What is Osteogenic Sarcoma (osteosarcoma)?
Osteogenic sarcoma, also known as osteosarcoma, is the most common type of bone cancer. It’s often found in the limbs like the legs or arms, and is notably seen in two age groups, once before the age of 25 (75% of cases), and again after the age of 50 (highest at age 70). The latter group of patients often have a disease called Paget’s disease or have been exposed to radiation.
The most common subtype of this cancer is what’s called a high-grade conventional intramedullary osteosarcoma. This is a very aggressive form of the cancer that’s complex at a biological level. It tends to affect the fast-growing parts of the bones in the limbs, such as near the knee, upper shin, and upper arm.
If the cancer remains localized – meaning it hasn’t spread elsewhere – doctors usually opt to remove it surgically. However, about 10 to 20 percent of people have signs that the cancer has spread (metastasized) at the time of diagnosis, most commonly to the lungs. It’s also assumed that many more people have small, undetectable spread of cancer cells at diagnosis, given that over 80% of patients end up having metastases even when the original cancer spot was controlled, before the use of chemotherapy. With the regular use of chemotherapy, about two-thirds of children and teens achieve long-term recovery from the disease.
What Causes Osteogenic Sarcoma (osteosarcoma)?
Osteosarcoma, a type of bone cancer, can have several risk factors. Past radiation treatments, a bone condition called Paget’s disease, and certain genetic disorders could increase your risk. These genetic conditions include Li-Fraumeni syndrome, Wermer’s syndrome, Rothmund Thompson syndrome, and familial retinoblastoma syndrome. Mutations or changes in certain genes are also common in osteosarcoma. For example, most cases have mutations in either the retinoblastoma gene, linked to retinoblastoma syndrome, or the p53 gene, linked to Li-Fraumeni syndrome.
Further, mutation related to a molecule controlled by the K-ras gene (RAS associated family member 1a) has been found to occur in osteosarcoma cancer cells. Similarly, a mutation in the PI3K/mTOR pathway, a biological process linked to the Ras pathway, is also associated with osteosarcoma.
Moreover, specific biological signaling systems involved in body structure formation and cell growth, known as Notch signaling, are thought to be implicated in the development of this disease. Changes in the way genetic material is packaged and controlled, a process called epigenetics, have also been reported. Particularly, there are changes in how histone deacetylases, a type of protein, are suppressed.
There is ongoing research into new treatments for osteosarcoma. Inhibitors of Aurora kinases and DNA methyltransferases – proteins involved in cell division and gene regulation, respectively – have shown potential as treatment options.
Risk Factors and Frequency for Osteogenic Sarcoma (osteosarcoma)
Osteosarcoma is a type of cancer that affects the bone. Each year, approximately 900 cases are diagnosed in the United States. This disease is relatively rare, making up less than 1% of all new tumors in adults and about 4% in children. It is most frequently found in teenagers, excluding blood-related cancers, and is more common in boys.
When diagnosed, 20% of patients already have the cancer spread, or “metastasized,” to other parts of their body. The lungs are the most common site for this (60-70% of cases), followed by other bones (20-30% of cases).
- Osteosarcoma usually originates near the bone surface, with the most common type being parosteal osteosarcoma, which accounts for 1 to 6% of cases.
- Within the pelvis, the Ilium bone is most often affected by osteosarcoma.
- Vertebral osteosarcomas, affecting the spine, comprise 4 to 15% of spinal tumors and 1 to 3% of all osteosarcomas.
- High-grade craniofacial osteosarcomas, affecting the skull and face, usually develop in an older age group compared to conventional osteosarcomas.
Signs and Symptoms of Osteogenic Sarcoma (osteosarcoma)
Osteosarcoma is a type of bone cancer that usually presents with pain and swelling, often at the ends of long bones in the arms or legs. It’s often mistaken for other bone conditions because it doesn’t typically have signs of an infection. Sometimes, patients share a history of previous injury or radiation therapy to that area. These factors might hint towards a diagnosis of osteosarcoma.
