**Abstract**

Osteosarcoma is classically defined as a high-grade spindle-shaped neoplasm with malignant cells that produce osteoid. It is the most common primary malignant bone tumor in children and young adults. It is <1% of all cancers diagnosed, approximately 3.4% of all childhood cancers. The age-adjusted incidence of osteosarcoma is bimodal, with an initial peak in adolescence and then a second peak in patients over 60 years of age. Osteosarcoma is divided into two main groups. In most of the osteosarcomas, the etiological agent cannot be determined and it is called primary osteosarcoma. Osteosarcoma, which develops due to etiologies such as Paget's disease, radiotherapy or osteonecrosis, is called seconder osteosarcoma. Osteosarcomas are most commonly located in the appendicular skeleton. The most common settlement here is the knee circumference. The distal femur and proximal tibia are the most common locations in the knee. A multidisciplinary approach is indicated in the management of osteosarcoma. The treatment is multimodal, including systemic chemotherapy and local therapy. In this section, we will outline the current standard of care for the systemic and surgical approach to osteosarcoma treatment, as well as an overview of current studies.

**Keywords:** osteosarcoma, recent advances, management, current approach, treatment

#### **1. Introduction**

Osteosarcoma is the most common primary malignant bone tumor. It consists of malignant mesenchymal cells that tend to form osteoid matter. It is defined as the most common bone malignant tumor after multiple myeloma and metastases [1, 2].

Three-quarters of all cases are between the ages of 10–25. The age-adjusted incidence of osteosarcoma is bimodal, with an initial peak in adolescence and then a second peak in patients over 60 years of age [3].

Osteosarcoma is most often located around the knee. Distal femur and proximal tibia are the most common knee localizations. The most common location after knee circumference is the proximal humerus. The most common location of the tumor in the bone is the metaphysis like many other tumors. It can rarely settle in the diaphysis [4].

## **2. Etiology and risk factors**

In osteosarcoma cases in pediatric patients, almost all cases do not have any identifiable associated risk factors.

It has been determined that in almost half of the osteosarcoma cases seen in adult patients, various risk factors such as Paget's disease and radiation are involved in the etiology. In addition, some syndromes such as Li Fraumeni Syndrome, hereditary retinoblastoma syndrome, have been reported as risk factors for osteosarcoma [5].

Studies have been conducted on the genetic profile of osteosarcoma in recent years. Studies have reported that Germline TP53 mutations may be high in osteosarcomas, especially at younger ages. In osteosarcomas seen at a young age, if the location of the tumor is unusual, further examination is recommended in terms of Li-Fraumeni syndrome [6].

### **3. Classification**

Osteosarcoma is divided into two main groups as primary and secondary osteosarcoma. Primary osteosarcoma is divided into subtypes such as classical osteosarcoma, telangiectatic osteosarcoma, small cell osteosarcoma, multicentric osteosarcoma, high grade central osteosarcoma, low gradesurface osteosarcoma, and superficial (parosteal-periosteal) osteosarcoma [7].

Various etiological factors play a role in secondary osteosarcoma. Osteosarcoma secondary to Paget's disease, osteosarcoma secondary to radiotherapy, osteosarcoma secondary to osteonecrosis, osteosarcoma secondary to fibrous dysplasia are some of the secondary osteosarcoma types [5].

### **4. Clinical findings and diagnosis**

The most common clinical finding is pain and is seen in approximately 90% of patients. The second most common finding is swelling in the bone localization and is detected in approximately 50% of cases. Generally, patients present with complaints of pain and swelling in that area for weeks-months. Another finding is limitation of movement and is seen in approximately 45% of cases. In addition, patients rarely present with pathological fractures (about 8%) [8].

Alkaline phosphatase was found to be high in about half of osteosarcoma patients. High levels of lactate dehydrogenase at the time of diagnosis were found to be associated with relapse. In addition, Lactate dehydrogenase levels are also high in metastatic patients [8, 9].

In radiological evaluation, firstly, anteroposterior and lateral radiographs of the relevant region should be taken (**Figure 1**). When direct X-ray findings, bone involving the lesion, location of the tumor in the bone, age and gender of the patient are evaluated together, a correct diagnosis can be made in most of the cases (more than three quarters of the cases) [10].

Cortex destruction, geographic or moth-eaten-like medullary lesion, sunlightlike periosteal reaction, Codman triangle, and soft tissue shadow in the bone neighborhood can be seen on plain X-ray [11].

Whenever there is any doubt about the nature of a bone lesion in a young patient, CT and/or MRI should be performed. Thus, new bone formation, cortical destruction, or soft tissue component that may indicate malignancy can be detected (**Figure 2**). In addition to imaging the primary tumor, MRI should be taken to view the entire bone to detect possible skip metastases [12].

Performing the MRI test before any biopsy attempt is vital, as reactive changes due to biopsy reduce staging accuracy [13].

**89**

soft tissue [11, 14].

**Figure 1.**

surgical incision [2].

**5. Staging**

diagnosis [15].

