Radiotherapy For Left-sided Breast Cancer:Focusing On Heart Dosimetry

Breast cancer is the leading cause of morbidity in women with malignant tumors.Radiotherapy,as a part of systematic therapy,plays an important role in breast cancer.Adjuvant radiotherapy after surgery remains the indispensible care for most breast cancer,with a proven local control benefit while associated with an increasing in heart risk.Modern accurate radiotherapy technique could spare the heart from radiation to some extent.In this article,we illustrate the heart issue brought by breast cancer radiotherapy from four aspects.The first three chapters were all about dosimetric studies of human heart when doing left breast radiotherapy.The last chapter roughly investigated the pathologic changes to cardiovascular damage of irradiated hearts of mice.In chapter one,we assess the value of maximum heart distance(MHD)in predicting the dose of tangential field heart irradiation in left-sided breast cancer.A total of 40 left-sided breast cancer patients who were given adjuvant tangential field irradiation on the left chest wall after modified radical mastectomy were enrolled.The following parameters were derived using three-dimensional treatment planning system for each patients:MHD,mean dose and equivalent uniform dose to organs at risk including the whole heart,left anterior descending coronary artery(LAD),left ventricle(LV),and anterior myocardial territory(AMT).The relationship between MHD and each Dmean or EUD was analyzed by curve fitting equation.The R2 values of first-,second-,and third-order curve fitting equations were great than 0.8 respectively,between MHD and whole heart Dmean or EUD.The R2 values of first-,second-,and third-order curve fitting equations were great than 0.7 respectively,between MHD and AMT Dmean.MHD is a reliable predictor of the mean dose to organs at risk(whole heart and AMT)in tangential field radiotherapy for left-sided breast cancer.In chapter two,we explored the application of non-rigid image registration in accurate radiotherapy and image guided radiotherapy.The error caused by the different methods of non-rigid image registration is a research point at issue.We use the methods ANACONDA and MORFEUS,which provided by the Raystation commercial treatment planning system to compare dosimetric deviation.It suggested that the two methods of error of algorithm chosen revealed no significant differences in evaluation of heart doses.In order to evaluate the dosimetric impact of respiratory motion and patient setup on the dose delivered to heart during free-breathing left breast radiotherapy,a planning dose,four dimensional dose and an accumulated actual dose were computed and compared using four dimensional computer tomograph(4DCT)and cone-beam computer tomograph(CBCT)phases.The result shows that the maximum errors of mean heart dose,V10 and max heart dose were 10.33%,18.86%and 2.50%versus 32.40%,29.43%and 7.10%,respectively when 4DCT and CBCT phases were utilized.We must take the respiratory motion into consideration when evaluating heart doses in breast radiotherapy and pay more attention to dosimetric deviation of heart when practicing the planning.In chapter three,eight left-lesion patients with early stage breast cancer underwent conserved breast surgery,and free breathing as well as deep inspiration breath hold(DIBH)computed tomographic scans.Simultaneous integrated boost with either conformal or intensive modulated whole breast hypofractionated radiation plannings were done for all of eight patients.Parameters of organs at risk of heart were compared and analyzed.Values of most parameters in DIBH phase were less than these in free breathing phase,which suggested that DIBH technique could spare heart from left breast radiotherapy.In the same phase,values of parameters reflecting high dose or high dose with small volume in conformal radiotherapy(CRT)planning were more than those in intensity modulation radiated therapy(IMRT)planning(P<0.05).It indicated that the use of IMRT instead of CRT could reduce high dose area of organs at risk.Values of parameters reflecting low dose with big volume in IMRT planning were more than those in CRT planning.It indicated that low dose area were more vast in IMRT planning rather than CRT planning.Our findings suggest that IMRT combined with DIBH could further reduce doses to heart.In chapter four,we want to know the pathologic change of hearts of mice after single radiation of relatively high dose.Single dose of 16 Gy was delivered to the hearts of mice and pathologic change was assessed at 12,and 30 weeks afterwards,relative to age matched controls.Microvascular density(MVD)in the radiated hearts was progressively decreased at 12 and 30 weeks after single radiation of 16 Gy,which indicates loss of microvessels and endothelial cells in a time dependent way;while MVD expression of CD34+ and von Willebrand Factor were increased,which indicates damage of thrombotic endothelial cells.Our mice study provided some clues to the mechanisms of damaged human hearts after irradiated.In brief,our animal experiment and radiophysical dosimetric study will be helpful to further understand the mechanism of heart damage after radiation and several methods to spare heart from left breast irradiation.