Osteosarcoma

Osteosarcoma, also called osteogenic sarcoma is the most common primary malignant bone tumor, popularly often, but not medically quite correctly as " bone cancer " refers to. His proliferating cells are capable of forming bone and osteoid ( uncalcified bone matrix ). Osteosarcoma is characterized by aggressive growth with destruction of the surrounding bone and, where appropriate joint. It metastasizes early via the blood stream ( hematogenous spread ) to the lungs. Already 20% of patients approximately another 60 % at the time of diagnosis have metastases and appreciated invisible micrometastases. By an extended operation with pre-and post-operative intensive chemotherapy about 60 to 75% of the patients are cured. Since a change in the RB gene plays a role in the tumorigenesis of osteosarcoma, sick children disproportionately more likely to retinoblastoma.

Frequency localization

The incidence in Central Europe is about 0.2-0.3 per 100,000. This cancer is among the rarer cancers. Extrapolated to the whole of Germany to give about 200 new cases per year ( in Switzerland and Austria each about 10 to 15 cases / year ). The median age at diagnosis is 18 years, and most diseases are diagnosed in the age group between 10 and 25 years old. Male patients are affected slightly more often. Osteosarcoma is thus the most common malignant solid tumor of adolescence. Osteosarcomas occur mainly near the joint in the long bones ( femur, humerus, tibia ) of the skeletal system. 50 % of osteosarcomas are located in close proximity to the knee joint and about 10% near the shoulder joint. The localization of the cranial bone or spinal column can be found, however, rare.

Etiology

Numerous risk factors for the development of soft tissue sarcoma have been described, but they explain only a fraction of the sarcomas.

One of the possible causes of osteosarcoma is a previous radiotherapy or radioactive exposure. In a cohort study of more than forty years to more than 80,000 survivors of the atomic bombings in Hiroshima and Nagasaki, a linearly increasing risk for the development of a malignant bone cancer with a relative risk of 7.5 per Gray irradiation from a lower limit of 0.85 Gray showed upwards.

Classification / subclassification

The central ( medullary ) Osteosarcoma

• Classical osteosarcoma ( chondroblastisch, fibroblastic, osteoblastic )
• Teleangiektatisches osteosarcoma
• Well- differentiated central ( low-grade ) O.
• Small cell osteosarcoma

Superficial (peripheral ) Osteosarcoma

• Parosteales osteosarcoma
• Periosteales O.
• High-grade O.

As a condition secondary osteosarcoma can occur after previous radiation exposure and disease Osteitis deformans in Paget.

Histology

Histologically, the cells of osteosarcoma are highly polymorphic and irregular. It is characteristic that the tumors synthesize primitive bone ( osteoid ), without that you can see a cartilage matrix.

Diagnostics

• X-ray photograph
• Sampling (biopsy) and histological examination
• Magnetic resonance imaging ( MRI) is important for assessing the propagation in tissue.
• Bone scintigraphy and computed tomography of the lungs (CT ) are necessary for the metastasis- search.

Especially the occurrence in adolescence often leads to misdiagnosis. Therefore, bone pain, especially in the knee joint, are controlled not later than four weeks by means of X-ray examination.

Therapy

Simplified Overview in chronological order:

Detailed overview:

• Neoadjuvant chemotherapy according to the study protocol (COSS, EURAMOS, EUROBOSS ) in an oncology center

After neoadjuvant chemotherapy biopsies with regard to tumor size, tumor type, margin status and degree of regression are re-examined. To determine the degree of regression work-up of a tumor slice in the largest diameter is necessary. What matters is how much residual tumor is found in this slice ( Responders: less than 10 % residual tumor). Thus, a prediction is possible, the extent to which a substance changes is indicated for the occurrence of metastases.

• Removal of the tumor into healthy, that is around the tumor apparently healthy tissue removed with

The amount of healthy tissue varies, 2 cm of bone up to a fat slat (1 mm) in vascular / nerve. This can, depending on the place of occurrence of the tumor and contact with the neurovascular as the main structure lead to large residual defects can be reconstructed in several ways:

A) Biologically

• Bone shortening, rotation plastic, amputation
• Bone grafting with autogenous bone with or without vascular access, pivotings ( clavicle per humero )
• Allograft transplantation (allograft )
• Replantation of " eg radiation sterilized ' own bone

B) Endoprothetisch

• Tumormegaendoprothesen
• Adjuvant chemotherapy to reduce the risk of metastasis (even surgical removal of metastases)
• Possibly additionally ( approved immunomodulator since 2009 in the EU) Mifamurtide

• Cancer follow-up every 3 months by chest CT to detect any lung metastases and the surgical site for 2 years
• Cancer follow-up every 6 months by chest CT to detect any lung metastases and the surgical site for another 3 years
• Cancer follow-up every 12 months by chest CT to detect any lung metastases and the surgical site for another 5 years

Tumors can be treated with neoadjuvant chemotherapy. An exception is the very rare parosteal osteosarcomas (G1 ), whose division and metastasis rate is considered very low. There is a surgical removal of all tumors ( primary tumor and metastases) in healthy subjects ( = at a safe distance ). Osteosarcoma is little sensitive to radiation, so radiation is generally not used.

Course and prognosis

Under therapy, the 5-year survival rate is 70% on average. Lung metastases are a poor prognostic sign. However, lung metastases can be restored by surgery, so that patients with lung metastases can achieve a cure. The most important prognosis factor is the response to chemotherapy (COSS schema ): If the chemotherapy is not responsive, that is, less than 90 % of the tumor cells could be killed, the survival rate is less than 50%. The number of killed cells is determined after the completion of preoperative chemotherapy on surgical specimen ( tumor-bearing bone ). Almost always have a prosthesis must be implanted, or reversing plastic are applied.

Osteosarcoma in veterinary medicine

Veterinary Medical osteosarcoma occurs especially in large breeds of dogs frequently. Affected is V.A. the median age category, with some studies also describe a predisposition for castrated animals. Osteosarcoma is thereby usually clinically as painful swelling of the long bones under the principle elbow joint remote - Kniegelenksnah. Case usually is in the typical sunburst pattern to see a resolution bone ( osteolysis) On a radiograph.

The prognosis in canine osteosarcoma is very bad. Most are already in the diagnosis (microscopic or macroscopic ) lung metastases present. Amputation, radiotherapy and chemotherapy are possible treatment measures, but usually purely palliative.

In some breeds ( Saint Bernard, Deerhound ) was described beside a familial incidence of osteosarcoma cases. In addition, several mutations are known in dogs, which increase the risk of osteosarcoma.

Swell

• The orthopedist 11/2003: Surgical treatment of malignant primary bone tumors.
• The oncologist 2/2006: Recent developments in the chemotherapy of osteosarcoma.
• Uhl / Herget: Radiologic diagnosis of bone tumors. Thieme- Verlag 2008
• Seeber / Schütte: therapeutic concepts oncology. Chapter 46: osteosarcoma. 5th edition 2007. Springer -Verlag, ISBN 978-3-540-28588-5
• Diagnosis and treatment of osteosarcoma