Solid organ second malignant neoplasms among children diagnosed with malignant bone tumors treated on Children Cancer Study Group/Pediatric Oncology Group protocols after 1980

Abstract

9007 Background: The growing number of individuals surviving childhood cancer has increased the awareness and recognition of long-term sequelae. One of the most worrisome complications following cancer therapy is the development of second malignant neoplasms (SMN), in particular, late-occurring solid second malignancies related radiation therapy. Methods: We describe the incidence of solid organ SMN in survivors of pediatric malignant bone tumors (MBT) treated on legacy CCG/POG protocols from 1980 to 2005. This retrospective cohort study included 2,842 patients, 1,686 treated for osteosarcoma (OS) and 1,156 treated for Ewings Sarcoma (ES). The cohort included 56% males and 44% females, with a median age at primary diagnosis of 13 years. The median length of follow-up was 4.3 years (range: 0 to 20.9 years). Results: At the time of the analysis, 64% of patients in this study are alive. Seventeen patients with solid organ SMN were identified, and included three patients with breast cancer, three with malignant fibrous histiocytoma, two with osteosarcoma, and 9 patients with other solid organ malignancies. The standardized incidence ratio (SIR=observed/expected cases) was 2.9 (95% confidence interval [CI], 1.4–5.4) for patients treated for OS and 5.0 (95%CI 2.6–9.4) for patients treated for ES. The median time from diagnosis to develop solid organ SMN was 7 years (range: 1 to 13 years). The 10-year cumulative incidence of solid organ SMN for the entire cohort was 1% (95%CI 0.6–2%). In univariate analysis, treatment with etoposide, cyclophosphamide or radiotherapy were each associated with a higher than expected incidence of cancer with SIR of 4.8 (95% CI, 2.5–9.5), 5.8 (95% CI, 3.5–9.5) and 4.1 (95% CI, 2.4–7.1), respectively. Conclusions: Solid organ SMNs are rare after treatment for OS and ES, although higher in patients treated for ES. Recurrence remains the most significant problem for patients diagnosed with MBT and development of improved therapies with fewer long-term consequences remains paramount. However, solid organ cancers are likely to increase with longer follow-up. Therefore, surveillance should focus on monitoring for both recurrence of primary malignancies and development of SMN. No significant financial relationships to disclose.