Some patients have a pathological fracture, a break in a bone weakened by disease, either from the primary tumor or cancer spread to other bones. Those with metastasis, or spreading of cancer, have symptoms related to the affected organ. For example, if the cancer has spread to the lungs, there might be consistent coughing and coughing up blood.
On physical examination, a palpable mass may be felt, and limitation of joint movement and pain on weight-bearing. The affected area may feel warm and show signs of redness. However, general indications of illness, such as fatigue or weight loss, might not show up until the disease has advanced.
When osteosarcoma occurs in the spine, potential neurological problems can be evaluated according to a specific grading system. The location and grade of spinal tumors can be classified using the Tomita system.
Testing for Osteogenic Sarcoma (osteosarcoma)
When trying to determine if you have osteosarcoma (a type of bone cancer), several types of investigations are used:
Imaging: Doctors start with a simple X-ray to look for signs of the disease, like abnormal bone growth, known as a ‘periosteal reaction’. This can look like a sunburst or a triangle (Codman’s triangle) on the X-ray image. However, an X-ray might not always conclusively show if a sarcoma is present, especially when it’s in the face or skull. Here, X-rays might show areas that look less dense than usual to areas that look denser than surrounding bone tissue, depending on how much new bone or ‘osteoid’ formation there is. If the X-ray is inconclusive, or if there’s still pain, an MRI might be needed to check the bone in more detail.
Even then, certain features, such as areas where the bone surface has been destroyed, tiny specks of calcium known as microcalcifications, and abnormal bone growth at the site, might be seen better with a different imaging tool called a CT scan. Your doctor might suggest a CT scan if an MRI can’t be used for any reason or if the diagnosis is still uncertain. They might also carry out a scan of the whole body using a radioactive substance called Tc 99 or F 18 – FDG PET. This is done to check for ‘metastasis’ or spread of the cancer to other bones, or for ‘skip lesions,’ which are isolated spots of cancer separate from the main tumor.
Blood tests: A full blood count and biochemistry tests, along with tests for a protein called serum ALP (alkaline phosphatase) and the ESR (erythrocyte sedimentation rate) are typically carried out. These can help provide more information about your overall health and how the disease might be affecting your body.
Biopsy: A biopsy, where a small sample of tissue is removed from the bone for testing, is usually needed to confirm the diagnosis. This can often be done using a needle and guided by ultrasound, MRI, or CT imaging. The extracted tissue is tested for the presence of cancer. More detailed tests might also be carried out to look for genetic changes and to rule out any infection. While traditional thinking was that all tissue along the path of the needle should be removed to avoid spreading cancer, newer research suggests this might not be necessary. However, if an open surgery is done to get the biopsy, that pathway should be removed.
There’s also a newer method called a ‘liquid biopsy,’ where your blood is examined for bits of cancer cells or their DNA. This method’s role in diagnosing osteosarcoma still isn’t clear, but it might be used if the tissue biopsy results are unclear.
Pre-chemotherapy evaluation: If you’re going to receive chemotherapy, your doctors will also want to check your hearing, kidney function, and heart health. This involves a hearing test, more blood tests to evaluate your kidneys, and an echocardiogram to check your heart. This is because chemotherapy can sometimes have side effects affecting these systems.
Treatment Options for Osteogenic Sarcoma (osteosarcoma)
Osteosarcoma, a type of bone cancer, is typically treated using a combination of chemotherapy (medication to kill cancer cells) and surgery. This combined approach has greatly improved treatment outcomes over the past several decades, with limb-saving surgical procedures able to be performed in over 90% of cases today compared to just 53% in the 1980s. These procedures aim to remove the cancer while preserving the limb, leading to better overall quality of life and survival rates similar to amputation.
Doctors recommend considering clinical trials, which test new treatments, for all patients with osteosarcoma. The specific treatment options may vary depending on the severity and location of the cancer. For instance, low-grade osteosarcomas that haven’t spread are often treated with surgery alone, while high-grade tumors usually first receive chemotherapy followed by surgery. Doctors will base their treatment decision on how the cancer responds to initial chemotherapy treatments.
If the osteosarcoma has spread to other parts of the body but can still be removed with surgery, chemotherapy is typically given first, followed by surgery to remove both the primary tumor and any areas where the cancer has spread. If the cancer can’t be removed with surgery, additional chemotherapy or radiation may be used to control its growth.
