Osteosarcoma - Current Intervention Strategies

Introduction:

Sarcomas are extremely uncommon malignant tumors originating from mesenchymal tissues. There are two main types of sarcomas they are bone sarcoma, which is a type of cancer that arises in the bone and makes up 15 percent of the total pediatric tumors, and soft tissue sarcoma, which is composed of fat, muscle, and blood vessels, fibrous connective tissues, and peripheral nerves and occurs in less than 10 percent of solid tumors in adults. Surgery is the main treatment method for the majority of sarcoma cancers. Chemotherapy has been used to treat patients with metastatic cancers.

What Is Osteosarcoma?

Osteosarcoma is one of the most common primary malignant bone tumors in children and adolescents. It usually appears as a high-grade cancer with severe metastases to the lungs and other bones in the body. It accounts for about 20 percent of the total number of primary bone tumors.

Osteosarcoma arises in two forms:

1. Primary (no underlying bone disease).

2. Secondary (underlying bone disease that has undergone malignant degeneration or conversion).

The clinical manifestation of osteosarcomas can be quite variable, allowing for the separation of the disease into multiple subgroups based on the location within the bone, histological variance, and degree of differentiation. They also differ in demographics, biological behavior, and imaging appearance. Surgery and chemotherapy have been considered the main treatments for osteosarcomas for the past three decades.

What Are the Causes of Osteosarcoma?

Several factors cause osteosarcoma, and it is still unclear. However, studies have found that primary osteosarcoma patients have several genetic abnormalities.

• Hereditary Retinoblastoma: The most common feature of retinoblastoma is the lack of the “red reflex” in one or both of the eyes of the affected child. This condition increases the chance of osteosarcoma at a later stage of life.

• LI - Fraumeni Syndrome: This syndrome has been found in up to three percent of children with osteosarcoma. Individuals suffering from this syndrome also have an increased chance of developing multiple other cancers at a very young age.

• Rothmund-Thomson Syndrome: This syndrome is associated with an increased risk for osteosarcoma, as well as alopecia (hair loss), infantile rash, premature cataracts, chronic digestive problems, and dysplastic osseous structures.

• Boom Syndrome: This syndrome has an increased risk of osteosarcoma, and the patients may appear with short stature, poor subcutaneous fat, and UV (ultraviolet radiation)-induced rashes.

Several risk factors, such as cause secondary osteosarcoma,

1. Electrical burns.

2. Trauma.

3. Alkylating agent exposure.

4. Beryllium exposure.

5. FBJ (Finkel-Biskis-Jinkins murine) virus.

6. Fibrous dysplasia.

7. Osteochondromatosis (a benign condition affecting the synovial membrane of the joints).

8. Enchondromatosis (a skeletal disorder characterized by multiple enchondromas).

9. Orthopedic prosthetics.

10. Bone infection and infarction.

What Are the Treatment Interventions for Osteosarcoma?

There are various treatment options for children with osteosarcoma or UPS (undifferentiated pleomorphic sarcoma) of bone. Some therapies are standard procedures, while others are being investigated in clinical studies.

The five common treatments are:

• Surgery.

• Chemotherapy.

• Radiation therapy.

• Samarium.

• Targeted therapy.

Surgery:

The surgery involves the partial or entire removal of the tumor. Chemotherapy may be used before or after surgery to reduce the size of the tumor, and it is referred to as neoadjuvant chemotherapy. Chemotherapy reduces the amount of bone tissue that needs to be used and postoperative complications.

1. Wide Local Excision: Excision of the cancer and a portion of the surrounding tissue.

2. Limb Sparing Surgery: This surgery removes a tumor without amputating a limb and preserves the appearance of the limb and its function. Limb-sparing surgery is an effective therapy for the majority of individuals with osteosarcoma. The tumor is removed with a wide local excision. The excised bone or tissue is replaced with synthetic bone or a graft from another body area. Limb-sparing surgery is possible when the fracture is discovered at diagnosis or during chemotherapy before surgery. An amputation may be necessary if the surgeon is unable to remove the tumor completely and leave enough healthy tissue surrounding it.

3. Amputation: The surgical removal of all or a portion of an arm or leg. When limb-sparing surgery cannot remove the entire tumor, amputation can be done. A prosthesis or artificial limb may be fixed following amputation.

4. Rotationplasty: This surgery involves the removal of the tumor as well as the knee joint. The leg below the knee is then connected to the leg above the knee, with the foot pointing backward. The ankle joint acts as a knee. The food is then fixed with a prosthesis.

Chemotherapy:

Chemotherapy is a type of cancer treatment in which drugs are used to kill or inhibit the growth of cancerous cells. Chemotherapy agents can enter the bloodstream and target cancer throughout the body. Combination chemotherapy involves taking many anticancer medications. Chemotherapy is frequently administered before and after surgery to remove the primary tumor.

Radiation Therapy:

Radiation therapy uses high-energy X-rays or other radiation forms to kill or inhibit the growth of cancer cells.

Samarium:

The radioactive drug samarium targets tumor cells in bone or other locations of bone cell proliferation. It destroys blood cells in the bone marrow and helps relieve pain caused by bone cancer.

Targeted Therapy:

Targeted therapy is the use of medication or other chemicals to prevent certain proteins, enzymes, or other molecules from acting on tumor cells. The types of targeted therapy are:

1. Kinase Inhibitor Therapy: This therapy blocks the protein required for cancer cell division. Sorafenib is a kinase inhibitor drug used to treat recurrent osteosarcoma. Cabozantinib is under investigation for the treatment of newly diagnosed localized and metastatic osteosarcoma.

2. Mammalian Target of Rapamycin (mTOR) Inhibitors: It decreases the activity of the protein known as mTOR, which may inhibit the proliferation of cancer cells. Recurrent osteosarcoma is also treated with Everolimus.

Conclusion:

An interdisciplinary team of experts from radiology, orthopedics, pathology, and medical or surgical oncology is recommended to manage patients suffering from osteosarcoma. Musculoskeletal radiologists or pathologists must interpret images and tissue specimens for a reliable diagnosis and prognosis. Oncologists are essential members of the healthcare team to administer the proper adjuvant and neoadjuvant chemotherapy treatments and help with long-term monitoring for nearby and distant relapses of the tumor.