External beam accelerated partial breast irradiation: dosimetric assessment of conformal and three different intensity modulated techniques

For this study 40 patients were selected, who were previously treated with early-stage invasive breast cancer at our institution between 2006 and 2014 in a phase II APBI trial^.13,15 The study protocol was evaluated and accepted by the institutional and national ethics committees, and all patients provided written informed consent before enrolment. The trial was registered at ClinicalTrials.gov with identifier number NCT02003560. During breast-conserving surgery titanium surgical clips were placed in each patient to mark the boundaries of the excision cavity, which increased the accuracy of defining the resection cavity and consequently the planning target volume (PTV).

During planning CT scan, patients were positioned supine in a wingboard fixation device (Civco, USA). Around both breasts and on the surgical scar metal wires were placed to increase the precision of contouring. CT scans started from the mandible and included the complete volume of the lungs and the volumes of both breasts. The most crucial part of partial breast irradiation is the exact localization of the excision cavity. Using titanium clips and the 3 mm thickness of the planning CT slices, the borders of surgical cavity could be defined in accepTable precision.

The contouring and 3D-CRT plans were made with Pinnacle 8.0m (Philips, The Netherlands) treatment planning system, while for the plans of SS, SW and RA the Eclipse 11 (Varian, USA) planning software was used. In the first step of target volume definition, the tumour bed was contoured by the radiation oncologist based on the seroma and the surrounding clips. In the second step, on the basis of the intact surgical margins and pathological results, it was expanded in 6 directions with margins of different size to define CTV. The minimal and maximal value of the extension between the tumour bed and the CTV was 5 and 18 mm, respectively.16 The CTV was limited by the border of ipsilateral breast tissue. The safety margin between the CTV and PTV was 5 mm. As the skin is an organ at risk during partial breast irradiation, a 5 mm thick volume of the skin was cropped from PTV to create PTVeval. Heart, ipsilateral and contralateral breasts and lungs, non-target breast were contoured as organs at risk. Non-target breast was created with the extraction of PTV from ipsilateral breast.

36.9 Gy in 9 fractions was delivered on 5 consecutive days, twice a day with at least 6 hours interval between fractions. 100% of the PTVeval had to be covered with at least 95% of the prescribed dose. The allowed maximum dose was 110%. To make the techniques comparable, the same target coverage was achieved for all plans. Based on our protocol, the dose limits of the organs at risk were as follows: V_100% < 35% and V_50% < 60% for the ipsilateral breast, V_30% < 20% for the ipsilateral lung, V_15% < 10% for the heart in case of right sided tumours, while in case of left sided tumours, the value of heart V_5% had to be smaller than for conventional whole breast irradiation. V_xx% is the percentage of a region of interest (ROI) receiving at least the XX percent of the prescribed dose. These requirements were fulfilled in all of the plans. For contouring and for planning aims the NSABP B-39/RTOG 041317 guideline was used.

The 3D-CRT plans were created with 4 or 5 wedged conformal non-coplanar fields from tangential directions (Figure 1). The IMRT plans were created with 5 or 6 coplanar fields covering 190°, four of these fields positioned in the medial “first” and lateral “last” 30°. The RA plans consisted of two coplanar arcs created between the most medial field of the IMRT plans and gantry angle of 180° (Figure 1). Avoidance sectors were not applied, only strict constrains were given for ipsilateral lung, heart and spine. All plans were created for linear accelerator equipped with 5 mm wide MLC and 6 MV photon energy was used. CCC algorithm in Pinnacle and AAA algorithm in Eclipse were used for dose calculations.

Figure 1

For all techniques and all contoured organs volumes, minimum -, maximum and mean doses were recorded. Also V_xx% and D_xx% parameters were evaluated for all ROIs.

