While radiotherapy and antineoplastic chemotherapy often control malignancies they may, paradoxically, cause new cancers to develop as long-term complications. Although almost any type of neoplasm can occur, radiation-induced malignancies are most likely to affect the myelopoietic tissues and the thyroid gland. The former tissues are also most frequently involved by chemotherapy. The combination of intensive radiotherapy and intensive chemotherapy is particularly leukemogenic. Acute myeloid leukemia has occurred with increased frequency following treatment of Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, ovarian cancer, polycythemia vera, carcinoma of the thyroid gland, and carcinoma of the breast.
Radiation-induced malignancies usually occur in the field of irradiation. For example, radiotherapy for carcinoma of the cervix may be followed by the development of carcinomas of the endometrium, vagina, urinary bladder, colon, rectum, and anus, as well as mesotheliomas of the peritoneum and osteosarcomas of the pelvis. Tumors developing in an irradiated field include a substantial number of soft tissue sarcomas or osteosarcomas. There is a 20-fold increase of second cancers following treatment of childhood malignancies, mostly sarcomas of bone and soft tissues, but including leukemia, and carcinomas of the thyroid gland, skin, and breast.
The latent period between radiotherapy and the appearance of a second cancer ranges from 2 years to several decades, often being 10-15 years. With chemotherapy the mean latent period is shorter, approximately 4 years.
The mechanism of oncogenesis by radiotherapy or chemotherapy is poorly understood and probably involves a complex interplay of somatic mutation, co-oncogenic effects, depression of host immunity, stimulation of cellular proliferation, and genetic susceptibility.
The danger of developing second malignancies following radiotherapy or chemotherapy emphasizes the need for lifelong follow-up of patients given these forms of treatment; particularly in those with a long life expectancy as are those treated for childhood neoplasms.