Osteosarcoma – An Introduction

OsteosarcomaAlso called osteosarcoma, osteogenic sarcoma is one of the most common types of bone cancer in children and accounts for nearly 3% of all childhood cancers. About 400 children are diagnosed with osteosarcoma each year.

The disease usually occurs in the long bones, such as the arms (humerus), legs (femur/tibia) and pelvis. It rarely occurs in the jaw and fingers, but often occurs at the ends of these bones near growth plates. Osteosarcoma most often affects children between 10 and 25 years of age.

This cancer also is more prevalent in males than in females, possibly because of the rapid growth rate at this age. Prior to adolescence, the percentage of affected males and females is equal.

Osteogenic sarcoma cancer cells also can spread (metastasize) to other areas of the body. Most commonly, these cells spread to the lungs. However, bones, kidneys, the adrenal gland, the brain and the heart also can be sites of metastasis.

Most cancers in the bone have spread (metastasized) to the bone from another area in the body (the “primary” site, e.g., lung, breast, kidney) or are related to a cancerous tumor of blood cells (e.g, myeloma).  On rare occasion, however, a cancer can begin in the bone itself from cancerous cells that make bone tissue.  A malignant tumor that forms bone tissue from the cancerous cells is called an osteosarcoma.  Although cancers that begin in the bone (primary bone cancer) are much less common that those that metastasize to the bone, among the primary bone cancers, osteosarcoma is the most common type.

Epidemiology and anatomic site

Osteosarcoma is a rare tumor and only about 2000 new cases are diagnosed in the USA per year and this comprises < 1% of all new cancer cases in the USA annually.  The vast majority of these tumors develop in patients with bones that are growing rapidly, namely adolescents or young adults.  However, a smaller concentration of osteosarcomas also affects the elderly age group, in part due to another disease, Paget’s disease, that occurs in the elderly and may turn into an osteosarcoma.  The higher prevalence of osteosarcoma in the young age group is intuitive if one thinks of cancer as an error in cellular growth resulting in uncontrolled growth.  During the pubertal growth spurt, a higher number of bone cells are multiplying and it is more likely that an error in the cellular duplicating machinery might occur at that time.

Just as osteosarcomas tend to occur in the rapidly growing adolescent, the tumors tend to occur in those bony sites growing most rapidly, namely the distal femur (figure 1), proximal tibia, and proximal humerus.  Tumors may also start growing in the spinal column or the pelvis.  Obviously, depending upon the extent of the tumor, these anatomic sites are much more difficult to operate upon completely eradicate the mass.

The different types of osteosarcoma

There are many different types of osteosarcoma that are quite different in natural history and their potential for lethal growth (table 1).  By far the most common osteosarcoma is the so called classical or conventional high grade central type which accounts for 90% of all osteosarcomas.  The “grade” is a term used to indicate the level of aggressive growth and potential for metastasis, usually based upon the appearance of the tumor under microscopic analysis.  Several other unusual high grade types are the telangiectatic, small cell and secondary (associated with another pre-existing disease such as Paget’s disease or prior radiation exposure) type.  There are low grade types of osteosarcoma too.  They include the surface or juxtacortical low grade osteosarcoma (also known by the names parosteal or periosteal osteosarcoma), and low grade central osteosarcoma.  For the most part, a simplified way to view osteosarcoma for purposes of treatment and management is into 2 groups: high grade and low grade.  Most, but not all, tumors arising from the central or medullary portion of the bone are high grade while most, but not all, tumors arising from the surface of the bone are low grade.

 World Health Organization Classification of Osteosarcoma

A. Conventional central (medullary)
  1. Chondroblastic
  2. fibroblastic
  3. osteoblastic  
B. Telangiectatic
C. Small cell
D. Low grade central
E. Secondary
F. Surface
  1. Parosteal
  2. Periosteal
G. High grade surface

What causes osteogenic sarcoma?