In cases where the cancer has come back or hasn’t responded to initial treatments, a combination of additional surgery and chemotherapy may be used. If the disease continues to progress, supportive treatments focused on symptom control and quality of life may be offered.
It’s important to note that the patient’s response to chemotherapy prior to surgery can help predict their survival outcomes. Osteosarcomas that showed 10% or fewer living cells after initial chemotherapy treatment generally had better disease-free survival rates.
For certain types of osteosarcoma called surface osteosarcomas which generally have a lower risk of spreading, surgery remains the central treatment. However, chemotherapy could be added to the treatment plan if the surgically removed specimen shows high-grade (more serious) areas.
Regardless of the specific situation, the ultimate goals of osteosarcoma treatment are to control the cancer’s growth, alleviate symptoms, and improve the patient’s quality of life as much as possible.
What else can Osteogenic Sarcoma (osteosarcoma) be?
Osteoblastic osteosarcoma, a type of bone cancer, can sometimes be mistaken for an osteoblastoma or a fracture callus, both of which are related to bone conditions but are different from cancer. Here’s why:
- Osteoblastic osteosarcoma originates in the middle parts of the bones, especially in the legs or arms. It’s characterized by abnormal cells spread throughout a bony material called osteoid. It also invades the surrounding soft tissue. There’s a high rate of abnormal cell division.
- Contrastingly, osteoblastoma is typically well-defined, with a surrounding layer of reactive bone. It’s made up of loose fibrous tissue with a blood supply and there is no abnormal cell division.
- A fracture callus, the bone healing tissue that forms after a fracture, is typically accompanied by a history of trauma. It is marked by structured deposits of new bone material and it transitions from immature to mature bone cells.
Just like osteoblastic osteosarcoma, there are other types of osteosarcomas that can be confused with various conditions. Some examples include:
- Chondroblastic osteosarcoma is similar to conventional skeletal chondrosarcoma and dedifferentiated chondrosarcoma.
- Fibroblastic osteosarcoma can resemble fibrosarcoma or desmoplastic fibroma, types of soft tissue sarcomas.
- The telangiectatic variant of osteosarcoma, which is filled with blood-filled spaces, can be mistaken for an aneurysmal bone cyst, a noncancerous bone tumor filled with fluid.
- Small cell variants of osteosarcoma might resemble Ewing sarcoma, a rare type of cancer that occurs in bones or in the soft tissue around the bones.
- Low-grade intraosseous osteosarcoma might be confused with fibrous dysplasia, a bone disorder where normal bone gets replaced with fibrous bone tissue.
- Giant cell-rich osteosarcoma, a rare type with large cells, needs to be differentiated from a giant cell tumor of the bone.
There are also surface osteosarcomas, which originate from the outer layer of the bone. These types have their close resemblances too:
- Low-grade parosteal osteosarcoma might be mistaken for osteochondroma, heterotropic ossification, or surface osteoma.
- Chondroblastic osteosarcoma and periosteal chondrosarcoma can closely resemble periosteal osteosarcoma (intermediate grade surface osteosarcoma).
- High-grade surface osteosarcoma might be confused with other reactive surface lesions of the bone.
Simply put, it’s very important for healthcare providers to carefully differentiate between these different conditions to reach an accurate diagnosis.
Surgical Treatment of Osteogenic Sarcoma (osteosarcoma)
Surgery remains the go-to treatment method for this type of illness. Over the years, medical professionals have shifted focus to surgeries that can save a patient’s limb. The main objectives of the surgery are not only to fully remove the tumor, ensuring none is left behind, but also to retain as much functionality of the affected area as possible.
What counts as full removal of the tumor can change depending on the evolutionary developments in the approach to treating the illness. In some circumstances, doctors can now remove tumors located in a specific part of the bone, avoiding the need to operate on the joint and healthy bone around it. This approach can provide patients with a better quality of life after surgery. However, surgical procedures can vary depending on the patient’s response to chemo before surgery, and surgeons may need to make amputations or perform rotationplasty – a procedure in which a part of the bone is removed, the remaining bone is then turned around and reconnected, allowing the ankle to work as a knee joint.
