Lee, Choonsik

Abstract Background Estimating effective dose (E) for CT is often done with dose‐length product (DLP) and effective dose conversion factors, a.k.a. k ‐factors. Previous studies have primarily focused on k ‐factor values derived from certain fixed‐sized phantoms but have not extensively explored all the contributing factors and associated variations in E. Purpose In this study, we investigated the contributing factors and variations of E using k ‐factors as surrogates in adult and pediatric CT exams and provided empirical formula to estimate a comprehensive new set of k ‐factors. Methods Effective dose was estimated using NCICT (National Cancer Institute, USA), including organ and effective dose conversion coefficient library estimated by Monte‐Carlo radiation transport techniques. The k ‐factors were derived as a surrogate of DLP‐normalized E, via E/DLP (unit: mSv/mGy·cm). We examined the variations of effective dose estimates for different phantom and scan parameters represented by the calculations of k ‐factors. This included variations in patient sex, weight, height, kVp, and scan length across typical adult and pediatric CT examinations of anatomical regions such as the head, neck, chest, abdomen, and pelvis. Multivariable regression analyses with/without standardization were conducted to evaluate the significance of the dependency of k ‐factors on the studied parameters. Tube current modulation (TCM) parameters, modeled as a function of patient attenuation using variable modulation strengths, were also incorporated to reflect realistic clinical CT dose variations. Results The variations of DLP‐normalized E were substantially affected by multiple factors, exceeding 100% for adults (weight for adult pelvis) and more than 200% for pediatrics (height for pediatric head). The analysis of standardized regression coefficients revealed that patient weight is the most critical factor, except for head scans in adults, where scan length and patient height are the main determinants. In pediatric CT, both patient weight and height had critical impact. Similarly, for pediatric head CT scans, patient height and scan length are the dominant factors, as observed in adults. Consequently, the k ‐factors have a wide range, from 0.0099 to 0.0357 mSv/mGy·cm for adult chest and from 0.0085 to 0.0363 mSv/mGy·cm for adult abdomen. Empirical formulas to estimate k ‐factors were obtained based on multi‐variable regression with adjusted R square ranging from 0.71 to 0.93. Based on NCICT's TCM model, the use of TCM resulted in an additional average variation of 110% in the k ‐factor compared to non‐TCM results. Conclusions Our study demonstrated the large variations of DLP‐normalized effective dose. Standardized coefficients revealed that patient weight, height and/or scan length were the most crucial determinants. Depending on the specific TCM model used, even greater variations may be observed. This work also provided a practical framework for estimating CT effective dose using the traditional k ‐factor method with updated new conversion factors.

PURPOSE Radiation-associated cardiac disease is a major cause of morbidity/mortality among childhood cancer survivors. Radiation dose-response relationships for cardiac substructures and cardiac diseases remain unestablished. METHODS Using the 25,481 5-year survivors of childhood cancer treated from 1970 to 1999 in the Childhood Cancer Survivor Study, we evaluated coronary artery disease (CAD), heart failure (HF), valvular disease (VD), and arrhythmia. We reconstructed radiation doses for each survivor to the coronary arteries, chambers, valves, and whole heart. Excess relative rate (ERR) models and piecewise exponential models evaluated dose-response relationships. RESULTS The cumulative incidence 35 years from diagnosis was 3.9% (95% CI, 3.4 to 4.3) for CAD, 3.8% (95% CI, 3.4 to 4.2) for HF, 1.2% (95% CI, 1.0 to 1.5) for VD, and 1.4% (95% CI, 1.1 to 1.6) for arrhythmia. A total of 12,288 survivors (48.2%) were exposed to radiotherapy. Quadratic ERR models improved fit compared with linear ERR models for the dose-response relationship between mean whole heart and CAD, HF, and arrhythmia, suggesting a potential threshold dose; however, such departure from linearity was not observed for most cardiac substructure end point dose-response relationships. Mean doses of 5-9.9 Gy to the whole heart did not increase the risk of any cardiac diseases. Mean doses of 5-9.9 Gy to the right coronary artery (rate ratio [RR], 2.6 [95% CI, 1.6 to 4.1]) and left ventricle (RR, 2.2 [95% CI, 1.3 to 3.7]) increased risk of CAD, and to the tricuspid valve (RR, 5.5 [95% CI, 2.0 to 15.1]) and right ventricle (RR, 8.4 [95% CI, 3.7 to 19.0]) increased risk of VD. CONCLUSION Among children with cancer, there may be no threshold dose below which radiation to the cardiac substructures does not increase the risk of cardiac diseases. This emphasizes their importance in modern treatment planning.

10027 Background: Thoracic radiotherapy (RT) is a risk factor for cardiac disease among survivors of childhood cancer based on studies considering RT doses to the entire heart. Dose to specific cardiac substructures may provide more precise dose-response associations to guide RT planning. We report associations between RT dose to cardiac substructures and risk of specific cardiac outcomes. Methods: We determined the cumulative incidences of CTCAE grade 3 – 5 coronary artery disease (CAD), heart failure (HF), and valvular disease (VD) among 25,481 5-year childhood cancer survivors diagnosed 1970 – 1999 in the CCSS. Median age at diagnosis was 6.1 years (0 – 20 years) and at last follow-up 29.8 years (5.6 – 65.9 years). For the 12,228 individuals receiving RT, fields were reconstructed on an age scaled computational phantom. Mean doses to the entire heart, cardiac chambers, valves, and left main, anterior descending (LAD), circumflex, and right coronary (RCA) arteries were estimated. Adjusted piecewise exponential models (including cumulative anthracycline dose) evaluated associations between mean RT dose to each structure and outcomes. Results: At 30 years from diagnosis, the cumulative incidences of grades 3 – 5 CAD, HF, and VD were 2.3% (95% CI 2.0 – 2.5), 2.6% (95% CI 2.4 – 2.9), and 0.6% (95% CI 0.5 – 0.8) respectively. Low dose RT (mean 5 – 9.9 Gy) to the RCA (relative rate [RR] = 2.6, 95% CI 1.6 – 4.1, p < 0.001), LAD (RR = 1.9, 95% CI 1.1 – 3.3, p = 0.019), and left ventricle (RR = 2.2, 95% CI 1.3 – 3.7, p = 0.002) was associated with increased risk of CAD relative to those not exposed; mean dose of 5 – 9.9 Gy to the entire heart was not (RR = 1.1, 95% CI = 0.8 – 1.6, p = 0.59). Table shows the associated cumulative incidences of CAD for these structures. Mean RT doses of 5 – 9.9 Gy to the aortic valve (RR = 4.6, 95% CI 1.5 – 14.0, p = 0.008) and tricuspid valve (RR = 5.5, 95% CI 2.0 – 15.1, p = 0.001) were associated with risk of VD compared to those with no RT; mean heart dose 5 – 9.9 Gy was not (RR = 0.6, 95% CI = 0.2 – 1.3, p = 0.16). No cardiac structure was significantly associated with an increased risk of HF at a mean dose of 5 – 9.9 Gy. Mean RT doses below 5 Gy were not associated with increased risks of CAD, HF, or VD; doses ≥10 Gy to nearly all substructures and the entire heart were. Conclusions: Low dose RT to the coronary arteries and cardiac valves (5 – 9.9 Gy) from RT is associated with increased risk of CAD and VD, respectively. Sensitivity to low dose RT may vary across the heart and doses to specific structures may be more predictive of late cardiac disease than whole heart dose. These data can guide RT planning to prioritize substructures for avoidance.[Table: see text]