**6. Treatment management**

*Recent Advances in Bone Tumours and Osteoarthritis*

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**Figure 2.**

*noted in post-contrast series.*

Osteosarcoma most often metastasizes to the lungs. This is followed by bone metastases. Contrast-enhanced thin-section CT of the lung is the gold standard in detecting the presence of metastasis in the lung. Skip metastases in the same bone and distant bone metastases can be detected by Whole-Body Bone Scintigraphy. PET-CT is valuable in showing all body metastases and evaluating the chemotherapy

*MRI images involving the right femur distal and joint; a) coronal T1 sequence, b) coronal T2 - STIR image, c) axial T2 sequence and d) T1 + contrast image. In the images, the distal third of the right femur has an extension to the superior part of the inner femoral condyle and the midline distal of the femur, and has a satellite nodular structure of approximately 5.5 mm in the epiphyseal line, especially in the T1A series, the heterogeneous hyperintense signal in the T2A series, infiltrating bone marrow fat 12.5 there is a mass lesion of x4cm. Especially when T2 sequence was examined, it was determined that the mass showed extra cortical and extra osseous spread in the inner part, periosteal reaction and accompanying a soft tissue mass in the intramuscular localization with an intramuscular localization of approximately 84x48mm with a heterogeneous necrotic contrast in the soft tissue. Low-intensity, especially peripherally wavy rim-style contrast enhancement was* 

response after treatment. Also useful for detecting nucleus [7, 8, 11].

In the past, patients with osteosarcoma were tried to be treated with amputation, but patients were lost due to micro-metastatic disease and lung metastases. With the discovery that chemotherapy can eliminate micro-metastases (1970's), limb-sparing surgeries came to the fore [16]. The application of neoadjuvant chemotherapy and limb-sparing surgeries became standard in the 1980s. This paved the way for the development of limb salvage procedures that can achieve limb with better functional and cosmetic results. With the advances in treatment, studies on long-term functional and cosmetic extremity acquisition methods have increased.

With the development of induction and adjuvant chemotherapy protocols and advances in surgical techniques and radiological staging studies, approximately 90–95% of patients are now treated with limb-sparing methods instead of amputation. In limb-sparing surgery, reconstruction is applied in necessary patients in addition to tumor resection. And after all these advances, the chance of long-term survival and cure rate of these patients increased to 60–80% in localized (nonmetastatic) diseases [17].

In classical osteosarcoma, the general treatment plan is preoperative (neoadjuvant) chemotherapy, extremity conserving surgery if possible, and postoperative chemotherapy regimen based on the extent of tumor necrosis. In surgical treatment, the tumor is resected with wide margins. Amputation is performed for patients who cannot undergo limb-sparing surgery [18]. Osteosarcoma is a radioresistant tumor and radiotherapy does not have therapeutic properties.

The high-dose methotrexate with leucovorin rescue (HDMTX), doxorubicin and cisplatin (MAP) trio is the basis of standard systemic chemotherapy and is administered for approximately 30 weeks [16]. In a newly diagnosed osteosarcoma patient, 2 cycles of neoadjuvant chemotherapy (2 MAP cycles for approximately 10 weeks) are applied first.

After the HDMTX infusion administered for 2 weeks, a 1-week break is taken, then doxorubicin and cisplatin are administered for 2 days. And a 2-week break is given for bone marrow recovery. And the cycle repeats. Then, surgical treatment is applied [19].

Histological response value evaluated during surgical treatment is a strong prognostic factor. High tumor necrosis rate has better clinical outcomes after neoadjuvant chemotherapy [20].

The results of surgery alone are very poor in osteosarcoma treatment. And with chemotherapy alone, only about 10% of the patients responded [21].

Local control can be achieved through limb salvage surgery or ablative surgery (**Figure 3**). There is no significant difference between amputation and wide resection in local surgery in terms of recurrence and survival rates. Metastasectomy should be considered in lung metastases [14].

In recent years, many studies have been conducted on reconstruction after tumor resection with wide margins in local treatment and reconstruction options have been diversified. Custom-made or modular tumor resection prostheses are one of them. In addition, osteoarticular allografts and composite allografts are other options. With the advances in microsurgery, vascular fibula and myo-cutaneous flaps have also become an alternative for reconstruction. Another option is the method of recovered bone (reconstruction of the bone with the tumor tissue covered by removing the tumor, autoclaving or irradiating it or treating the bone with liquid nitrogen) [11, 22].

After the HDMTX infusion administered for 2 weeks, a 1-week break is given, then doxorubicin and cisplatin are administered for 2 days. And a 2-week break is

#### **Figure 3.**

*Right femur distal located osteosarcoma, post-operatively a) anteroposterior and b) lateral radiography. There was skip metastasis in the epiphysis localization of the distal femur. Tumor resection with white margins and reconstruction operation with distal femur tumor resection prosthesis were performed as local treatment.*

given for bone marrow recovery. And the cycle repeats. Then, surgical treatment is applied [16].

Overall survival for lower limb reconstructions ranges from about 70–85% at 5 years [23].

Adjuvant MAP therapy should be initiated within 3 weeks after surgical treatment. Because especially in patients with low tumor necrosis rate, a delay of more than 3 weeks is associated with high recurrence rates. Current standard adjuvant chemotherapy includes a total of 29 weeks of MAP cycles.

## **7. Prognosis**

Several prognostic factors have been identified in the management and followup of osteosarcoma. Stage (local-systemic spread) is a poor prognostic factor. As the tumor stage increases, the prognosis worsens. Another prognostic factor is tumor grade. Low grade types are parosteal osteosarcoma, periosteal osteosarcoma and low-grade intramedullary osteosarcoma. Tumor size is poor prognostic. As the tumor size increases, the prognosis worsens. Tumor localization affects the prognosis. Tumors located distal to the elbow in the upper extremity and tumors located distal to the knee in the lower extremity have a relatively better prognosis. It has been reported that the presence of pathological fractures does not affect the prognosis. Gender has also been reported as a prognostic factor. The prognosis is

**93**

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

disease is another poor prognostic factor.

postoperatively.

