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Cardiac Structure Injury After Radiotherapy for Breast Cancer
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The aim of this study was to evaluate the effect of radiation on specific cardiac segments in 456 women who underwent radiotherapy (RT) for breast cancer and then later experienced a major coronary event. Of women with left ventricular (LV) injury, 243 had left-sided breast cancer and 171 had right-sided breast cancer (ratio of left vs right, 1.42), reflecting the higher typical LV radiation doses in left-sided cancer (average dose left-sided, 8.3 Gy; average dose right-sided, 0.6 Gy). For women with coronary artery disease, the ratios of left-sided versus right-sided RT for six individual coronary artery segments were estimated.
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Higher radiation doses were strongly associated with more frequent injury to individual LV and coronary artery segments, suggesting the radiosensitivity of all cardiac segments and indicating the need to minimize radiation doses to all segments.
- Jeffrey Wiisanen, MD
abstract
This abstract is available on the publisher's site.
Access this abstract nowPurpose
Incidental cardiac irradiation can cause cardiac injury, but little is known about the effect of radiation on specific cardiac segments.
Methods
For 456 women who received breast cancer radiotherapy between 1958 and 2001 and then later experienced a major coronary event, information was obtained on the radiotherapy regimen they received and on the location of their cardiac injury. For 414 women, all with documented location of left ventricular (LV) injury, doses to five LV segments were estimated. For 133 women, all with documented location of coronary artery disease with ≥ 70% stenosis, doses to six coronary artery segments were estimated. For each segment, numbers of women with left-sided and right-sided breast cancer were compared.
Results
Of women with LV injury, 243 had left-sided breast cancer and 171 had right-sided breast cancer (ratio of left v right, 1.42; 95% CI, 1.17 to 1.73), reflecting the higher typical LV radiation doses in left-sided cancer (average dose left-sided, 8.3 Gy; average dose right-sided, 0.6 Gy; left minus right dose difference, 7.7 Gy). For individual LV segments, the ratios of women with left- versus right-sided radiotherapy were as follows: inferior, 0.94 (95% CI, 0.70 to 1.25); lateral, 1.42 (95% CI, 1.04 to 1.95); septal, 2.09 (95% CI, 1.37 to 3.19); anterior, 1.85 (95% CI, 1.39 to 2.46); and apex, 4.64 (95% CI, 2.42 to 8.90); corresponding left-minus-right dose differences for these segments were 2.7, 4.9, 7.2, 10.4, and 21.6 Gy, respectively ( Ptrend < .001). For women with coronary artery disease, the ratios of women with left- versus right-radiotherapy for individual coronary artery segments were as follows: right coronary artery proximal, 0.48 (95% CI, 0.26 to 0.91); right coronary artery mid or distal, 1.69 (95% CI, 0.85 to 3.36); circumflex proximal, 1.46 (95% CI, 0.72 to 2.96); circumflex distal, 1.11 (95% CI, 0.45 to 2.73); left anterior descending proximal, 1.89 (95% CI, 1.07 to 3.34); and left anterior descending mid or distal, 2.33 (95% CI, 1.19 to 4.59); corresponding left-minus-right dose differences for these segements were -5.0, -2.5, 1.6, 3.5, 9.5, and 38.8 Gy ( Ptrend = .002).
Conclusion
For individual LV and coronary artery segments, higher radiation doses were strongly associated with more frequent injury, suggesting that all segments are sensitive to radiation and that doses to all segments should be minimized.
Additional Info
Disclosure statements are available on the authors' profiles:
Cardiac Structure Injury After Radiotherapy for Breast Cancer: Cross-Sectional Study With Individual Patient Data
J. Clin. Oncol 2018 May 23;[EPub Ahead of Print], C Taylor, P McGale, D Brønnum, C Correa, D Cutter, FK Duane, B Gigante, MB Jensen, E Lorenzen, K Rahimi, Z Wang, SC Darby, P Hall, M EwertzFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
The long-term impact of chest radiotherapy in the treatment of cancer continues to be a topic of concern in cardio-oncology, despite the use of contemporary techniques where modern 3D CT–based planning and other strategies have significantly reduced cardiac radiation exposure. In addition, the cardiovascular impact of radiotherapy in cancer survivors who were treated throughout the mid- to late 20th century has been documented in many epidemiological studies.
A historical analysis provided by Taylor et al examines 456 women from Sweden and Norway with breast cancer and expands upon their landmark 2013 study,1 which originally showed a linear increase of major coronary events with the mean dose to the heart by 7.4%/gray (Gy). The women studied in this cohort who were treated with radiation between 1958 and 2001 all experienced a major coronary event. Radiation doses and the coronary artery segments that were affected were estimated based on review of medical records and the patient’s radiotherapy chart. The average dose of left-sided radiotherapy was 8.3 Gy and right-sided radiotherapy was 0.6 Gy. The authors found a correlation with higher radiation doses with more frequent left ventricular injury regardless of historical radiotherapy techniques; the apex, anterior, and septal segments were frequently affected, and there was a statistically significant incidence of coronary artery disease in the left anterior descending artery.
Although the study has its limitations—for instance, individual CT information was unavailable due to these techniques being performed before the advent of modern 3D CT radiotherapy planning, requiring more estimation than precise localization of cardiac involvement—this study is an important addition to studying the sequelae of radiotherapy. Although modern techniques have theoretically reduced direct cardiac irradiation, techniques such as internal mammary radiotherapy—which have shown improved breast cancer survival rates—may still involve the heart in its fields. At risk as well are patients with unfavorable anatomy where cardiac involvement cannot be avoided. Ongoing efforts are needed to risk-stratify breast cancer patients at risk for developing radiation-induced heart disease, with the need to design trials to formulate preventative pharmacologic interventions and long-term cardiotoxicity surveillance strategies, if such evolving radiotherapy techniques can ensure prolonged cancer survival rates.
Reference