Osteosarcoma

What is Osteosarcoma?

Osteosarcoma is the most common type of bone cancer in children, developing from early bone-forming cells. Sometimes it occurs in healthy bones, while other times it develops in bones that have other diseases and transforms into cancer, making up around 20% of all primary bone cancers. This type of cancer can vary greatly, ranging in how mature the cells are, where in the bone it is, and what it looks like under a microscope. These differences influence how it looks in medical scans, who gets it, and its behavior in the body. Thanks to the continuous efforts of many healthcare and research professionals, treatment options and chances of survival have greatly improved in recent years.

What Causes Osteosarcoma?

While the lives of people battling osteosarcoma, a type of bone cancer, have greatly improved in recent years, science hasn’t yet determined exactly why some people develop this disease. Researchers have looked into many areas including factors like genetics, where and when people live, and the environment around them.

Studying osteosarcoma gets complicated due to the differing groups of chromosomes typically found in these tumor cells, making it tricky to consistently pinpoint specific genetic changes. However, in initial cases of osteosarcoma, several genetic irregularities have been discovered:

– Hereditary Retinoblastoma: This is a genetic condition where mutations in the RB1 gene lead to a type of eye cancer called retinoblastoma, typically diagnosed in children younger than one. People with this condition are found to be at a higher risk of developing osteosarcoma later in life.

– Li-Fraumeni Syndrome: A genetic disorder caused by mutations in the p53 tumor suppressor gene, observed in some children with osteosarcoma. People with this syndrome also face a high risk of getting several other types of cancer at a very young age.

– Rothmund-Thompson Syndrome: This is a genetic condition caused by a mutation in the RECQL4 gene, resulting in a higher likelihood of osteosarcoma. Other symptoms include a rash in infancy, abnormal bone structures, hair loss, early cataracts, and long-term stomach discomfort.

– Bloom Syndrome: A genetic disorder due to mutations in the BLM gene, responsible for maintaining the stability of DNA during replication. People with this syndrome may also develop osteosarcoma and other cancers, and typically present with rashes induced by ultraviolet (UV) light, short height, and low levels of fat beneath the skin.

– Werner Syndrome: Also known as adult progeria, affects the WRN gene, resulting in premature aging, bilateral cataracts, brittle bones, short height, skin changes resembling a disease called scleroderma, and a propensity for osteosarcoma.

Studies have also found links between secondary osteosarcoma and situations such as Paget’s disease, electrical burns, trauma, exposure to a metal called beryllium, exposure to chemical agents called alkylating agents, FBJ virus, bone abnormalities including osteochondromatosis, enchondromatosis, fibrous dysplasia, orthopedic prosthetics, bone infarction (death of bone tissue due to a lack of blood supply), and infections. Moreover, osteosarcoma has been associated with exposure to ionizing radiation, radium, and old varieties of contrast agents such as thorotrast, used in medical imaging.

Risk Factors and Frequency for Osteosarcoma

Osteosarcoma is a type of bone cancer that typically affects two specific age groups. The first group is aged 10 to 14, which coincides with the adolescent growth spurt. This is when most primary osteosarcomas occur. As for the second group, it involves adults over 65. In their case, the osteosarcoma is usually secondary, developing from conditions such as Paget disease or sites of bone infarction. Survival tends to be worse in the older age group.

Statistics show that osteosarcoma makes up around 2.4% of all childhood cancers, making it the eighth most common type. More common childhood cancers include leukemia, central nervous system malignancies, and several others such as neuroblastoma, Wilms tumor, non-Hodgkin lymphoma, rhabdomyosarcoma, and retinoblastoma.

The ethnic group most affected by osteosarcoma is Blacks, followed closely by Hispanics. Whites have a lower incidence of this disease. Also, there’s a slightly higher rate of osteosarcoma in males compared to females. Despite these variations, the overall 5-year survival rate for patients with osteosarcoma is approximately 68%.

