Osteosarcoma

Pediatric oncology related presentation hope it will be interesting

1. OSTEOSARCOMA Presented E Ngabonziza , medical student

2. Contents Definition Epidemiology Aetiology Role of genetics Clinical presentation Diagnosis Types of osteosarcoma Prognosis Principles of treatment Long term complication Long term follow up References

3. DEFINITION Osteosarcoma is a type of cancer in which tumor cells produce immature bone known as  osteoid . Is the most common primary malignant bone tumor in children and young adults It is a tumor that arises most frequently in the long bones of adolescents and young adults Typically, the tumor presents as a rapidly enlarging mass with a characteristic “ Sunburst pattern ” x-rays

4. Skeletal distribution Femur – 42%, 75% of which is in the distal femur Tibia – 19%, 80% of which on proximal tibia Humerus – 10%, 90% of which is in the proximal humerus Skull and jaw – 8% Pelvis – 8%

5. EPIDEMIOLOGY osteosarcoma is a relatively rare cancer, it is the eighth most common cancer in children and adolescents and it is the most common of the bone cancer . Data from the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Pediatric Monograph 1973-2004 are as follows :   Blacks – 3.4 cases per million per year (5.0 per million < 25 years) Whites – 3.0 cases per million per year (4.2 per million < 25 years)

6. Cont’ The incidence rates were estimated to be relatively consistent throughout the world, with Italy, parts of Latin America, Sudan, and Uganda reporting slightly higher rates than in other regions. No data available for Rwanda

7. ETIOLOGY Etiology of ostosarcoma is divided in 3 parts Genetics Epidemiological Environmental N.B : The exact cause of osteosarcoma is unknown. However, a number of risk factors have been identified

8. G enetics Genetic predisposition plays a role. Bone dysplasias , including Paget disease, fibrous dysplasia, enchondromatosis , and hereditary multiple exostoses and retinoblastoma ( germline form) are risk factors .

9. Epidemiological The incidence of osteosarcoma is slightly higher in males than in females Factors related to patient characteristics include age, gender, ethnicity. slightly higher in blacks than in whites Osteosarcoma is very rare in young children (0.5 cases per million per year in children < 5 years).

10. Environmental The only known environmental risk factor is exposure to radiation. Radiation-induced osteosarcoma is a form of secondary osteosarcoma radiation therapy can be effective for destroying cancer cells, it can also damage the DNA of healthy bone cells, causing those cells to undergo abnormal changes.

11. Role of genetics Cancers can be caused by gene changes that turn on oncogenes or turn off tumor suppressor genes Some people inherit gene mutations (changes) from a parent that increase their risk of cancer and other are acquired

12. Inherited gene changes Some inherited DNA mutations cause syndromes that are linked with an increased risk of osteosarcoma for example: The Li- Fraumeni syndrome is usually caused by inherited mutations that turn off the TP53 tumor suppressor gene Rothmund -Thomson syndrome ( i.e., autosomal recessive association of congenital bone defects, hair and skin dysplasias , hypogonadism , cataracts) is associated with an increased risk of osteosarcoma

13. Acquired gene changes Most osteosarcomas are not caused by inherited gene mutations, but instead are the result of gene changes acquired during the person’s lifetime . Sometimes these gene changes are caused by radiation therapy used to treat another form of cancer, because radiation therapy can damage the DNA inside cells.

14. Clinical presentation Symptoms of osteosarcoma may be present for weeks or months (occasionally longer) before patients are diagnosed . The most common presenting symptom is pain, particularly pain with activity Bone fractures Swelling to the affected areas

15. cont’ Systemic symptoms, such as : fever and night sweats, are rare. Respiratory finding- late stage with lung metastasis Lymphadenopathy - unusual focal and regional lymph node

16. Diagnosis Clear history taking Identify whether is in risk of developing osteosarcoma Laboratory studies – Serum alkaline phosphotase

17. Cont’ Radiologic imaging X-ray – sunburst pattern, Codman’s triangle when there is periosteal reaction MRI – to know soft tissue extent CT scan – usually no much use only CT chest to detect lung metastasis Bone scan

18. Cont’ Angiogram Determine vascularity of the tumor Detect vascular displacement Relationship of vessels to the tumor

19. Biopsy To confirm the diagnosis Types Fine needle aspiration Core needle biopsy Open incision biopsy

20. Types of osteosarcoma It is broadly categorised into two types Primary - occurring as result of abnormality in bone development Secondary – Occurring as result of another condition Note : Primary OS– childrens and teenagers ( whose bones are still growing) Secondary OS – Adults ( bones fully formed)

21. Primary osteosarcoma (15-25 Yrs) It has some subtypes which are as follows Conventional osteosarcoma ( most common) Low grade intramedullary osteosarcoma Paraosteal osteosarcoma Periosteal osteosarcoma High grade surface osteosarcoma Telangiectatic osteosarcoma Small cell osteosarcoma

22. Secondary osteosarcoma ( > 50 Yrs) Mostly commonly a premalignant condition like Paget disease Previous radiation treatment Endochondromatosis

23. Staging of the tumor

24. Prognosis Extent of the disease – Patients with pulmonary, non pulmonary ( bone ) or skip metastasis have poor prognosis Grade of the tumor – High grade tumor have poor prognosis

25. Cont’ Size of the primary lesion – Large size tumors have worse prognosis than small size tumors Skeletal location – Proximal tumors do worse than distal tumors Secondary osteosarcoma – Poor prognosis

26. Principles of treatment The types of treatments used for osteosarcoma include: Chemotherapy Surgey Radition therapy

27. Chemotherapy Neoadjuvant – Chemotherapy given preoperatively Adjuvant – Given postoperatively Advantages of neoadjuvant chemotherapy Regression of the primary tumor, making a successful limb salvage operation easier May decrease the spread of tumor cells at time of surgery Effectively treating micro metastases at the earliest time possible Given for about 3-4 weeks before definitive procedure

28. Cont’ The drugs used most often to treat osteosarcoma are: Methotreaxate with leucovorin ( folic acid ) Doxorubicin ( adriamycin ) Cisplastin or carboplatin Etoposide Actinomycin D Bleomycin

29. Surgery The main goal of surgery is to safely and completely remove the tumor In the past amputation was advised Limb salvage procedures now can provide rates of local control and longterm survival equal to amputation The biopsy to diagnose cancer Limb salvage surgery is removing the tumor with a wide margin of normal tissue surrounding it while preserving vascular and nerve supply to the extremity

30. Radiotherapy Radiation therapy has no major role in osteosarcoma Radiation therapy may be useful in some cases where the tumor can not be completely removed by surgery . E.g. In pelvic bones or in the bones of the face

31. Long-term complications Osteosarcoma might affect personal’s health later in life, younger people in particular are at risks for possible late effects of their treatment The risk depend on many factors such as: Specific treatment received Doses of treatment Age when treated E.g. loss of limb Heart or lung problems Loss of hearing Slow growth and development Changes in sexual development and ability to have children

32. Long-term follow up Signs of recurrence, metastasis and treatment related complications Physical examination , radiographs of the primary site, serial chest imaging , Bone scans and laboratory examinations 50% cases with high grade osteosarcoma have some type of relapse in months If recurrence is detected , additional surgery ( radical amputation ) and chemotherapy may be warranted Checking heart and hearing functions due to chemotherapy

33. References Ilustrated textbook of paediatrics , 4th Edition by Dr tom lissauer UpToDate Medscape World health organisation recommendations Paediatric and adolescent osteosarcoma