Secondary bone/soft tissue sarcoma in childhood cancer survivors: a nationwide hospital-based case-series study in Japan.

BACKGROUND: Secondary cancer is the most life-threatening late effect of childhood cancer. We investigated the clinical features of secondary bone/soft tissue sarcoma among childhood cancer survivors (CCSs). METHODS: We conducted a retrospective case-series study of 10 069 CCSs newly diagnosed with cancer between 1980 and 2009 across 15 Japanese hospitals. Twenty-one cases of pathologically diagnosed secondary bone/soft tissue sarcoma were selected, and the respective clinical courses were determined using additional questionnaires. RESULTS: The primary cancers included retinoblastoma (n = 7), acute lymphoblastic leukemia (n = 5), lymphoma (n = 5), osteosarcoma (n = 1), rhabdomyosarcoma (n = 1), brain tumor (n = 1) and Langerhans cell histiocytosis (n = 1). The median age at the primary cancer diagnosis was 2.9 years, and the male-to-female ratio was 16:5. The histological classifications of the secondary sarcoma included osteosarcoma (n = 10), malignant peripheral nerve sheath tumor (n = 4), rhabdomyosarcoma (n = 3), Ewing's sarcoma (n = 3) and primitive neuroectodermal tumor (n = 1). The median latency period to the secondary sarcoma was 10.2 years. Significant risk factors for secondary sarcoma in the multivariate Cox regression model included a history of retinoblastoma as the primary cancer (hazard ratio [HR], 20.9; 95% confidence interval [CI], 5.70-76.5) and autologous stem cell transplantation (SCT) (HR, 2.56; 95% CI, 1.08-6.03). Seventeen CCSs with secondary sarcoma underwent radiation, and nine, hematopoietic SCT. Twelve CCSs with secondary sarcoma achieved disease-free survival, while CCSs with hematological cancer or relapsed primary cancer who developed secondary sarcoma had the worst prognoses. CONCLUSION: The prognoses of CCSs with secondary sarcoma may depend on the primary cancer or prior relapse of primary cancer.