<script language="JavaScript1.2" type="text/javascript" charset="ISO-8859-1" src="http://as.emedicine.com/js.ng/Params.

richmedia=yes&amp;transactionID=7796624 5&amp;tile=77966245&amp;site=1&amp;affiliate=2&amp;ssp=8&amp;artid=10120531 &amp;cg=ckb&amp;pub=140&amp;pubs=140&amp;ct=&amp;pf=0&amp;usp=0&amp;s t=&amp;occ=0&amp;tid=0&amp;pos=101"></script>

Home Specialties Reference Centers

Search: eMed Search

All Sources MEDLINE

eMedicine

Medscape

Drug Reference

Quick Find Authors & Editors Introduction Indications Relevant Anatomy Contraindications Workup Treatment Complications Outcome and Prognosis Future and Controversies Multimedia References

<script language="JavaScript1.2" type="text/javascript" charset="ISO-8859-1" src="http://as.emedicine.com/js.ng/Params.richmedia=yes&transactionID=77966245&til e=77966245&site=1&affiliate=2&ssp=8&artid=10120531&cg=ckb&pub=140&pubs=14 0&ct=&pf=0&usp=0&st=&occ=0&tid=0&pos=130"></script> <script language="JavaScript1.2" type="text/javascript" charset="ISO-8859-1" src="http://as.emedicine.com/js.ng/Params.richmedia=yes&transactionID=77966245&til e=77966245&site=1&affiliate=2&ssp=8&artid=10120531&cg=ckb&pub=140&pubs=14 0&ct=&pf=0&usp=0&st=&occ=0&tid=0&pos=160"></script>

Patient Education

Click here for patient education.

Email to a colleague

You are in: eMedicine Specialties > Orthopedic Surgery > NEOPLASMS

Osteosarcoma
Article Last Updated: Mar 28, 2008

AUTHOR AND EDITOR INFORMATION

Section 1 of 12 Authors and Editors Introduction Indications Relevant Anatomy Contraindications Workup Treatment Complications Outcome and Prognosis Future and Controversies Multimedia References Author: Charles T Mehlman, DO, MPH, Director, Musculoskeletal Outcomes Research, Associate Professor, Division of Pediatric Orthopedic Surgery, Cincinnati Children's Hospital Medical Center Charles T Mehlman is a member of the following medical societies: American Academy of Pediatrics, American Fracture Association, American Medical Association, American Orthopaedic Foot and Ankle Society, American Osteopathic Association, Arthroscopy Association of North America, North American Spine Society, Ohio State Medical Association, Pediatric Orthopaedic Society of North America, and Scoliosis Research Society Coauthor(s): Timothy P Cripe, MD, PhD, Associate Professor of Pediatric Hematology/Oncology, University of Cincinnati; Director, Translational Research Trials Office, Department of Pediatrics, Cincinnati Children's Hospital Medical Center Editors: Miguel A Schmitz, MD, Consulting Surgeon, Department of Orthopedics, Klamath Orthopedic and Sports Medicine Clinic; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Sean P Scully, MD, PhD, Professor, Department of Orthopedics, University of Miami; Dinesh Patel, MD, FACS, Associate Clinical Professor of Orthopedic Surgery, Harvard Medical School; Chief of Arthroscopic Surgery, Department of Orthopedic Surgery, Massachusetts General Hospital; Harris Gellman, MD, Consulting Surgeon, Broward Hand Center, Voluntary Clinical Professor of Orthopedic Surgery and Plastic Surgery, Departments of Orthopedic Surgery and Surgery, University of Miami School of Medicine Author and Editor Disclosure Synonyms and related keywords: osteogenic sarcoma, osteoblastic osteosarcoma, chondroblastic osteosarcoma, fibroblastic osteosarcoma, multifocal osteosarcoma, highgrade intramedullary osteosarcoma, typical osteosarcoma, classic osteosarcoma, conventional osteosarcoma, variant osteosarcoma, primary osteosarcoma, synchronous osteosarcoma, metachronous osteosarcoma, unicameral bone cyst, osteofibrous dysplasia, Campanacci tumor, periosteal osteosarcoma, malignant bone cancer, bone cancer

INTRODUCTION
Section 2 of 12 Authors and Editors Introduction Indications Relevant Anatomy Contraindications Workup Treatment Complications Outcome and Prognosis Future and Controversies Multimedia References

This article focuses on high-grade intramedullary osteosarcoma (also referred to as simply osteosarcoma), including its classic osteoblastic form and its fibroblastic and chondroblastic forms. Osteosarcoma is the most common malignant bone tumor.1, 2 This disease is thought to arise from primitive mesenchymal bone-forming cells, and its histologic hallmark is the production of malignant osteoid. Other cell populations may also be present, as these types of cells may also arise from pluripotential mesenchymal cells, but any area of malignant bone in the lesion establishes the diagnosis as osteosarcoma. The mainstay of therapy is surgical removal of the malignant lesion. Most often, limbsparing (limb-preserving) procedures can be used to treat patients with this disease and, thus, preserve function. Chemotherapy is also required to treat micrometastatic disease, which is present but often not detectable in most patients (about 80%) at the time of diagnosis. For excellent patient education resources, visit eMedicine's Cancer and Tumors Center. Also, see eMedicine's patient education articles Cancer: What You Need to Know and Understanding Lung Cancer Medications. Related eMedicine topic: Osteosarcoma, Variants Related Medscape topics: Resource Center Cancer: Biologic Therapies Specialty Site Oncology Specialty Site Orthopaedics CME/CMLE Highlights of ASCP 2007 Annual Meeting Chemotherapy Plus Muramyl Tripeptide Improves Osteosarcoma Survival Orthopedic Surgery Options for the Treatment of Primary Osteosarcoma Spectrum's Levoleucovorin Approved by US FDA for Treatment of Osteosarcoma

History of the Procedure

Osteosarcoma is an ancient disease that is still incompletely understood. The term

"sarcoma" was introduced by the English surgeon John Abernathy in 1804 and was derived from Greek roots meaning "fleshy excrescence."3 In 1805, the French surgeon Alexis Boyer (personal surgeon to Napoleon) first used the term "osteosarcoma."3, 4 Boyer realized that osteosarcoma is a distinct entity from other bone lesions, such as osteochondromas (exostoses). Evidence of further organized thought and purposeful investigation regarding this disease was found by the mid 1800s. Peltier recorded that in 1847, the Baron Guillaume Dupuytren demonstrated his intimate knowledge of the gross pathologic appearance of osteosarcoma when he wrote the following3: "Osteosarcoma, which is a true cancerous degeneration of bone, manifests itself in the form of a white or reddish mass, lardaceous and firm at an early stage of the disease; but presenting at a later period, points of softening, cerebriform matter, extravasating blood, and white or straw colored fluid of a viscid consistence in its interior."3 Under the auspices of the American College of Surgeons, Ernest Amory Codman (along with James Ewing and Joseph Bloodgood) created the Registry of Bone Sarcoma in 1921.5 This was a significant step forward in studying these rare and ominous tumors, as individual surgeons had only limited experience to guide them. Another major institution that began to take shape in the early 1900s was the Rizzoli Institute in Bologna, Italy. This institute, whose bone tumor roots were nurtured by Vittorio Putti (1880-1940), prospered under the later guidance of persons such as Scaglietti and Campanacci.6 Major contributions from this institution have included innovative treatment for unicameral bone cysts (Scaglietti) and intense study of osteofibrous dysplasia (Campanacci tumor). By the mid 1900s, great strides were being made in the United States in the field of bone pathology by Henry L. Jaffe (1896-1979) and his colleague Louis Lichtenstein (1906-1977). Each of these men published textbooks devoted to bone pathology. Jaffe is also often credited with bringing order to the chaos that was orthopedic pathology. Together, Jaffe and Lichtenstein established virtually all of the key histologic criteria that are used to diagnose most of the commonly encountered bone tumors. A different Dr Jaffe (Norman Jaffe), along with other researchers, helped expand the use of a variety of effective chemotherapeutic agents in the 1970s and early 1980s.7 Not the least of these agents were Adriamycin and methotrexate. These medications (and others that followed) dramatically improved the treatment of patients with osteosarcoma through their ability to treat the micrometastatic disease that was thought to be present in approximately 80% of patients.8 These drugs were found to be useful both preoperatively and postoperatively in patients with osteosarcoma, a discovery made at the Sloan-Kettering Memorial Cancer Center somewhat serendipitously while custom-made prostheses were being fabricated for patients awaiting surgery.9 Such preoperative use of chemotherapy came to be referred to as neoadjuvant chemotherapy. An orthopedic surgeon from Gainesville, Florida, William F. Enneking, MD, introduced his surgical staging system for musculoskeletal sarcomas.10, 11 This staging system helped organize the orthopedic surgical approach to both biopsy and definitive tumor resection for osteosarcoma, as well as for other musculoskeletal sarcomas. Dr. Enneking's influence extended far beyond his staging system because of his intense commitment to educating others regarding musculoskeletal tumors. He has educated numerous orthopedic oncology fellows, published numerous research articles, and continued to conduct a yearly continuing medical education course focusing on benign and malignant tumors.

Problem
Osteosarcoma is a deadly form of musculoskeletal cancer that most commonly causes patients to die from pulmonary metastatic disease.3, 6, 12, 13, 14 Image 1 illustrates the chest radiograph of a patient who died from pulmonary metastatic disease. Most osteosarcomas

arise as solitary lesions within the fastest growing areas of the long bones of children. The top 3 affected areas are the distal femur, the proximal tibia, and the proximal humerus, but virtually any bone can be affected. Images 2-6 illustrate the clinical and radiologic findings of a patient who presented with osteosarcoma of the proximal humerus. Not all osteosarcomas arise in a solitary fashion, as multiple sites may become apparent within a period of about 6 months (synchronous osteosarcoma), or multiple sites may be noted over a period longer than 6 months (metachronous osteosarcoma).12 Such multifocal osteosarcoma is decidedly rare, but when it occurs, it tends to be in patients younger than 10 years.12

Frequency
In the United States, the incidence of osteosarcoma is 400 cases per year (4.8 per million population <20 y).15 The overall 5-year survival rate for patients diagnosed between 1974 and 1994 was 63% (59% for males, 70% for females). The incidence is slightly higher in blacks than in whites. Data from the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Pediatric Monograph 1975-1995 are as follows15:

Blacks 5.2 cases per million per year (persons <20 y) Whites 4.6 cases per million per year

The incidence of osteosarcoma is slightly higher in males than in females. In males, it is 5.2 per million per year. In females, the incidence is 4.5 per million per year. Osteosarcoma is very rare in young children (0.5 cases per million per year in children <5 y). However, the incidence increases steadily with age, increasing more dramatically in adolescence, corresponding with the adolescent growth spurt.

Age 5-9 years 2.6 (black) or 2.1 (white) cases per million per year Age 10-14 years 8.3 (black) or 7 (white) cases per million per year Age 15-19 years 8.9 (black) or 8.2 (white) cases per million per year

Etiology
The exact cause of osteosarcoma is unknown. However, a number of risk factors are apparent, as follows3, 6, 12, 13, 14, 16, 17, 18, 19, 20, 21:

Rapid bone growth: Rapid bone growth appears to predispose persons to osteosarcoma, as suggested by the increased incidence during the adolescent growth spurt, the high incidence among large-breed dogs (eg, Great Dane, St. Bernard, German shepherd), and osteosarcoma's typical location in the metaphyseal area adjacent to the growth plate (physis) of long bones. Environmental factors: The only known environmental risk factor is exposure to radiation. Radiation-induced osteosarcoma is a form of secondary osteosarcoma and is not discussed further in this article. Genetic predisposition: Bone dysplasias, including Paget disease, fibrous dysplasia, enchondromatosis, and hereditary multiple exostoses and retinoblastoma (germ-line form) are risk factors. The combination of constitutional mutation of the RB gene (germline retinoblastoma) and radiation therapy is associated with a particularly high risk of developing osteosarcoma, Li-Fraumeni syndrome (germline p53 mutation), and Rothmund-Thomson syndrome (autosomal recessive association of congenital bone defects, hair and skin dysplasias, hypogonadism, and cataracts).

