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Understanding Osteosarcoma and its Treatment Methods
Osteosarcoma and Osteoprogenitor Cells
Most osteosarcomas develop in the ends (the’metaphyses’) of long bones, especially the knee bone and the upper arm bone. However, tumors may also form in flat bones and in other locations throughout the body.
Doctors usually treat osteosarcoma with surgery and chemotherapy drugs. They might use high-energy X-rays to kill cancer cells in a procedure called radiation therapy.
At first, tumor cells look and act like regular bone cells. But as they grow, they create immature, irregular bone tissue that is malignant (cancerous). The cancer cells spread through the blood to other bones and soft tissues in the body. They also grow and reproduce, creating more tumors.
Tumor cells can be killed by chemotherapy drugs or radiation therapy, which kills cancer cells with high-energy beams, such as X-rays and protons. Radiation can be used when surgery isn’t possible or when surgeons can’t remove all the cancer cells during an operation.
Adoptive immunotherapy with gene-modified T cells is another way to treat osteosarcoma. These cells can be made to target specific epitopes, such as MAGE-A family members or NY-ESO-1. The expression of these epitopes is often lowered in tumor cells due to gene silencing and can be restored by demethylating treatments, such as 5-aza-2′-deoxycytidine (DAC). This strategy may improve outcomes in patients with advanced osteosarcoma who fail conventional therapies.
Osteoprogenitor cells are multipotent progenitors that contribute to vascularization and osteogenic differentiation. They are derived from different sources including pericytes, VSMCs, monocytes and stromal cells. Loss of inhibitors and induction of promoters can lead to an osteogenic phenotype in these cells. Osteoprogenitor cells can induce both intimal and medial calcification, contributing to arterial stiffness, hypertension and cardiovascular disease.
Recent studies have revealed that the phenotype of OSCs is influenced by microenvironmental factors. CD117-Stro-1 double-positive cells have been identified as OSCs in both human and murine OS, exhibiting high multipotency, invasiveness and drug resistance .
However, experimental models of OS are primarily based on cell lines and have not fully addressed the question of the cellular origin of this tumor. The data obtained from a number of genetically engineered murine models is most supportive of the hypothesis that OS is derived from committed mesenchymal precursors rather than an MSC population. Moreover, the penetrance of OS in these models is highest when cells from a more committed pool, such as preosteoblasts, are targeted for transformation . This cancer information summary is provided by the National Institutes of Health’s PDQ®. It is intended to inform and help patients, families, and caregivers.
Initiating cells are the smallest subpopulation of cancer stem cells that possess self-renewal and differentiation abilities. These cells are thought to play key roles in tumor initiation, metastasis, therapeutic resistance and recurrence. Targeting of these cells may offer a new approach for the treatment of osteosarcoma.
Recently, a study showed that multiple disseminated tumor-initiating cells (TIC) clones were detected in peripheral blood samples of patients with osteosarcoma. Moreover, these cells were highly metastatic and able to form lung metastases in mice. The underlying cellular and molecular mechanisms of this phenomenon remain unclear.
It is important to identify and isolate OSCs for effective therapy. However, this is challenging because of the difficulty in identifying OSCs with specific cell surface markers. Moreover, the current methods of isolating OSCs, including sphere-forming assays and side population cell sorting, are only partially successful. In addition, OSCs display intrinsic drug-resistance, presumably through their high expression of ABC multidrug efflux transporters. This drug-resistance mechanism is mediated by DNA damage and a poor mismatch repair system.
Cancer cells that survive chemotherapy can recur (grow again). This is called a relapse. Recurrent tumors often have more aggressive characteristics than initial tumours and can lead to a poorer prognosis.
Scientists are searching for ways to identify these recurrent cancer cells. This could help them find new ways to treat osteosarcoma.
A key to treatment is to kill all of the cancer cells, not just some. This is a challenge with osteosarcoma because the cancer cells look a lot like normal bone cells.
Osteosarcoma most commonly starts in osteoblasts, which are cells that create new bone. It usually forms in the long bones of the arms and legs, such as the femur (thigh bone) or tibia (shin bone) near the knee. It can also form in the humerus (upper arm bone) or in soft tissues of the chest and abdomen. This type of sarcoma is most common in teenagers, with an average age at diagnosis of 15. This may be because it often occurs during the growth spurt that happens in teenagers.
Bone Cancer in Young People: Causes, Symptoms, Diagnosis, and Treatment Options
Osteosarcoma develops in the bones of young people. Most often it occurs around the knee, hip or shoulder of growing kids. It’s not clear what causes this cancer. But it probably happens when changes in a gene cause immature bone cells to grow out of control.
It is important to note that some data in the SEER database may be incomplete or inaccurate.
The most common symptom of osteosarcoma is pain near the bone where the tumor is. This pain often gets worse with activity and may cause a limp if it is in a leg bone. Swelling near the site of the tumor is also common.
Sometimes bone cancer can spread to other parts of the body, especially the lungs. This is called metastatic bone disease.
Doctors find out if someone has bone cancer by asking about their past health and doing a physical exam. They also do imaging tests, such as x-rays, CT scans, or magnetic resonance imaging (MRI) scans to look for changes in the bones.
