Skin reaction is major problem during whole breast radiotherapy. To identify factors related to skin reactions during whole breast radiotherapy, various personal, clinical, and radiation dosimetric parameters were evaluated. From January 2012 to December 2013, a total of 125 patients who underwent breast conserving surgery and adjuvant whole breast irradiation were retrospectively reviewed. All patients had both whole breast irradiation and boost to the tumour bed. Skin reaction was measured on the first day of boost therapy based on photography of the radiation field and medical records. For each area of axilla and inferior fold, the intensity score of erythema (score 1 to 5) and extent (score 0 to 1) were summed. The relationship of various parameters to skin reaction was evaluated using chi-square and linear regression tests. The
Breast conserving surgery is an initial approach for treating early breast cancer because it preserves cosmetic appearance and reduces major surgical sequelae. Adjuvant radiotherapy after breast conserving surgery reduces local recurrence and improves overall survival by irradiating the remaining cancer cell foci [
Conventional radiotherapy to whole breast uses the opposed tangential fields with an appropriate wedge filter. Progress in techniques used to calculate radiation dose distribution and accurate delivery of the radiation beams has resulted in modified radiotherapy techniques, such as the field-in-field technique that can be applied to whole breast irradiation. Recent trials have reported that these methods reduce the occurrence of moist desquamation, changes in breast appearance, and palpable induration [
However, some patients continue to experience severe skin reaction during radiotherapy. Skin toxicity affects quality of life [
When radiotherapy is planned through virtual simulation, the various dosimetric parameters are used as references to evaluate not only the coverage of target volume but also avoidance of organs at risk. Through the analyses of these parameters, the quality of radiotherapy can be improved. In our study, we evaluated various dosimetric parameters, in addition to personal and clinical parameters, to identify factors related to skin reactions.
In our retrospective study, patients with adjuvant whole breast irradiation including the boost after breast conserving surgery due to breast cancer from January 2012 to December 2013 had been enrolled in Ansan Hospital, Korea University Medical Center. Patients undergoing supraclavicular or axillary irradiation with another field were excluded because the overlapping fields between whole breast and axillary area can be a bias for skin reactions. Other exclusion criteria were (1) being <20 years of age and >70 years of age; (2) bolus during irradiation; (3) artificial implant in the ipsilateral breast; (4) whole breast treatment duration >40 days, except for the cause of skin toxicity; (5) bilateral breast irradiation; (6) history of other radiotherapies; and (7) concomitant primary malignancy that required adjuvant therapy. Medical records and technical radiotherapy reports were reviewed after Institutional Review Board approval of our study.
The dose prescriptions were identical. A total of 50 Gy divided into 25 fractions with 6 MV X-ray was delivered to the whole breast, and the tumour bed boost was continued with an intended dose of 10 Gy with 5 fractions or 15 Gy with 7 fractions. A Brilliance Big Bore Oncology computed tomography (CT) system (Philips Medical Systems, Best, the Netherlands) was utilized, and the Breastboard (Civico, Orange City, IA, USA) was used as an immobilization device. The setup was performed with the patient in the supine position with both arms elevated above the head. The CT scans were sliced with a 5 mm thickness. Varian Eclipse version 8.6.1.5 (Varian Medical Systems Inc., Palo Alto, CA, USA) was used for radiotherapy planning. The planning target volume (PTV) of the whole breast was edited 5 mm from the body surface. The source-to-surface distance method and the anisotropic analytical algorithm calculation model were applied. One to three subsegments were used in each medial and lateral beam direction to create our field-in-field technique for whole breast irradiation. In general, the radiotherapy plan of whole breast irradiation was used if it satisfied the following criteria:
Acute skin toxicity was checked on the first day of the tumour bed boost by radiation oncologist and written down in our medical record. For this study, a photographic comparison between the initial whole breast setup and the initial boost setup and a review of medical data were retrospectively done by a 15-year experienced radiation oncologist and a 7-year experienced nurse. The breast skin reaction was measured on each axilla and inferior fold area. The intensity of the skin reaction was divided into five levels according to skin colour changes and erythema. Scores of 1, 2, 3, 4, and 5 were given for faint, mild, moderate, severe, and wet desquamation skin reactions, respectively. If radiotherapy was delayed by desquamation during whole breast irradiation, it was given a score of 5. If the score was ≥3 and the reaction was greater than palm size, a score of 1 was added to the intensity score. Therefore, the final acute skin reaction score was 1–6.
The clinical/individual parameters were as follows: age (year), body mass index (kg/m2), laterality (right side versus left side), pT-stage (0 or 1 versus 2 or 3), pN-stage (0 versus 1), method of axillary dissection (no surgery or sentinel node dissection versus axillary node dissection), chemotherapy before adjuvant radiotherapy, and hormonal therapy during radiotherapy.
