Second malignancies in very-long-term survivors of childhood cancer.

Purpose: Although most second malignancies are treatment related, their occurrence also may be due to an underlying systemic disease or chromosomal abnormalities shared by multiple organs in which they are tumorigenic. We attempted to identify unusual tumor pairs that might provide a clue to shared genetic etiologies.

Patients And Methods: Medical records and tumor registry correspondence of 1,743 patients (0 to 18 years at diagnosis) were reviewed. For those said to have a second malignancy, biopsy and autopsy records and slides were reviewed to confirm initial and secondary diagnoses.

Results: Two hundred fifty-eight patients had follow-up of at least 10 years and 157 of at least 20 years. Second malignancies were identified in 14 patients. The estimated cumulative incidence of a second cancer was approximately 1% within 10 years. At 20 years after diagnosis, the actuarial estimate was 3%. Although most second cancers were likely treatment related, several tumor pairs could not clearly be explained on that basis, including thyroid carcinoma followed by an ovarian sarcoma, and acute lymphoblastic leukemia associated with renal leiomyosarcoma. Based on one case in this series and a review of the literature, associations between Wilms' tumor, abdominal radiation, and adenocarcinoma of the colon and hepatocellular carcinoma are suggested.

Conclusions: We conclude that continued surveillance of very-long-term survivors of childhood cancer, which is usually accomplished by internists, family practitioners, and adult oncologists, may be one approach to defining the life-time incidence of second malignancies. In addition, although the yield is likely to be small, descriptions of unexpected tumor pairs may target families for studies of pleiotropic genetic abnormalities.