Related eMedicine topics: Enchondroma and Enchondromatosis Fibrous Dysplasia

Li-Fraumeni Syndrome Paget Disease Retinoblastoma Rothmund-Thomson Syndrome

Pathophysiology
Osteosarcoma is a bone tumor and can occur in any bone, usually in the extremities of long bones near metaphyseal growth plates. The most common sites are the femur (42%, 75% of which are in the distal femur), tibia (19%, 80% of which are in the proximal tibia), and humerus (10%, 90% of which are in the proximal humerus). Other significant locations are the skull and jaw (8%) and pelvis (8%). A number of variants of osteosarcoma exist, including conventional types (osteoblastic, chondroblastic, and fibroblastic), telangiectatic, multifocal, parosteal, and periosteal. This article only addresses conventional osteosarcoma.

Clinical
Symptoms may be present for weeks or months (occasionally longer) before patients are diagnosed. The most common presenting symptom of osteosarcoma is pain, particularly pain with activity. Patients may be concerned that their child has a sprain, arthritis, or growing pains. Often, there is a history of trauma, but the precise role of trauma in the development of osteosarcoma is unclear. Pathologic fractures are not particularly common. The exception is the telangiectatic type of osteosarcoma, which is more commonly associated with pathologic fractures. The pain in an extremity may result in a limp. There may or may not be a history of swelling, depending on the size of the lesion and its location. Systemic symptoms, such as fever and night sweats, are rare. Tumor spread to the lungs only rarely results in respiratory symptoms and usually indicates extensive lung involvement. Metastases to other sites are extremely rare, and, therefore, other symptoms are unusual. Physical examination findings are usually limited to the site of the primary tumor, as follows:

Mass: A palpable mass may or may not be present. The mass may be tender and warm, although these signs are indistinguishable from osteomyelitis. Increased skin vascularity over the mass may be discernible. Pulsations or a bruit may be detectable. Decreased range of motion: Involvement of a joint should be obvious on physical examination. Lymphadenopathy: Involvement of local or regional lymph nodes is unusual. Respiratory findings: Auscultation is usually uninformative unless the disease is extensive.

Related eMedicine topics: Osteomyelitis, Acute Pyogenic Osteomyelitis, Chronic

INDICATIONS
Section 3 of 12 Authors and Editors Introduction Indications

Relevant Anatomy Contraindications Workup Treatment Complications Outcome and Prognosis Future and Controversies Multimedia References

The 2 main procedures performed by orthopedic surgeons in patients with osteosarcoma are biopsy and wide resection. Neither of these procedures should be undertaken unless complete tumor staging has been completed preoperatively. Such staging would typically include (but not be limited to) the following:

Plain radiography of the involved bone, including the joint above and the joint below the affected region Total body bone scanning Magnetic resonance imaging (MRI) of the primary tumor area to include the entire bone of origin Computed tomography (CT) scanning of the lungs

The biopsy of malignant bone lesions is not an insignificant procedure. An improperly performed biopsy can result in the amputation of an otherwise salvageable extremity. It has also been shown repeatedly that oncologic outcomes are optimized when the biopsy is performed by the same surgeon who will be responsible for the definitive tumor resection (if one is needed).22, 23 Incisional biopsies or core needle biopsies (Craig needle biopsy) are the most common types of biopsies performed by orthopedic surgeons.24 Open lines of communication between the orthopedic surgeon and the pathologist are vital to help ensure that adequate tissue is obtained for diagnostic purposes (see Images 10-11). Wide resection is the goal for patients in whom primary tumor resection is contemplated. Simply defined, a wide resection means that the entire malignant tumor has been surgically excised, and no microscopic evidence of tumor cells at the resection margins remains (ie, negative margins). Over the years, many authors have suggested variable and arbitrary amounts of the normal tissue cuff to remove along with the primary tumor to increase the likelihood of negative margins. No universally accepted definition exists of the appropriate thickness of the normal cuff. In a technical sense, a wide margin still exists even if the distance between the normal tissue and tumor is 1 cell thick. From an oncologic standpoint, the width achieved is less important (limb-sparing surgery vs amputation) than the achievement of a negative margin. In other words, a limb-sparing surgery without wide margins could do the patient less of a service than an amputation with wide margins. This would apply in most cases in which maximal preservation of life is considered the primary goal.

RELEVANT ANATOMY
Section 4 of 12 Authors and Editors Introduction Indications Relevant Anatomy Contraindications Workup

Treatment Complications Outcome and Prognosis Future and Controversies Multimedia References

See Surgical therapy.

CONTRAINDICATIONS
Section 5 of 12 Authors and Editors Introduction Indications Relevant Anatomy Contraindications Workup Treatment Complications Outcome and Prognosis Future and Controversies Multimedia References

Because osteosarcoma is a deadly form of cancer, no absolute contraindications to treatment exist. Relative contraindications would include situations in which the patient is so frail that the risks of general anesthesia outweigh any potential benefits of surgery. Another relative contraindication would be a situation in which the patient has extensive, overwhelming metastatic disease, and the benefits of comfort and/or hospice care outweigh the potential benefits of surgical intervention.

WORKUP
Section 6 of 12 Authors and Editors Introduction Indications Relevant Anatomy Contraindications Workup Treatment Complications Outcome and Prognosis Future and Controversies Multimedia References

Lab Studies

Most of the laboratory studies that are obtained relate to the use of chemotherapy. It is important to assess organ function before administering chemotherapy and to monitor function after chemotherapy. The only blood tests with prognostic significance are lactic dehydrogenase (LDH) and alkaline phosphatase (ALP). Patients with an elevated ALP at diagnosis are more likely to have pulmonary metastases. In patients without metastases, those with an elevated LDH are less likely to do well than are those with a normal LDH. Important laboratory studies include the following:
o o o o o o o o

LDH ALP (prognostic significance) Complete blood cell (CBC) count, including differential Platelet count Liver function tests: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, and albumin Electrolyte levels: Sodium, potassium, chloride, bicarbonate, calcium, magnesium, phosphorus Renal function tests: blood urea nitrogen (BUN), creatinine Urinalysis

Imaging Studies

Plain films Primary, posteroanterior (PA), and lateral chest views Obtain plain films of the suspected lesions in 2 views. No single feature on a radiograph is diagnostic. o Osteosarcoma lesions can be purely osteolytic (approximately 30% of cases), purely osteoblastic (approximately 45% of cases), or a mixture of both. o Elevation of the periosteum may appear as the characteristic Codman triangle. Codman described this entity in 1909, stating, "In many cases near the junction of the healthy bone with the tumor, there is a reactive new bone formation beneath the periosteum. At the edge of the tumor, this layer of new bone ends abruptly and gives a characteristic appearance in the skiagraph [radiograph]."3 o Extension of the tumor through the periosteum may result in a so-called sunburst appearance (approximately 60% of cases). Obtain an image of the entire bone and adjacent joint to assess for skip lesions or joint involvement. Telangiectatic osteosarcomas are often very cystic and can be mistaken for an aneurysmal bone cyst. CT scanning
o o o o

Obtain a CT scan of the primary lesion and a CT scan of the chest (high resolution). CT scanning of the primary lesion helps delineate the location and extent of the tumor and is critical for surgical planning. CT scanning of the chest is more sensitive than is plain film radiography for assessing pulmonary metastases. Ideally, obtain the CT scan of the chest before performing a biopsy to avoid ambiguity that can arise from postanesthesia atelectasis. MRI of the primary lesion is the best method to assess the extent of intramedullary disease as well as associated soft-tissue masses and skip lesions. This imaging modality is perhaps the single most important study for accurate surgical staging of the lesion with use of the Enneking staging

MRI
o

system. Radionuclide bone scanning with technetium-99 (99mTc)-methylene diphosphonate (MDP/MDI) It is important to evaluate for the presence of metastatic or multifocal disease with a bone scan. o Subsequently, obtain an image of abnormal areas with CT scanning or MRI. Echocardiography or multiple gated acquisition scanning: Assess cardiac function before, and at various intervals following, treatment with Adriamycin.
o

Related eMedicine topic: Aneurysmal Bone Cyst Related Medscape topics: Resource Center Adverse Drug Events Reporting Resource Center Cancer: Biologic Therapies

Other Tests

Audiography: Hearing loss is an adverse effect of cisplatin. Hearing loss typically occurs during treatment. Once treatment is completed, obtaining audiograms is not typically a part of long-term follow-up care.

Related Medscape topics: Resource Center Adverse Drug Events Reporting Resource Center Cancer: Biologic Therapies

Diagnostic Procedures

Biopsies should be performed by an orthopedic surgeon (see Surgical therapy). Definitive resection
o o o

Resections of the primary lesion and of any pulmonary metastases are essential for cure. These resections should be performed by orthopedic (primary lesion) and thoracic surgeons (pulmonary metastases) (see Surgical therapy). Presurgical (neoadjuvant) chemotherapy often aids the surgeon in performing the resection by shrinking tumors as well as enables the assessment of histopathologic tumor responsiveness, a major predictor of outcome.

Histologic Findings
Two elements are important to the histologic examination of the tumor. The first can be assessed on the biopsy, the tumor type. The second can be assessed on the definitive resection following chemotherapy, the response to treatment. In general, the characteristic feature of osteosarcoma is the presence of osteoid in the lesion, even at sites distant from bone (eg, lung). Although osteoid formation is usually obvious, electron microscopy occasionally may be required to reveal this process. Stromal cells may be spindle-shaped and atypical, with irregularly shaped nuclei. A number of different histologic types of osteosarcoma exist. The conventional type is the most common in childhood and adolescence and has been subdivided based on the predominant features of the cells (osteoblastic, chondroblastic, fibroblastic), although the subtypes are clinically indistinguishable. The telangiectatic type contains large, blood-filled spaces and is seen commonly in adolescence and early adulthood. The parosteal type usually arises from the bone cortex, has an intermediate prognosis, and can be seen in childhood or adulthood. It most commonly

arises on the distal posterior aspect of the femur. Periosteal osteosarcoma is a low- to intermediate-grade tumor that typically arises immediately below the periosteum in children. It most frequently involves the tibia.

