Individualized estimates of second cancer risks after contemporary radiation therapy for Hodgkin lymphoma

BACKGROUND. Estimates of radiation-related second cancer risk among Hodgkin lymphoma survivors are largely based on radiation therapy (RT) fields and doses no longer in use, and these estimates do not account for differences in normal tissue dose among individual patients. This study gives individualized estimates for the risks of lung and female breast cancer expected with contemporary involved-field RT and low-dose (20 Gy) RT for mediastinal Hodgkin lymphoma. METHODS. Three RT plans were constructed for 37 consecutive patients with mediastinal Hodgkin lymphoma: 35 Gy mantle RT, 35 Gy involved-field RT (IFRT), and 20 Gy IFRT. For each of the 111 RT plans, individual-level dosimetry data were incorporated into a cell initiation/inactivation/proliferation model to estimate the excess relative risk (ERR) and cumulative incidence of radiation-induced second cancer. RESULTS. ERR estimates were compatible with results of epidemiological studies. Compared with 35 Gy mantle radiation therapy, 35 Gy IFRT was predicted to reduce the 20-year ERRs of breast and lung cancer by 63% and 21%, respectively, primarily because of lower normal tissue doses with the omission of axillary RT. Low-dose (20 Gy) IFRT was associated with a 77% and 57% decrease in these ERRs. Patient-specific differences in normal tissue dose with IFRT led to 11-fold and 3.6-fold variations among individual's estimates of breast and lung cancer ERR, respectively. CONCLUSIONS. Contemporary IFRT is predicted to substantially reduce risk of secondary breast and lung cancer compared with mantle RT, with considerable variation in risk among individuals. Individualized prospective risk estimates could facilitate patient-specific counseling and the development of more effective RT techniques.