Osteosarcoma
BACKGROUND
Name the 2 most common types of malignant bone tumors in the pediatric population.
The 2 most common types of malignant bone tumors in the pediatric population are osteosarcoma (56% of total) and Ewing sarcoma (36% of total). (SEER 2009) Both cancers are relatively rare.
Osteosarcoma is associated with what other pediatric tumor?
Pts with retinoblastoma (Rb) have an increased risk of osteosarcoma, both within and outside the irradiated tissue (i.e., the osteosarcoma can occur as a secondary malignancy within bone that rcvd radiation or in distant long bone sites, putatively due to the germline mutation, which increases risk of both Rb and osteosarcoma).
Describe the distribution of osteosarcoma cases as a function of population age.
Osteosarcoma has a bimodal distribution as a function of age, with most cases arising during the teenage years with a second spike in an older (age >65 yrs) population, which are often associated with other conditions (Paget Dz, fibrous dysplasia)
What is the incidence of osteosarcoma in the U.S. population?
800 cases/yr of osteosarcoma are diagnosed in the U.S. population, with nearly half occurring in pts >20 y/o. Osteosarcoma is ∼2 times more common than Ewing sarcoma.
What are the most common risk factors associated with the development of osteosarcoma?
A high rate of bone production and turnover (as in puberty or Paget Dz) is associated with the development of osteosarcoma. Osteosarcoma is also the most common secondary cancer in adults who received radiation or chemotherapy for a childhood solid tumor.
Describe the sex and ethnicity factors associated with osteosarcoma.
Osteosarcoma is more common in boys (> girls) and in blacks (> whites).
What is another name for the shaft of a long bone? End of the bone? Flared region between the shaft and end?
The diaphysis is the shaft of the bone. The epiphysis is the end of the bone, and the growth plate is located in this region. The conical area of bone between the diaphysis and epiphysis is the metaphysis.
Osteosarcoma is most likely to develop in what part of the bone?
Osteosarcoma arises most frequently in the appendicular skeleton (80% of cases) at the metaphyseal portions of the femur, tibia, and humerus.
Osteosarcoma most commonly arises in which bone?
The distal femur is the location in which osteosarcoma most commonly arises. The proximal tibia is 2nd most common. Thus, the most common site is above and below the knee.
Describe the histologic defining feature of osteosarcoma.
Production of immature “osteoid” bone is the defining feature of osteosarcoma. Most are high-grade “intramedullary” tumors.
Describe 2 genetic syndromes associated with osteosarcoma.
Osteosarcoma is associated with Li-Fraumeni syndrome as well as retinoblastoma. Inactivation of tumor suppression pathways is very common in osteosarcoma.
What is the difference between conventional osteosarcoma and juxtacortical osteosarcoma?
Conventional or “classic” osteosarcoma refers to the most common (75% of all cases) variant of osteosarcoma, which typically presents within areas of rapidly proliferating intramedullary bone. Juxtacortical osteosarcoma refers to a set of more rare osteosarcoma variants that arise adjacent to the outer surface of cortical bone.
Describe juxtacortical osteosarcoma in terms of pathologic grade and prognosis.
Juxtacortical osteosarcoma is usually low grade (parosteal) or intermediate grade (periosteal). Parosteal osteosarcoma rarely metastasizes and is highly curable with surgery alone. Periosteal osteosarcoma has approximately a 20% risk of metastasis and the role of chemotherapy is controversial. (Grimer RJ et al., Eur J Cancer 2005)
What % of osteosarcoma pts have localized Dz at Dx?
90% of pts with osteosarcoma have localized Dz at Dx.
What % of osteosarcoma pts with localized Dz will develop DMs without chemo?
90% of pts with localized Dz will develop mets without chemo. (Link M et al., Clin Pediatr Oncol 1991). Chemotherapy is now a standard part of treatment for localized osteosarcoma.
What are the 2 most common presenting Sx of osteosarcoma?
Pts with osteosarcoma typically present with localized bone pain (often associated with an injury) of several mos duration and a soft tissue mass. Diagnosis may be delayed as the symptoms may be attributed to “growing pains.”