The dosimetric parameters were as follows: breast height (the distance between the posterior filed border and the apex of breast at the nipple axis), breast separation (the distance from medial to lateral radiation field border at the central axis), absolute volume including the PTV,
Diagram to measure various dosimetric factors. (a) Breast height (red line) means the distance between the posterior filed border and the apex of breast and breast separation (blue line) means the distance from medial to lateral radiation field border on central axis.
The statistical analysis was conducted on skin toxicity and risk factors using SPSS version 20.0 software (SPSS Inc., Chicago, IL, USA). The chi-square test (linear to linear correlation) and the Pearson correlation analyses were used to assess the relationship between skin toxicity scores and risk factors, which were presented as categorical and continuous variables, respectively. The absolute values of Pearson’s correlation coefficients (
A total of 125 patients among 134 who received whole breast irradiation with a tumour bed boost were enrolled. The causes of exclusion were age >70 years (two patients), use of a bolus (one patient), breast implant (one patient), and long treatment period for whole breast irradiation without skin desquamation (five patients). Median age was 47 years (range, 28–70 years). Seven patients had ductal carcinoma in situ and others had malignancies. Of the 78 patients who underwent chemotherapy, 17 and 47 patients received doxorubicin-based and docetaxel-based chemotherapy, respectively. The intervals from operation to the first day of radiotherapy and from the first fraction of whole breast therapy to the first fraction of the tumour bed boost were a median of 111 days (range, 26–219 days) and a median of 37 days (range 35–62 days), respectively (Table
Patient characteristics.
Parameters | Median (range) or |
---|---|
Age (years) | 47 (28–70) |
Laterality (right : left) | 67 : 58 |
Body mass index (kg/m2) | 23.4 (17.8–37.9) |
T-stage (Tis, T0 : T2) | 91 : 34 |
N-stage (N0 : N1) | 106 : 19 |
Method of axillary dissection (no, SLND† : ALND‡) | 89 : 36 |
Chemotherapy (no : yes) | 47 : 78 |
Hormonal therapy (no : yes) | 32 : 93 |
Time interval from surgery to radiotherapy (days) | 111 (26–219) |
Period of whole breast irradiation (days) | 36 (33–46) |
Breast volume (mL) | |
Planning target volume | 499 (179–1444) |
|
351 (154–909) |
|
708 (310–1732) |
|
882 (401–2184) |
|
1050 (494–2547) |
|
1319 (653–2973) |
Breast height (cm) | 3.4 (1.6–6.5) |
Breast separation (cm) | 19.8 (15.1–26.7) |
Calculated dose/prescribed dose (%) | |
Axilla | 92.4 (71.2–99.3) |
Inferior fold | 95.8 (80.8–101.5) |
Inner half | 76.2 (51.9–89.1) |
|
17.5 (15.5–20.5) |
Distance from distal humerus head to upper border (cm) | 1.3 (0–4.3) |
Ratio of lateral to medial separation on upper border | 1.62 (1.06–2.31) |
Two patients had their treatment interrupted due to skin desquamation. Scores of 1-2, 3-4, and 5-6 were received for axilla skin reactions in 26.4%, 40.8%, and 32.8% of patients, respectively, and 44.8%, 25.6%, and 29.6% presented for inferior fold skin reactions, respectively (Table
The extent of skin reaction during adjuvant radiotherapy.
Score | Axilla | Inferior fold |
---|---|---|
1 | 3 (2.4%) | 24 (19.2%) |
2 | 30 (24.0%) | 32 (25.6%) |
3 | 29 (23.2%) | 12 (9.6%) |
4 | 22 (17.6%) | 20 (16.0%) |
5 | 38 (30.4%) | 33 (26.4%) |
6 | 3 (2.4%) | 4 (3.2%) |
No parameters including laterality, T-stage, N-stage, extent of axillary dissection, chemotherapy, or hormonal therapy were significant for acute skin reaction; however, the young age group (≤50 years) had a tendency to have more severe skin reactions than those in the old age group (
Chi-square tests for skin toxicity (linear-to-linear correlation).
