British Journal of Radiology 75 (2002),444-447 © 2002 The British Institute of Radiology
Predictive factors for skin telangiectasia following post-mastectomy electron beam irradiation
E Y Huang, MD,
H C Chen, MD,
C J Wang, MD,
L M Sun, MD and
H C Hsu, MD
Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung Hsien, Taiwan
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Abstract
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This study evaluated the predictive factors associated with skin telangiectasia following post-mastectomy electron beam irradiation of the chest wall and regional lymph nodes in patients with breast cancer. From July 1987 to December 1994, 120 women with stages II and III breast cancer received electron beam irradiation following modified radical mastectomy. Doses of 50–50.4 Gy per 25–28 fractions were given to the chest wall (with bolus), the internal mammary nodes, the supraclavicular nodes and the axillary lymph nodes using a 12 MeV or 15 MeV single portal electron beam. 19 patients received an additional 10–16 Gy boost to the surgical scar using a 9 MeV electron beam. Univariate and multivariate analyses for the development of skin telangiectasia showed 5- and 7-year actuarial rates of telangiectasia to be 59% and 72%, respectively. In univariate analysis, an additional surgical scar boost (p=0.023) as well as no treatment interruption (p=0.028) were associated with a significantly increased risk of skin telangiectasia. In multivariate analysis, the only significant independent factor for the development of skin telangiectasia was surgical scar boost (p=0.026); no treatment interruption showed a trend but did not achieve significance (p=0.051). Thus, patients given an additional boost to the surgical scar are more likely to develop skin telangiectasia. Shorter treatment courses may result in a higher probability of skin telangiectasia following electron beam irradiation.
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Introduction
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Post-mastectomy irradiation of the chest wall and regional lymph nodes plays an important role in reducing locoregional recurrence in patients with a high risk of recurrence of breast cancer. Skin telangiectasia is a common side effect of radiotherapy. The effects of dose [1–3], fraction size [4–6], moist desquamation [3, 7], treatment time [8] and individual radiosensitivity [4, 9] have been discussed, and the variations between patients in the development of late complications have been noted.
An electron beam has been used in our department since 1987 for post-mastectomy chest wall and regional lymph node irradiation. In this paper, we report the actuarial probability of skin telangiectasia after long-term follow-up, and we retrospectively analyse the predictive factors of this late side effect.
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Materials and methods
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Patients and treatment characteristics
From July 1987 to December 1994, 120 women with stages II and III breast cancer were referred for single portal electron beam irradiation of the chest wall and peripheral lymphatic drainage areas following modified radical mastectomy. The median age was 48 years (range 22–73 years). Details of the technique have been described elsewhere [10, 11]. A 12 MeV or 15 MeV electron beam was used to irradiate the chest wall and peripheral lymphatics. The dose was prescribed at the 90% isodose. Bolus was applied to the chest wall to reduce the lung dose and to increase the skin dose. Patients were treated with 1.8–2 Gy fractions daily, 5 days a week. A total dose of 50–50.4 Gy was given to the chest wall and peripheral lymphatics. 19 patients received an additional 10–16 Gy boost to the surgical scar using a 9 MeV electron beam. 72 patients received adjuvant chemotherapy. Six courses of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) were given to 65 patients; 6 patients had six courses of CMF prior to radiotherapy; 12 patients had six courses of CMF following radiotherapy; and 47 patients had "sandwich" CMF and radiotherapy (i.e. CMF–radiotherapy–CMF). Six cycles of cyclophosphamide, epirubicin and 5-fluorouracil (CEF) were given to 7 patients; 3 patients had six cycles of CEF prior to radiotherapy; and 4 patients had "sandwich" CEF and radiotherapy. 52 patients received tamoxifen.
Follow-up and statistics
After the completion of radiotherapy, patients were followed up regularly every 2 months in the first year and every 3–4 months after the first year. The median duration of follow-up was 76 months (range 8-146 months). The interval between radiotherapy and skin telangiectasia was defined as the interval between the completion of radiotherapy and the date of first appearance of telangiectasia. The actuarial probability of telangiectasia was calculated using the Kaplan–Meier method. Predictive factors for the development of telangiectasia were analysed by log-rank test for univariate analysis. The Cox regression model with stepwise forward procedure was used for multivariate analysis. All variables were managed as binomial data. A p-value of 0.05 or less indicated statistical significance. Data processing and statistics were carried out on a personal computer using the SPSS 8.0 for Windows software (SPSS Inc., USA).
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Results
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The 5- and 7-year actuarial rates for telangiectasia were 59% and 72%, respectively. In univariate analysis, boost to the surgical scar (p=0.023) (Figure 1
) as well as no treatment interruption (p=0.028) (Figure 2) significantly predicted an increased risk of skin telangiectasia. The 5- and 7-year actuarial probabilities of each parameter studied are shown in Table 1. In multivariate analysis, the only independent factor for the development of skin telangiectasia was boost to the surgical scar (p=0.026). No treatment interruption showed a trend but did not reach significance (p=0.051). All other factors showed no significant association with the development of skin telangiectasia (Table 2).
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Figure 1. Kaplan–Meier curves showing the probability of skin telangiectasia according to whether or not the patient received a boost to the surgical scar.
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Figure 2. Kaplan–Meier curves showing the probability of skin telangiectasia according to whether or not there was an interruption to treatment.