For the PTVeval homogeneity index and conformation number were calculated. Homogeneity index was calculated according to the ICRU83:

H I = D 2 % −<!-- − --> D 98 % D 50 % $HI=\frac{D_{2}{\text{%}}-D_{98}{\text{%}}}{D_{50}\text{%}}$

And the conformation number is:

CN= PT V ref V PTV x PT V ref V ref $CN=\frac{PT{{V}_{ref}}}{{{V}_{PTV}}}x\frac{PT{{V}_{ref}}}{{{V}_{ref}}}$

where PTV_ref is the volume of PTVeval which is covered by the reference isodose, V_PTV is the volume of PTVeval and V_ref is the tissue volume encompassed by the reference isodose curve.18 The plan quality index (PQI), defined by Leung et al.19, was calculated for all plans to include all the previous parameters in one quantity. The sum of monitor units (MU) was also recorded.

Statistical analysis was performed for all parameters with repeated measures ANOVA and Tukey post hoc test or Friedman test and Dunn post hoc test in GraphPad Instat (GraphPad Software, USA).

The mean volume of the tumour bed, CTV and PTV were 15.4 cm³, 80.8 cm³ and 155.5 cm³, respectively. The ratios of CTV and PTV to the ipsilateral breast volume was 8.6% (range: 4–19.1%) and 16.8% (range: 8.3–40.1%), respectively.

For each technique the V_95% value of PTVeval was at least 99.5%, except for 5 cases with 3D-CRT technique. There were no significant differences between the techniques in the values of V_95% and V_90% (Table 1), neither for PTVeval nor for CTV. Figure 2 shows dose distributions for the four irradiation techniques in a representative case. The homogeneity index was significantly better with SW technique than with 3D-CRT, SS or RA techniques. The difference between 3D-CRT and RA technique was also significant. The average conformation numbers of 3D-CRT, SS, SW and RA were 0.60, 0.80, 0.82 and 0.89, respectively, being all differences significant. The average values of homogeneity index, conformal number and PQI and the significance levels are summarized in Table 1.

Figure 2

Table 2 contains all the dosimetric values of the critical organs and their comparisons between different techniques.

With respect to the ipsilateral breast, the best results for dose reduction were achieved with RA technique which was also confirmed by the conformation number. The V_50% values of non-target breast for 3D-CRT, SS, SW and RA were 39.6%, 29.9%, 29.6%, 19.8%, respectively. In the non-target ipsilateral breast the maximum doses were 105.1%, 105.8%, 103.8% and 106.4%, respectively.

With respect to the ipsilateral lung, we received significantly better results for dose-volume values for non-coplanar 3D-CRT in low dose ranges such as 10% of the prescribed dose, while RA resulted in the largest low dose bath (V_10%). For higher dose ranges the two static IMRT techniques achieved significantly better results for V_40% than the other two.

The heart was better protected from low doses by the 3D-CRT technique. For the V_15% values RA technique still provided the worst results, while the static-filed IMRTs reached the lowest doses for the heart.

Both contralateral lung and contralateral breast received low dose with all techniques. Noticeable values and differences can only be found at 5% of the prescribed dose, and only very small volume received a higher dose than 10%. For both organs the 3D-CRT had significantly better results. With 3D-CRT technique, the average maximum doses for the contralateral lung and the contralateral breast were 0.8 Gy and 2.1 Gy, respectively. With static-field IMRT techniques the average values were 3 Gy and 3.1 Gy and with RA 3.5 Gy and 2.5 Gy, respectively.

The PQI values of 3D-CRT, SS, SW and RA techniques were 0.50, 0.36, 0.34 and 0.43. By definition, low PQI values mean high overall plan quality. The two static-field IMRT PQI values were significantly better than the ones for the other two techniques, and RA was also significantly better compared to 3D-CRT. With respect to monitor units, 3D-CRT (677 MU) and SS (814 MU) techniques were significantly lower than with SW (1077 MU) and RA (1136 MU). The difference between SW and RA was also significant.

The results of this study in comparison with other dosimetric studies in APBI can be found in Table 320, 21, 22 and Table 4 for the 3D-CRT and IMRT techniques, respectively.