Osteosarcoma

Classification according to ICD-10
C40	Malignant neoplasm of the bone and articular cartilage of the extremities
C41	Malignant neoplasm of bone and articular cartilage in other and unspecified locations
ICD-10 online (WHO version 2019)

The osteosarcoma , and osteogenic sarcoma called, is the most common primary malignant bone tumor , often in the vernacular, but not entirely accurate medically termed as "bone cancer". Its proliferating cells are able to form bones and osteoid (uncalcified basic bone substance). The osteosarcoma is characterized by aggressive growth with destruction of the surrounding bone and possibly the joint. It metastasizes early via the bloodstream (hematogenous) into the lungs . At the time of diagnosis, 20% of patients already have metastases and an estimated 60% have invisible micrometastases. Extensive surgery with intensive pre- and post-operative chemotherapy can cure around 60 to 75% of patients. Since a change in the RB gene plays a role in the development of tumors in the osteosarcoma , affected children are disproportionately more likely to develop retinoblastomas .

Frequency, location

The growth is the mineralized part of an osteosarcoma of this thigh bone from the ancient Egyptian 5th dynasty.

The incidence in Central Europe is around 0.2-0.3 per 100,000. This type of cancer is one of the rarer types of cancer. Extrapolated to the whole of Germany, there are around 200 new cases per year, in Switzerland and Austria around 10 to 15 cases per year. The median age of onset is 18 years, and most diseases are diagnosed between the ages of 10 and 25. Male patients are affected slightly more often. The osteosarcoma is therefore the most common malignant solid tumor in adolescence. Osteosarcomas mainly develop near the joints in the long tubular bones (thigh, upper arm, shin) of the skeletal system. 50% of osteosarcomas are in close proximity to the knee joint and around 10% in the vicinity of the shoulder joint . A localization on the cranial bone or on the spine is rarely found.

The typical changes to the skeleton have also been proven historically and prehistorically. The oldest evidence of an osteosarcoma in a human ancestor - probably from the genus Australopithecus - comes from a 1.7 million year old fossil from South Africa, from which a damaged foot bone has been preserved.

etiology

One of the possible causes of osteosarcoma is prior radiation therapy or radioactive exposure . In a cohort study over more than forty years of over 80,000 survivors of the atomic bombs in Hiroshima and Nagasaki , there was a linearly increasing risk of developing malignant bone cancer with a relative risk of 7.5 per Gray irradiation from a lower limit of 0.85 Gray upwards.

Classification / sub-classification

Central (medullary) osteosarcoma

• classic osteosarcoma (chondroblastic, fibroblastic, osteoblastic)
• telangiectatic osteosarcoma
• Well-differentiated central (low-grade) osteosarcoma
• small cell osteosarcoma

Superficial (peripheral) osteosarcoma

• parosteal osteosarcoma
• periosteal osteosarcoma
• high-grade osteosarcoma

As a secondary disease, osteosarcoma can occur after previous exposure to radiation and in Paget's disease osteodystrophia deformans .

histology

Histologically, the cells of the osteosarcoma are highly polymorphic and irregular. It is characteristic that the tumors synthesize primitive bone substance (osteoid) without being able to recognize a cartilage matrix.

Diagnosis

X-ray of an affected bone in a dog

• X-ray image
• Sampling ( biopsy ) and tissue examination
• Magnetic resonance imaging (MRI) is important for assessing the spread in tissue.
• Skeletal scintigraphy and computed tomography of the lungs (CT) are necessary to search for metastases .

The occurrence in adolescence often leads to misdiagnosis. Therefore, bone pain, especially in the knee joint, should be checked by means of an X-ray examination after four weeks at the latest .

therapy

Simplified overview in chronological order:

1. Biopsy (tissue sample from suspicious area)
2. Preoperative chemotherapy ( neoadjuvant therapy , i.e. chemotherapy is administered before the operation)
3. Operation with complete removal of the tumor
4. Postoperative ( adjuvant ) chemotherapy, possibly together with an immunomodulator ( mifamurtide )

Detailed overview:

• neoadjuvant chemotherapy according to study protocol (COSS, EURAMOS, EUROBOSS) in an oncological center

After neoadjuvant chemotherapy, biopsies are again examined for tumor size, tumor type, resection status and degree of regression. To determine the degree of regression, it is necessary to process a tumor disc with the largest diameter. The decisive factor is how much residual tumor is found in this disc (responder: less than 10% residual tumor). It is thus possible to predict the extent to which a substance change is indicated when metastases occur.