**8. Recent advances**

thought [20, 27].

**9. Conclusions**

time of diagnosis.

**Conflict of interest**

standard therapy [20, 27].

relatively better in female patients. Prognosis is worse in secondary osteosarcoma. Five-year survival is less than 10% in osteosarcoma patients developing on the basis of Paget's disease, and 5-year survival is less than 20% in patients with osteosarcoma developing on a radiation background [11, 14, 24]. The presence of metastatic

Patients should be followed for at least five years in terms of systemic metastases

Studies on intensified chemotherapy are continuing in patients who underwent surgery after neoadjuvant chemotherapy and in patients with poor histological response detected during surgery. Poor histological responders are defined as patients who maintain more than 10% viable tumors following surgery. Current studies report that chemotherapy intensification has less successful results than

Several clinical studies have been investigating the intensification of adjuvant chemotherapy by adding high-dose ifosfamide with or without etoposide to MAP for poor histological responders following definitive surgery. However, it has not been shown to be superior to standard chemotherapy. In addition, studies with cytokine interferon alfa-2b showed that this agent did not provide superiority to

Studies with high-dose ifosfamide to avoid the long-term nephrotoxic effects of methotrexate have shown equivalent effect rates [28]. Similarly, studies have been conducted with dexrazoxane to avoid long-term nephrotoxic effects of doxorubicin. [29].

The current standard of care for a patient with newly diagnosed osteosarcoma includes 2 cycles of MAP neoadjuvant chemotherapy followed by local tumor surgery and 29 weeks of adjuvant MAP chemotherapy. With this standard approach, disease-free survival is approximately 70% in patients with localized disease at the

Treatment outcomes for patients with osteosarcoma, for localized, metastatic, or relapse patients, have not improved significantly and have not gotten better in the

The poor results of patients with low necrosis during surgery after neoadjuvant chemotherapy still appear as a treatment challenge. It has been shown that intensified chemotherapy methods, which have been emphasized in recent years, are not

last 10 years, despite many improvements and extensive studies.

The authors declare no conflict of interest.

superior to conventional treatment. It is clear that more work is needed.

In patients with macro-metastasis at the time of diagnosis, despite systemic chemotherapy and surgery, 5-year disease-free survival is approximately 20% [25].

In addition, 10-year survival is less than 20% in relapse cases [26].

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

relatively better in female patients. Prognosis is worse in secondary osteosarcoma. Five-year survival is less than 10% in osteosarcoma patients developing on the basis of Paget's disease, and 5-year survival is less than 20% in patients with osteosarcoma developing on a radiation background [11, 14, 24]. The presence of metastatic disease is another poor prognostic factor.

Patients should be followed for at least five years in terms of systemic metastases postoperatively.

In patients with macro-metastasis at the time of diagnosis, despite systemic chemotherapy and surgery, 5-year disease-free survival is approximately 20% [25]. In addition, 10-year survival is less than 20% in relapse cases [26].

### **8. Recent advances**

*Recent Advances in Bone Tumours and Osteoarthritis*

given for bone marrow recovery. And the cycle repeats. Then, surgical treatment

*Right femur distal located osteosarcoma, post-operatively a) anteroposterior and b) lateral radiography. There was skip metastasis in the epiphysis localization of the distal femur. Tumor resection with white margins and reconstruction operation with distal femur tumor resection prosthesis were performed as local treatment.*

Overall survival for lower limb reconstructions ranges from about 70–85% at

Adjuvant MAP therapy should be initiated within 3 weeks after surgical treatment. Because especially in patients with low tumor necrosis rate, a delay of more than 3 weeks is associated with high recurrence rates. Current standard adjuvant

Several prognostic factors have been identified in the management and followup of osteosarcoma. Stage (local-systemic spread) is a poor prognostic factor. As the tumor stage increases, the prognosis worsens. Another prognostic factor is tumor grade. Low grade types are parosteal osteosarcoma, periosteal osteosarcoma and low-grade intramedullary osteosarcoma. Tumor size is poor prognostic. As the tumor size increases, the prognosis worsens. Tumor localization affects the prognosis. Tumors located distal to the elbow in the upper extremity and tumors located distal to the knee in the lower extremity have a relatively better prognosis. It has been reported that the presence of pathological fractures does not affect the prognosis. Gender has also been reported as a prognostic factor. The prognosis is

chemotherapy includes a total of 29 weeks of MAP cycles.

**92**

is applied [16].

5 years [23].

**Figure 3.**

**7. Prognosis**

Studies on intensified chemotherapy are continuing in patients who underwent surgery after neoadjuvant chemotherapy and in patients with poor histological response detected during surgery. Poor histological responders are defined as patients who maintain more than 10% viable tumors following surgery. Current studies report that chemotherapy intensification has less successful results than thought [20, 27].

Several clinical studies have been investigating the intensification of adjuvant chemotherapy by adding high-dose ifosfamide with or without etoposide to MAP for poor histological responders following definitive surgery. However, it has not been shown to be superior to standard chemotherapy. In addition, studies with cytokine interferon alfa-2b showed that this agent did not provide superiority to standard therapy [20, 27].

Studies with high-dose ifosfamide to avoid the long-term nephrotoxic effects of methotrexate have shown equivalent effect rates [28]. Similarly, studies have been conducted with dexrazoxane to avoid long-term nephrotoxic effects of doxorubicin. [29].