• Osteosarcoma usually happens in two age groups: 10 to 14-year-old adolescents and adults over 65 years old.
• It represents 2.4% of cancers in children, making it the eighth most common childhood cancer.
• Most common types of cancer in children are: leukemia, malignancies of the central nervous system, neuroblastoma, Wilms tumor, non-Hodgkin lymphoma, rhabdomyosarcoma, and retinoblastoma.
• Blacks have the highest rate of osteosarcoma, followed by Hispanics. White individuals have a lower incidence of osteosarcoma.
• There’s a slightly higher incidence in males compared to females.
• The overall 5-year survival rate for osteosarcoma is about 68%, regardless of sex.

Signs and Symptoms of Osteosarcoma

Osteosarcoma refers to a type of bone cancer that can be quite challenging to identify quickly as symptoms can take weeks or even months to become apparent. The primary symptom is typically bone pain, particularly during physical activity. Often, this pain can be mistaken for a sprain, arthritis, or simply growing pains in children.

Unusual fractures are not common with osteosarcoma, except for a specific variety known as ‘telangiectatic osteosarcoma,’ which can lead to such fractures. This condition can result in a limp due to the pain. A swelling or bump may also be noticed depending on the size and location of the tumor. Unlike lymphoma, systemic symptoms like fever and night sweats are uncommon.

Respiratory symptoms are also remarkably rare and usually indicate that the disease has advanced significantly, affecting the lungs. Additional symptoms are less frequent as the disease rarely spreads to other parts of the body.

During a physical examination, the doctor usually focuses on the area where the primary tumor is located. They may find:

• A palpable mass that may be tender and warm, including possible pulsations (though these signs are non-specific)
• Joint issues with decreased range of motion
• Local or regional lymph node swelling (unusual)
• Respiratory findings with diseases that have spread

Testing for Osteosarcoma

If you’re being checked for osteosarcoma, a type of bone cancer, here’s what you may go through. Your doctor will first take a detailed medical history and perform a physical examination. Following this, you’ll go through some laboratory tests. Two specific substances – lactate dehydrogenases (LDH) and alkaline phosphatase (ALP) – will be checked in these tests. These substances can help confirm the diagnosis and give an idea about how the disease might progress. High levels of ALP are usually linked with osteosarcoma due to the increased activity of bone-forming cells (osteoblasts). Extremely high levels may suggest a large amount of tumor and could indicate a worse disease outcome.

After these tests, you’ll undergo imaging tests to visualize the primary tumor site. Initially, your doctor will take simple x-rays. If they reveal a potential bone mass, more advanced imaging tests like magnetic resonance imaging (MRI) may be performed to get a better picture of the tumor. MRI is crucial in defining the exact extent of the tumor within and outside the bone, and also helps in examining the nearby tissues. It helps check whether the tumor has involved any joints or the nearest neurovascular bundle, which are nerves and blood vessels bundled together.

An MRI scan uses different sequences to help visualize different components of the tumor. The scan results might show a high or low signal intensity that helps describe the nature of different tumor parts. The signal depends upon the chronicity or the time duration of the respective component.

Computed Tomography (CT), another type of imaging scan, will be primarily used to assist in biopsy planning and disease staging, understanding the disease extent and severity. If the tumor is predominantly lytic, meaning it destroys the bone, a CT scan might help identify small amounts of mineralized material that cannot be seen with x-rays and MRI. A CT scan of the chest will also be done specifically to check for the potential spread of cancer.

Positron Emission Tomography (PET) and Radionuclide Bone Scan are two other types of scans that may be used. PET scans can help identify highly metabolic lesions, which use energy at a very high rate. It’s useful for assessing tumor extent and checking for subtle lesions that might have been missed initially. Radionuclide bone scans are effective in detecting the spread of cancer to the bones and are a less expensive but less specific alternative to PET imaging. If there are sites of possible spread identified on these scans, a repeat MRI or CT scan may be necessary.