Staging
The purpose of staging tumors is to stratify risk groups. The conventional staging used for other solid tumors is not appropriate for skeletal tumors because these tumors rarely involve lymph nodes or regional spread. Rather, the staging devised and introduced by Enneking in 1980 is based on grade, extracompartmental spread, and whether or not metastases are present. This system applies to all musculoskeletal tumors (both bone and soft tissue). The Enneking staging system (also referred to as the staging system of the Musculoskeletal Tumor Society) has been credited with bringing order to the surgical treatment of a group of tumors for which treatment was previously approached rather haphazardly. The key components to the staging system are the histologic grade of the tumor (low grade vs high grade), the anatomic location of the tumor (intracompartmental vs extracompartmental), and the absence or presence of metastatic disease. The staging system is typically depicted as follows:

Low-grade tumor, intracompartmental I-A Low-grade tumor, extracompartmental I-B High-grade tumor, intracompartmental II-A High-grade tumor, extracompartmental II-B Any tumor with evidence of metastasis III

The definition of "a compartment" is a central and crucial concept related to the Enneking staging system. In general, a compartment may be defined as any individual bone (ie, each bone is a compartment unto itself), intra-articular space (ie, a purely intra-articular lesion is intracompartmental), and clearly identified fascially enclosed space (eg, the anterior compartment of the lower leg). Many of these compartments are the same ones that a surgeon would release in the setting of compartment syndrome; these relate much more to soft-tissue tumors than to bone tumors such as an osteosarcoma. Some areas of the body are considered to be extracompartmental by definition according the Enneking staging scheme. These areas include the antecubital fossa, the inguinal region, the popliteal space, and intrapelvic and paraspinal lesions. Because of the unique challenges of spinal tumors, an entirely separate staging system has been proposed for these areas by Weinstein, Boriani, and Biagin. It is referred to as the WBB staging system and was introduced in 1996. This system focuses on the general anatomic location about the spine (conceptualizing a spinal segment as if it were the face of a clock), as well as the specific anatomic location about the spine (eg, extraosseous soft-tissue extension into muscular areas vs intradural extraosseous extension). Just as spinal anatomy is complex, the WBB staging system is complex, but its use is slowly increasing. For osteosarcoma, the foremost initial question regarding staging is whether the tumor has metastasized. Other features of the tumor, although not technically used in the staging, may impact the prognosis. These include the LDH and ALP measurements (see Lab studies), site of primary tumor (mostly related to ease of complete resection), histologic response to chemotherapy, and cause of the disease (patients with osteosarcomas arising from Paget disease have a particularly poor prognosis). Patients with isolated jaw lesions tend to do better and have a lower incidence of metastases.

Stage I Low-grade lesions Stage II High-grade lesions Stage III Metastases

o

Substage A Intracompartmental lesion (intramedullary lesion for bone tumors)

Substage B Extracompartmental lesion (extramedullary spread for bone tumors) Site of primary tumor
o

Distal extremity Best Distal femur Intermediate Axial skeleton Worst Size of the initial tumor: In a retrospective study by Kim et al, the records of 331 patients with stage II osteosarcoma who underwent surgery and chemotherapy were reviewed.26 The authors found that the initial tumor size appears to be associated with histologic response and is an important prognostic factor in osteosarcoma. Histologic response: Patients with tumors that have a good histologic response (the definition of which is still under debate) to preoperative chemotherapy appear to have a better prognosis, although this still is under investigation.

o o o

Related eMedicine topics: Compartment Syndrome, Lower Extremity Compartment Syndrome, Upper Extremity

TREATMENT
Section 7 of 12 Authors and Editors Introduction Indications Relevant Anatomy Contraindications Workup Treatment Complications Outcome and Prognosis Future and Controversies Multimedia References

Medical therapy
Before the use of chemotherapy (which began in the 1970s), osteosarcoma was treated primarily with surgical resection (usually amputation). Despite such good local control, more than 80% of patients subsequently developed recurrent disease that typically presented as pulmonary metastases. The high recurrence rate indicates that most patients have micrometastatic disease at the time of diagnosis. Therefore, the use of adjuvant (postoperative) systemic chemotherapy is critical for the treatment of patients with osteosarcoma. So-called neoadjuvant (preoperative) chemotherapy has been found not only to facilitate subsequent surgical removal by causing tumor shrinkage but also to provide oncologists with an important risk parameter. Patients in whom there has been a good histopathologic response to neoadjuvant chemotherapy (>95% tumor cell kill or necrosis) have a better prognosis than those whose tumors do not respond as favorably. Thus, future chemotherapy trials will incorporate adjuvant tumor cell kill to provide risk-adapted treatment regimens. Patients receiving methotrexate should not be given folate supplementation or Bactrim, both of which interfere with the effects of methotrexate. Otherwise, the patient's diet is not

restricted. Consultations As usual for any child with cancer, consultations should be made with an oncologist, as well as with any provider with a subspecialty related to the specific clinical circumstances. Social services, psychology, dentistry, and child life specialists are usually involved with these patients and their families throughout their treatment course. Activity Restrictions on activity vary with the location of the tumor and the type of surgical procedure required for treatment. Related Medscape topics: Resource Center Adverse Drug Events Reporting Resource Center Cancer: Biologic Therapies

Surgical therapy
The orthopedic surgeon is of paramount importance in the care of patients with osteosarcoma. Often, patients thought to have osteosarcoma are referred to the orthopedic surgeon first to make the diagnosis. In addition, because osteosarcomas are not particularly responsive to radiotherapy, surgery is the only option for definitive tumor removal (local control). In addition, an oncologic type of total joint prosthesis or complex bone reconstruction may be required following surgical resection. Therefore, close involvement of the orthopedic surgeon with the medical oncologist at the time of diagnosis, as well as during and after chemotherapy, is critical. Biopsy Biopsy procedures include open biopsy (preferred to avoid sampling error and to provide adequate tissue for biologic studies), trephine biopsy or core needle biopsy (preferred for vertebral bodies and many pelvic lesions), or fine needle aspiration (not recommended). Images 7-8 illustrate the Craig needle (core needle) biopsy set. Carefully plan the incision for an open biopsy to avoid tumor contamination of the neurovascular structures and to facilitate removal of the biopsy tract en bloc during definitive surgery. Image 9 illustrates excision of the biopsy tract during definitive tumor resection. Regardless of the technique, a frozen section should be examined to be certain that the tumor has been sampled accurately. Images 10-11 illustrate intraoperative consultation with the pathologist for purposes of evaluation of the frozen-section specimen. If possible, extraosseous components should be sampled rather than bone to lessen the risk of fracture. Seal bone holes with Gelfoam or a similar material to decrease the risk of hematoma and tumor spread. Drains should be of the closed-suction variety, and they should be placed directly in line with the skin incision (a short distance away). Definitive resection The primary aim of definitive resection is patient survival. As such, margins on all sides of the tumor must contain normal tissue (wide margin). The thickness of the margin is important only for the marrow, where an adequate margin is thought to be 5-7 cm from the edge of an abnormality depicted on MRI or bone scan. Radical margins, defined as removal of the entire involved compartment (bone, joint to joint; muscle, origin to insertion), are usually not required for cure. A less-than-wide margin (marginal or intralesional margin) may be functionally helpful as a debulking therapy, but intrinsically, it will not be locally curative. Amputation may be the treatment of choice in some circumstances. If possible, a number of options exist for limb-salvage reconstruction, which must be chosen based on individual considerations, as follows:

Autologous bone graft: These may be vascularized or nonvascularized. Rejection does not occur with these grafts, and the rate of infection is low. The growth plates of patients who are skeletally immature may limit options for stable bone fixation (osteosynthesis). Allograft: Graft healing and infection can be problematic, particularly during chemotherapy. Immunologic rejection can also occur. Allograft-prosthesis composites are also an option. Prosthesis: Prosthetic joint reconstruction can be solitary or expandable, although it is usually expensive. The longevity of such implants is a major concern in young children. Rotationplasty: This technique is particularly suited for patients with distal femur and proximal tibia tumors, particularly large tumors in which a high amputation is the only alternative. Lesions located in other areas of the femur or tibia may also be amenable to this treatment approach. Images 12-13 are clinical photographs that illustrate several aspects of a Van Ness rotationplasty procedure. Patients who are very young or athletic may benefit greatly from this procedure from a functional standpoint and this procedure may also serve to minimize the number of future surgeries needed. Following tumor resection, vessels are repaired in an end-to-end fashion in most instances to optimize vessel patency. The distal portion of the leg is then rotated 180 and reattached to the thigh at the proximal edge of the resection. Other osteosynthesis variations are also possible.1, 26 The rotation allows the ankle to become a functional knee joint, so the length of the leg should be adjusted to match the contralateral knee. o It is best if before the decision to pursue a Van Ness rotationplasty procedure, patients and families either meet or review a videotape of a patient who has had the procedure. Resection of pulmonary nodules: Metastatic lung nodules can be cured by complete surgical resection, most often by wedge resection. Lobar resection or pneumonectomy may occasionally be required for clear margins. This procedure should be performed at the time of the primary tumor resection. Although bilateral nodules can be resected via a median sternotomy, surgical exposure is superior with a lateral thoracotomy. Therefore, bilateral thoracotomies are recommended for bilateral disease (each side separated by a few weeks). For an osteosarcoma that recurs as one or more lung lesions only more than 1 year after the patient is off therapy, surgical resection alone can be curative, as the likelihood of metastases to other sites is low. Chemotherapy is warranted if recurrence occurs earlier, as the risk of other micrometastatic disease is high.
o

Follow-up
Inpatient care

Further cycles of chemotherapy: These generally require inpatient admission for administration and monitoring. Active drugs include methotrexate, cisplatin, doxorubicin, and ifosfamide. Patients treated with high-dose alkylating agents are at higher risk for myelodysplasia and leukemia. Therefore, a CBC count should be performed periodically. Fever and neutropenia: Admission is required for intravenous (IV) antibiotics and monitoring. Local control: Admission is required perioperatively for local control (surgical resection, amputation), usually around week 10 of therapy. Resection of metastatic disease (eg, lung nodules) is also performed at this time. Other: Patients may require admission for a multitude of other medical problems during their chemotherapy treatment phase, including, but not limited to, varicella infection (for IV acyclovir and monitoring), mucositis (for narcotics), dehydration, meningitis, constipation, fungal pneumonia, and cystitis.

Outpatient care

CBC count: Perform a CBC measurement twice each week for patients on granulocyte colony-stimulating factor (G-CSF), so that G-CSF can be discontinued when the absolute neutrophil count has reached a predetermined level (usually 1000 or 5000/L). Blood chemistries: It is important to monitor the blood chemistries and liver function test results for patients on parenteral nutrition or who have a history of toxicity (especially if nephrotoxic or hepatotoxic antibiotics or other drugs are continued). Monitoring for recurrence: Patients should continue to have blood work and radiographic scans on an outpatient basis, with the frequency decreasing over time. Generally, these visits occur every 3 months for the first year; every 6 months for the second and, perhaps, third year; and yearly thereafter. Long-term follow-up: When patients have been without therapy for 5 or more years, they are considered long-term survivors. These individuals should be seen annually in a late-effects clinic and monitored with appropriate studies depending on their therapy and side effects. Visits may include hormonal, psychosocial, cardiology, and neurologic evaluations.

COMPLICATIONS
Section 8 of 12 Authors and Editors Introduction Indications Relevant Anatomy Contraindications Workup Treatment Complications Outcome and Prognosis Future and Controversies Multimedia References

Hearing loss is an adverse effect of cisplatin. Fever and neutropenia may occur, and if they do, patient admission is required for IV antibiotics and monitoring. Patients may require admission for a multitude of other medical problems during their chemotherapy treatment phase, including, but not limited to, varicella infection (for IV acyclovir and monitoring), mucositis (for narcotics), dehydration, meningitis, constipation, fungal pneumonia, and cystitis.

OUTCOME AND PROGNOSIS

Section 9 of 12 Authors and Editors Introduction Indications Relevant Anatomy Contraindications Workup Treatment Complications

Outcome and Prognosis Future and Controversies Multimedia References

The present understanding of outcome and prognosis for osteosarcoma is driven by certain serum markers, clinical staging, and histologic response to chemotherapeutic agents. The overall 5-year survival rate for patients diagnosed between 1974 and 1994 was 63% (59% for males, 70% for females). Patients with an elevated ALP at diagnosis are more likely to have pulmonary metastases. In patients without metastases, those with an elevated LDH are less likely to do well than are those with a normal LDH. See Staging for a discussion of prognosis as it relates to clinical staging. In a retrospective study by Kim et al, the records of 331 patients with stage II osteosarcoma who had underwent surgery and chemotherapy were reviewed.25 The authors found that the initial tumor size appears to be associated with histologic response and is an important prognostic factor in osteosarcoma. Other studies have shown that patients in whom a good histopathologic response to neoadjuvant chemotherapy has been achieved (>95% tumor cell kill or necrosis) have a better prognosis than those whose tumors do not respond as favorably.