Osteosarcoma in most instances is not due to any previous behavioral, dietary, environmental, or genetic factor.  It is a random event and there is no predisposing factor or decision that a patient, parent or other family member could have made that would have any bearing on developing the tumor.  No patient or parent should believe that they somehow contributed to one’s having the tumor.  In some very rare cases, there is a genetic link to the disease (see below).

Osteosarcoma imageIt has been suggested that repeated trauma to an area may be a risk factor for developing this type of cancer. It is uncertain whether trauma is a cause or effect of the disease. Cancer lesions in the bone can make that area of the bone weaker, thus, making injury more likely. However, repeated injuries to a certain area of the bone may lead to an increased production of osteoid tissue to repair the damaged area. The rapid production of osteoid tissue may lead to the malignancy. It is thought, most often, that injury simply brings the condition to attention and has no causal relationship.

Genetics may play an important role in developing osteosarcoma. Children and adults with other hereditary abnormalities, including exostoses (bony growths), retinoblastoma, Ollier’s disease, osteogenesis imperfecta, polyostotic fibrous dysplasia and Paget’s disease, have an increased risk for developing osteosarcoma.

This form of cancer also has been linked to exposure to ionizing irradiation associated with radiation therapy for other types of cancer (i.e., Hodgkin’s and non-Hodgkin’s disease).

What are the symptoms of osteogenic sarcoma?

The following are the most common symptoms of osteogenic sarcoma; however, each child may experience symptoms differently:

  • Pain (sharp or dull) at the site of the tumor.
  • Swelling and/or redness at the site of the tumor.
  • Increased pain with activity or lifting.
  • Limping.
  • Decreased movement of the affected limb.

The symptoms may have been present over a short period of time or may have been occurring for six months or more. Often, an injury brings a child into a medical facility, where an X-ray may indicate suspicious bone lesions.

The symptoms of osteogenic sarcoma may resemble other conditions or medical problems. Always consult your child’s physician for a diagnosis.

Signs or symptoms suggestive of the tumor and establishing the diagnosis

There are no particular signs or symptoms the herald the onset of this cancer.  Although patients usually will have pain and subsequent swelling of a body part, some patients do not have pain and only notice the swelling.  An injury may direct attention to a particular body part but usually the tumor precedes the injury.  If the tumor has eroded enough bone to reduce its structural integrity, a fracture may occur with only a slight amount of force applied to the bone.  A fracture greatly compromises treatment and therefore any patient experiencing pain with weight bearing (lower extremities) or lifting (upper extremities) should notify their physician immediately so that appropriate steps can be taken to minimize the risk for a fracture.  The tumor’s presence is seen on xrays most commonly and xrays are the best screening tool for this tumor.  Additional complementary information is gained from magnetic resonance imaging scansw which define the extent of the tumor and its relationship to surrounding anatomic structures much more clearly, a so called anatomic “map”.  Other tests that might be performed on newly diagnosed patients are bone scans, positron emission tomography (PET) scans, and various blood tests looking at how active the body is at making or remodeling bone tissue.

Once a tumor is suspected based upon imaging tests, a tissue sampling (biopsy) is necessary before embarking upon treatment plans.  The appearance of the tumor cells under the microscope is characteristic in most cases but other tests can help establish the diagnosis by ruling out other types of tumors.  Some of these other tumors’ microscopic appearance may resemble osteosarcoma so diagnosing this tumor is greatly facilitated by also viewing the imaging studies.  Having experts in the disciplines pathology, radiology and orthopaedic surgery working together as a team is the optimal means making accurate diagnoses.