Most people with osteosarcoma need surgery, chemotherapy, and sometimes radiation therapy. Chemo uses strong medications to kill cancer cells and stop them from growing. The drugs are given into a vein (IV). They may also put a port, a small tube, into a person’s chest to help them get chemotherapy.
Osteosarcoma is a bone cancer that starts in immature bone cells. These grow faster than normal bone cells, and the resulting mass forms a tumor in the bone. It can also occur in soft tissues outside of the bones.
The most common place for osteosarcoma to develop is around the knee or hip of growing kids. It can also form in the femur (thigh bone), tibia (shin bone), or upper arm bone near the shoulder. It rarely happens in the spine.
A physical exam and a medical history are the first steps to diagnose this condition. Your doctor will look for lumps or unusual growths in and around your body, and order X-rays, CT scans, or MRIs to see what’s happening inside the bone.
Most people who get this cancer have pain, swelling or a limp. Treatment can help relieve these symptoms and prevent the tumor from spreading to other parts of the body. Treatment may include surgery, chemotherapy or radiation therapy. You may have limb-sparing surgery, in which doctors remove the tumor and part of the bone that it grew from. They might use a medical device or a bone graft to fill in the space left by the removed bone.
The prognosis (outlook) for osteosarcoma can vary depending on where it is located and whether it spreads to other bones or tissues. It is generally better when it is found early and treated quickly. This is why it is important for people to let their doctors know if they have bone pain, swelling or a limp.
Bone cancers are usually diagnosed with x-rays and an MRI scan. The MRI scan is used to find out how far the cancer has spread and whether it has touched other bones or tissues.
Treatment for osteosarcoma includes surgery and chemotherapy. The type of chemotherapy depends on how advanced the tumor is. It may include a combination of drugs.
Patients can regain their strength with rehabilitation programs that focus on hip mobility. Some research shows that patients can return to high levels of sports after hip reconstruction with techniques like the Harrington procedure, modular endoprosthesis, allograft prosthesis composite or hip arthrodesis.
If the cancer hasn’t spread to the lungs, surgery may remove the tumor and nearby tissue with wide local excision. This helps to reduce the chance that the cancer will come back in the place where it started.
A type of bone cancer that grows quickly can be treated with a medicine called mifamurtide, which encourages the body to produce cells that kill cancerous cells. This is given along with other treatments, such as chemotherapy and radiation.
Some tumors that grow in the ends of long bones (arms or legs) can be removed with a procedure called limb-salvage surgery. This allows a person to keep the use and appearance of the arm or leg. If the tumor is near a joint, the surgeon might need to remove the whole joint and replace it with a metal implant or with a piece of bone from another part of the body (a bone graft). For some types of bone cancer, such as Ewing sarcoma, surgery to remove the bone might be followed by a surgery to fuse the bones together (arthrodesis). Your care team will explain these options.
The Treatment and Prognosis of Osteosarcoma
Is Osteosarcoma Fatal?
Most people with osteosarcoma get surgery, chemotherapy and radiation therapy. This combination helps to control the cancer and reduce the chance that it will return.
The chemo drugs used to treat osteosarcoma help to shrink the tumor and kill any cancer cells that are floating around in the blood. Doctors give this treatment before surgery as neoadjuvant chemotherapy and again after surgery as adjuvant chemotherapy.
The first step in treating osteosarcoma is to figure out if the cancer has spread to other bones or tissues. Doctors use imaging and other tests to find out, a process called staging.
Most osteosarcomas are staged as low-grade (G1) or intermediate-grade (G2). That means the tumor cells look more like normal cells and grow and spread slower than high-grade cells.
Treatment usually includes chemotherapy, or medicine that kills cancer cells and stops them from growing. Your child will get these drugs through a vein, or intravenously. Doctors will give your child a combination of medicines, including doxorubicin, cisplatin, cyclophosphamide, high-dose methotrexate and dactinomycin. This regimen is known as MAP and has improved survival rates for patients with localized osteosarcoma.
St. Jude doctors are also leaders in limb-sparing surgery, which saves bone and tissue and helps patients walk, move and live as normal as possible after treatment. They work closely with laboratory researchers to bring new treatments from the lab to the clinic.
As with any cancer, the prognosis for osteosarcoma can vary greatly from person to person. It depends on the type and stage of the tumor, as well as treatment options.
The first signs of osteosarcoma may be a lump or mass in the bone, pain with movement, limited motion and possible broken bones. The diagnosis is made when a sample of tissue is taken from the tumor and examined under a microscope (biopsy).
Chemotherapy is given to kill cancer cells and prevent them from coming back. This can be done through injections into a vein or by mouth. It is most often used with other treatments, such as surgery or radiation therapy.
If a limb is removed because it’s too damaged to save, the patient may need to learn how to use a prosthetic leg. Patients must also deal with the long-term side effects of chemotherapy, although new methods are being discovered to decrease these effects.
The most common symptom of osteosarcoma is pain, usually with activity. This tumor usually develops in long bones, like the legs and arms. It happens most often in teenagers during the rapid growth that occurs when they are going through a growth spurt. It is more common in boys than in girls. It also happens more often in tall kids than in short kids.