FUTURE AND CONTROVERSIES

Section 10 of 12 Authors and Editors Introduction Indications Relevant Anatomy Contraindications Workup Treatment Complications Outcome and Prognosis Future and Controversies Multimedia

References

The genetic roots of cancer are irrefutable, and gene-focused basic science research holds tremendous promise for risk stratification as well as effective and innovative treatments. Multidrug-resistant varieties of osteosarcoma are a case in point. These cell lines have been shown to be genetically encoded with a certain membrane-bound glycoprotein that helps render these cancer cells "immune" to many chemotherapeutic agents. Early identification of such patients (perhaps at the time of the initial biopsy) would allow for a tailored approach to neoadjuvant chemotherapy. Metastatic or locally recurrent osteosarcoma presents an especially tough treatment challenge that remains incompletely answered. Patients in such cases find themselves in a particularly poor survival bracket. Future efforts need to be aimed at improving chemotherapeutic and surgical treatments that can be offered to these patients. One potential example of this is the bone-seeking radioisotope samarium (153-samarium ethylene diamine tetramethylene phosphonate), which has the potential to selectively deliver high doses of radiation to osteosarcoma cells. The safety and efficacy of this agent are being studied in patients with metastatic and locally recurrent osteosarcoma.

MULTIMEDIA
Section 11 of 12 Authors and Editors Introduction Indications Relevant Anatomy Contraindications Workup Treatment Complications Outcome and Prognosis Future and Controversies Multimedia References

Media file 1: Chest radiograph of patient with osteosarcoma who died from pulmonary metastatic disease. Note the presence of a pneumothorax as well as radiodense (boneforming) metastatic lesions. View Full Size Image

Media type: X-RAY Media file 2: Clinical appearance of a teenager who presented with osteosarcoma of the proximal humerus (same patient in Images 2-6). Note the impressive swelling throughout the deltoid region, as well as the disuse atrophy of the pectoral musculature.

View Full Size Image

Media type: Photo Media file 3: Radiographic appearance (plain radiograph) of a proximal humeral osteosarcoma (same patient in Images 2-6). Note the radiodense matrix of the intramedullary portion of the lesion, as well as the soft-tissue extension and aggressive periosteal reaction. View Full Size Image

Media type: X-RAY Media file 4: Intense radionuclide uptake of the proximal humerus is noted on a bone scan (same patient in Images 2-6). View Full Size Image

Media type: Nuclear Image Media file 5: A comparison bone scan of the involved shoulder (right image) with the uninvolved shoulder (left image) (same patient in Images 2-6). View Full Size Image

Media type: Nuclear Image

Media file 6: Magnetic resonance image appearance (T1-weighted image) of osteosarcoma of the proximal humerus (same patient in Images 2-6). Note the dramatic tumor extension into the adjacent soft-tissue regions. View Full Size Image

Media type: MRI Media file 7: Core needle biopsy instruments commonly used for bony specimens. Craig needle set. View Full Size Image

Media type: Photo Media file 8: Close-up view of Craig needle biopsy instruments. Cutting cannula with T-handle attached (top) and sheath through which the cutting cannula passes (bottom). View Full Size Image

Media type: Photo Media file 9: Resected specimen of a proximal tibia osteosarcoma. The primary lesion was such that the knee joint was resected with the primary lesion. Note that the previous longitudinal biopsy tract was completely excised with the specimen. View Full Size Image

Media type: Photo Media file 10: Intraoperative consultation with the pathologist, in which the surgeon and pathologist view the microscopic appearance of the biopsy specimen.

View Full Size Image

Media type: Photo Media file 11: Intraoperative consultation with the pathologist. A frozen section of the biopsy specimen is being performed. View Full Size Image

Media type: Photo Media file 12: Intraoperative photograph of a Van Ness rotationplasty procedure. Osteosynthesis of the tibia to the residual femur is being performed. Courtesy of Alvin H. Crawford MD, FACS. View Full Size Image

Media type: Photo Media file 13: Clinical photograph taken at the conclusion of a Van Ness rotationplasty procedure (same patient as in Image 12). Note that the new "knee" of the operative side (left side) is purposely reconstructed distal to the normal right knee. This is in anticipation of the future growth potential of the unoperated limb. Courtesy of Alvin H. Crawford MD, FACS. View Full Size Image

Media type: Photo

REFERENCES
Section 12 of 12 Authors and Editors Introduction Indications Relevant Anatomy Contraindications Workup Treatment Complications Outcome and Prognosis Future and Controversies Multimedia References

1. Marulanda GA, Henderson ER, Johnson DA, Letson GD, Cheong D. Orthopedic surgery options for the treatment of primary osteosarcoma. Cancer Control. Jan 2008;15(1):13-20. [Medline]. [Full Text]. 2. Vander Griend RA. Osteosarcoma and its variants. Orthop Clin North Am. Jul 1996;27(3):575-81. [Medline]. 3. Peltier LF. Tumors of bone and soft tissues. Orthopedics: A History and Iconography. San Francisco, Calif: Norman Publishing; 1993:264-91. 4. Rutkow IM. The nineteenth century. Surgery: An Illustrated History. St Louis, Mo: Mosby-Year Book; 1993:321-504. 5. Mallon WJ. The registry of bone sarcoma. Ernest Amory Codman: The End Result of a Life in Medicine. Philadelphia, Pa: WB Saunders Co; 2000:107-21. 6. Campanacci M. Preface. Bone and Soft Tissue Tumors: Clinical Features, Imaging, Pathology and Treatment. 2nd ed. New York, NY: Springer-Verlag; 1999. 7. Link MP, Goorin AM, Miser AW, et al. The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity. N Engl J Med. Jun 19 1986;314(25):1600-6. [Medline]. 8. Jaffe N. Historical perspective of the treatment of osteosarcoma: an interview with Dr Norman Jaffe. Interview by Margaret Pearson. J Pediatr Oncol Nurs. Apr 1998;15(2):90-4. [Medline]. 9. Rosen G, Murphy ML, Huvos AG, Gutierrez M, Marcove RC. Chemotherapy, en bloc resection, and prosthetic bone replacement in the treatment of osteogenic sarcoma. Cancer. Jan 1976;37(1):1-11. [Medline]. 10. Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res. Nov-Dec 1980;153:10620. [Medline]. 11. Enneking WF, Spanier SS, Goodman MA. Current concepts review. The surgical staging of musculoskeletal sarcoma. J Bone Joint Surg Am. Sep 1980;62(6):102730. [Medline]. [Full Text]. 12. Weis LD. Common malignant bone tumors: osteosarcoma. In: Simon MA, Springfield D, eds. Surgery for Bone and Soft-Tissue Tumors. Philadelphia, Pa: Lippincott-Raven; 1998:265-74. 13. Link MP, Eilber F. Osteosarcoma. In: Pizzo PA, Poplack DG, eds. Principles and Practice of Pediatric Oncology. 3rd ed. Philadelphia, Pa: LippincottRaven; 1997:889-920. 14. Arceci RJ, Weinstein HJ. Neoplasia. In: Avery GB, Fletcher MA, MacDonald MG, eds. Neonatology: Pathophysiology and Management of the Newborn. 4th ed. Philadelphia, Pa: JB Lippincott; 1994:1211-28. 15. Ries LAG, Smith MA, Gurney JG, et al. Cancer incidence and survival among

children and adolescents: United States SEER program 1975-1995. Bethesda, Md: National Cancer Institute; 1999. NIH Pub No 994649. Available at http://seer.cancer.gov/publications/childhood/. Accessed March 21, 2008. 16. Clark JC, Dass CR, Choong PF. A review of clinical and molecular prognostic factors in osteosarcoma. J Cancer Res Clin Oncol. Mar 2008;134(3):28197. [Medline]. 17. Pochanugool L, Subhadharaphandou T, Dhanachai M, et al. Prognostic factors among 130 patients with osteosarcoma. Clin Orthop Relat Res. Dec 1997;345:20614. [Medline]. 18. Tsuchiya H, Tomita K. Prognosis of osteosarcoma treated by limb-salvage surgery: the ten-year intergroup study in Japan. Jpn J Clin Oncol. Oct 1992;22(5):34753. [Medline]. 19. Taylor WF, Ivins JC, Unni KK, et al. Prognostic variables in osteosarcoma: a multiinstitutional study. J Natl Cancer Inst. Jan 4 1989;81(1):21-30. [Medline]. 20. Hudson M, Jaffe MR, Jaffe N, et al. Pediatric osteosarcoma: therapeutic strategies, results, and prognostic factors derived from a 10-year experience. J Clin Oncol. Dec 1990;8(12):1988-97. [Medline]. 21. Meyer WH, Schell MJ, Kumar AP, et al. Thoracotomy for pulmonary metastatic osteosarcoma. An analysis of prognostic indicators of survival. Cancer. Jan 15 1987;59(2):374-9. [Medline]. 22. Mankin HJ, Lange TA, Spanier SS. The hazards of biopsy in patients with malignant primary bone and soft-tissue tumors. J Bone Joint Surg Am. Oct 1982;64(8):11217. [Medline]. [Full Text]. 23. Mankin HJ, Mankin CJ, Simon MA. The hazards of the biopsy, revisited. Members of the Musculoskeletal Tumor Society. J Bone Joint Surg Am. May 1996;78(5):65663. [Medline]. 24. Craig FS. Vertebral-body biopsy. J Bone Joint Surg Am. Jan 1956;38-A(1):93102. [Medline]. [Full Text]. 25. Kim MS, Lee SY, Cho WH, et al. Initial tumor size predicts histologic response and survival in localized osteosarcoma patients. 1: J Surg Oncol. Feb 12 2008;97(5):456-61. [Medline]. 26. Winkelmann WW. Rotationplasty. Orthop Clin North Am. Jul 1996;27(3):50323. [Medline]. 27. Antunes M, Bernardo J, Salete M, et al. Excision of pulmonary metastases of osteogenic sarcoma of the limbs. Eur J Cardiothorac Surg. May 1999;15(5):5926. [Medline]. 28. Aparicio J, Segura A, Montalar J, et al. Long-term results after combined modality treatment for non-metastatic osteosarcoma. Med Oncol. Dec 1999;16(4):25560. [Medline]. 29. Bacci G, Briccoli A, Mercuri M, et al. Osteosarcoma of the extremities with synchronous lung metastases: long-term results in 44 patients treated with neoadjuvant chemotherapy. J Chemother. Feb 1998;10(1):69-76. [Medline]. 30. Bacci G, Ferrari S, Longhi A, et al. Pattern of relapse in patients with osteosarcoma of the extremities treated with neoadjuvant chemotherapy. Eur J Cancer. Jan 2001;37(1):32-8. [Medline]. 31. Boriani S, Biagini R, De Iure F, et al. En bloc resections of bone tumors of the thoracolumbar spine. A preliminary report on 29 patients. Spine. Aug 15 1996;21(16):1927-31. [Medline]. 32. Boriani S, Weinstein JN, Biagini R. Primary bone tumors of the spine. Terminology and surgical staging. Spine. May 1 1997;22(9):1036-44. [Medline]. 33. Davis AM, Devlin M, Griffin AM, Wunder JS, Bell RS. Functional outcome in amputation versus limb sparing of patients with lower extremity sarcoma: a matched case-control study. Arch Phys Med Rehabil. Jun 1999;80(6):615-8. [Medline]. 34. Delepine N, Delepine G, Cornille H, et al. Dose escalation with pharmacokinetics monitoring in methotrexate chemotherapy of osteosarcoma. Anticancer Res. MarApr 1995;15(2):489-94. [Medline]. 35. Eilber F, Giuliano A, Eckardt J, et al. Adjuvant chemotherapy for osteosarcoma: a randomized prospective trial. J Clin Oncol. Jan 1987;5(1):21-6. [Medline]. 36. Ferrari S, Bacci G, Picci P, et al. Long-term follow-up and post-relapse survival in patients with non-metastatic osteosarcoma of the extremity treated with neoadjuvant chemotherapy. Ann Oncol. Aug 1997;8(8):765-71. [Medline].

