Journal: Journal of the American Academy of Orthopaedic Surgeons Global Research & Reviews
Who: Isaac G. Freedman, MD, MPH, Hollie N. Dowd, MPH, Meera M. Dhodapkar, BA, Scott J. Halperin, BS, Jonathan N. Grauer, MD
Overview: Osteosarcoma is the most common primary bone tumor in children, adolescents, and young adults worldwide, with an incidence of 3.4 million people per year. It is usually found in appendicular skeleton, such as the distal femur (43%), proximal tibia (23%), or humerus (10%), but may also arise axially. Although most common in younger patients, there is an increasing prevalence among elderly patients.
With improvements in treatments leading to greater numbers of osteosarcoma survivors, there is a critical need for more information regarding the potential development of second primary malignancies (SPMs), sometimes also referred to as second malignant neoplasms (SMNs). Treatment-related effects have been implicated in the increased rate of many second cancers, including breast cancer and Hodgkin lymphoma. However, there is also evidence from both prospective and retrospective studies that individuals who develop a first primary cancer may inherently be at greater risk of developing subsequent cancers because of complex genetic, environmental, and behavioral factors, which are not fully understood.
The National Cancer Institute's Surveillance, Epidemiology, and End Results 18 database was queried for all osteosarcoma cases from 2000 through 2015. Standardized incidence ratio (SIR) and absolute excess risk (AER) of SPM per 10,000 persons (AER) relative to representative population-level data were calculated across for various anatomic locations.
In total, 3,438 patients with osteosarcoma were identified. Of these patients, 79 (2.3%) developed SPMs, with an SIR of 2.84 (95% confidence interval [CI] 2.35 to 3.39, P < 0.0001) and an AER of 44.96. The most common SPMs were tumors of the bones or joints (SIR 73.07, CI, 38.90 to 124.94, P < 0.0001, AER 7.48), tumors of soft tissues including the heart (SIR 15.19, CI, 5.58 to 33.07, P < 0.0001, AER 3.27), and leukemia (SIR 22.28, CI, 15.03 to 31.80, P < 0.0001, AER 16.74).
This study demonstrated that osteosarcoma survivors in the United States are at an increased risk for developing a range of SPMs, characterizes those SPMs by age of development and tumor location, and updates prior estimates. As the treatments for osteosarcoma improve leading to increased survival rates, the results of this study demonstrate the importance of routine monitoring of patients who have had osteosarcoma. Further studies should investigate the association between chemotherapeutics, radiation therapy, and SPMs in osteosarcoma survivors.