A doctor can diagnose osteosarcoma with a physical exam and blood tests. They can also find it by taking a sample of bone tissue (biopsy) under anesthesia. A lab will check the biopsy for cancer cells.
Most people with osteosarcoma need surgery and chemotherapy. They may also get radiation therapy. If the cancer is in a bone in your arm or leg, doctors can remove it without removing the whole limb. They can replace the lost bone and tissue with a graft from another part of your body or an artificial bone.
Currently, there is no known way to prevent bone cancer. But catching it early can offer the best chance for success with treatment. It is important to talk with your doctor about your personal risk factors and how to reduce them.
Some risks can’t be changed, such as age and family history. But other risk factors, like past exposure to radiation or certain genetic conditions, can. Li-Fraumeni syndrome, Von Recklinghausen’s Disease, and familial retinoblastoma are all linked to an increased risk of osteosarcoma.
Also, some illnesses or injuries that can cause bone pain may increase the chances of a diagnosis of bone sarcoma, such as trauma, long-term immobilization, or inflammatory arthritis. The surgery to remove the tumour and the part of the bone that it was attached to can change how people live after a bone sarcoma recurs in the lung. Some patients may need to use an artificial limb (prosthesis). Others might need surgery to remove the metastases from the lungs or other parts of the body.
Osteosarcoma – Causes, Symptoms, and Treatment in Children
Osteosarcoma – Why is Osteosarcoma More Common in Males?
If your child has bone pain, a doctor can do tests to check for osteosarcoma. These tests include x-rays, magnetic resonance imaging (MRI), and computerized tomography (CT) scans.
Most children with osteosarcoma have chemotherapy. Your child may get the medicines doxorubicin and two or three other drugs through an implantable venous port in their chest.
Most people with osteosarcoma find out they have the tumor because of pain, swelling or a limp. Because children play so much and are active, when they experience bone pain or a limp, they may attribute it to sports injuries.
Doctors will take an x-ray to look for a bone lesion. Then they will do a biopsy of the area to get a sample for testing. The doctors will also probably do a CT scan, a bone scan and an MRI to check if the cancer has spread.
The treatment for osteosarcoma is surgery and chemotherapy. Some people need radiation therapy too. The doctors might do limb-sparing surgery, which means they will remove the tumor in the arm or leg but not all of the surrounding bones. They will then use a medical device or bone graft to fill in the area that was removed. In some cases, doctors might also do amputation to remove the whole affected area.
Each year, about 400 children and teens are diagnosed with osteosarcoma. It happens most often in the large bones of the arms and legs. It can also happen in the jaw bone and in soft tissue and organs in the body. It occurs more often in boys and girls who are growing rapidly, especially during the teen years.
Symptoms of osteosarcoma include pain near a joint, which doesn’t go away with rest or medicines. It may get worse with activity and be aggravated by impact activities or by putting weight on the affected limb. It’s important to let your health care provider know if you have these symptoms.
To make a diagnosis, your doctor will do a physical exam and ask you about your past health. Your doctor will also order imaging tests, like X-rays, CT scans, and magnetic resonance imaging (MRI) scans, to look for unusual lumps around the bones. These are usually done before surgery to help doctors find and plan treatment. Chemotherapy is usually given before surgery to shrink the tumor and kill any cancer cells that are still in the blood and surrounding tissues.
Most osteosarcoma happens in the end of the thigh bone (femur) closest to the knee and in the upper arm bone (humerus). It can also occur in the pelvis, jaw, and spine.
The first sign of osteosarcoma is pain in a bone. It can be hard to diagnose. Your doctor will ask about your health history and do a physical exam. They will check for unusual lumps in your bones. They will order imaging tests, such as X-rays and CT scans. Bone scans or MRIs can show whether there are any cancer cells in your bones.
Most osteosarcomas are treated with surgery and chemotherapy. Chemotherapy uses drugs to kill cancer cells and stop them from growing. Your doctor may use radiation therapy to help with treatment. This uses high-energy X-rays to kill cancer cells in your bone and surrounding tissue. They might also give you drugs to help prevent cancer cells from growing in your lungs after surgery.
The etiology of most osteosarcoma remains unknown. However, epidemiology studies have provided important clues. These include its association with puberty and its peak incidence during the teen years. Its male predominance also appears to be related to the adolescent growth spurt.
Germline mutations in genes regulating bone growth have been associated with an increased risk of osteosarcoma. These include Rothmund Thomas syndrome (RTS), a rare autosomal recessive disorder caused by mutations in the DNA helicase gene RECQL4. RTS causes skeletal dysplasias, a sun-sensitive rash and short stature. It also increases the risk of cancers including leukemia, lymphoma and sarcomas.
Mutations in other genes affecting cell division have also been associated with osteosarcoma risk, such as alterations of CDK inhibitors. These can occur through chromothripsis, an abnormal process in which parts of a chromosome are broken apart and set in a new configuration. This can lead to amplifications of related oncogenes (CDK4, MDM2, COPS3) or deletions/loss of tumor suppressor genes (TP53, RB1), or both .