Abstract Background: Regional nodal irradiation (RNI) in addition to the chest wall and/or breast can maximize local regional control and improve overall survival, but has been associated with late cardiac morbidity. We examined NPBC patients treated with RNI using 3D-CT based radiation therapy (RT) to evaluate incidence and type of cardiac events. Methods: Between 2000 and 2007, 156 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 left ventricle and the atria. Prescription dose was typically 50Gy in 25 fractions (range 44-54 Gy) to the chest wall and/or breast PTVeval. 37% received a boost to the chest wall and 73% to the lumpectomy cavity. The mean prescription dose to the axilla and supraclavicular lymph nodes was 47.6 Gy (range 43.2 – 54 Gy) and 46.8 Gy to the IMN (range 35.3 – 50.4 Gy). The dose-volume cardiac data and incidence of cardiac events is reported. Results: Median follow-up of surviving patients was 7 years (range, 0.3-10.6). Median patient age was 50 (range, 27-91), 52% were premenopausal, 76% estrogen receptor positive, and 18% were HER-2 positive. The IMN received > 40 Gy in 66%. Chemotherapy was used in 94% of patients, and it was anthracycline-based in 82.3%. At the time of RT, 12.5% smoked, 9% had diabetes, 33% with HTN, and 4.4% had a history of CAD. Average mean heart dose for the cohort was 5.2 Gy (range, 0.2 - 25.3 Gy). Mean cardiac V25 was 5.4% (range, 0-20%), mean cardiac V45 was 1.7% (range, 0-13.3%), and mean maximum cardiac point dose was 45.4 Gy. There was 1 (0.7% of cohort) right sided patient with cardiac events and 8 (5.1% of cohort) left experiencing cardiac events. A total of 18 cardiac diagnoses were experienced among the 9 patients: Coronary artery disease with or without myocardial infarction (4), congestive heart failure (6), cardiomyopathy (3), and arrhythmia (5). Conclusions: The cardiac event rate among these NPBC patients treated with RNI and anthracycline-based chemotherapy was low, but more common in women with left-sided breast cancer compared to right. Additional analysis using 3DCRT volumes are important to validate these findings and better define the dose-volume parameters for cardiac toxicity. Citation Format: Bradley JA, Sparks I, Prior P, Bergom C, Walker A, Wilson JF, Li XA, White J. Analysis of cardiac events among node positive breast cancer (NPBC) patients treated with three-dimensional conformal radiation therapy (3D-CRT) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-11-06.

Regional nodal irradiation in lymph node (LN) positive breast cancer (BC) post lumpectomy / mastectomy can be subject to controversy due to the potential for treatment morbidity. Three-D-CRT methods have been associated with reduced treatment related toxicity in other disease sites, but little is known about outcomes in LN positive BC. Between 2000 and 2007, 172 women with node positive BC were treated with regional nodal irradiation following lumpectomy or mastectomy using 3DCRT. In all cases, target and normal tissue volumes were delineated on treatment CT scans with field arrangement and beam modification to meet established treatment goals. Patient population and tumor characteristics as well as recurrence rates are reported. Toxicities were scored using the Common Toxicities Criteria for Adverse Effects v3.0. Data was analyzed using summary statistics. Median follow-up (f/u) of surviving patients was 7 (1-10.6) years. Median patient age was 50 (27-91), 52.35% were premenopausal, 75.74% had positive estrogen receptors, 66.27% had positive progesterone receptors, and 15.92% were HER-2 positive (3+ Hercept or amplified by FISH). Mean number of all LNs recovered was 17.1 (1-46), mean positive LNs: 5 (1-29), extra capsular invasion: 47.31%). Mean microscopic tumor size was 3.73 (0.1-21) cm. Staging was pII in 43.3% and pIII in 52%. 52.3% underwent lumpectomy and 45.93% mastectomies. 93.0% had systemic chemotherapy (63.4% adjuvant and 29.7% neoadjuvant), with 90.3% anthracycline based regiment. The grade of acute dermatitis was 1 for 83.0%, 2 for 13.4%, and 3 for 2.91%. Moist desquamations-confined to skin folds-was present in 14% and outside of folds 3.5%. Grade > 2 fatigue occurred in 18.6%. Late toxicities included: Grade 1 (24.7%) and Grade 2 (1.9%) hyperpigmentation, Grade 1 (9%) and Grade 2-3 (3.2%) telangiectasia, and Grade 2-3 fibrosis (5.13%). One case (0.6%) each of pneumonitis and pericarditis occurred. There were no incidences of brachial plexopathy. Decreased range of motion (ROM) at last f/u was 3%, with-overall physical therapy referral post RT for ROM at 16.6%. 96% had arm circumference measurements: 16.4% developed lymphedema as determined by >2 cm arm circumference difference. Local control was achieved in 94.7% (local recurrence rates were 7.9% post-lumpectomy and 2.5% post-mastectomy (p > 0.1) and regional LN control in 99.4% (0% supraclavicular or internal mammary recurrences). Our study demonstrates that the use of 3D-CRT resulted in excellent locoregional cancer control and with low incidences of post RT toxicities in these relatively higher risk node positive BC patients treated comprehensively.

Abstract 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 > 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 < 9 % in 74.4% of patients, mean V45 is 1.8% (0-13.3%), V45 is < 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.