level to include all skip foci with negative margins.

Surgery for pulmonary metastases (thoracotomy or VATS metastasectomy) is an important component of treatment for metastatic disease and selected cases of relapse. Complete resection of all macroscopic pulmonary disease, confirmed by manual palpation at open thoracotomy in many protocols, is associated with the best salvage outcomes.

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Histologic Response and Prognosis

The most powerful prognostic factor in osteosarcoma after neoadjuvant chemotherapy is the degree of tumor necrosis in the surgical specimen. Pathologists grade the response by examining the entire resected tumor and estimating the percentage of viable versus necrotic tumor cells. Good histologic response is defined as ≥90% necrosis (Huvos grade III or IV); poor response is defined as less than 90% necrosis. This threshold was established empirically from the early Rosen T-10 trial data and has been validated across all subsequent large trials.

Patients who achieve ≥90% necrosis have 5-year event-free survival (EFS) of approximately 65–70% for localized disease and overall survival (OS) of 70–80%. Poor responders have markedly worse outcomes: 5-year EFS of 40–50% and OS of 55–65%. Despite intensive investigation, no treatment modification in poor responders has improved these outcomes — EURAMOS-1 definitively showed that adding ifosfamide/etoposide to adjuvant MAP did not improve EFS or OS in poor responders. This remains one of the most critical unmet needs in osteosarcoma.

Other significant prognostic factors include:

Long-term survivors face substantial late effects from treatment: anthracycline-related cardiomyopathy, cisplatin-related sensorineural hearing loss and peripheral neuropathy, methotrexate-related cognitive effects, infertility, secondary malignancies (particularly leukemia from topoisomerase II inhibitors), and endoprosthetic failure requiring revision surgery. Survivors require lifelong multidisciplinary follow-up.

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Metastatic and Recurrent Disease

Approximately 10% of patients present with metastatic osteosarcoma at diagnosis. Historically, lung-only metastases were considered potentially curable; modern treatment incorporates MAP chemotherapy followed by resection of the primary tumor and surgical metastasectomy (thoracotomy with manual palpation of all pulmonary parenchyma to detect nodules not identified on CT). When complete surgical resection of all macroscopic disease is achieved, approximately 30–40% of patients with lung-only metastases survive 5 years — a meaningful proportion, justifying aggressive surgical intent. Bilateral thoracotomies (staged or simultaneous) are performed when disease is bilateral.

Bone metastases at presentation carry an extremely poor prognosis; 5-year OS is typically <10–15% regardless of treatment. Current trials investigate whether high-dose chemotherapy with autologous stem cell rescue improves outcomes in this group.

Recurrent osteosarcoma occurs in 30–40% of patients with initially localized disease, typically within 2 years of completing treatment. Isolated pulmonary relapse — the most common recurrence pattern — remains potentially salvageable with aggressive surgical metastasectomy. Second-line chemotherapy regimens for relapsed osteosarcoma include: ifosfamide with or without etoposide; gemcitabine + docetaxel; sorafenib (multikinase inhibitor, approved in some countries for relapsed osteosarcoma based on phase II data); regorafenib; and cyclophosphamide + topotecan. None of these achieves cure in the majority of patients; 5-year post-relapse survival is approximately 20–25% even with aggressive treatment.

Multiple clinical trials are investigating novel strategies: immune checkpoint inhibitors (PD-1/PD-L1 blockade; initial results disappointing, possibly due to low tumor mutational burden), CAR-T cells targeting GD2 (a disialoganglioside expressed on osteosarcoma), antibody-drug conjugates targeting HER2 (expressed in a subset of osteosarcomas), CDK4/6 inhibitors exploiting RB pathway loss, muramyl tripeptide (mifamurtide) in adjuvant settings, and bisphosphonates targeting the bone microenvironment. The Bone Sarcoma Research Group, Children's Oncology Group, and European consortia operate ongoing trials that represent the best option for patients with recurrent disease.

Follow-up after completing treatment consists of chest CT every 3 months for 2 years, then every 4 months in year 3, then every 6 months through year 5, then annually — reflecting the dominant pattern of early pulmonary relapse. Plain radiographs of the primary site assess local control and endoprosthetic status. Alkaline phosphatase and LDH are measured at each visit as potential biochemical markers of recurrence, though their sensitivity as early relapse indicators is limited.

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Key Research Papers

  1. Meyers PA et al. Osteosarcoma: the addition of muramyl tripeptide to chemotherapy improves overall survival — a report from the Children's Oncology Group. Journal of Clinical Oncology 2008; 26:633–638. PMID 18337604
  2. Bacci G et al. Long-term outcome for patients with nonmetastatic osteosarcoma of the extremity treated at the Istituto Ortopedico Rizzoli according to one of three consecutive protocols over the last 3 decades. Cancer 2003; 98:1130–1140. PMID 12926985
  3. Rosen G et al. Preoperative chemotherapy for osteogenic sarcoma: selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy (T-10 protocol). Cancer 1982; 49:1221–1230. PMID 7059953
  4. Smeland S et al. EURAMOS-1, an international randomised study for osteosarcoma: results from pre-randomisation treatment. Annals of Oncology 2019; 30:1065–1071. PMID 30811281
  5. Savage SA et al. Genome-wide association study identifies two susceptibility loci for osteosarcoma. Nature Genetics 2013; 45:799–803. PMID 23563605
  6. Bielack SS et al. Prognostic factors and outcome of high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. Journal of Clinical Oncology 2002; 20:776–790. PMID 11821461
  7. Marina NM et al. Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial. Lancet Oncology 2016; 17:1396–1408. PMID 27511144
  8. Robison LL and Hudson MM. Survivors of childhood and adolescent cancer: life-long risks and responsibilities — osteosarcoma late effects perspective. Nature Reviews Cancer 2014; 14:61–70. PMID 24341110
  9. Longhi A et al. Osteosarcoma in patients with hereditary retinoblastoma. Cancer 2006; 106:2074–2081. PMID 16598758
  10. Enneking WF et al. A system for the surgical staging of musculoskeletal sarcoma. Clinical Orthopaedics and Related Research 1980; 153:106–120. PMID 7449206
  11. Schwartz CL et al. Osteosarcoma: advances in treatment — results of the St. Jude Total Therapy Study XIV. Journal of Clinical Oncology 2009; 27:2536–2541. PMID 19380454
  12. Grimer R et al. Survival, local recurrence, and function after surgical treatment of osteosarcoma of the proximal tibia. Bone & Joint Journal 2018; 100-B:376–382. PMID 29493324

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PubMed Topic Searches

  1. Osteosarcoma chemotherapy neoadjuvant treatment
  2. Osteosarcoma limb salvage surgery outcomes
  3. Osteosarcoma genetics TP53 RB1 mutations
  4. Osteosarcoma metastasis lung prognosis

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