Managing axial bone sarcomas in childhood

ABSTRACT

Introduction: Axial osteosarcoma and Ewing sarcoma are rare, aggressive neoplasms with a worse prognosis than with tumors involving the extremities because they are more likely to be associated with larger tumor volumes, older age, primary metastases, and a poor histological response to chemotherapy. The 5-year OS rates are reportedly in the range of 18–41% for axial osteosarcoma, and 46–64% for Ewing sarcoma.

Area covered: The treatment of axial bone tumors is the same as for extremity bone tumors, and includes chemotherapy, surgery and/or radiotherapy.

Expert opinion: Local treatment of axial tumors is particularly difficult due to their proximity to neurological and vascular structures, which often makes extensive and en bloc resections impossible without causing significant morbidity. The incidence of local relapse is consequently high, and this is the main issue in the treatment of these tumors. Radiotherapy is an option in the case of surgical resections with close or positive margins, as well as for inoperable tumors. Delivering high doses of RT to the spinal cord can be dangerous. Given the complexity and rarity of these tumors, it is essential for this subset of patients to be treated at selected reference institutions with specific expertise and multidisciplinary skills.

KEYWORDS:

• Axial osteosarcoma
• ewing sarcoma
• surgery
• radiotherapy
• chemotherapy
• targeted drugs

Article highlights

• Osteosarcoma and Ewing sarcoma are the most common bone malignancies in the first two decades of life.

• Axial osteosarcoma accounts for 10-14% of all cases of osteosarcoma, with pelvic osteosarcoma making up 5-10% of all cases, and spinal osteosarcoma just 1-3%.

• Axial Ewing sarcoma accounts for 20-25% of all cases of Ewing sarcoma, involving the pelvis in 15-20% of all cases, and the spine in only 3-5%.

• Axial bone tumors are aggressive neoplasms with a worse prognosis than extremity tumors because they are more likely to involve larger tumor volumes, occur in older-aged patients, with a higher likelihood of primary metastases, and a weaker histological response to chemotherapy.

• The majority of patients with axial osteosarcoma are excluded from clinical trials, which usually only enroll patients with tumors of the extremities.

• The current treatment strategy for axial osteosarcoma and Ewing sarcoma is the same as for extremity bone tumors, and includes neo-adjuvant and adjuvant chemotherapy, surgery and/or radiotherapy.

• The local treatment of axial tumors poses a challenge especially as regards for local control. The chances of achieving an R0 resection are lower than for extremity tumors, and the incidence of local relapse is consequently higher. Local recurrence is a major concern in the treatment of these tumors.

• Proximity to neurological and vascular structures makes extensive resections difficult in most cases, and en bloc resection is often impossible without causing significant morbidity.

• Patients who achieve a complete surgical remission have better survival prospects than those who undergo non-radical surgery.

• Radiotherapy may be an important option in the case of resections with close or positive surgical margins, or for patients with inoperable tumors.

• High doses of radiotherapy are required for OS and ES axial tumors, but delivering them to such ‘critical sites’ as the spinal cord can be dangerous. Modern radiation techniques may be a better option because proton and carbon ion therapies achieve a superior biological dose distribution, while sparing normal tissue. The long-term outcome and morbidity of these new techniques remains to be seen, for now.

• The prognosis for patients with axial OS and ES is worse than for those with extremity tumors, the 5-year overall survival rates reportedly being 18-41% and 46-64%, respectively.

• Collaborative efforts to improve our understanding of the biology of OS and ES, and the use of preclinical models to test novel agents will be crucial to the identification of ways to improve patient outcomes.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper received no funding.