Role of Radiotherapy in SNs
Radiotherapy has been repeatedly reported to increase the risk for SMNs in the CCSS cohort. As a result of meticulous collection of radiation therapy records, we have been able to examine the risk of SMN by radiation dose for several SMN types. Our nested case-control study of 69 cases of subsequent thyroid cancer and 265 matched controls without thyroid cancer revealed an increased risk of thyroid cancer with radiation doses as high as 29 Gy (odds ratio [OR] = 9.8; 95% CI, 3.2 to 34.8) but a decrease in the risk of secondary thyroid cancer at doses greater than 30 Gy (Fig 2A).20 This finding is consistent with a cell-killing effect. Radiobiologically based statistical models were applied to describe the dose response and estimate the ERR, which was 1.3/Gy at doses less than 6 Gy with a decrease of 0.2% per unit dose squared with increasing dose.18 Dose response was most pronounced with age younger than 10 years at diagnosis. Chemotherapy exposure was not associated with risk of subsequent thyroid cancer in this study.