37. Gebhardt MC. What's new in musculoskeletal tumor surgery. J Bone Joint Surg Am. Apr 2001;83-A(4):629-34. [Medline]. [Full Text]. 38. Gherlinzoni F, Picci P, Bacci G, Campanacci D. Limb sparing versus amputation in osteosarcoma. Correlation between local control, surgical margins and tumor necrosis: Istituto Rizzoli experience. Ann Oncol. Apr 1992;3(suppl 2):S237. [Medline]. 39. Goorin A, Strother D, Poplack D, et al. Safety and efficacy of l-leucovorin rescue following high-dose methotrexate for osteosarcoma. Med Pediatr Oncol. Jun 1995;24(6):362-7. [Medline]. 40. Goorin AM, Shuster JJ, Baker A, et al. Changing pattern of pulmonary metastases with adjuvant chemotherapy in patients with osteosarcoma: results from the multiinstitutional osteosarcoma study. J Clin Oncol. Apr 1991;9(4):6005. [Medline]. 41. Gralla RJ, Osoba D, Kris MG, et al. Recommendations for the use of antiemetics: evidence-based, clinical practice guidelines. American Society of Clinical Oncology. J Clin Oncol. Sep 1999;17(9):2971-94. [Medline]. [Full Text]. 42. Hart RA, Boriani S, Biagini R, Currier B, Weinstein JN. A system for surgical staging and management of spine tumors. A clinical outcome study of giant cell tumors of the spine. Spine. Aug 1 1997;22(15):1773-82; discussion 1783. [Medline]. 43. Kelley SP, Ashford RU, Rao AS, Dickson RA. Primary bone tumours of the spine: a 42-year survey from the Leeds Regional Bone Tumour Registry. Eur Spine J. Mar 2007;16(3):405-9. [Medline]. [Full Text]. 44. Krailo M, Ertel I, Makley J, et al. A randomized study comparing high-dose methotrexate with moderate-dose methotrexate as components of adjuvant chemotherapy in childhood nonmetastatic osteosarcoma: a report from the Childrens Cancer Study Group. Med Pediatr Oncol. 1987;15(2):69-77. [Medline]. 45. Link MP, Goorin AM, Horowitz M, et al. Adjuvant chemotherapy of high-grade osteosarcoma of the extremity. Updated results of the Multi-Institutional Osteosarcoma Study. Clin Orthop Relat Res. Sep 1991;270:8-14. [Medline]. 46. Makley JT, Krailo M, Ertel IJ, et al. The relationship of various aspects of surgical management to outcome in childhood nonmetastatic osteosarcoma: a report from the Childrens Cancer Study Group. J Pediatr Surg. Feb 1988;23(2):146-51. [Medline]. 47. Morgan E, Baum E, Bleyer WA, et al. Treatment of patients with metastatic osteogenic sarcoma: a report from the Children's Cancer Study Group. Cancer Treat Rep. Apr 1984;68(4):661-4. [Medline]. 48. Pignatti G, Bacci G, Picci P, et al. Telangiectatic osteogenic sarcoma of the extremities. Results in 17 patients treated with neoadjuvant chemotherapy. Clin Orthop Relat Res. Sep 1991;270:99-106. [Medline]. 49. Provisor AJ, Ettinger LJ, Nachman JB, et al. Treatment of nonmetastatic osteosarcoma of the extremity with preoperative and postoperative chemotherapy: a report from the Children's Cancer Group. J Clin Oncol. Jan 1997;15(1):7684. [Medline]. 50. Simon MA. Biopsy of musculoskeletal tumors. J Bone Joint Surg Am. Oct 1982;64(8):1253-7. [Medline]. [Full Text]. 51. Simon MA, Biermann JS. Biopsy of bone and soft-tissue lesions. J Bone Joint Surg Am. Apr 1993;75(4):616-21. [Medline]. [Full Text]. 52. Skrzynski MC, Biermann JS, Montag A, Simon MA. Diagnostic accuracy and charge-savings of outpatient core needle biopsy compared with open biopsy of musculoskeletal tumors. J Bone Joint Surg Am. May 1996;78(5):644-9. [Medline]. 53. Weeden S, Grimer RJ, Cannon SR, Taminiau AH, Uscinska BM, and the European Osteosarcoma Intergroup. The effect of local recurrence on survival in resected osteosarcoma. Eur J Cancer. Jan 2001;37(1):39-46. [Medline]. 54. Winkler K, Beron G, Kotz R, et al. Neoadjuvant chemotherapy for osteogenic sarcoma: results of a Cooperative German/Austrian study. J Clin Oncol. Jun 1984;2(6):617-24. [Medline]. 55. Winkler K, Bieling P, Bielack S, et al. Local control and survival from the Cooperative Osteosarcoma Study Group studies of the German Society of Pediatric Oncology and the Vienna Bone Tumor Registry. Clin Orthop Relat Res. Sep 1991;270:79-86. [Medline]. 56. Withrow SJ, Powers BE, Straw RC, Wilkins RM. Comparative aspects of osteosarcoma. Dog versus man. Clin Orthop Relat Res. Sep 1991;270:159-

68. [Medline].

Osteosarcoma excerpt

Article Last Updated: Mar 28, 2008

Artikel ini berfokus pada high grade osteosarcoma intramedulla (juga disebut hanya sebagai osteosarcoma), termasuk bentuk klasik osteoblastik dan bentuk fibroblastik dan chondroblastic. Osteosarcoma adalah tulang ganas yang paling umum tumor.1, 2 Penyakit ini diperkirakan muncul dari primitif mesenchymal pembentuk tulang sel, dan ciri histologis adalah produksi osteoid ganas. Populasi sel lain juga dapat hadir, karena ini jenis sel juga dapat timbul dari sel-sel mesenchymal pluripotential, tetapi setiap daerah tulang ganas di lesi menetapkan diagnosis sebagai osteosarcoma. Andalan terapi adalah operasi pengangkatan lesi ganas. Paling sering, ekstremitas-sparing (ekstremitas-melestarikan) prosedur dapat digunakan untuk mengobati pasien dengan penyakit ini dan, dengan demikian, mempertahankan fungsi. Kemoterapi juga diperlukan untuk mengobati penyakit micrometastatic, yang hadir tetapi sering tidak terdeteksi pada kebanyakan pasien (sekitar 80%) pada saat diagnosis. Untuk sumber daya pendidikan pasien yang sangat baik, kunjungi Kanker dan Tumor eMedicine Pusat. Juga, melihat pendidikan pasien eMedicine Kanker artikel: Apa yang Harus Anda Ketahui dan Pengobatan Paru Memahami Kanker. Terkait eMedicine topik: Osteosarcoma, Varian Terkait Medscape topik: Resource Center Kanker: Terapi biologis Khusus Situs Onkologi Khusus Situs Orthopaedics CME / CMLE Highlights dari ASCP 2007 Pertemuan Tahunan Kemoterapi Ditambah muramyl tripeptide Meningkatkan Kelangsungan Hidup Osteosarcoma Ortopedi Bedah Pilihan untuk Pengobatan Osteosarcoma Primer Spectrum Levoleucovorin Disetujui oleh US FDA untuk Pengobatan Osteosarcoma Sejarah Prosedur Osteosarcoma adalah penyakit kuno yang masih tidak sepenuhnya dipahami. The "sarcoma" Istilah diperkenalkan oleh ahli bedah Inggris John Abernathy pada 1804 dan berasal dari akar Yunani yang berarti "bonggol berdaging." 3 Pada tahun 1805, ahli bedah Prancis, Alexis Boyer (ahli bedah pribadi kepada Napoleon) pertama kali menggunakan "osteosarcoma." Istilah 3, 4 Boyer menyadari bahwa osteosarkoma merupakan entitas yang berbeda dari lesi tulang lainnya, seperti osteochondromas (exostoses). Bukti pemikiran terorganisir lebih lanjut dan penyelidikan mengenai tujuan penyakit ini ditemukan oleh pertengahan 1800-an. Peltier mencatat bahwa pada tahun 1847, Baron Guillaume Dupuytren menunjukkan pengetahuan yang mendalam mengenai penampilan patologis kotor osteosarcoma ketika ia menulis following3: "Osteosarcoma, yang merupakan degenerasi kanker tulang sejati, memanifestasikan dirinya dalam bentuk massa putih atau kemerahan, lardaceous dan perusahaan pada tahap awal penyakit, tetapi presentasi di lain waktu, titik pelunakan, cerebriform materi,