WORKUP/STAGING
Define the lab and radiographic studies used in the workup and staging of osteosarcoma.
Osteosarcoma workup: basic labs (CBC, CMP) as well as alk phos, LDH, and ESR. After plain films of the affected bone are obtained, MRI of the primary site and chest imaging are needed. PET or bone scan may be used for systemic staging.
Define 3 principles used in the Bx of a suspected bone tumor.
Principles used in the Bx of a suspected bone tumor:
1. Bx should be performed at the same institution where the definitive resection will take place, preferably by the same surgeon who will undertake the definitive resection.
2. Bx should be placed carefully to avoid contamination of other areas, as may happen with a hematoma formation.
3. The Bx should not increase the extent of subsequent surgery.
What radiographic features distinguish osteosarcoma from Ewing sarcoma?
Osteosarcoma is usually sclerotic, involves the metaphysis, and has periosteal new bone formation (sunburst pattern), whereas Ewing sarcoma is usually lytic, located in the diaphysis, and displays an onion skin effect. (Lee B et al., Handbook of Radiation Oncology 2007)
What is the most common site of mets from osteosarcoma?
The lung is the most common site of osteosarcoma mets. Hence, chest imaging is important part of osteosarcoma staging.
What are the AJCC 7th edition (2011) TNM stage categories for bone tumors? (Note: Lymphoma and multiple myeloma have separate staging systems)
T1: ≤8 cm
T2: >8 cm
T3: discontinuous tumors in primary bone site
N0: no regional LN mets
N1: regional LN mets
M0: no DMs
M1a: DMs to lung
M1b: DMs to nonpulmonary sites
What is the AJCC stage grouping for bone tumors?
Stage IA: T1N0, low grade
Stage IB: T2–3N0, low grade
Stage IIA: T1N0, high grade
Stage IIB: T2N0, high grade
Stage III: T3N0, high grade
Stage IVA: M1a
Stage IVB: N1 or M1b
TREATMENT/PROGNOSIS
What is the standard Tx paradigm for conventional or high-grade osteosarcoma?
Osteosarcoma standard Tx paradigm: preop chemo → surgical resection → adj chemo.
What data support the use of multiagent chemo in the management of osteosarcoma?
Multiple randomized studies have established the role of adj and neoadj chemo in osteosarcoma management. Link et al. was 1 of the 1st studies that compared multiagent chemo to no adj management in 36 pts who underwent definitive surgery. At 2 yrs, the RFS was 17% in the control group and 66% in the Tx group. (NEJM 1986) More recent studies show doublet chemo using doxorubicin and cisplatin to be better tolerated with no difference in survival for localized, operable osteosarcoma. (Souhami RL et al., Lancet 1997)
Define 3 roles for RT in the management of osteosarcoma.
RT is useful in the management of osteosarcoma for pts with close or positive surgical margins that cannot be improved, for surgically inoperable lesions, or for palliation of painful primary tumors in pts with metastatic Dz.
What is the preferred dose of RT for management of an unresectable osteosarcoma or following an R2 resection (definitive paradigm)?
For unresectable Dz, a dose of at least 60–70 Gy is recommended. The preferred dose following an R2 resection is >55 Gy with boost to 64–68 Gy to the area of highest risk. In 1 retrospective review, pts receiving doses of >55 Gy had improved LC. (DeLaney TF et al., IJROBP 2005)
What radioisotope is currently being investigated for use in the management of osteosarcoma?
Samarium-153 is a bone-seeking radioisotope that has been investigated and found to be safe and effective in a dose-finding study in poor prognosis pts who had been heavily pretreated with chemo. Because of the osteoid production, metastatic Dz outside bone will also take up samarium.
What is the 5-yr survival rate for nonmetastatic and metastatic osteosarcoma treated with chemo and surgery?
The 5-yr survival for nonmetastatic osteosarcoma treated with chemo and surgery is 60%–70%; for metastatic osteosarcoma, survival is ∼20%.
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