Dose-modeling study to compare external beam techniques from protocol NSABP B-39/RTOG 0413 for patients with highly unfavorable cardiac anatomy
ABSTRACT The aim of this study was to select patients with heart anatomy that is specifically unfavorable for tangential irradiation in whole-breast radiotherapy (WBRT), to be used as an experimental cohort to compare cardiac dosimetric and radiobiological parameters of three-dimensional conformal external beam accelerated partial breast irradiation (3D-CRT APBI) to WBRT with techniques as defined by the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39/Radiation Therapy Oncology Group (RTOG) 0413 clinical trial.
A dosimetric modeling study that compared WBRT and 3D-CRT APBI was performed on CT planning data from 8 patients with left-sided breast cancer. Highly unfavorable cardiac anatomy was defined by the measured contact of the myocardium with the anterior chest wall in the axial and para-sagittal planes. Treatment plans of WBRT and 3D-CRT APBI were generated for each patient in accordance with NSABP B-39/RTOG 0413 protocol. Dose-volume relationships of the heart, including the V5min (minimum dose delivered to 5% of the cardiac volume), biological effective dose (BED) of the V5min, and normal tissue complication probability (NTCP) were analyzed and compared.
Despite expected anatomic variation, significantly large differences were found favoring 3D-CRT APBI in cumulative dose-volume histograms (p < 0.01), dose to the entire heart (mean difference 3.85 Gy, p < 0.01), NTCP (median difference, 1.00 Gy; p < 0.01), V5min (mean difference, 24.53 Gy; p < 0.01), and proportional reduction in radiobiological effect on the V5min (85%, p < 0.01).
Use of 3D-CRT APBI can demonstrate improved sparing of the heart in select patients with highly unfavorable cardiac anatomy for WBRT, and may result in reduced risk of cardiac morbidity and mortality.
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ABSTRACT: After breast conserving surgery, early stage breast cancer patients are currently treated with a wide range of radiation techniques including whole breast irradiation (WBI), accelerated partial breast irradiation (APBI) using high-dose rate (HDR) brachytherapy, or 3D-conformal radiotherapy (3D-CRT). This study compares the mean heart's doses for a left breast irradiated with different breast techniques. An anthropomorphic Rando phantom was modified with gelatin-based breast of different sizes and tumors located medially or laterally. The breasts were treated with WBI, 3D-CRT, or HDR APBI. The heart's mean doses were measured with Gafchromic films and controlled with optically stimulated luminescent dosimeters. Following the model reported by Darby (1), major cardiac were estimated assuming a linear risk increase with the mean dose to the heart of 7.4% per gray. WBI lead to the highest mean heart dose (2.99 Gy) compared to 3D-CRT APBI (0.51 Gy), multicatheter (1.58 Gy), and balloon HDR (2.17 Gy) for a medially located tumor. This translated into long-term coronary event increases of 22, 3.8, 11.7, and 16% respectively. The sensitivity analysis showed that the tumor location had almost no effect on the mean heart dose for 3D-CRT APBI and a minimal impact for HDR APBI. In case of WBI large breast size and set-up errors lead to sharp increases of the mean heart dose. Its value reached 10.79 Gy for women with large breast and a set-up error of 1.5 cm. Such a high value could increase the risk of having long-term coronary events by 80%. Comparison among different irradiation techniques demonstrates that 3D-CRT APBI appears to be the safest one with less probability of having cardiovascular events in the future. A sensitivity analysis showed that WBI is the most challenging technique for patients with large breasts or when significant set-up errors are anticipated. In those cases, additional heart shielding techniques are required.Frontiers in Oncology 10/2014; 4:284. DOI:10.3389/fonc.2014.00284
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ABSTRACT: Cardiac toxicity is a side-effect of anti-cancer treatment including radiotherapy and this translational study was initiated to characterize radiation-induced cardiac side effects in a population of breast cancer patients and in experimental models in order to identify novel therapeutic target. The size of the heart was evaluated in CO-HO-RT patients by measuring the Cardiac-Contact-Distance before and after radiotherapy (48months of follow-up). In parallel, fibrogenic signals were studied in a severe case of human radiation-induced pericarditis. Lastly, radiation-induced cardiac damage was studied in mice and in rat neonatal cardiac cardiomyocytes. In patients, time dependent enhancement of the CCD was measured suggesting occurrence of cardiac hypertrophy. In the case of human radiation-induced pericarditis, we measured the activation of fibrogenic (CTGF, RhoA) and remodeling (MMP2) signals. In irradiated mice, we documented decreased contractile function, enlargement of the ventricular cavity and long-term modification of the time constant of decay of Ca(2+) transients. Both hypertrophy and amyloid deposition were correlated with the induction of Epac-1; whereas radiation-induced fibrosis correlated with Rho/CTGF activation. Transactivation studies support Epac contribution in hypertrophy stimulation and showed that radiotherapy and Epac displayed specific and synergistic signals. Epac-1 has been identified as a novel regulator of radiation-induced hypertrophy and amyloidosis but not fibrosis in the heart.Radiotherapy and Oncology 04/2014; DOI:10.1016/j.radonc.2014.01.025 · 4.86 Impact Factor