P3-13-05: Analysis of Heart Dose-Volume Parameters and Cardiac Events among Node Positive Breast Cancer (NPBC) Patients Treated with Three-Dimensional Conformal Radiation Therapy (3D-CRT).
Authors: Bradley J , Prior P , Sparks I , Xiang Q , Santana-Davila R , Walker A , Wilson JF , Li XA , White J 
Published: June 2012

Background

For NPBC patients the use of regional nodal irradiation (RNI) to the supraclavicular, axillary, internal mammary lymph nodes (IMN) in addition to the chest wall and/or breast can maximize locoregional control and improve overall survival. However, comprehensive RNI for breast cancers located on the left side has been linked to late cardiac morbidity, potentially lessening the therapeutic benefit of treatment. The optimal radiation dose-volume constraints for the heart in this setting are not fully understood. We examined NPBC patients treated with RNI using 3D-CT based radiation therapy (RT) to evaluate cardiac dose and incidence of cardiac events.

Methods: Between 2000 and 2007, 150 NPBC patients were treated with RNI following lumpectomy or mastectomy using 3D-CRT. In all cases, treatment target and normal tissue volumes were delineated on treatment CT scans. The heart contour included the ventricles and the left atrium. The dose-volume histogram of the cardiac doses delivered and the incidence of cardiac events is reported.

Results: Median follow-up of surviving patients is 7 (1-10.6) years. Median patient age is 50 (27-91). 52.35% are premenopausal, 75.7% estrogen receptor positive, 66.3% progesterone receptor positive and 15.92% HER-2 positive. Mean positive lymph nodes is 5 (1-29). Extracapsular extension is present in 47.31%. Mean microscopic tumor size is 3.73 (0.1-21) cm. The IMN receive &gt; 40 Gy in 65.5%. 94% had chemotherapy, and in 82.3% it was anthracycline-based. At the time of RT, 12.2% smoked, 9.5% had diabetes, 32.4% with hypertension, and 4.7% with a history of coronary artery disease.

There was 1 (0.7%) right sided patient with cardiac events and 4 (2.7%) left sided experiencing cardiac events (p = 0.121, Fisher's Exact test). A total of 10 cardiac diagnoses were experienced among the 5 patients: coronary artery disease with myocardial infarction (3), congestive heart failure (2), cardiomyopathy (2), and arrhythmia (3). The median time interval to onset of the events is 2.5 years (0-4.3 years).

The cardiac doses among 150 patients are as follows: mean V25 is 5.7, (0.0 - 20.0%), V25 is &lt; 9 % in 74.4% of patients, mean V45 is 1.8% (0-13.3%), V45 is &lt; 5.5% in 91.8%. The mean maximum point dose is 42.8 Gy, and the mean heart dose is 5.6 Gy (0.2−25.3 Gy). The mean V25 and V45 in those 5 patients with a cardiac event is 6.7% (0.9−11.9%) and 3.7% (0-6.6%), respectively; in the 145 remaining patients, 5.7% (0-20.0%) and 1.7% (0-13.3%), respectively. The mean heart dose in those with an event is 5.2 Gy (2.4−7.3 Gy) versus 5.6 Gy (0.2−25.3 Gy) in the remaining patients.

Conclusions: The cardiac event rate among these NPBC patients treated with RNI and anthracycline-based chemotherapy is low. However, those patients with cardiac events have a higher mean V45. No other dose-volume relationships are discernible. Additional analysis using 3DCRT volumes are important to validate these findings and better define the dose-volume parameters for cardiac toxicity.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-13-05.