Bone cancer: Osteosarcoma and Ewing's sarcoma

Bone cancer refers to the abnormal growth of malignant cells within the bones. The most common form of bone cancer is metastatic bone cancer, which occurs when cancer from another part of the body such as the breast or prostate, spreads (metastasizes) to the bones.

However, primary bone cancer originates directly within the bone itself. These types of bone cancers are rare, making them more challenging to diagnose.

The most common primary bone cancers are osteosarcoma and Ewing's sarcoma.

The primary types of bone cancer include:

• Osteosarcoma: This is the most common type of primary bone cancer, where malignant cells develop directly in the bone. It most commonly affects adolescents and young adults, typically occurring in the bones around the knee. Other common sites include the shoulder and leg. In older adults, osteosarcoma can appear in any bone. It often metastasizes to the lungs.
• Ewing's Sarcoma: A rare type of bone cancer, Ewing's sarcoma (also known as primitive neuroectodermal tumor) is distinct from osteosarcoma in its cellular appearance under a microscope. It primarily affects adolescents and is most commonly found in the pelvis, femur (thigh bone), humerus (upper arm bone), and ribs. Like osteosarcoma, it often spreads to the lungs.
• Chondrosarcoma: This cancer originates in cartilage, a softer tissue attached to bone. It most often occurs in the pelvis, shoulders, and legs, and is more common in individuals over 40 years of age.
• Chordoma: A very rare spinal tumor, chondroma usually occurs in older adults, often in the sacrum or neck. People with a hereditary condition called tuberous sclerosis have a higher risk of developing chordoma in childhood.

Other rare types of bone cancer include malignant fibrohistiocytoma (MFH) and fibrosarcoma.

Additionally, some malignant bone tumors arise from benign tumors that, for unknown reasons, begin to destroy bone and may spread through the bloodstream. Examples include giant cell tumors of bone (also called osteoclastoma) and osteoblastoma.

As with all cancers, the prognosis and treatment options depend on several factors, including the tumor’s size, location, type, stage, duration of symptoms, and the patient’s overall health.

Several factors may increase the risk of developing bone cancer, including:

• Genetic Disorders: Certain inherited conditions can predispose individuals to bone cancer. For example, children with retinoblastoma, a rare eye cancer, are at higher risk due to an abnormal gene.
• Paget’s Disease: This inherited condition, which causes abnormal bone growth and deformities, is associated with an increased risk of bone cancer.
• Radiation Exposure: Exposure to high levels of radiation, particularly from radiation therapy for other cancers or contact with radioactive substances like radium and strontium, can elevate the risk of bone cancer.
• Chemotherapy History: Certain chemotherapy drugs, particularly alkylating agents, may raise the risk of bone cancer.
• Bone Marrow Transplant: Individuals who have undergone bone marrow transplants may have an elevated risk of developing bone cancer.

It’s important to note that trauma or fractures have not been proven to cause bone cancer. However, such injuries may lead to the incidental discovery of an existing bone abnormality or cancer, for example, during diagnostic imaging like X-rays.

In some cases, primary bone cancer may not cause any symptoms. However, when symptoms do appear, they can include:

• Pain.
• Swelling or a lump (a soft, warm mass at the affected bone site).
• Unexplained fever.
• Fractures (spontaneous or unusually easy fractures).

Diagnosing bone cancer involves a series of tests and procedures to confirm the presence of cancerous cells and determine their characteristics.

The definitive diagnostic test is a bone biopsy, which involves examining a sample of the affected bone under a microscope to identify cancerous features.

A bone biopsy can be performed using a needle, by removing a portion of the tumor, or by excising the entire tumor. This complex procedure should be done by an experienced orthopedic oncologist. A pathologist will then analyze the sample using various tests to establish a final diagnosis.

To determine the best site for the biopsy, doctors use imaging tests such as:

• X-rays.
• Bone scan.
• Computed tomography (CT).
• Magnetic resonance imaging (MRI).
• Positron emission tomography (PET).
• Angiography.

