Forty-year experience with second malignancies after treatment of childhood cancer: Analysis of outcome following the development of the second malignancy

As the cure rate for childhood malignancies increases, the number of patients at risk for development of second malignancies also increases. Due to the potentially long remaining life span, long-term follow-up is difficult and patients are often at risk after presumptive cures. Some authors believe that cure rates for second malignancies are similar to cure rates for primary malignancies. We reviewed the records of 162 patients seen at our institution who had developed a second malignancy after treatment for childhood cancer. Presentation, age at diagnosis, tumor histology, extent of tumor, treatment (including radiotherapy with dosage when available, and chemotherapy) plus outcome were recorded. Mean age at diagnosis of the primary malignancy was 10.3 years. The most common primary malignancy was Hodgkin's disease (33) followed by soft tissue sarcoma (28), retinoblastoma (20), bone tumor (17), central nervous system (CNS) tumor (13), leukemia (8), Wilms' tumor (7), non-Hodgkin's lymphoma (6), neuroblastoma (5), thyroid neoplasm (5), and others (20). The average interval between diagnosis of the first and second malignancy was 10.8 years. These second tumors carried a high mortality. Only 56 patients have no evidence of disease. Five patients are known to be alive with disease and 92 patients have expired due to their second malignancy. Disease status in 8 patients is unknown. The most common second malignancy was osteosarcoma (35) followed by soft tissue sarcoma (24), breast cancer (15), leukemia (14), thyroid carcinoma (14), CNS tumors (12), melanoma (8), nonmelanomatous skin cancer (8), lymphoma (5), and others (27). Eighteen of 35 bone sarcomas developed in irradiated fields and the mean dosage was 44.0±16.3 (10 to 64 Gy). Seventeen of 19 patients who developed a hematologic malignancy received an alkylating agent when treated for their primary malignancy. Of 162 patients developing second malignancies, only 34.6% were cured. When patients with thyroid lesions are excluded, only 28.9% were cured. These poor results are most likely due to two main factors: (1) a high percentage of tumors were not able to be cured due to local unresectability, and (2) the biology of many of these lesions is more aggressive than similar tumors arising "de novo." The more aggressive nature of these neoplasms may in part be due to genetic mutations present at the time of initial diagnosis and/or due to DNA damage resulting from irradiation or administration of alkylating agents.