If cancer treatment may affect your fertility, your doctor may suggest a fertility consultation. After the physical exam, lab tests, and imaging confirm the presence of a tumor consistent with osteosarcoma, your doctor will perform a biopsy, which means taking a small piece of the tumor to analyze under a microscope. This is an important step to confirm the diagnosis. The final surgery will include removing the path taken for the biopsy to prevent the spread of cancer cells. Core biopsy, which uses a needle, is preferred over an open biopsy as there is less risk of infection and improper wound healing. The tissue sample taken during the biopsy will be analyzed by pathologists, who will make the definitive diagnosis, grade the tumor, and subtype it histologically, all of which will guide the treatment plan.

Treatment Options for Osteosarcoma

The National Comprehensive Cancer Network have put together guidelines in 2020 for managing a type of bone cancer known as osteosarcoma.

For a less severe form of osteosarcoma, with no cancer spread, the recommended treatment is an operation called wide excision, without the need for drugs to treat cancer (neoadjuvant chemotherapy) before the surgery. If, after surgery, the cancer still shows less severe features, then no further drug treatment (adjuvant chemotherapy) is needed. If, however, the cancer shows signs of being more severe, then drug treatment must be considered.

In some cases of osteosarcoma, referred to as “periosteal”, drug treatment comes first, followed by the wide excision surgery. Whether or not additional drug treatment is needed after surgery will depend on how serious the cancer is.

For a more severe form of osteosarcoma, with no cancer spread, the initial treatment is drugs. Then, the cancerous area is reassessed. If the cancer looks operable, wide excision is performed. Depending on whether or not all the cancer was successfully removed and the effectiveness of the drug treatment, additional therapies, such as more surgery, or radiation therapy, might be needed.

If cancer has spread at the time of diagnosis, the treatment will depend on whether those cancerous areas (metastases) can be removed with surgery (metastasectomy). If they can, follow the guidelines for the more severe type of osteosarcoma mentioned above. If they can’t be removed, patients should consider drugs and radiation therapy, and reassess the original cancer location.

Following treatment, a surveillance schedule is recommended. This involves regular check-ups, with the frequency decreasing over time. These visits usually include a physical exam to assess the organ’s function and imaging of the post-operation site and chest. Some additional tests, like a PET/CT or bone scan and blood tests, may also be suggested based on symptom presentation. If the cancer comes back, chemotherapy and more surgery, where possible, are advised.

The effectiveness of these treatments will be evaluated with images of the original cancer site and the site of recurrence. If there’s a good response, you’ll re-enter the surveillance schedule noted above. Poor response, or worsening of the disease, could lead to more surgery, taking part in a clinical trial, palliative radiation treatment, or supportive care.

Finally, for osteosarcoma developing outside of the bones, the guidelines recommend treatment as for soft tissue sarcoma.

What else can Osteosarcoma be?

When a patient is suspected to have osteosarcoma, which is a type of bone cancer, the doctor needs to rule out a few other conditions. These include different types of tumors, some of which are cancerous and some are not. They also need to consider other conditions which affect the bones but are not due to tumors. The following conditions may imitate the symptoms of osteosarcoma:

• Osseous metastasis (spread of cancer from other parts of the body to the bones)
• Ewing sarcoma (another type of bone cancer)
• Malignant fibrous histiocytoma (a rare type of cancer that affects the soft tissues)
• Fibrosarcoma (a cancer that develops in the fibrous tissues of the body)
• Giant cell tumors (a usually non-cancerous bone tumor)
• Lymphoma (cancer of the lymphatic system)
• Osteoblastoma (a rare, usually benign bone tumor)
• Cortical desmoid (a type of benign bone tumor often found in the upper arms)
• Osteomyelitis (an infection in the bone)
• Aneurysmal bone cyst (a non-cancerous bone tumor)
• Fibrous dysplasia (a bone disorder in which scar-like tissue develops in place of normal bone)

Surgical Treatment of Osteosarcoma

The main goal of treating osteosarcoma, a type of bone cancer, is to completely get rid of the tumor. This is usually achieved by surgical removal of the tumor, ensuring there is healthy tissue all around it to decrease the chance of it coming back. Usually, one of two surgical approaches can be taken: limb salvage and amputation.

