Dosimetric Analysis of Cardiac Toxicity after Breast Radiotherapy

Purpose: Radiotherapy is common primary and secondary cancer treatment. For the lungs, CNS substructures, and other organs, dose limits are clearly established [1,2]. However, specific guidelines are not established for the heart. A NEJM study looked at cardiac toxicity and radiation dose to certain heart structures; however, this was done using a single CT scan to represent all patients [3]. Our study aims to evaluate cardiac toxicity after breast cancer radiation, using individually-contoured CT scans to (1) quantify changes in dose to heart structures over time, and (2) quantify changes in cardiac toxicity rates over time.

Methodology: Patients who received radiotherapy at the Washington University Department of Radiation Oncology beginning in 2014 (n=334) and 2017 (n=388) were included in the study (n=722). For each patient, cardiac toxicities (listed below), death, and dosimetric data for the whole heart, left atrium, right atrium, left ventricle, right ventricle, LAD, RCA and each heart valve were obtained. Fisher Exact test and 2-sample t-tests were used to detect differences in toxicity rate and dose over time.

Results: The mean dose to the whole heart was 414 cGy and 317 cGy in 2014 and 2017 respectively. The mean dose to all ten structures studied was significantly lower in 2017 than 2014 (p<=0.001 in all cases). Overall toxicity rates were 4% for cardiomyopathy, 5% for arrhythmia, 3% for ischemia, and 5% for death. From 2014-2017, the rate of arrhythmia decreased from 7% to 3% (p=0.02) and the rate of death decreased significantly from 8% to 3% (p < 0.05).

Conclusions: Our results showing decreased dose to the heart and its substructures over time are consistent with increasing adoption of hypofractionation and IMRT. Furthermore, decreased rates of cardiac events suggest that decreased dose to the heart may contribute to lower toxicity risk. Further studies exploring potential dose-response relationships are essential for future establishment of standardized dose limits for the heart and its substructures.

References: Lawrence YR, Li XA, el Naqa I, Hahn CA, Marks LB, Merchant TE, Dicker AP. Radiation dose-volume effects in the brain. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl). doi:10.1016/J.IJROBP.2009.02.091
2. Marks LB, Bentzen SM, Deasy JO, Kong FM (Spring), Bradley JD, Vogelius IS, El Naqa I, Hubbs JL, Lebesque J V., Timmerman RD, Martel MK, Jackson A. Radiation Dose Volume Effects in the Lung. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl):S70. doi:10.1016/J.IJROBP.2009.06.091
3. Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Brønnum D, Correa C, Cutter D, Gagliardi G, Gigante B, Jensen M-B, Nisbet A, Peto R, Rahimi K, Taylor C, Hall P. Risk of Ischemic Heart Disease in Women after Radiotherapy for Breast Cancer. N Engl J Med. 2013;368(11):987-998. doi:10.1056/NEJMOA1209825/SUPPL_FILE/NEJMOA1209825_DISCLOSURES.PDF