Second malignancies

The secondary development of malignant tumors after the treatment of Hodgkin's disease has been termed the price of success, but is relevant also to other types of cancer and gives an opportunity to study mechanisms of carcinogenesis and tumor induction. The authors review here their experience with second malignant neoplasms (SMN) as well as the result of an extensive search of the recent literature. The primary malignancies discussed in this article include Hodgkin's disease, pediatric cancer, breast cancer, lung cancer and other types of tumors. The international literature was searched (Medline 1989-1995) for reports of SMN with special emphasis on risk factors and the molecular mechanisms of tumor induction. In Hodgkin's disease, a 3 to 5-fold elevated risk for SMN was recognized, with a 15-year cumulative incidence in the range of 11-18%. All types of malignancies have a statistically increased risk (leukemias, non-Hodgkin's lymphomas, solid tumors). The risk for leukemia is related to the intensity of treatment with alkylating agents. Some solid tumors like lung cancer or breast cancer are related to radiation therapy. Present-day treatments may carry a lower risk of inducing secondary malignancies than treatments in the past. For non-Hodgkin's lymphoma as primary malignancy, fewer data exist on SMN. In pediatric cancer, no general risk estimate can be given and the genetic influence is greater as a cause of SMN. The improved prognosis for acute lymphoblastic leukemia has led to a changing pattern of pediatric SMN. In head and neck- and in lung cancer, the same etiologic factors which cause the primary tumor may also cause SMN. SMN occur as part of familial cancer syndromes. Two types of treatment related leukemias (mostly AMLs) exist and can be recognized by cytogenetic and molecular analysis. A complete follow-up is necessary to fully appreciate the risk of second malignancy. The goal to prevent SMN must be reached without decreasing the cure rates of the primary tumor. New treatment approaches need to be carefully monitored for SMN. Improved tests of mutagenesis and molecular screening may help to recognize patients prone to develop SMN and permit to estimate certain types of risk. Screening and prevention strategies are useful in high-risk situations.