Risk of second malignancies with low dose cyclophosphamide maintenance in survivors of childhood rhabdomyosarcoma

Survivors of childhood rhabdomyosarcoma (RMS) are at increased risk of second malignant neoplasms (SMNs), influenced by treatment type and genetic predisposition. Recently, addition of maintenance therapy with low-dose cyclophosphamide and vinorelbine has improved survival outcomes for patients with high-risk disease. However, the potential SMN risk from increased cumulative alkylating agent exposure is unclear. In the RMS2005 study, researchers from the European Pediatric Soft Tissue Sarcoma Study Group analyzed 1633 patients who did or did not receive maintenance chemotherapy. After a median follow-up of 9.3 years (range 0.6-17.7), 27 patients (1.7%) had developed a SMN. Eight had known cancer predisposition syndrome (Li-Fraumeni syndrome or neurofibromatosis type1). The 8-year cumulative incidence of SMN in the entire cohort was 1.3% (95% CI 0.8-2.0). SMNs occurred in 1.6% of patients without maintenance therapy and in 1.9% of patients who received maintenance therapy (p=0.75). The authors conclude that maintenance chemotherapy was not associated with increased SMN risk. Genetic predisposition was a major contributor to SMN development, supporting risk-adapted survivorship care.