Amputations are usually done in situations where removing the entire tumor would result in a dysfunctional limb, or when the patient prefers a prosthetic limb, which could provide more functionality despite losing the aesthetic look of a natural limb.
New advancements in surgical methods, such as compressive osteointegration (a method of attaching artificial limbs to the bone), allograft bone reconstruction (utilizing cadaver bones for repair), and a combined approach that uses special plates to help cement the internal fixation, have shown potential to improve the healing and recovery process after surgery, ultimately improving patients’ quality of life.
Moreover, for the management of a single lung metastasis (cancer spread to the lungs), local ablative therapies, i.e. targeted therapies such as precision radiotherapy, freezing treatment (cryotherapy), or heat treatment (radiofrequency) could be considered.
What to expect with Osteogenic Sarcoma (osteosarcoma)
Before the invention of chemotherapy, the 5-year survival rate for patients was only between 10% to 20%. Nowadays the five-year survival rate for a type of cancer called localized extremity osteosarcomas is close to 70%. However, pelvic osteosarcomas, another form of the disease, usually have a worse prognosis with a five-year survival rate of only 30%.
If a surgical procedure fails to completely remove the tumor (positive margin), or if there is a poor response to initial chemotherapy (poorer percentage of necrosis), the outlook is often not as good. This is also true if a patient has a bone fracture related to the disease.
If a patient has metastatic disease, meaning that the cancer has spread to other parts of the body, the prognosis is usually worse, with overall survival rates between 20 to 30%. Metastases to the bone and other non-lung areas are usually a worse prognosis than those that have spread only to the lungs.
Men, people of non-white ethnicities, elevated levels of ALP and LDH (two substances found in the blood), and osteosarcomas occurring in bones affected by other diseases like Paget’s disease, typically have a worse prognosis.
The specific type of tumor also plays a role in the prognosis. Some types of tumors, like those known as telangiectatic and fibroblastic, tend to respond better to chemotherapy and patients with these types of tumors generally have a better prognosis compared to those with chondroblastic and osteoblastic tumors.
When osteosarcomas are found in the head or face (known as craniofacial osteosarcomas), they are typically low-grade tumors and generally carry a better prognosis compared to osteosarcomas found in the limbs. However, osteosarcomas related to previous radiation therapy are usually more aggressive.
There are also scoring systems like the Naples prognostic score and predictive models that include levels of different blood chemicals and cells and which can also be used to predict prognosis. These methods correlate with the stage of the disease, the presence of fractures, recurrence of the disease, and spread to other organs.
Possible Complications When Diagnosed with Osteogenic Sarcoma (osteosarcoma)
When dealing with a pathological fracture, both non-surgical and surgical approaches can be utilized. The choice depends on factors like the extent of bone damage, changes in the pain experienced, whether there’s a single bone metastasis that could indicate another primary tumor, and so on. These evaluations are made as part of a focused group discussion within a disease management team, who tailor to the specific nature of the disease.
A referral to an orthopedic surgeon can be necessary in various scenarios – if preventive fixing of the bone is required, if there’s a high risk of an imminent pathological fracture (determined via assessment tools like Mirel’s score or Harrington’s criteria), if bone reconstruction is needed after a pathological fracture, or if spinal cord stability needs to be ensured.
To determine the risk of a pathological fracture in the thigh bone near the hip region (proximal femur), Harrington’s criteria includes:
- Case of more than 50% damage to the outer layer of the bone
- Persistent pain even after radiation therapy
- Thighbone lesions larger than 2.5cm
- Thighbone lesions with an attached fragment of the hip bone (greater trochanter)
An interventional radiology review might be necessary for the treatment of metastatic bone disease through heat (radiofrequency ablation). Additionally, minimally invasive approaches like cement injection in the spinal vertebrae can be considered for painful vertebral fractures.
Secondary cancers can increase in patients who receive chemotherapy, with the incidence rate rising by 2.5% to 4%. These secondary cancers usually include blood cancers but can also comprise of breast cancer, thyroid cancer, and soft tissue tumors.