extravasating darah, dan putih atau berwarna jerami cairan dari konsistensi kental dalam interior "3. Di bawah naungan American College of Surgeons, Ernest Amory Codman (bersama dengan James Ewing dan Joseph Bloodgood) menciptakan Registry Sarkoma Bone 1.921,5 Ini adalah langkah maju yang signifikan dalam mempelajari tumor langka dan menyenangkan, sebagai ahli bedah individu hanya terbatas pengalaman untuk membimbing mereka. Lain lembaga besar yang mulai terbentuk pada awal 1900-an adalah Institut Rizzoli di Bologna, Italia. Lembaga ini, yang akar tumor tulang yang dipelihara oleh Vittorio Putti (1880-1940), makmur di bawah bimbingan kemudian orang-orang seperti Scaglietti dan Campanacci.6 kontribusi Mayor dari lembaga ini telah termasuk perawatan inovatif untuk kista tulang unikameral (Scaglietti) dan intens studi displasia osteofibrous (Campanacci tumor). Pada pertengahan 1900-an, langkah besar sedang dibuat di Amerika Serikat di bidang patologi tulang oleh Henry L. Jaffe (1.896-1.979) dan rekannya Louis Lichtenstein (1.906-1.977). Masing-masing pria diterbitkan buku yang ditujukan untuk tulang patologi. Jaffe juga sering dikreditkan dengan membawa untuk kekacauan yang ortopedi patologi. Bersama-sama, Jaffe dan Lichtenstein didirikan hampir semua kriteria histologis kunci yang digunakan untuk mendiagnosis sebagian besar tumor tulang biasa ditemui. Dr A yang berbeda Jaffe (Norman Jaffe), bersama dengan peneliti lain, membantu memperluas penggunaan berbagai agen kemoterapi yang efektif di tahun 1970 dan awal 1980s.7 Tidak sedikit dari agen-agen yang adriamycin dan metotreksat. Obat-obat ini (dan lain-lain yang diikuti) secara dramatis meningkatkan perawatan pasien dengan osteosarcoma melalui kemampuan mereka untuk mengobati penyakit micrometastatic yang dianggap hadir di sekitar 80% dari patients.8 Obat ini ditemukan untuk menjadi berguna baik sebelum operasi dan pasca operasi di pasien dengan osteosarcoma, sebuah penemuan yang dilakukan di Sloan-Kettering Cancer Memorial Center agak kebetulan sementara custom-made prostheses sedang dibuat untuk pasien menunggu surgery.9 penggunaan preoperative seperti kemoterapi datang untuk disebut sebagai kemoterapi neoadjuvant. Seorang ahli bedah ortopedi dari Gainesville, Florida, William F. Enneking, MD, memperkenalkan sistem pementasan bedah untuk muskuloskeletal sarcomas.10, 11 Sistem pementasan membantu mengatur pendekatan bedah ortopedi untuk kedua biopsi dan reseksi tumor definitif untuk osteosarcoma, serta untuk lainnya muskuloskeletal sarkoma. Pengaruh Dr Enneking ini diperpanjang jauh melampaui sistem pementasan karena komitmen yang kuat untuk mendidik orang lain tentang tumor muskuloskeletal. Dia telah mendidik rekan-rekan onkologi ortopedi banyak, menerbitkan artikel berbagai penelitian, dan terus melakukan kursus pendidikan berkelanjutan tahunan medis berfokus pada tumor jinak dan ganas. Masalah Osteosarcoma adalah bentuk mematikan kanker muskuloskeletal yang paling sering menyebabkan pasien meninggal akibat metastasis, paru disease.3 6, 12, 13, 14 Gambar 1 menggambarkan rontgen dada seorang pasien yang meninggal akibat penyakit metastasis paru. Osteosarcomas Kebanyakan timbul sebagai lesi soliter dalam daerah yang paling cepat berkembang dari tulang panjang anak. 3 atas daerah yang terkena adalah femur distal, tibia proksimal, dan humerus proksimal, tapi hampir setiap tulang dapat terpengaruh. Gambar 2-6 menggambarkan temuan klinis dan radiologis pasien yang disajikan dengan osteosarcoma humerus proksimal. Tidak semua osteosarcomas muncul secara soliter, seperti beberapa situs dapat menjadi jelas dalam waktu sekitar 6 bulan (osteosarcoma sinkron), atau beberapa situs dapat dicatat selama lebih dari 6 bulan (osteosarcoma metachronous) .12 osteosarcoma multifokal tersebut adalah jelas jarang terjadi, tetapi ketika hal itu terjadi, itu cenderung pada pasien lebih muda dari 10 years.12 Frekuensi Di Amerika Serikat, kejadian osteosarcoma adalah 400 kasus per tahun (4,8 per juta penduduk <20 y) .15 5 tahun tingkat kelangsungan hidup secara keseluruhan untuk pasien yang didiagnosis antara tahun 1974 dan 1994 adalah 63% (59% untuk pria, 70% untuk perempuan).

Insiden ini sedikit lebih tinggi pada orang kulit hitam dibandingkan kulit putih. Data dari National Cancer Institute (NCI) Surveillance, Epidemiologi, dan Hasil Akhir (SIER) Monografi Pediatric 1975-1995 adalah sebagai follows15: Blacks - 5,2 kasus per juta per tahun (orang <20 y) Whites - 4,6 kasus per juta per tahun Insiden osteosarcoma sedikit lebih tinggi pada laki-laki daripada perempuan. Pada lakilaki, itu adalah 5,2 per juta per tahun. Pada perempuan, kejadian adalah 4,5 per juta per tahun. Osteosarcoma adalah sangat jarang pada anak-anak (0,5 kasus per juta per tahun pada anak-anak <5 y). Namun, kejadian tersebut terus meningkat dengan bertambahnya usia, meningkat lebih dramatis pada masa remaja, sesuai dengan pertumbuhan remaja. Usia 5-9 tahun - 2,6 (hitam) atau 2,1 (putih) kasus per juta per tahun Usia 10-14 tahun - 8,3 (hitam) atau 7 (putih) kasus per juta per tahun Usia 15-19 tahun - 8,9 (hitam) atau 8,2 (putih) kasus per juta per tahun Etiologi Penyebab pasti dari osteosarkoma tidak diketahui. Namun, sejumlah faktor risiko yang jelas, seperti follows3,, 6 12, 13, 14, 16, 17, 18, 19, 20, 21: pertumbuhan tulang cepat: pertumbuhan tulang cepat muncul untuk mempengaruhi orang untuk osteosarcoma, seperti yang disarankan oleh peningkatan insiden selama percepatan pertumbuhan remaja, kejadian tinggi di antara besar-breed anjing (misalnya, Great Dane, St Bernard, German shepherd), dan osteosarcoma yang khas lokasi di daerah metafisis berdekatan dengan lempeng pertumbuhan (fisis) dari tulang panjang. Faktor lingkungan: Faktor risiko hanya dikenal lingkungan adalah paparan radiasi. Radiasi osteosarcoma adalah bentuk osteosarcoma sekunder dan tidak dibahas lebih lanjut dalam artikel ini. Predisposisi genetik: Tulang displasia, termasuk penyakit Paget, displasia fibrosa, enchondromatosis, dan exostoses beberapa keturunan dan retinoblastoma (germ-line bentuk) merupakan faktor risiko. Kombinasi mutasi gen konstitusional RB (germline retinoblastoma) dan terapi radiasi dikaitkan dengan risiko tinggi berkembang osteosarcoma, Li-Fraumeni sindrom (mutasi germline p53), dan Rothmund-Thomson syndrome (asosiasi resesif autosomal cacat tulang bawaan , rambut dan kulit dysplasias, hipogonadisme, dan katarak). Terkait eMedicine topik: Enchondroma dan Enchondromatosis Berserat Displasia Li-Fraumeni Syndrome Paget Penyakit Retinoblastoma Rothmund-Thomson Sindrom Patofisiologi Osteosarcoma adalah tumor tulang dan dapat terjadi pada setiap tulang, biasanya di tulang panjang ekstremitas dekat piring pertumbuhan metafisis. Situs yang paling umum adalah femur (42%, 75% di antaranya berada di femur distal), tibia (19%, 80% di antaranya berada di tibia proksimal), dan humerus (10%, 90% di antaranya berada di humerus proksimal). Lokasi penting lainnya adalah tengkorak dan rahang (8%) dan panggul (8%). Sejumlah varian osteosarcoma ada, termasuk jenis konvensional (osteoblastik, chondroblastic, dan fibroblastik), telangiectatic, multifocal, parosteal, dan periosteal. Artikel ini hanya membahas osteosarkoma konvensional. Klinis Gejala mungkin ada selama beberapa minggu atau bulan (terkadang lebih lama) sebelum pasien didiagnosis. Adalah gejala yang paling umum adalah rasa sakit osteosarcoma, terutama nyeri dengan aktivitas. Pasien mungkin khawatir bahwa anak mereka memiliki keseleo, arthritis, atau sakit tumbuh. Seringkali, ada riwayat trauma, tetapi peran yang tepat dari trauma dalam pengembangan osteosarkoma tidak jelas. Fraktur patologis tidak sangat umum. Pengecualian adalah jenis telangiectatic dari osteosarcoma, yang lebih sering dikaitkan dengan patah tulang patologis. Rasa sakit di ekstremitas dapat mengakibatkan pincang. Mungkin ada atau mungkin tidak menjadi sejarah pembengkakan, tergantung pada ukuran dan lokasi lesi. Gejala sistemik, seperti demam dan berkeringat di malam hari, jarang terjadi. Tumor menyebar ke paru-paru jarang menghasilkan gejala pernapasan dan biasanya menunjukkan keterlibatan paru yang

luas. Metastasis ke situs lain yang sangat langka, dan, karena itu, gejala lainnya adalah tidak biasa. Temuan pemeriksaan fisik biasanya terbatas pada lokasi tumor primer, sebagai berikut: Massa: Massa teraba mungkin atau mungkin tidak hadir. Massa mungkin lembut dan hangat, meskipun tanda-tanda yang bisa dibedakan dari osteomyelitis. Peningkatan kulit vaskularisasi atas massa mungkin dilihat. Pulsations atau bruit mungkin terdeteksi. Penurunan rentang gerak: Keterlibatan sendi harus jelas pada pemeriksaan fisik. Limfadenopati: Keterlibatan kelenjar getah bening lokal atau regional tidak biasa. Temuan Pernapasan: Auskultasi biasanya tidak informatif kecuali penyakit luas. Terkait eMedicine topik: Osteomyelitis, akut piogenik Osteomyelitis, kronis RELEVAN ANATOMI Bagian 4 dari 12 Penulis dan Editor Pendahuluan Indikasi Relevan Anatomi Kontraindikasi pemeriksaan Pengobatan Komplikasi Hasil dan Prognosis Masa Depan dan Kontroversi Multimedia Referensi Lihat terapi bedah. KONTRAINDIKASI Bagian 5 dari 12 Penulis dan Editor Pendahuluan Indikasi Relevan Anatomi Kontraindikasi pemeriksaan Pengobatan Komplikasi Hasil dan Prognosis Masa Depan dan Kontroversi Multimedia Referensi Karena osteosarcoma adalah bentuk mematikan kanker, tidak ada kontraindikasi absolut terhadap pengobatan ada. Kontraindikasi relatif akan mencakup situasi di mana pasien sangat lemah bahwa risiko anestesi umum lebih besar daripada potensi manfaat dari operasi. Lain kontraindikasi relatif akan menjadi situasi di mana pasien memiliki luas, penyakit metastatik yang luar biasa, dan manfaat perawatan kenyamanan dan / atau rumah sakit lebih besar daripada manfaat potensial dari intervensi bedah. Pemeriksaan Bagian 6 dari 12 Penulis dan Editor Pendahuluan Indikasi Relevan Anatomi Kontraindikasi

 pemeriksaan Pengobatan Komplikasi Hasil dan Prognosis Masa Depan dan Kontroversi Multimedia Referensi Lab Studi Sebagian besar penelitian laboratorium yang diperoleh berhubungan dengan penggunaan kemoterapi. Hal ini penting untuk menilai fungsi organ sebelum pemberian kemoterapi dan untuk memonitor fungsi setelah kemoterapi. Tes darah hanya dengan makna prognostik yang dehidrogenase laktat (LDH) dan alkaline phosphatase (ALP). Pasien dengan ALP ketinggian di diagnosis lebih mungkin memiliki metastasis paru. Pada pasien tanpa metastasis, mereka yang memiliki LDH tinggi cenderung untuk melakukannya dengan baik daripada mereka dengan LDH normal. penelitian laboratorium penting meliputi: o LDH o ALP (signifikansi prognostik) o sel darah lengkap (CBC) count, termasuk diferensial o trombosit count o Tes fungsi hati: aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, dan albumin o Elektrolit tingkat: Natrium, kalium, klorida, bikarbonat, kalsium, magnesium, fosfor o Tes fungsi ginjal: blood urea nitrogen (BUN), kreatinin o Urinalisis Studi pencitraan Plain film - Primer, posteroanterior (PA), dan pandangan dada bagian samping o Mendapatkan film polos dari lesi yang dicurigai dalam 2 views. Tidak ada fitur tunggal pada radiograf adalah diagnostik. lesi Osteosarcoma o dapat murni osteolitik (sekitar 30% dari kasus), murni osteoblastik (sekitar 45% dari kasus), atau campuran keduanya. Elevation o periosteum mungkin muncul sebagai segitiga Codman karakteristik. Codman menggambarkan entitas ini pada tahun 1909, yang menyatakan, "Dalam banyak kasus di dekat persimpangan tulang sehat dengan tumor, ada pembentukan tulang reaktif baru di bawah periosteum. Pada tepi tumor, ini lapisan tulang baru berakhir tiba-tiba dan memberikan penampilan karakteristik di skiagraph [radiograf] "3. Perpanjangan o dari tumor melalui periosteum dapat mengakibatkan penampilan sunburst disebut (sekitar 60% dari kasus). Mendapatkan gambar dari tulang dan sendi yang berdekatan seluruh untuk menilai lesi loncat atau keterlibatan sendi. Osteosarcomas Telangiectatic seringkali sangat kistik dan bisa salah untuk sebuah kista tulang aneurismal. CT scan o Mendapatkan CT scan dari lesi primer dan CT scan dada (resolusi tinggi). o CT scan dari lesi primer membantu menggambarkan lokasi dan luasnya tumor dan sangat penting untuk perencanaan bedah. o CT scan dada lebih sensitif daripada film radiografi polos untuk menilai metastasis paru. Idealnya, mendapatkan CT scan dada sebelum melakukan biopsi untuk menghindari ambiguitas yang dapat muncul dari atelektasis postanesthesia. MRI o MRI dari lesi primer adalah metode terbaik untuk menilai sejauh mana penyakit intramedulla serta terkait jaringan lunak massa dan melewatkan lesi. o Ini modalitas pencitraan mungkin merupakan studi yang paling penting untuk pementasan bedah akurat dari lesi dengan penggunaan sistem pementasan Enneking. tulang pemindaian radionuklida dengan technetium-99 (99mTc)-metilen diphosphonate (MDP / MDI)