Limb Salvage

Limb salvage is the preferred treatment and used in about 85-90% of osteosarcoma cases. This procedure involves removing the tumor while keeping as most of the limb intact as possible. This is a two step process: the resection, or removal, of the tumor, and then the reconstruction, which is the restoration of function of the affected limb. In the first step, the tumor, and also the site where the tumor sample was taken from, are removed with at least 2 cm of healthy tissue on all sides. This is to ensure all cancer cells are removed, reducing the possibility of the disease coming back. Complex imaging can be used to plan this surgery, especially for large or difficultly located tumors.

For younger patients, this surgery can be difficult as it may involve removing the ‘growth plate’, an area of growing tissue near the ends of the long bones in children and adolescents. This could potentially disturb normal growth. However, with the development of surgical tools that can be adjusted as the child grows, this is no longer an obstacle. Reconstruction of the limb after removal of the tumor mainly serves to restore function. For bones that do not bear weight, like the fibula or collarbone, no reconstruction is needed. However, for weight-bearing bones, reconstruction can be more complex and there are several options.

Allograft/Autograft Bone Reconstruction: This is the use of bone obtained from a deceased donor (allograft) or the patient’s own bone (autograft) to fill the space left by the tumor. Allograft bone is preferred as it is readily available and has few complications such as infection and rejection. On the other hand, autograft bone is taken from the patient, treated to kill the cancer cells and then implanted which makes it a perfect fit. This can be a cheaper option, but has limited indication.

Metallic Prosthetics: These artificial implants made of metal can be used to replace large parts of the bone and joints connecting them. They have made reconstruction a lot easier with readily available ‘off the shelf’ options. There are also expandable prosthetics that can be gradually made longer, helping maintain the same limb length in young patients whose bones are still growing.

Tissue Regeneration: This is a new and emerging field where the patient’s own cells, growth factors and specially designed scaffold materials are used to grow new bone. Surgery techniques that use external devices to stretch the bone and make it grow can also be used.

Amputation

Amputation used to be the main treatment method for osteosarcoma. Nowadays, it is only used for tumors that are impossible to remove without also removing important structures in the limb like muscles, tendons, and blood vessels. Rotationplasty is a special type of amputation where the lower leg is turned 180 degrees backwards and reattached, with the ankle joint serving as a new knee joint.

Studies have shown that people who go through limb salvage surgery might have a slightly higher chance of their cancer coming back compared to those who had amputation. However, the overall survival rate is comparable. Additionally, some studies have shown higher survival rates in patients who went through limb salvage surgery, making it the preferred treatment method by most doctors.

What to expect with Osteosarcoma

The likelihood of someone recovering from osteosarcoma, a type of bone cancer, depends on many different factors, including:

1. Age: Older people, particularly those over 40 years old, generally have a harder time surviving osteosarcoma. This is mainly because they often have other health complications at the same time, like other forms of cancer or tumors. Older patients, especially those older than 60 years, also tend to reject aggressive treatments like chemotherapy or surgery, which are typical treatments for this type of cancer.

2. Gender: Men have a lesser chance of surviving osteosarcoma because they do not respond as well to chemotherapy, are more likely to face reoccurrence, and have an increased likelihood of falling ill again. Women, on the other hand, usually have a better chance of surviving, mainly because their tumors are more likely to be destroyed by chemotherapy.

3. Biomarker levels: Biomarkers are substances that can be measured in the body, and are used to monitor and predict health conditions. A biomarker called “serum alkaline phosphatase” is commonly found at high levels in osteosarcoma patients and can mean poorer chances of survival. Another biomarker, Lactate dehydrogenase (LDH), is also typically at high levels in patients, particularly in those whose cancer has spread to other parts of their bodies at diagnosis.

4. Tumor location: Where the tumor is located in the body can affect survival rates. If a tumor is found in the axial skeleton, which includes the skull, spine, and ribs, the person typically has a lower survival rate compared to someone whose tumor is in the appendicular skeleton, which includes arms and legs.

5. The size and spread of the tumor: As you might expect, larger tumors or tumors that have spread to other parts of the body are more difficult to treat, meaning survival rates are lower.