Axilla ( |
Inferior fold ( |
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---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | 2 | 3 | 4 | 5 | 6 | ( |
1 | 2 | 3 | 4 | 5 | 6 | ( |
||
Age | 50≤ | 3 | 19 | 21 | 13 | 33 | 3 | (2.908) | 15 | 21 | 9 | 14 | 29 | 4 | (6.355) |
50> | 0 | 11 | 8 | 9 | 5 | 0 | 0.088 |
9 | 11 | 3 | 6 | 4 | 0 | 0.012 | |
|
|||||||||||||||
Laterality | Right | 2 | 18 | 12 | 11 | 23 | 1 | (0.000) | 15 | 10 | 10 | 12 | 19 | 1 | (0.143) |
Left | 1 | 12 | 17 | 11 | 15 | 2 | 0.994 | 9 | 22 | 2 | 8 | 14 | 3 | 0.705 | |
|
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T-stage | is, 1 | 3 | 20 | 23 | 17 | 26 | 2 | (0.179) | 14 | 25 | 12 | 15 | 23 | 2 | (0.013) |
2 | 0 | 10 | 6 | 5 | 12 | 1 | 0.673 | 10 | 7 | 0 | 5 | 10 | 2 | 0.910 | |
|
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N-stage | 0 | 3 | 24 | 25 | 20 | 31 | 3 | (0.024) | 19 | 29 | 11 | 16 | 28 | 3 | (0.039) |
1 | 0 | 6 | 4 | 2 | 7 | 0 | 0.877 | 5 | 3 | 1 | 4 | 5 | 1 | 0.843 | |
|
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Axillary dissection | No, SLND |
2 | 22 | 20 | 16 | 27 | 2 | (0.007) | 17 | 24 | 10 | 12 | 22 | 4 | (0.122) |
ALND |
1 | 8 | 9 | 6 | 11 | 1 | 0.932 | 7 | 8 | 2 | 8 | 11 | 0 | 0.726 | |
|
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Chemotherapy | No | 3 | 12 | 9 | 11 | 12 | 0 | (1.961) | 12 | 12 | 4 | 7 | 11 | 1 | (1.564) |
Yes | 0 | 18 | 20 | 11 | 26 | 3 | 0.161 | 12 | 20 | 8 | 13 | 22 | 3 | 0.211 | |
|
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Hormonal therapy | No | 0 | 9 | 6 | 4 | 10 | 3 | (0.872) | 6 | 6 | 4 | 5 | 8 | 3 | (0.908) |
Yes | 3 | 21 | 23 | 18 | 28 | 0 | 0.350 | 18 | 26 | 8 | 15 | 25 | 1 | 0.341 |
Because the parameters for the various volumes were strongly correlated (
Pearson’s correlation analyses for skin toxicity.
Axilla | Inferior fold | |||
---|---|---|---|---|
|
|
|
|
|
Age (years) | 0.057 | 0.530 | 0.120 | 0.181 |
Body mass index (kg/m2) | 0.301 | 0.001 |
0.252 | 0.005 |
Breast height (cm) | 0.414 | <0.001 |
0.375 | <0.001 |
Breast separation (cm) | 0.272 | 0.002 |
0.215 | 0.016 |
|
0.404 | <0.001 |
0.381 | <0.001 |
Calculated dose on self-area/prescribed dose (%) | 0.319 | <0.001 |
0.110 | 0.220 |
Calculated dose on inner half/prescribed dose (%) | 0.114 | 0.205 | 0.160 | 0.074 |
|
0.130 | 0.173 | 0.105 | 0.242 |
Distance from humerus head to upper border (cm) | 0.135 | 0.142 | 0.037 | 0.691 |
Ratio of lateral to medial separation on upper border | 0.008 | 0.923 | 0.000 | 0.998 |
Length of axilla bulging (cm) | 0.011 | 0.907 | 0.040 | 0.658 |
A multivariate analysis was conducted with the risk parameters from the univariate analysis and with age, which was significant on a chi-square test. Age (
The residuals between the predictability model and observability were a mean value of 0 and a standard deviation of 0.99 for both the axilla (range. −2.26–2.88) and inferior fold (range, −2.29–2.12). The range of predicted score ±1 covered 64.8% (81/125) and 61.1% (77/125) of the observed scores for the axilla and inferior fold areas, respectively (Figure
Histograms of the residual between the predictability model and observability. (a) Axilla. (b) Inferior fold.
We performed the conventional fractionated whole breast radiotherapy in 125 consecutive patients to evaluate breast skin toxicity. Among various parameters including individual/clinical and radiotherapy dosimetric characteristics, younger age and a higher
Body mass index, breast height, and the volumetric factors (PTV,
In our study, median age was 47 years, and 53 patients were ≤45 years. Although continuous age was not significant in the univariate analysis, some associations were observed in ordinal variables for age; therefore, age was entered in the multivariate analysis. In contrast, a Western study reported that postmenopausal status is a risk factor, although patients undergoing mastectomy were eligible in that study and both the age distribution and skin reaction endpoints were different from those in our study [
The calculated radiation dose on the planning system was a focus of our study. The inner quadrant dose was lower than the axilla and inferior fold doses at similar depths, and skin reactions in the axilla and inferior fold were more prominent than those in the inner quadrant. However, the axilla dose was related to skin toxicity, whereas the inferior fold dose had no association with skin toxicity. Because some inferior fold cases had a steep gradient and the calculated dose was the point dose, the calculated dose for the inferior fold may have incorrectly represented the inferior fold area. Our measured depth for the calculated point dose on the planning system was approximately 2 mm. A study that examined skin thickness by ultrasound after a median of 20.5 months of adjuvant radiotherapy showed that skin thicknesses of the irradiated and contralateral healthy breast were
The
In conclusion, we evaluated parameters related to skin toxicity after adjuvant whole breast irradiation in a northeastern Asian cohort. Our results suggested that age and
The funding institute had no role in the design, collection, analysis, and interpretation of data, in the writing of the paper, and in the decision to submit the paper for publication.
The authors declare that they have no competing interests.
This work was supported by a grant from Korea University (K1326251).