Additionally, certain blood tests can help guide the diagnosis, including:

• Alkaline phosphatase.
• Lactic acid dehydrogenase (LDH).

Once bone cancer, such as osteosarcoma or Ewing's sarcoma, is diagnosed, additional tests are conducted to determine whether the cancer has spread to other parts of the body.

Currently, there is no formal staging system for bone cancer. Instead, patients are typically categorized based on the extent of the disease:

• Localized Disease – The cancer is confined to one area of the body.
• Disseminated Disease – The cancer has spread from its original location to other parts of the body.
• Recurrent Disease – The cancer returns after treatment, either in the bone or elsewhere in the body.

Osteosarcoma most commonly spreads to the lungs but can also metastasize to other bones.

Ewing's Sarcoma often spreads to the lungs, other bones, and the bone marrow (the soft tissue inside bones that produces blood cells). It can also spread to the lymph nodes (small structures that help the body fight infections) or the central nervous system (brain and spinal cord).

Treatment for bone cancer is highly individualized and requires close collaboration between orthopedic surgeons and oncologists.

Osteosarcoma Treatment

• Localized Osteosarcoma. Treatment may include:
  1. Surgery to remove the tumor, followed by adjuvant chemotherapy (in some cases, limb amputation is necessary).
  2. Chemotherapy before surgery, followed by surgery and adjuvant chemotherapy.
• Disseminated Osteosarcoma. Treatment may include:
  1. Surgery to remove the tumor, followed by adjuvant chemotherapy. If the cancer has spread to the lungs, surgery may also be needed to remove those tumors. In some cases, multiple surgeries are required.
  2. Chemotherapy before surgery, followed by surgery and adjuvant chemotherapy.
• Recurrent Osteosarcoma. Treatment depends on the location of recurrence, previous treatments, and other factors. Clinical trials exploring new chemotherapy combinations may be an option.

Ewing’s Sarcoma (Primitive Neuroectodermal Tumor) Treatment

• Localized Ewing’s Sarcoma: Treatment depends on the tumor’s location (e.g., elbow, knee, jaw, skull, shoulder, vertebrae). Options include:
  1. Combination chemotherapy.
  2. Surgery followed by combination chemotherapy.
  3. Radiation therapy combined with chemotherapy.
  4. Clinical trials testing new chemotherapy and radiation delivery methods.
  5. Clinical trials evaluating chemotherapy followed by surgery, with or without radiation.
  6. New chemotherapy doses and drug combinations are also under evaluation.
• Disseminated Ewing’s Sarcoma: Treatment may include:
  1. Combination chemotherapy.
  2. Radiation therapy with combination chemotherapy.
  3. Combination chemotherapy plus surgery to remove tumors that have spread to the lungs.
  4. Clinical trials testing new chemotherapy doses and combinations, with or without radiation.
• Recurrent Ewing’s Sarcoma. Treatment depends on the recurrence site, prior treatments, and individual factors. Radiation therapy may be used to alleviate symptoms. Clinical trials for new therapies are often recommended.

Treatment for Unusual Types of Bone Cancer

• Chondrosarcoma: If localized, treatment may involve curettage plus cryotherapy. In advanced cases, amputation of the affected area may be necessary, followed by radiation therapy. Chemotherapy is generally ineffective.
• Chondroma: Surgical treatment is challenging due to its location in the spine. The goal is to remove as much of the tumor as possible without damaging the spinal cord or nerves, followed by radiation therapy.
• Malignant Fibrohistiocytoma: Treated similarly to osteosarcoma, with a combination of surgery and chemotherapy.
• Fibrosarcoma: Treated with radical surgery and radiation therapy.
• Giant Cell Tumors of Bone: Typically treated like osteosarcomas, with extensive surgery and chemotherapy. If the tumor is very localized, curettage and cryotherapy may be an option. In difficult-to-operate locations, radiation therapy is used, though it is generally avoided due to the increased risk of recurrence.