Aim: To quantify the risk of second malignancies in patients with Hodgkin's disease treated at the Department of Radiotherapy, University Clinic Freiburg, with the object of comparing this risk with the international experience and as a contribution to the discussion about future treatment.
Patients and methods: Second malignancies were reviewed in 1,588 patients treated for Hodgkin's disease between 1940 and 1991. Treatment consisted of involved or extended field radiotherapy as a single modality or in combination with chemotherapy. Before the early 1970's, chemotherapy used (sequential) monodrug regimens. The mean follow-up was 8.3 years. The cumulative risk was calculated using the Kaplan-Meier method and related to the risk of a normal population taken from epidemiological data of the National Cancer Institute. An estimate of radiation dose at the site of origin of the second malignancy was obtained from representative measurements employing an Alderson phantom.
Results: After 5, 10, 15 and 20 years the cumulative risk for all malignancies was 1.5%, 4.2%, 9.4% and 21%, respectively; for solid tumors it came to 1.2%, 3.1%, 7.9% and 19%; for non-Hodgkin lymphoma (NHL) the risk amounted to 0.1%, 0.9%, 1.4% and 1.9%; and for leukemia it was 0.1%, 0.3%, 0.6% and 0.6%. For the same time points the relative risk for all malignancies was calculated to be 1.1, 1.4, 1.8 and 2.5; for solid tumors it came to 1.0, 1.1, 1.6 and 2.5; for NHL it amounted to 3.3, 11.8, 9.3 and 8.0; and for leukemia it was 3.3, 3.1, 3.4 and 2.1. For combinations of radiotherapy and chemotherapy the risk for second malignancies was highest in patients receiving ABVD any time during their treatment. 51% of the second malignancies were located infield, 22% at the field border and 27% outfield. In those cases for which the cause of death was known, Hodgkin's disease accounted for 79% followed by second malignancies accounting for 8%. The results obtained in Freiburg fell within the range reported in international publications.
Conclusion: The increased incidence of second malignancies in cured Hodgkin's patients is along-term risk making regular follow-up mandatory. Although part of the second malignancies are unrelated to therapy, there is a need to carefully collect the data from patients treated according to new protocols in order to detect any changes in the number or kind of second malignancies in due time. This may well lead to a reassessment of therapeutic concepts.