Outcome of Radiation-Related Osteosarcoma after Treatment of Childhood and Adolescent Cancer: A Study of 23 Cases

Reviewers: John Han-Chih Chang, MD
Source: Journal of Clinical Oncology 1999; Volume 17: pages 2789 ? 2795

Background

Survival and control rates of pediatric malignancies have continued to rise over the past decades. While combinations of surgery, chemotherapy (ChT) and radiation therapy (RT), have produced promising results, acute and long-term toxicities have also resulted. Among the most serious of the RT related effects are the development of secondary malignancies. When ionizing RT is utilized to treat malignancies in proximity to or directly in bone, osteosarcomas may develop after a latency period of approximately 10 - 12 years. 1-3 The rate of secondary osteosarcomas has been quoted as high as 13% at 30 years from treatment.4 The focus of this article was the treatment of secondary osteosarcomas in survivors of pediatric malignancies.

Summary/Critique/Conclusion

The data for this trial were collected from questionnaires sent to physicians participating in the French Society of Pediatric Oncology group of centers. Patients were excluded if they had a mutated retinoblastoma gene due to its link with osteosarcoma formation. Twenty-three patients from five centers were evaluated for outcome. Most patients were originally treated for Ewing's sarcoma, rhabdomyosarcoma, medulloblastoma and Hodgkin's disease. The median dose of RT had been 47Gy. Nearly all had ChT that included a high dose alkylating agent. The median latency time to development of secondary osteosarcoma was eight years.

The osteosarcoma treatment administered was with curative intent in 16 patients. Most patients received pre- and/or postoperative chemotherapy. One patient had gross residual disease after surgery. Thus, a complete resection was performed in 15 patients, of whom four relapsed. Twelve have remained alive without evidence of disease. Median follow-up from osteosarcoma therapy was 7.5 years. The event-free and overall survival of all 23 patients at eight years were 41% and 50%, respectively. The only important prognosticator was the ability to perform a complete surgical resection.

This trial compares favorably to other trials of RT-associated osteosarcomas, which have documented 5 year overall survivals in the 20 - 25% range. Eliminating patients with the retinoblastoma mutation may bias results towards improved survival. This retrospective review has demonstrated that secondary osteosarcomas can be successfully treated with surgery +/- ChT. The decrease in the use of RT along with judicious use of combined modality RT and high dose alkylating ChT agents in pediatric malignancies may reduce the incidence of secondary osteosarcomas in future survivors.