Second Malignancies after Radiation Therapy: Update on Pathogenesis and Cross-sectional Imaging Findings

A wide spectrum of second cancers occur as late complications of radiation therapy (RT) used to treat various malignancies. In addition to the type and dose of radiation, lifestyle, environmental, and genetic factors are important to the development of second malignancies in cancer survivors. Typically, RT-induced malignancies (RTIMs) are biologically aggressive cancers with a variable period of 5-10 years for hematologic malignancies and 10-60 years for solid tumors between RT and the development of the second cancer. Although carcinomas and leukemias commonly develop after low-dose RT, sarcomas occur in tissues or organs that receive high-dose RT. Angiosarcomas and unclassified pleomorphic sarcomas are the two most common RT-associated sarcomas; other sarcomas include malignant peripheral nerve sheath tumors, leiomyosarcomas, osteosarcomas, chondrosarcomas, and dedifferentiated or pleomorphic liposarcomas. Select RTIMs show tumor genetic characteristics that allow accurate diagnosis. Nearly all cutaneous angiosarcomas after RT for breast cancer and 90% of RT-associated malignant peripheral nerve sheath tumors are characterized by MYC gene amplifications and loss of H3 K27me3 expression, respectively. Classic papillary thyroid carcinomas that develop after RT frequently harbor RET/PTC rearrangements and have a favorable prognosis, despite their advanced stage at patient presentation. Select RTIMs demonstrate characteristic imaging findings and typically develop in the prior radiation field. Imaging is essential to early diagnosis, characterization, localization, and staging of RTIMs. Familiarity of radiologists with the diverse spectrum of RTIMs is essential for early diagnosis and optimal management.