No difference in dose distribution in organs at risk in postmastectomy radiotherapy with or without breast implant reconstruction

The Swedish National Breast Cancer Register was used for patient identification, and all women diagnosed with breast cancer and operated on with total mastectomy within the Stockholm-Gotland area between January 1 2009 and December 31 2011 and receiving postmastectomy radiotherapy were eligible. Data on type and date of breast cancer surgery, tumor characteristics (laterality, size and lymph nodes) and planned treatment characteristics (radiotherapy, chemotherapy, endocrine therapy, and immunotherapy) were obtained from the registry. Subsequently, these patients were identified in the ARIA© (Varian Medical Systems, Palo Alto, California)- an oncology information system prospectively maintained at two RT units at Karolinska University Hospital. Individual information on dates of radiotherapy (start and end), target volume (chest wall or chest wall plus lymph nodes), total dose, number of fractions, boost and bolus (if any), were retrieved from the RT charts in ARIA©.

The inclusion criteria were patients undergoing mastectomy as their primary surgery for breast cancer and completing a full course of PMRT to ipsilateral chest wall +/- regional lymph nodes.

Patients were excluded for the following reasons (Figure 1):

All patients received full course of RT at one of the units, either at the Karolinska University Hospital in Solna (n = 425) or at the Southern Hospital (n = 393), Stockholm, Sweden. When CW only was included in the CTV the treatment technique consisted of two tangential fields. For those cases where the CTV included the lymph nodes, an isocentric technique was used, consisting of tangential fields covering CW and usually three fields covering the lymph nodes in the supraclavicular fossa and in the axillary regions. According to the institution’s local practice, internal mammary nodes (IMNs) were not specifically targeted. Both in the treatment of the chest wall and in the treatment of the chest wall plus lymph nodes field-in-field solutions were applied where necessary [15].

Conventional tangential external-beam radiotherapy with 6-MV photons was used in all cases, some patients also received additional 15-MV (n = 56, 6.8%) or 18-MV (n = 21, 2.6%) photon fields. Total prescribed dose was 50 Gy in 2 Gy daily fractions. Additional boost dose to the mastectomy scar, bolus, or a combination was utilized in 24 (3.0%), 31 (3.9%), and 3 (0.4%) cases, respectively.

Dose calculations were performed with the Eclipse Treatment Planning System using the Analytical Anisotropic Algorithm, AAA (Varian). The dose was prescribed so that the CTV would be encompassed between 95% and 105% isodoses. According to the local protocols the constraints to the ipsilateral lung was V_20Gy (% of volume receiving 20 Gy) <30%. The constraints to the heart were mean dose < 5 Gy, V_25Gy <10%, and normal tissues complications probability (NTCP) <1% [16, 17].

Three types of implants were used during the study period (Figure 2 and Figure 3): type I, temporary expanders with a single lumen and an integrated magnetic port at the center of the implant for postoperative expansion; type II, expandable implants that are designed for a definitive one-stage breast reconstruction. They contain an outer chamber with silicon gel and a smaller inner chamber that may be inflated postoperatively with saline via the remote injection port placed subcutaneously on the chest wall; type III, permanent implants filled with silicon gel with a predefined volume.

At the same operation as the mastectomies, the implants were placed under total muscular coverage on the chest wall. No acellular dermal matrices have been used during the study period. In patients with expandable implants, the gradual expansion was performed in several sessions taking into consideration covering tissues.

Currently we avoid using expanders with the integrated magnetic ports in patients that are likely to receive PMRT. Potential problems with the magnetic port include difficulties in imaging (Figure 3a) [18, 19] and cause perturbation in dose distribution around the magnet [20‐22]. In the current study, we did not focus on these issues and thus excluded this subgroup from the CTV dosimetric assessment. An experimental study on this particular type of implants will be reported separately.

The data obtained from the Swedish National Breast Cancer Registry, i.e. laterality of cancer, laterality of RT, reconstruction vs. mastectomy alone, were additionally verified for each patient in ARIA.

Dose Volume Histograms (DVHs) as well as dose statistics for ipsilateral lung, heart, and CTV were retrieved from the system. Ipsilateral lung dosimetry was assessed using minimum, maximum and mean dose to the lung, as well as V_20Gy. The heart dosimetry was evaluated only in patients with left-sided breast cancer due to the fact that irradiation of the heart in the right-sided plans was negligible. Heart variables included minimum, maximum, mean dose and V_25Gy.