• Removal of the tumor in the healthy, d. that is, apparently healthy tissue around the tumor is also removed

The amount of healthy tissue varies, from 2 cm for bones to a fat lamella (1 mm) for vessels / nerves. Depending on the location of the tumor and the contact with the vascular nerves as the most important structure, this can lead to large remaining defects that can be reconstructed in various ways:

A) Biologically

• Bone shortening, rotational plastic surgery , amputation
• Bone transplantation with own bone with or without vascular connection, swiveling ( clavicle pro humero )
• Foreign bone transplant (allograft)
• Replantation of “z. B. radiation-sterilized "own bones"

B) Endoprosthetic

• Tumor mega-prostheses
• adjuvant chemotherapy to reduce the risk of metastasis (possibly also surgical removal of the metastases)
• possibly also mifamurtide (immunomodulator, approved in the EU since 2009)
• Tumor follow-up every 3 months using chest CT to reveal possible lung metastases and the surgical area for 2 years
• Tumor follow-up every 6 months using chest CT to reveal possible lung metastases and the surgical area for a further 3 years
• Tumor follow-up every 12 months using chest CT to reveal possible lung metastases and the surgical area for a further 5 years

Tumors can only be treated with neoadjuvant chemotherapy . The very rare parossal osteosarcomas (G1), whose rate of division and metastasis is classified as very low, are an exception. All tumors (primary and metastases) are surgically removed in healthy subjects (= with a safety margin). The osteosarcoma is not very sensitive to radiation, so that radiation is usually not used.

Course and prognosis

During therapy, the 5-year survival rate averages 70%. Lung metastases are a bad prognostic sign. However, lung metastases can be repaired through an operation so that patients with lung metastases can also achieve a cure. The most important prognostic factor is the response to chemotherapy (COSS scheme): If the chemotherapy does not respond, i.e. less than 90% of the tumor cells have been killed, the chance of survival is less than 50%. The number of cells killed is determined on the surgical specimen (tumor-bearing bone) after the preoperative chemotherapy has been completed. Almost always an endoprosthesis has to be implanted or a reverse plastic has to be used.

Osteosarcoma in veterinary medicine

Osteosarcoma on the left foreleg in an Anatolian Shepherd Dog

From a veterinary perspective , osteosarcoma is particularly common in large breeds of dogs. Affected is v. a. the middle age category, although some studies also describe a predisposition to castrated animals. The osteosarcoma usually shows up clinically as a painful swelling on the long tubular bones according to the principle of the distal elbow joint - close to the knee joint . An X-ray usually shows bone dissolution (osteolysis) in the typical sunburst pattern .

The prognosis for canine osteosarcoma is very poor. Usually (microscopic or macroscopic) lung metastases are already present at the time of diagnosis. Amputation, radiotherapy and chemotherapy are possible treatment measures, but usually purely palliative .

In some breeds ( St. Bernard , Deerhound ) a familial accumulation of osteosarcoma cases has been described. In addition, various gene mutations are known in dogs that increase the risk of osteosarcoma.

Web links

Commons : Osteosarcoma  - Collection of pictures, videos and audio files

swell

• Der Orthopäde 11/2003: Surgical therapy of primarily malignant bone tumors.
• Der Onkologe 2/2006: Current developments in chemotherapy for osteosarcoma.
• Uhl / Herget: Radiological diagnosis of bone tumors. Thieme-Verlag 2008
• Seeber / Schütte: Oncology Therapy Concepts. Chapter 46: Osteosarcoma. 5th edition 2007. Springer-Verlag, ISBN 978-3-540-28588-5
• Diagnosis and therapy of osteosarcoma

Individual evidence

1. ↑ A. Luetke et al. a .: Osteosarcoma treatment - where do we stand? A state of the art review. Cancer Treat Rev 2014; 40: 523-32. PMID 24345772
2. ↑ SS Bielack et al .: Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. In: J Clin Oncol 20, 2002, pp. 776-790. PMID 11821461
3. ^ Edward J. Odes et al .: Earliest hominin cancer: 1.7-million-year-old osteosarcoma from Swartkrans Cave, South Africa. In: South African Journal of Science. Published online on July 28, 2016, doi: 10.17159 / sajs.2016 / 20150471
   Cancer on a Paleo-diet? Ask someone who lived 1.7 million years ago. On: eurekalert.org of July 28, 2016
4. ↑ Dino Samartzis, Nobuo Nishi, Mikiko Hayashi, John Cologne, HM Cullings, Kazunori Kodama, Edward F. Miles, Sachiyo Funamoto, Akihiko Suyama, Midori Soda, Fumiyoshi Kasagi: Exposure of ionizing radiation and development of bone sarcoma: new insights based on atomic-bomb survivors of Hiroshima and Nagasaki . Journal of Bone and Joint Surgery 2011, Volume 93-A, Issue 11, June 1, 2011, pages 1008-1015
5. ↑ Autologous bone transplantation: http://www.tumororthopaedie.org/autologe-knochentransplantation.html
6. ↑ Allogeneic bone transplantation: http://www.tumororthopaedie.org/allogene-knochentransplantation.html
7. ↑ Replantation of autologous sterilized bone segments: http://www.tumororthopaedie.org/knochenreplantation.html
8. ↑ Tumor endoprostheses ("megaprotheses"): http://www.tumororthopaedie.org/uebersicht-1.html
9. ↑ Summary of the European public assessment report (EPAR) for Mepact (mifamurtide): http://www.ema.europa.eu/docs/de_DE/document_library/EPAR_-_Summary_for_the_public/human/000802/WC500026562.pdf
10. ^ Bech-Nielsen et al: Frequency of osteosarcoma among first-degree relatives of St. Bernard dogs. In: J Natl Cancer Inst 60, 1978, pp. 349-353
11. ↑ R. Ferracini include: MET oncogene aberrant expression in canine osteosarcoma. In: J Orthop Res 18, 2000, pp. 253-256.

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