In addition to a complete medical history and physical examination of your child, diagnostic procedures for osteogenic sarcoma may include the following methods of multiple imaging studies of the tumor and sites of possible metastasis, such as:

X-rays – a diagnostic test that uses invisible electromagnetic energy beams to produce images of internal tissues, bones and organs onto film. This test is used to measure and evaluate the curve.
Bone scans – a nuclear imaging method to evaluate any degenerative and/or arthritic changes in the joints; to detect bone diseases and tumors; to determine the cause of bone pain or inflammation. This test is to rule out any infection or fractures.
Magnetic resonance imaging – a diagnostic procedure that uses a combination of large magnets, radiofrequencies and a computer to produce detailed images of organs and structures within the body. This test is done to rule out any associated abnormalities of the spinal cord and nerves.
Computed tomography scan (also called a CT or CAT scan) – a diagnostic imaging procedure that uses a combination of X-rays and computer technology to produce cross-sectional images (often called slices), both horizontally and vertically, of the body. A CT scan shows detailed images of any part of the body, including the bones, muscles, fat and organs. CT scans are more detailed than general X-rays.

Other tests will include:

  • Complete blood count – a measurement of size, number and maturity of different blood cells in a specific volume of blood.
  • Blood tests – including blood chemistries.
  • Biopsy of the tumor.

Treatment for osteogenic sarcoma

Specific treatment for osteogenic sarcoma will be determined by your child’s physician based on:

  • Your child’s age, overall health and medical history.
  • Extent of the disease.
  • Your child’s tolerance for specific medications, procedures or therapies.
  • Expectations for the course of the disease.
  • Your opinion or preference.

Treatment may include, but is not limited to, one or more of the following methods:

  • Surgery – i.e., biopsy, resections, bone/skin grafts, limb-salvage procedures, reconstructions.
  • Amputation.
  • Chemotherapy.
  • Radiation therapy.
  • Resections of metastases – spreading of the tumor to other locations.
  • Rehabilitation including physical and occupational therapy and psychosocial adapting.
  • Prosthesis fitting and training.
  • Supportive care – for the side effects of treatment.
  • Antibiotics – to prevent and treat infections.
  • Continued follow-up care – to determine response to treatment, detect recurrent disease and manage the side effects of treatment.

In the USA, and also in many other developed countries, most patients are enrolled upon various clinical trials or protocols established by national experts in osteosarcoma.  Nearly all major cancer centers work together participating in cooperative groups which gather these experts together frequently to design modify and implement these protocols.  This improves the rate of and ability of gaining meaningful information about the chances for success or level of effectiveness of a treatment plan.

For classical, high grade, conventional osteosarcoma (and other high grade types), most major cancer centers will recommend treatment consisting of systemic multiagent chemotherapy initially for several months, followed by surgical excision with limb reconstruction or amputation, as appropriate.  Chemotherapy then resumes as soon as the surgical incision has healed sufficiently, usually around 2 weeks post-operatively, and usually continues for many more months.  The chemotherapy is given in cycles with various drugs during each cycle.  The blood cell counts drop due to the chemotherapy but recover to an adequate level in between each cycle.  The most commonly used drugs effective against osteosarcoma are adriamycin, ifosfamide, cis-platin, methotrexate, and vincristine, The response to the chemotherapy is closely observed using various tests and scans.  Frequently patients wonder why chemotherapy is given first before surgical removal of the tumor as one might think the tumor should be removed immediately.  However, giving chemotherapy prior to surgery theoretically stops the growth of microscopic deposits of tumor cells elsewhere in the body that are undetectable despite the most powerful scanners and if the chemotherapy shrinks the tumor, the surgery is greatly facilitated.  Clinical studies have not shown any drop in a treatment’s success when chemotherapy is given prior to tumor excision.

For surface osteosarcoma (and other low grade types), chemotherapy is generally not advisable and instead surgical excision is performed with reconstruction of the remaining extremity after bone or joint loss using various types of bone grafts, prosthetic implants, or a combination of the two.  In general, radiation is not considered an effective treatment against an osteosarcoma in the usual doses given to patients.

 Does removal of the tumor require an amputation?