 o Hal ini penting untuk mengevaluasi adanya penyakit metastasis atau multifokal dengan scan tulang. o Selanjutnya, mendapatkan gambar dari daerah abnormal dengan CT scan atau MRI. Ekokardiografi atau pemindaian akuisisi beberapa gated: Menilai fungsi jantung sebelumnya, dan pada berbagai interval mengikuti, pengobatan dengan adriamycin. Terkait eMedicine topik: Aneurismal Tulang Kista Terkait Medscape topik: Sumber Events Center efek samping obat Pelaporan Resource Center Kanker: Terapi biologis Tes lainnya Audiography: Gangguan pendengaran merupakan efek samping dari cisplatin. Gangguan pendengaran biasanya terjadi selama pengobatan. Setelah pengobatan selesai, mendapatkan audiogram tidak biasanya bagian jangka panjang tindak lanjut perawatan. Terkait Medscape topik: Sumber Events Center efek samping obat Pelaporan Resource Center Kanker: Terapi biologis Diagnostik Prosedur Biopsi harus dilakukan oleh seorang ahli bedah ortopedi (lihat Terapi bedah). Definitif reseksi reseksi o dari lesi primer dan dari setiap metastasis paru sangat penting untuk penyembuhan. o ini reseksi harus dilakukan oleh ortopedi (lesi primer) dan ahli bedah toraks (metastasis paru) (lihat Terapi bedah). o presurgical (neoadjuvant) kemoterapi sering membantu ahli bedah dalam melakukan reseksi dengan menyusutnya tumor serta memungkinkan penilaian respon tumor histopatologi, prediktor utama dari hasil. Temuan histologis Dua elemen penting untuk pemeriksaan histologis tumor. Yang pertama dapat dinilai pada biopsi, jenis tumor. Yang kedua dapat dinilai pada reseksi definitif setelah kemoterapi, respon terhadap pengobatan. Secara umum, fitur karakteristik osteosarcoma adalah adanya osteoid di lesi, bahkan di tempat yang jauh dari tulang (misalnya, paru-paru). Meskipun formasi osteoid biasanya jelas, mikroskop elektron sesekali mungkin diperlukan untuk mengungkapkan proses ini. Sel stroma mungkin berbentuk gelendong dan atipikal, dengan inti berbentuk tidak teratur. Sejumlah jenis histologis yang berbeda osteosarcoma ada. Jenis konvensional adalah yang paling umum pada anak-anak dan remaja dan telah dibagi berdasarkan fitur-fitur utama dari sel-sel (osteoblastik, chondroblastic, fibroblastik), meskipun subtipe secara klinis tidak dapat dibedakan. Jenis telangiectatic mengandung besar, darah penuh ruang dan terlihat umumnya pada masa remaja dan dewasa awal. Jenis parosteal biasanya timbul dari korteks tulang, memiliki prognosis menengah, dan dapat dilihat pada masa kanak-kanak atau dewasa. Ini paling sering muncul pada aspek posterior distal femur. Osteosarcoma periosteal adalah rendah ke menengah-grade tumor yang biasanya muncul langsung di bawah periosteum pada anak-anak. Ini paling sering melibatkan tibia. Pementasan Tujuan dari pementasan tumor adalah untuk stratifikasi kelompok risiko. Pementasan konvensional yang digunakan untuk tumor padat lainnya tidak sesuai untuk tumor tulang karena tumor jarang melibatkan kelenjar getah bening atau penyebaran regional. Sebaliknya, pementasan dirancang dan diperkenalkan oleh Enneking tahun 1980 didasarkan pada kelas, penyebaran extracompartmental, dan apakah atau tidak metastasis yang hadir. Sistem ini berlaku untuk semua tumor muskuloskeletal (tulang dan jaringan lunak). Sistem pementasan Enneking (juga disebut sebagai sistem pementasan Society Tumor otot) telah dikreditkan dengan membawa untuk pengobatan bedah sekelompok tumor yang pengobatan sebelumnya didekati agak sembarangan.

Komponen kunci untuk sistem pementasan adalah kelas histologis tumor (kelas kelas vs rendah tinggi), lokasi anatomi tumor (intracompartmental vs extracompartmental), dan tidak adanya atau kehadiran penyakit metastasis. Sistem pementasan biasanya digambarkan sebagai berikut: Low-grade tumor, intracompartmental - I-A Low-grade tumor, extracompartmental - I-B High-grade tumor, intracompartmental - II-A High-grade tumor, extracompartmental - II-B Setiap tumor dengan bukti metastasis - III Definisi "kompartemen" adalah sebuah konsep sentral dan penting yang berkaitan dengan sistem pementasan Enneking. Secara umum, kompartemen dapat didefinisikan sebagai setiap tulang individu (misalnya, tulang setiap kompartemen tersendiri), intra-artikular ruang (yaitu, murni intra-artikular lesi yang intracompartmental), dan jelas mengidentifikasi ruang fascially tertutup (misalnya, kompartemen anterior dari kaki bagian bawah). Banyak dari kompartemen adalah orang-orang yang sama yang ahli bedah akan merilis dalam pengaturan sindrom kompartemen, ini berhubungan lebih banyak untuk jaringan lunak tumor daripada tumor tulang seperti osteosarkoma suatu. Beberapa area tubuh dianggap extracompartmental menurut definisi sesuai skema pementasan Enneking. Daerah ini termasuk fossa antecubital, daerah inguinal, ruang poplitea, dan lesi intrapelvic dan paraspinal. Karena tantangan unik dari tumor tulang belakang, sistem pementasan yang sama sekali terpisah telah diajukan untuk daerahdaerah dengan Weinstein, Boriani, dan Biagin. Hal ini disebut sebagai sistem pementasan WBB dan diperkenalkan pada tahun 1996. Sistem ini berfokus pada lokasi anatomi umum tentang tulang belakang (konseptualisasi segmen tulang belakang seolah-olah wajah jam), serta lokasi anatomi spesifik tentang tulang belakang (misalnya, extraosseous jaringan lunak ekstensi ke daerah otot vs intradural extraosseous ekstensi). Sama seperti anatomi tulang belakang adalah kompleks, sistem pementasan WBB adalah kompleks, namun penggunaannya secara perlahan meningkat. Untuk osteosarcoma, pertanyaan awal tentang pementasan utama adalah apakah tumor telah menyebar. Fitur lain dari tumor, meskipun tidak secara teknis digunakan dalam pementasan, dapat mempengaruhi prognosis. Ini termasuk pengukuran dan LDH ALP (lihat studi Lab), lokasi tumor primer (sebagian besar terkait dengan kemudahan reseksi lengkap), respon histologis terhadap kemoterapi, dan penyebab penyakit (pasien dengan osteosarcomas timbul dari penyakit Paget memiliki prognosis yang sangat buruk ). Pasien dengan lesi rahang terisolasi cenderung untuk berbuat lebih baik dan memiliki insiden lebih rendah dari metastasis. Tahap I - Low-grade lesi Tahap II - High-grade lesi Tahap III - Metastasis o A Sub - lesi Intracompartmental (lesi intramedulla untuk tumor tulang) o Sub-B - lesi Extracompartmental (extramedullary spread untuk tumor tulang) Situs dari tumor primer o ekstremitas distal - Terbaik o Distal femur - Menengah o Axial skeleton - Terburuk Ukuran dari tumor awal: Dalam sebuah penelitian retrospektif oleh Kim et al, catatan dari 331 pasien dengan osteosarcoma II tahap yang menjalani operasi dan kemoterapi adalah reviewed.26 Para penulis menemukan bahwa ukuran tumor awal muncul terkait dengan respon histologis dan merupakan faktor prognostik penting dalam osteosarcoma. Respon histologis: Pasien dengan tumor yang memiliki respon histologis yang baik (definisi yang masih dalam perdebatan) terhadap kemoterapi sebelum operasi tampaknya memiliki prognosis yang lebih baik, meskipun hal ini masih sedang diselidiki. Terkait eMedicine topik: Kompartemen Syndrome, Ekstremitas Bawah Kompartemen Syndrome, Ekstremitas Atas PENGOBATAN Bagian 7 dari 12 Penulis dan Editor

 Pendahuluan Indikasi Relevan Anatomi Kontraindikasi pemeriksaan Pengobatan Komplikasi Hasil dan Prognosis Masa Depan dan Kontroversi Multimedia Referensi Terapi medis Sebelum penggunaan kemoterapi (yang dimulai pada 1970-an), osteosarcoma diperlakukan terutama dengan reseksi bedah (biasanya amputasi). Meskipun kontrol lokal seperti baik, lebih dari 80% dari pasien kemudian dikembangkan penyakit berulang yang biasanya disajikan sebagai metastasis paru. Tingkat kekambuhan tinggi menunjukkan bahwa sebagian besar pasien memiliki penyakit micrometastatic pada saat diagnosis. Oleh karena itu, penggunaan adjuvant (pasca operasi) kemoterapi sistemik sangat penting untuk pengobatan pasien dengan osteosarkoma. Jadi yang disebut neoadjuvant (pra operasi) kemoterapi telah ditemukan tidak hanya untuk memfasilitasi operasi pengangkatan berikutnya dengan menyebabkan penyusutan tumor tetapi juga untuk menyediakan ahli kanker dengan parameter risiko penting. Pasien yang telah terjadi respon histopatologi yang baik untuk neoadjuvant kemoterapi (> 95% sel tumor membunuh atau nekrosis) memiliki prognosis yang lebih baik daripada mereka yang tumornya tidak menanggapi dengan positif. Dengan demikian, uji coba kemoterapi masa depan akan menggabungkan sel tumor adjuvant membunuh untuk memberikan risiko-disesuaikan rejimen pengobatan. Pasien yang menerima metotreksat tidak boleh diberikan suplementasi folat atau Bactrim, baik yang mengganggu efek dari metotreksat. Jika tidak, makanan pasien tidak dibatasi. Konsultasi Seperti biasa untuk setiap anak dengan kanker, konsultasi harus dilakukan dengan seorang ahli onkologi, serta dengan penyedia dengan subspesialisasi terkait dengan keadaan klinis tertentu. Pelayanan sosial, psikologi, kedokteran gigi, dan spesialis anak hidup biasanya terlibat dengan pasien dan keluarga mereka selama kursus pengobatan mereka. Aktivitas Pembatasan aktivitas bervariasi dengan lokasi tumor dan jenis prosedur bedah yang diperlukan untuk pengobatan. Terkait Medscape topik: Sumber Events Center efek samping obat Pelaporan Resource Center Kanker: Terapi biologis Bedah Terapi Ahli bedah ortopedi adalah sangat penting dalam perawatan pasien dengan osteosarkoma. Seringkali, pasien dianggap memiliki osteosarcoma dirujuk ke ahli bedah ortopedi pertama untuk membuat diagnosis. Selain itu, karena osteosarcomas tidak terlalu responsif terhadap radioterapi, operasi adalah satu-satunya pilihan untuk menghilangkan tumor definitif (kontrol lokal). Selain itu, jenis oncologic rekonstruksi tulang total sendi protesa atau kompleks mungkin diperlukan setelah reseksi bedah. Oleh karena itu, keterlibatan erat ahli bedah ortopedi dengan onkologi medis pada saat diagnosis, serta selama dan setelah kemoterapi, sangat penting. Biopsi Prosedur Biopsi termasuk biopsi terbuka (lebih disukai untuk menghindari kesalahan sampling dan untuk menyediakan jaringan yang memadai untuk studi biologis), trephine biopsi atau inti biopsi jarum (lebih disukai untuk tubuh vertebral dan lesi panggul banyak), atau aspirasi jarum halus (tidak disarankan). Gambar 7-8 menggambarkan jarum Craig (core needle) biopsi ditetapkan. Hati-hati merencanakan sayatan untuk biopsi terbuka untuk menghindari kontaminasi tumor dari struktur neurovaskular dan untuk memfasilitasi penghapusan blok saluran biopsi en selama operasi definitif. Gambar 9 menggambarkan eksisi saluran biopsi selama reseksi tumor definitif.

