Second malignant neoplasms among survivors of pediatric Hodgkin disease treated with low-dose radiation (15–25.5 Gy) and chemotherapy

Abstract

10003 Background: Second malignant neoplasms (SMN) are a known complication of Hodgkin disease (HD) treatment. While it is theorized that lower radiation doses may be associated with lower SMN risk, long-term follow-up of children treated with low-dose radiation is lacking. We report the occurrence of SMN among pediatric HD survivors treated at Stanford with chemotherapy and low-dose radiation from 1970 to 1990. Methods: Patients received 6 cycles of MOPP (mechlorethamine, vincristine, prednisone, procarbazine) with 15–25.5 Gy radiation ± 10 Gy boost or 3 MOPP and 3 ABVD cycles (doxorubicin, bleomycin, vinblastine, dacarbazine) with 15 Gy radiation ± 10 Gy boost. Follow-up was obtained through 9/1/2007. Standardized incidence ratios (SIRs) and absolute excess risk (AER) for SMN were calculated using the SEER9 database (1973–2004). Cumulative SMN incidence was determined by the Kaplan-Meier method. Univariate associations were evaluated with the chi-square test or t-test. Multivariate analysis was performed with Cox proportional hazards regression using chronological age as the time scale. Results: One hundred ten of 112 patients achieved remission; median follow-up is 20.6 years. Four patients developed secondary leukemia. Fifteen patients developed 17 secondary solid tumors (5 thyroid carcinomas, 6 breast carcinomas, 4 sarcomas, 1 bladder paraganglioma, 1 melanoma) at a median of 15.4 years. All solid tumors except the melanoma occurred within or at the margin of radiation fields, ranging in dose from 15–26.5 Gy. There were no cases of lung, gastric, or colorectal carcinoma. Cumulative incidence of any SMN is 17% (95%CI 10.5–26.7) at 20 years following HD diagnosis. The SIR for any SMN is 22.9 (95%CI 14.2–35) with an AER of 93.7 cases per 10,000 person-years. In univariate analysis, older age at HD diagnosis (>11 years) and female gender were associated with SMN (p<0.05). In multivariate analysis, there were no statistically significant associations. Conclusions: The incidence of SMN in pediatric HD survivors is elevated following treatment with chemotherapy and low-dose radiation. Sarcomas, breast, and thyroid carcinomas occurred with similar frequency and latency as found in studies of HD survivors who received high-dose radiation. No significant financial relationships to disclose.