CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Second malignancy after Hodgkin disease treated with radiation therapy with or without chemotherapy: long-term risks and risk factors

The excess risk of second malignancy after Hodgkin disease is an increasing problem. In light of the long-term data, guidelines for follow-up of survivors of Hodgkin disease need to be redefined. In this study we attempt to analyze the longterm risks and temporal trends, identify patientand treatment-related risk factors, and determine the prognosis of patients who develop a second malignancy after radiation treatment with or without chemotherapy for Hodgkin disease. Among 1319 patients with clinical stage I-IV Hodgkin disease, 181 second malignancies and 18 third malignancies were observed. With a median follow-up of 12 years, the relative risk (RR) and absolute excess risk of second malignancy were 4.6 and 89.3/10 000 person-years. The RR was significantly higher with combined chemotherapy and radiation therapy (6.1) than with radiation therapy alone (4.0, P .015). The risk increased with increasing radiation field size (P .03) in patients who received combined modality therapy, and with time after Hodgkin disease. After 15 and 20 years, there was a 2.3% and 4.0% excess risk of second malignancy per person per year. The 5-year survival after development of a second malignancy was 38.1%, with the worst prognosis seen after acute leukemia and lung cancer. The excess risk of second malignancy after Hodgkin disease continues to be increased after 15 to 20 years, and there does not appear to be a plateau. Our analysis suggests that the risk may be reduced with smaller radiation fields, as are used in current trials of abbreviated chemotherapy and limitedfield radiation therapy. (Blood. 2002;100: 1989-1996)