Decades ago, amputations were much more commonly needed as a means of eradicating the main tumor.  Presently, however, most extremities are preserved after removing the tumor and reconstructing the remaining limb.  The tumor removal involves resecting the tumor with a layer of normal tissue surrounding it (wide local excision) so that the wound is not exposed or contaminated with tumor cells as it is gradually taken out.  To the extent possible, the nerve and major blood vessels will be preserved as long as it does not compromise an adequate tumor removal.  Reconstruction of the joint defect is done with specialized artificial joint prostheses (figure 3).  Bone is reconstructed with either a structural bone graft or a prosthetic implant.  Soft tissue and muscle function restoration, at times, requires tendon reattachment.   Major arteries can successfully be reconstructed using either autogenous vein grafts or a tube made of gortex® material.  The goal of limb salvage surgery and reconstruction is primarily complete removal of the tumor and secondarily reconstruction to achieve as normal function as possible (figure 4-5).

Some unusually challenging situations are patients with lower extremity tumors who have yet to go through their growth spurt.  In this situation, the growing limb can either be reconstructed with an expanding type of prosthesis, the opposite limb can be shortened slightly, or an unusual surgery removing the tumor and knee but using the healthy lower ankle to function as a knee by rotating the remaining limb 180 degrees and transporting the ankle to the knee level (Van Ness rotationplasty) can be performed.

 How effective are the treatments for osteosarcoma and what is the prognosis?

The likelihood of being alive and completely free of all osteosarcoma cancer cells 5 years after diagnosis of an osteosarcoma that hasn’t metastasized is in the range of 65-75% for nearly all major cancer centers.  The response to the chemotherapy is one of the most important predictive factors of outcome.  This response can be assessed by using xrays and scans but the more important analysis is the percentage of tumor cells killed by the chemotherapy as judged by the appearance microscopically.

The functional outcome of treatment depends heavily upon where within the bone the tumor began and what structures must be sacrificed in order to completely remove the tumor.  Most types of reconstructions with limb salvage procedures will allow a gait independent of any aids but strenuous athletic activity is discouraged.  Any type of reconstruction will have a limited durability and lifespan.  Device failure through loosening, breakage, infection or fracture of the bone around the implant may result in a series of operations being done during the course of a patient’s lifetime.

Long-term outlook for a child with osteogenic sarcoma

Prognosis for osteogenic sarcoma greatly depends on:

  • Extent of the disease.
  • Size and location of the tumor.
  • Presence or absence of metastasis.
  • Tumor’s response to therapy.
  • Age and overall health of your child.
  • Your child’s tolerance of specific medications, procedures or therapies.
  • New developments in treatment.

As with any cancer, prognosis and long-term survival can vary greatly from child to child. Every child is unique, and treatment and prognosis are structured around the child’s needs. Prompt medical attention and aggressive therapy are important for the best prognosis. Continuous follow-up care is essential for a child diagnosed with osteogenic sarcoma. Side effects of radiation and chemotherapy, as well as second malignancies, can occur in survivors of osteogenic sarcoma. New methods are continually being discovered to improve treatment and to decrease side effects.

Is it genetic and do immediate family members need to be concerned about having the tumor too?

There are 2 instances in which there is a known genetic link for osteosarcoma.  An eye tumor known as retinoblastoma is associated with a mutation of a gene that also is associated with osteosarcoma.  In a second situation, a syndrome known as the Li-Fraumeni syndrome is characterized by an osteosarcoma occurring in one family member and a higher presence of breast cancer and other types of sarcomas in other family members.  Again a gene mutation is associated with this syndrome.  For this reason, any family history of cancers should be mentioned to a treating physician.

Summary

Osteosarcoma is a rare and challenging cancer to treat considering the multiple different types of this cancer and the functional consequences of partially losing a major bone or joint.  Fortunately, a multidisciplinary team approach, along with biological, surgical and technological advances has resulted in the majority of patients surviving their cancer and the majority of limbs being preserved.

About this article:

Note: This section based on and is used with permission from the author, Edward Y. Cheng, M.D., Mairs Family Professor, Department of Orthopaedic Surgery, University of Minnesota Cancer Center, RISF Charter Board member and is based on an article entitled: Osteosarcoma, “An unusual cancer arising in the bone”.