*Current Therapeutic Approaches for Osteosarcoma DOI: http://dx.doi.org/10.5772/intechopen.98434*

Radiological examinations are examined for the presence of findings specific to malignant bone tumors. These findings are sclerotic lesions that are located mostly in the metaphysis, progressing towards the epiphysis or diaphysis or laterally, radial calcified areas, disruption of the cortex integrity, fragmentation or elevation of the periosteum, Codman triangle and extension of the lesion to the

*Right femur distal located osteosarcoma, a) anteroposterior and b) lateral radiography.*

The definitive diagnosis is made after the histopathological examination of the biopsy specimen. Biopsy should be done by the team that will make the definitive treatment of the patient. The formation of osteoid material and the presence of atypical osteoblasts are diagnostic. CT-assisted needle biopsies and, if necessary, incisional biopsy should be performed in the trace of the original

Osteosarcoma is considered a systemic disease. Tumor cells are present in the circulating blood and tumor micro-metastases are possible in the lungs. Approximately 10–20% of osteosarcoma patients are metastatic at the time of

It is a three-grade system generally used in determining tumor grade. Grade 1 represents low grade. There is a well-differentiated tumor. Grade 2 represents middle grade, there is a moderately differentiated tumor. Grade 3 represents high grade, there is an undifferentiated tumor. If the tumor grade is low, the tumor is

resistant to chemotherapy and radiotherapy [2, 7].

*Current Therapeutic Approaches for Osteosarcoma DOI: http://dx.doi.org/10.5772/intechopen.98434*

*Recent Advances in Bone Tumours and Osteoarthritis*

for osteosarcoma [5].

**3. Classification**

Li-Fraumeni syndrome [6].

(parosteal-periosteal) osteosarcoma [7].

of the secondary osteosarcoma types [5].

**4. Clinical findings and diagnosis**

(more than three quarters of the cases) [10].

neighborhood can be seen on plain X-ray [11].

due to biopsy reduce staging accuracy [13].

the entire bone to detect possible skip metastases [12].

metastatic patients [8, 9].

It has been determined that in almost half of the osteosarcoma cases seen in adult patients, various risk factors such as Paget's disease and radiation are involved in the etiology. In addition, some syndromes such as Li Fraumeni

Syndrome, hereditary retinoblastoma syndrome, have been reported as risk factors

Studies have been conducted on the genetic profile of osteosarcoma in recent years. Studies have reported that Germline TP53 mutations may be high in osteosarcomas, especially at younger ages. In osteosarcomas seen at a young age, if the location of the tumor is unusual, further examination is recommended in terms of

Osteosarcoma is divided into two main groups as primary and secondary osteosarcoma. Primary osteosarcoma is divided into subtypes such as classical osteosarcoma, telangiectatic osteosarcoma, small cell osteosarcoma, multicentric osteosarcoma, high grade central osteosarcoma, low gradesurface osteosarcoma, and superficial

Various etiological factors play a role in secondary osteosarcoma. Osteosarcoma secondary to Paget's disease, osteosarcoma secondary to radiotherapy, osteosarcoma secondary to osteonecrosis, osteosarcoma secondary to fibrous dysplasia are some

The most common clinical finding is pain and is seen in approximately 90% of patients. The second most common finding is swelling in the bone localization and is detected in approximately 50% of cases. Generally, patients present with complaints of pain and swelling in that area for weeks-months. Another finding is limitation of movement and is seen in approximately 45% of cases. In addition,

Alkaline phosphatase was found to be high in about half of osteosarcoma patients. High levels of lactate dehydrogenase at the time of diagnosis were found to be associated with relapse. In addition, Lactate dehydrogenase levels are also high in

In radiological evaluation, firstly, anteroposterior and lateral radiographs of the relevant region should be taken (**Figure 1**). When direct X-ray findings, bone involving the lesion, location of the tumor in the bone, age and gender of the patient are evaluated together, a correct diagnosis can be made in most of the cases

Cortex destruction, geographic or moth-eaten-like medullary lesion, sunlight-

Performing the MRI test before any biopsy attempt is vital, as reactive changes

like periosteal reaction, Codman triangle, and soft tissue shadow in the bone

Whenever there is any doubt about the nature of a bone lesion in a young patient, CT and/or MRI should be performed. Thus, new bone formation, cortical destruction, or soft tissue component that may indicate malignancy can be detected (**Figure 2**). In addition to imaging the primary tumor, MRI should be taken to view

patients rarely present with pathological fractures (about 8%) [8].

**88**

**Figure 1.** *Right femur distal located osteosarcoma, a) anteroposterior and b) lateral radiography.*

Radiological examinations are examined for the presence of findings specific to malignant bone tumors. These findings are sclerotic lesions that are located mostly in the metaphysis, progressing towards the epiphysis or diaphysis or laterally, radial calcified areas, disruption of the cortex integrity, fragmentation or elevation of the periosteum, Codman triangle and extension of the lesion to the soft tissue [11, 14].

The definitive diagnosis is made after the histopathological examination of the biopsy specimen. Biopsy should be done by the team that will make the definitive treatment of the patient. The formation of osteoid material and the presence of atypical osteoblasts are diagnostic. CT-assisted needle biopsies and, if necessary, incisional biopsy should be performed in the trace of the original surgical incision [2].