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Discussion
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Variations in the incidence of radiation-induced skin telangiectasia have been reported. Gaffeny et al [12] gave 23.8–70.5 Gy (mean 52.89 Gy) (2.25 Gy per fraction, 4 days a week; or 1.8 Gy per fraction, 5 days a week) using electron arc irradiation. After a mean of 49 months follow-up (minimum 1 year) 13% of patients had developed telangiectasia. McNeely et al [13] reported 31% (14/45 patients) telangiectasia with 38–60 Gy (2.25 Gy per fraction, 4 days a week; or 1.8 Gy per fraction, 5 days a week) using electron arc irradiation (median follow-up 50 months). Bentzen et al [7] estimated the incidence of severe telangiectasia after 44 Gy per 22 fractions to be 49% and 27%, respectively, in patients with and without 
Grade 2 moist desquamation. Ramsay and Birrell [9] reported 24% (11/45 patients) Grades 2–4 late skin complications after 46–60 Gy per 20–30 fractions. Bentzen et al [14] estimated the time to expression of 90% of the ultimate frequency of moderate or severe telangiectasia to be 4.7 years after post-mastectomy irradiation with 36.6–51.36 Gy (12 fractions, 2 days a week; or 22 fractions, 5 days a week) (minimum follow-up 16 months). Turesson [15] found skin telangiectasia to be a continuously progressing endpoint, both in the individual patient and in terms of the number of patients who achieved a certain degree of damage. Hence, the cumulative incidence of skin telangiectasia depends on observation time. Bentzen et al [16] estimated that the average length of time to expression of 90% of the ultimately expected damage to be 6.6 years, 9.1 years and 14.8 years for Grade 1, Grade 2 and Grade 3 telangiectasia, respectively. Thus, increasing grades of telangiectasia occurred at progressively longer times of follow-up. A statistically significant correlation was found between the level of tissue injury and the latent period. Turesson [17] found that the individual variation in the rate of progression of telangiectasia was very large for the same treatment with a small documented variation in dose. The latent time for score 1 telangiectasia varies between 9 months and 96 months, for score 2 between 17 months and 90 months, for score 3 between 35 months and 95 months and for score 4 between 51 months and 108 months. In comparison with the above reports, a relatively higher incidence of late skin complications was noted in the present study owing to the longer follow-up period (median 76 months).
Many investigators have used the crude incidence to record radiation-induced skin telangiectasia. The actuarial estimation of the probability of late complications can overcome the problem of inadequate follow-up in a subset of the patients [3, 15–17]. Turesson et al [3] used the Cox regression model and the telangiectasia score, with the event being defined as the time to score 1–5. The development of skin telangiectasia strongly depends on the time course and we therefore suggest that it should be calculated by the actuarial method as for the estimation of survival. Hence, we have shown the actuarial probability of skin telangiectasia and have compared the difference between the stratified variables.
Romestaing et al [2] defined the role of a 10 Gy boost to the primary tumour in the conservative treatment of early infiltrating breast carcinoma treated by limited surgery and radiotherapy. The boost group had a higher rate of grades 1 and 2 telangiectasia. Pezner et al [1] also demonstrated that telangiectasia was significantly more frequent with the use of an electron beam boost that delivered a skin dose exceeding 16 Gy. Using univariate and multivariate analysis, Turesson et al [3] reported that dose was a significant factor in the development of telangiectasia. Boost to the surgical scar was a significant factor (p=0.023) in our univariate analysis. Furthermore, it was also a prognostic factor in multivariate analysis, and the result supported the concept that the latent time was strongly dose dependent [17].
Radiological research has shown that prolonging overall treatment time within the normal radiotherapy range makes little difference to late effects but has a large effect in sparing early reactions [18]. Interestingly, analysis of the Gothenburg telangiectasia data showed that the incidence of severe telangiectasia depended on overall treatment time [19]. This effect could be due to substantial slow repair (repair half time 3.5 h) of sublethal damage in the late-responding tissues. Our results may support this phenomenon but further studies are needed.
Moist desquamation is thought to influence the development of telangiectasia as it causes mechanical damage to the superficial capillary plexus, resulting in telangiectasia [3, 7]. Turesson et al [3] reported that the acute skin reaction was a significant factor in the development of telangiectasia in univariate and multivariate analyses. Bentzen and Overgaard [7] demonstrated that patients who developed moist desquamation had a statistically significantly increased risk of developing severe telangiectasia after a specific course of radiotherapy [7]. However, Tucker et al [4] found no clear evidence of a correlation between the acute and late endpoints. Our results do not support an association between moist desquamation and telangiectasia. Moist desquamation may result in the interruption of treatment and hence longer treatment times may counteract the effect of moist desquamation in the development of late effects.
However, longer treatment times may reduce tumor control and interruptions are not recommended.
In conclusion, radiation-induced skin telangiectasia is a progressive complication that increases with long-term follow-up. Patients receiving higher doses of irradiation had a shorter latent period to develop skin telangiectasia. In addition, shorter treatment courses may result in a higher probability of skin telangiectasia after electron beam irradiation owing to the breast cancer.
Received for publication July 4, 2001.
Revision received November 15, 2001.
Accepted for publication November 28, 2001.
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Abstract
Introduction
