A Randomized Comparison of Radiation Therapy Techniques in the Management of Node-Positive Breast Cancer: Primary Outcomes Analysis

Abstract

Although inverse-planned intensity modulated radiotherapy (IMRT) and deep inspiration breath hold (DIBH) may allow for more conformal dose distributions, it is unknown whether using these technologies reduces cardiac or pulmonary toxicity of breast radiotherapy. A randomized controlled trial compared IMRT-DIBH versus standard, free-breathing, forward-planned, three-dimensional conformal radiotherapy in patients with left-sided, node-positive breast cancer in whom the internal mammary nodal region was targeted. Endpoints included dosimetric parameters and changes in pulmonary and cardiac perfusion and function, measured by single photon emission computed tomography (SPECT) scans and pulmonary function testing performed at baseline and 1year post treatment. Of 62 patients randomized, 54 who completed all follow-up procedures were analyzed. Mean doses to the ipsilateral lung, left ventricle, whole heart, and left anterior descending coronary artery were lower with IMRT-DIBH; the percent of left ventricle receiving ≥5Gy averaged 15.8% with standard radiotherapy and 5.6% with IMRT-DIBH (P<.001). SPECT revealed no differences in perfusion defects in the left anterior descending coronary artery territory, the study's primary endpoint, but did reveal statistically significant differences (P=.02) in left ventricular ejection fraction (LVEF), a secondary endpoint. No differences were found for lung perfusion or function. The small but statistically significant benefit in preservation of cardiac LVEF observed here should motivate future studies that include LVEF as a potentially meaningful endpoint. Future studies should disaggregate the impact of IMRT from that of DIBH. Clinical practice should recognize the importance of minimizing cardiac dose, even when already low in comparison to historical levels.