Decreasing The Radiation Dose To Anterior Myocardial Territory As The New Strategies Of Heart Protection In Postoperative Radiation For Left-Sided Breast Cancer With Breast Conserving Surgery

Background and Purpose The treatment modalities of breast cancer included surgery, radiotherapy (RT), chemotherapy, hormone therapy and biotargeted therapy comprehensively. Compared with masterectomy and RT, breast conversed surgery (BCS) with postoperative RT resulted in the similar overall results and the long-term survival. Compared BCS alone, postoperative RT may result in lower local recurrence rate, longer survival period, better cosmetic effects and lesser radiation related side affects. The adjuvant RT techniques of breast cancer included conventional tangential field radiation and three dimensional conformal RT (3DCRT) or intensity modulation RT (IMRT), in which part of the heart volume, especially the anterior part of the heart, was included into the radiation fields and therefore received higher radiation dose than the other parts. Recently, more and more epidemiological data showed that, for breast cancer (especially for the left-sided patients), those who died due to the radiation-associated heart disease (RAHD) outnumbered the breast cancer itself after one or two decades of RT. However, majority of RAHD were ischemic heart disease (IHD) which the ischemic areas mainly located in the anterior part of the heart. So the decrease of radiation dose to the anterior part of the heart might result in lower incidence of long-term RAHD including IHD.Methods and Materials The archived computed tomographic (CT) scans of 23 patients who received adjuvant radiotherapy (RT) in our department were selected at random for this dosimetric study. All patients had left-sided breast cancer pathological stageⅠ/Ⅱand received BCS. The same radiation oncologist completed the delineation of contour——clinical target volume (CTV) and organ at risks (OARs) including both lungs, the right breast, the heart, left ventricle (LV) and anterior part of the heart that we defined as anterior myocardial territory (AMT). The AMT covered the myocardium from the anterior surface of the heart to 1.0 cm from the posterior surface and major epicardial coronary arteries at the anterior surface, such as the left anterior descending (LAD), the left circumflex, and the left and right main coronary artery. The CTV was defined as the palpable breast tissues. The anterior margin was parallel to, but 5 mm inside, the skin. The posterior margin ended at the junction of the breast tissues and the chest wall or pectoralis major muscles. No lymphatic region was irradiated electively. Planning target volume (PTV) was generated automatically with a 0.8-cm margin around the CTV and was modified when necessary. For each patient, eight radiation plans including one conformal tangential field (plan TF) and seven IMRT plans were generated. IMRT (H), IMRT (H+AMT), IMRT (H+LV), IMRT (H+AMT+LV), IMRT (AMT), IMRT (LV), IMRT (AMT+LV) address the heart, the heart and LV, the heart and AMT, the heart and AMT and LV, AMT, LV, AMT and LV respectively, as the OARs, in addition to both lungs and the right breast. To keep the comparability of all IMRT plans, all optimization parameters are the same in each patient. The prescribed dose (PD) was 50 Gy with 25 fractions. Setting plan TF and IMRT (H) as standard control. We firstly compared these two plans and IMRT with the heart and the AMT and/or LV as additional OAR respectively to find the advantages of IMRT plans and the preferred one. Also, we compared IMRT (H) with the AMT and/or LV as the replacing the heart to be OAR to find the preferred one. At last, we compared the found two preferred plans. For PTV, reported the mean, maximal, minimal dose and the percentage of volume receiving 110%,105%,98% and 95% of PD. Also, we calculated the homogeneity index (HI), conformity index (CI) and coverage index (CovI) of PTV. For OAR, the mean, maximal, minimal dose and Vn which means the percentage of volume receiving nGy or more were compared.Results Compared with TF plan, the mean dose to the heart in IMRT plans did not show significant differences, but the dose to AMT and LV decreased by 18.7%-45.4% and 10.8%-37.4%, respectively. The maximal dose to the heart decreased by 18.6%-35.3%, to AMT by 22.0%-45.1% and to LV by 23.5%-45.0%, as did the percentage volume≥V12, >V11 and>V10. The V5 of the heart, AMT, LV, both lungs and right breast showed a significant increase. In comparison with IMRT (H) plan, the mean dose to the heart, AMT and LV decreased by 17.5%-21.5%,25.2% -29.8% and 22.8%-29.8%, respectively, and the maximal dose by 13.6%-20.6%,23.1%-29.6% and 17.3%-29.1%. IMRT plans for both lungs and the right breast showed no significant differences. Compared with plan (H), the homogeneity index, conformity index, and coverage index were not compromised significantly. The mean dose to the heart, LV, and AMT decreased 5.32%-21.51% (p<0.05),19.86%-29.52%(p<0.05) and 13.25%-24.48%(p<0.05) in plan (AMT), plan (LV) and plan (LV+AMT) respectively. The V5, V10, V15, V20, and V30 of the heart, LV and AMT decreased significantly. The mean dose and V10 of the right lung increased by 9.2% and 27.6% in plan (LV), respectively and the mean dose and V2 and V5 of the right breast decreased significantly in plan (AMT) and plan (LV+AMT). Plan (AMT) was the preferred and then compared with plan (H+LV), the majority of DVH of OARs, including the heart, LV, AMT, both lungs and the right breast, did not show statistical differences. However, the V5 and V10 of LV increased by 4.21% and 19.14%, respectively, (p<0.05), and the V15 and V20 decreased by 26.48% and 26.04%, respectively (p<0.05) in plan (AMT). The V10, V15 of the right lung and the V5, V10 of right breast also decreased significantly (p<0.05).Conclusions Compared with tangential field radiation, for left-sided breast cancer with BCS, the IMRT technique in left-sided breast cancer may decrease the radiation dose to the heart, AMT and LV and the high dose volume of all the OARs with the cost of increasing low dose volume. In IMRT plan, both AMT and LV as the additional OAR may result in the decrease of maximal and mean dose to the heart, AMT and LV. What's more, the attitude of decrease between the AMT and LV as additional OAR is almost in the same level. Because LV could be contoured with its clear anatomic structure, we recommend that LV can be added in IMRT plan as OARs except for heart, both lungs and the right breast. As the AMT or LV replacing the heart as OAR, both IMRT plans can decrease the dose to the heart, AMT, LV by 5.32%-29.52% and IMRT with AMT as OAR was the preferred. In the comparison IMRT plan with AMT as OAR and both the heart and LV as OAR, both two IMRT plan can decrease the radiation dose to the heart, AMT, LV similarly. Because the IMRT plan with AMT as OAR may result in more decrease of the dose to right breast, right lung and part of LV (the high dose volume). Therefore, we recommend that AMT may replace the heart as OAR in left-sided breast IMRT, which might potentially translate into the radiation-related heart events in one or several decades later. The further research topics include the study with more patients and the other thoracic radiation techniques and the type of tumors were entered to investigate the indication of its use. Also the relationship of radiation dose to AMT with the cardiac events and the molecular mechanisms of the moderate or low radiation dose to the heart and the vascular damage warrant to be clarified further.