6. Type of tumor: Certain types of osteosarcoma tumors are more responsive to chemotherapy and have better chances of survival.

7. Response to chemotherapy before surgery: How much of the tumor is destroyed by chemotherapy before surgery is a good predictor of survival. If chemotherapy kills 90% or more of the tumor, the chances of survival are much greater.

8. Fractures: If the osteosarcoma patient suffers a fracture as a symptom of the disease, they have an increased chance of the cancer returning and decreased survival rates.

9. Body Mass Index (BMI): People with a high BMI, indicating overweight or obesity, tend to have lower survival rates.

It is essential to remember that everyone is unique, and these factors can vary widely from person to person. Your healthcare team can provide the most accurate information based on your specific circumstances.

Possible Complications When Diagnosed with Osteosarcoma

Osteosarcoma, or bone cancer, can lead to various complications. They can be caused either by the tumor itself or by the methods used to diagnose or treat it.

• Tumor-Specific Complications: The tumor can cause pathological fractures. These fractures might occur when the tumor is first detected or during treatment with preoperative chemotherapy. Individuals who experience these fractures generally have poorer outcomes.
• Biopsy-Related Complications: When taking a biopsy for osteosarcoma, there is a risk of spreading the tumor cells into the surrounding tissues. This risk increases if the biopsy must extend across multiple areas, potentially leading to a larger section needing to be removed and thereby increasing the risk of complications related to the treatment.
• Treatment-Related Complications:
  • Chemotherapy Side Effects: During chemotherapy treatment, you might experience nausea, malaise (a general feeling of discomfort), hair loss, anemia (low red blood cell count), and loss of appetite. These effects usually lessen or go away after the completion of the treatment. However, some long-term effects may include damage to your heart or lungs and even gradual hearing loss. There have also been cases of a secondary malignancy, a different type of cancer, developing after chemotherapy.
  • Radiation Side Effects: Radiation treatment can have surface-level effects like dry or peeling skin, itchiness, and rarely, burns. If the radiation treatment is directed at the pelvic area, it could potentially lead to menstrual changes, erectile dysfunction, and infertility. If the chest and abdomen need to be radiated, potential effects include diarrhea, incontinence, rectal bleeding, nausea, vomiting, dry mouth, difficult or painful swallowing, pneumonitis (inflammation of the lung tissue), and fibrosis (hardening or scarring of the organs).
• Periprosthetic Infections: Infections related to artificial body parts, such as prostheses, are a relatively common complication. They usually result from lengthy surgery times, multiple surgeries at the same location, and weakened immune system due to chemotherapy. If the infection doesn’t respond to initial treatments, the implant might need to be removed, followed by further cleaning and a new prosthesis insertion. In some tough cases, amputation might be required.
• Implant Failure: The most common cause of surgical reconstruction failure is mechanical breakdown of the mega prosthesis, especially in the tibia (the larger of the two bones in the lower leg). If this happens, the prosthesis needs to be replaced.
• Fracture or Non-Union of Allograft/Autograft: In some cases, the bones used in bone grafting procedures — either from another person (an allograft) or from the patient’s own body (an autograft) — may break or fail to grow together. Treatments like chemotherapy and radiation, or an extracorporeal treatment (treatment outside of the body), could make these complications more likely. If the condition doesn’t improve, metallic implant placement or amputation might be necessary.

Preventing Osteosarcoma

If you’re experiencing symptoms like bone pain, joint pain, or if you can physically feel a lump, it’s important to get them checked by a health professional. These symptoms could potentially link to a bone tumor, also known as osseous neoplasm. Pain is a primary concern when dealing with bone cancers like osteosarcoma, so it’s essential to understand how to manage this pain and become familiar with the different options available to you.

Feelings of depression and anxiety are quite common in such situations. That’s why, along with the patient, the family too should consider professional counseling. It’s crucial for both the patient and their family to get information about the different treatment choices, pain management strategies, and the support services available. Understanding these can help in dealing with the disease and its impact better.