CTV coverage was defined as percentage of clinical target volume covered by ≥95% of isodose (CTV V_95%). CTV V_95% was evaluated both in the absolute measures (cm³ covered with 95% of isodose) as well as the relative measures (% of CTV covered with 95% of isodose).

In order to take into account patients’ rib cage shape, the following parameters were also considered: internal transverse diameter (T), measured between the lateral-most points of the rib cage; anterioposterior diameter (AP), from the back of the sternum to the front of the vertebra; and hemithorax anterioposterior diameter, between the anterior-most point and posterior-most point of the ipsilateral index hemithorax. All measurements were performed at the mamillary slice of CT scans. Chest wall index (CWi) was defined as the ratio between the transverse and the antero-posterior diameter (T/AP) as suggested by Haller et al. [23].

Chest wall, CW (n = 242) and chest wall plus lymph nodes, CW + LN (n = 576) radiation plans were studied separately. For the purpose of statistical analysis, the outcome variables were dichotomized as follows: Lung: V_20Gy ≤ 30% vs. V_20Gy >30%; Heart: D_mean ≤5 Gy vs. D_mean > 5 Gy. In the assessment of heart avoidance, only left-sided RTPs were used. Univariate and multivariate regression models were performed to test the association of outcome variables and potential confounders (breast reconstruction, side of RT, CW index). The results were presented as odds ratios (OR) with 95%CI and p-value. Reported p-values from these models referred to the Wald-test. A two-tailed p < 0.05 was considered significant in all statistical tests.

This study was approved by the Regional Research Ethics Committee in Stockholm 2010/1242-31 and 2011/1861 32.

From 957 patients who fulfilled the inclusion criteria, 138 women were excluded and the remaining 818 were included into the study (Figure 1). Table 1 summarizes patients’ characteristics stratified for immediate breast reconstruction (IBR+) and no immediate breast reconstruction (IBR-).

Patients’ mean age at the time of mastectomy was 46 years (SD = 8.5) in IBR+ and 58 years (SD = 13.6) in IBR- subgroups (p < 0.001). In the IBR+ group, patients were younger (<55 years: 84.0% vs. 34.6%, p < 0.001), neoadjuvant chemotherapy was given less frequently (19.8% vs. 34.6%, p < 0.001).

The IBR+ subgroup had significantly higher rates of negative lymph nodes (pN0: 51.2% vs. 32.3%, p < 0.001) and consequently received RT to regional lymph nodes less frequently (50.6% vs. 75.3%, p < 0.001). In addition, this subgroup was treated with adjuvant chemotherapy and endocrine therapy less frequently (45.3% vs. 56.2%, p = 0.02 and 67.9% vs. 81.3%, p < 0.001, respectively).

Dosimetric characteristics of ipsilateral lung stratified for radiotherapy plan are presented in Table 2. In the chest wall subset, lung maximum dose was higher in IBR+ group (52.0 vs. 51.4 Gy, p = 0.002).

In the CW + LN subset, IBR+ patients were significantly different from IBR- with regards to lung mean dose (13.8 vs. 14.3 Gy, p = 0.05) and lung minimum dose (0.3 vs. 0.2 Gy, p < 0.001).

Heart dosimetry was obtained for 72 IBR+ and 355 IBR- patients with left-sided tumors. No statistically significant differences in heart dosimetric characteristics such as heart V_25Gy or mean dose were identified between the groups (Table 2).

CTV definition in patients with IBR always included implant that makes the direct dosimetric comparisons between the groups inaccurate, i.e. CTV was larger in IBR+ compared to IBR- for both CW (629.4 vs. 458.4 cm³, p < 0.001) and CW + LN (1074.7 vs. 787.9 cm³, p < 0.001) radiation plans (Table 3). There was a difference in the rib cage shape and in the chest wall index between the groups (Table 3).

The univariate analyses revealed no association between breast implant reconstruction and ipsilateral lung or heart dosimetry (Table 4) in neither the chest wall nor chest wall plus lymph nodes subsets. Among the possible confounders, only chest wall index was associated with lung V_20Gy in CW + LN subset (OR: 1.6, 95%CI, 1.1 to 2.2, p = 0.008). This association remained statistically significant in multivariate regression adjusting for reconstruction and side (Table 5).

In the IBR+ subgroup analysis we found no correlation between the type of implants and the three outcome dosimetric variables (data not shown). Time from mastectomy to radiotherapy start among patients with temporary expanders, permanent expanders, permanent implants, and no reconstruction was 4.5, 4.1, 4.8, and 3.8 months, respectively with no statistically significant difference (data not shown).