Terlepas dari teknik, bagian beku harus diperiksa untuk memastikan bahwa tumor telah sampel secara akurat. Gambar 10-11 menggambarkan konsultasi intraoperatif dengan patologi untuk tujuan evaluasi dari spesimen beku-section. Jika memungkinkan, komponen extraosseous harus sampel daripada tulang untuk mengurangi risiko patah tulang. Seal lubang tulang dengan gelfoam atau bahan serupa untuk mengurangi risiko hematoma dan penyebaran tumor. Saluran air harus dari berbagai tertutup-hisap, dan mereka harus ditempatkan secara langsung sejalan dengan sayatan kulit (jarak jauh). Definitif reseksi Tujuan utama dari reseksi definitif kelangsungan hidup pasien. Dengan demikian, margin pada semua sisi tumor harus berisi jaringan normal (margin yang lebar). Ketebalan margin penting hanya untuk sumsum, di mana margin yang memadai dianggap 5-7 cm dari tepi kelainan digambarkan pada MRI atau bone scan. Margin radikal, didefinisikan sebagai penghapusan kompartemen yang terlibat seluruh (tulang, sendi ke sendi, otot, asal penyisipan), biasanya tidak diperlukan untuk menyembuhkan. Sebuah marjin yang kurang lebar (marjin marjinal atau intralesi) mungkin fungsional membantu sebagai terapi debulking, tapi secara intrinsik, itu tidak akan lokal kuratif. Amputasi mungkin pengobatan pilihan dalam beberapa keadaan. Jika mungkin, sejumlah pilihan yang ada untuk ekstremitas-penyelamatan rekonstruksi, yang harus dipilih berdasarkan pertimbangan individu, sebagai berikut: cangkok tulang autologous: Ini mungkin vascularized atau nonvascularized. Penolakan tidak terjadi dengan cangkokan, dan tingkat infeksi rendah. Piring pertumbuhan dari pasien yang skeletally dewasa dapat membatasi pilihan untuk fiksasi tulang yang stabil (osteosynthesis). allograft: penyembuhan graft dan infeksi dapat bermasalah, terutama selama kemoterapi. Penolakan imunologi juga dapat terjadi. Allograft-prostesis komposit juga pilihan. prosthesis: rekonstruksi bersama Protese bisa soliter atau diperluas, meskipun biasanya mahal. Umur panjang implan tersebut merupakan perhatian utama pada anak-anak. Rotationplasty: Teknik ini sangat cocok untuk pasien dengan femur distal dan proksimal tibia tumor, tumor sangat besar di mana amputasi tinggi adalah satu-satunya alternatif. Lesi terletak di daerah lain femur atau tibia juga mungkin dapat digunakan untuk pendekatan pengobatan. Gambar 12-13 adalah foto-foto klinis yang menggambarkan beberapa aspek dari prosedur Ness Van rotationplasty. Pasien yang sangat muda atau atletik dapat mengambil manfaat besar dari prosedur ini dari sudut pandang fungsional dan prosedur ini juga dapat berfungsi untuk meminimalkan jumlah operasi masa depan yang dibutuhkan. o tumor reseksi Setelah, kapal yang diperbaiki dengan cara end-to-end dalam kebanyakan kasus untuk mengoptimalkan patensi kapal. Bagian distal dari kaki kemudian diputar 180 dan disambungkan ke paha di tepi proksimal dari reseksi. Variasi osteosynthesis lain juga possible.1, 26 Rotasi memungkinkan kaki untuk menjadi sendi lutut fungsional, sehingga panjang dari kaki harus disesuaikan dengan lutut kontralateral. o Cara terbaik adalah jika sebelum keputusan untuk mengejar Van Ness prosedur rotationplasty, pasien dan keluarga baik memenuhi atau meninjau sebuah rekaman video dari seorang pasien yang telah memiliki prosedur. Reseksi nodul paru: nodul paru-paru metastatik dapat disembuhkan dengan reseksi bedah lengkap, paling sering oleh reseksi baji. Lobar reseksi atau pneumonectomy sesekali mungkin diperlukan untuk margin yang jelas. Prosedur ini harus dilakukan pada saat reseksi tumor primer. Meskipun nodul bilateral dapat resected melalui sternotomy median, paparan bedah lebih unggul dengan torakotomi lateral. Oleh karena itu, thoracotomies bilateral dianjurkan untuk penyakit bilateral (setiap sisi dipisahkan oleh beberapa minggu). Untuk osteosarcoma yang berulang sebagai satu atau lebih lesi paruparu hanya lebih dari 1 tahun setelah pasien dari terapi, reseksi bedah sendiri dapat bersifat kuratif, karena kemungkinan metastasis ke situs lain rendah. Kemoterapi dibenarkan jika terjadi kekambuhan sebelumnya, sebagai risiko penyakit micrometastatic lainnya tinggi. Follow-up Rawat inap siklus kemoterapi lebih lanjut: Ini umumnya memerlukan rawat inap untuk administrasi dan monitoring. Obat yang aktif termasuk methotrexate, cisplatin, doxorubicin, dan ifosfamid. Pasien yang diobati dengan dosis tinggi agen alkilasi berada pada risiko tinggi

untuk myelodysplasia dan leukemia. Oleh karena itu, jumlah CBC harus dilakukan secara berkala. Demam dan neutropenia: Pendaftaran diperlukan untuk intravena (IV) antibiotik dan pemantauan. Lokal kontrol: Penerimaan diperlukan perioperatif untuk kontrol lokal (reseksi bedah, amputasi), biasanya sekitar 10 minggu terapi. Reseksi penyakit metastatik (misalnya, nodul paru-paru) juga dilakukan pada saat ini. Lain-lain: Pasien mungkin memerlukan masuk untuk banyak masalah kesehatan lainnya selama fase pengobatan kemoterapi mereka, termasuk, namun tidak terbatas pada, infeksi varicella (untuk IV asiklovir dan pemantauan), mucositis (untuk narkotika), dehidrasi, meningitis, sembelit, jamur pneumonia, dan sistitis. Rawat jalan CBC menghitung: Lakukan pengukuran CBC dua kali seminggu masing-masing untuk pasien granulocyte colony-stimulating factor (G-CSF), sehingga G-CSF dapat dihentikan jika jumlah neutrofil absolut telah mencapai tingkat yang telah ditentukan (biasanya 1000 atau 5000/L ). kimia darah: Penting untuk memantau kimia darah dan hasil tes fungsi hati untuk pasien pada nutrisi parenteral atau yang memiliki riwayat toksisitas (terutama jika antibiotik nefrotoksik atau hepatotoksik atau obat lain yang lanjutan). Pemantauan untuk kambuh: Pasien harus terus memiliki pekerjaan darah dan scan radiografi secara rawat jalan, dengan frekuensi menurun dari waktu ke waktu. Umumnya, kunjungan ini terjadi setiap 3 bulan untuk tahun pertama, setiap 6 bulan untuk tahun kedua dan ketiga, mungkin,, dan tahunan sesudahnya. Jangka panjang tindak lanjut: Bila pasien telah tanpa terapi selama 5 tahun atau lebih, mereka dianggap selamat jangka panjang. Orang-orang ini harus dilihat setiap tahun di sebuah klinik efek akhir-dan dipantau dengan studi yang tepat tergantung pada terapi dan efek samping. Kunjungan dapat mencakup hormonal, psikososial, kardiologi, dan evaluasi neurologis. KOMPLIKASI Bagian 8 dari 12 Penulis dan Editor Pendahuluan Indikasi Relevan Anatomi Kontraindikasi pemeriksaan Pengobatan Komplikasi Hasil dan Prognosis Masa Depan dan Kontroversi Multimedia Referensi Gangguan pendengaran merupakan efek samping dari cisplatin. Demam dan neutropenia dapat terjadi, dan jika mereka melakukannya, masuk pasien diperlukan untuk antibiotik IV dan pemantauan. Pasien mungkin memerlukan masuk untuk banyak masalah kesehatan lainnya selama fase pengobatan kemoterapi mereka, termasuk, namun tidak terbatas pada, infeksi varicella (untuk IV asiklovir dan pemantauan), mucositis (untuk narkotika), dehidrasi, meningitis, sembelit, pneumonia jamur, dan sistitis. HASIL DAN Prognosis Bagian 9 dari 12 Penulis dan Editor Pendahuluan Indikasi Relevan Anatomi Kontraindikasi pemeriksaan Pengobatan

 Komplikasi Hasil dan Prognosis Masa Depan dan Kontroversi Multimedia Referensi Pemahaman sekarang hasil dan prognosis untuk osteosarcoma didorong oleh penanda serum tertentu, stadium klinis, dan respon histologis terhadap agen kemoterapi. The 5-tahun tingkat kelangsungan hidup secara keseluruhan untuk pasien yang didiagnosis antara tahun 1974 dan 1994 adalah 63% (59% untuk pria, 70% untuk perempuan). Pasien dengan ALP ketinggian di diagnosis lebih mungkin memiliki metastasis paru. Pada pasien tanpa metastasis, mereka yang memiliki LDH tinggi cenderung untuk melakukannya dengan baik daripada mereka dengan LDH normal. Lihat Staging untuk diskusi prognosis yang berhubungan dengan stadium klinis. Dalam sebuah penelitian retrospektif oleh Kim et al, catatan dari 331 pasien dengan osteosarcoma tahap II yang telah menjalani operasi dan kemoterapi adalah reviewed.25 Para penulis menemukan bahwa ukuran tumor awal muncul terkait dengan respon histologis dan merupakan faktor prognostik yang penting dalam osteosarcoma. Penelitian lain telah menunjukkan bahwa pasien yang respon histopatologi yang baik untuk neoadjuvant kemoterapi telah tercapai (> 95% sel tumor membunuh atau nekrosis) memiliki prognosis yang lebih baik daripada mereka yang tumornya tidak menanggapi dengan positif.