Hypofractionated Accelerated Irradiation for Stage I–II Breast Carcinoma: A Phase II Study

To the Editor: There is no daily standard and total tumor dose for breast irradiation. The schedule that is commonly used in clinical practice is 50Gy in 25 daily fractions (Monday to Friday) with the optional addition of a boost to the primary site of 10-16Gy (1). Radiobiologic modeling can be used to compare different fractionation schedules by achieving the same biologically effective dose (2). The biological effective dose (BED) is regarded as a measure of the true biological dose delivered by a particular combination of dose per fraction and total dose to a given tissue characterized by a specific a ⁄b ratio value. The ratio a ⁄b is an inverse measure of the fractionation sensitivity of the tissue in question. The tumor control BED values were determined using a a ⁄b value of either 4 Gy, which has been suggested for breast carcinoma (3,4) or 10 Gy and is the approximate value used for most tumors (3). Biological effective dose calculations were also performed for normal tissue endpoints such as breast fibrosis, skin telangiectasia (late reacting tissues), and erythema (acute reacting tissue) using an a ⁄b value based on those reported in the previous studies (5). These values were 2.5, 4.0, and 8.0, respectively. Concerns that have been raised in the literature about rapid fractionation schedules related to two issues: the association of a large dose per fraction with the increased risk of late normal tissue toxicity and the reduction in total dose and potential for decreased effect on tumor control. The first concern arises from reports in older, retrospective case series (6). These studies were poorly controlled. They used older radiation therapy techniques. The radiation therapy was delivered with large dose per fractions (‡ 3 Gy) without reduction in the overall total dose. Radiobiologic models predict that normal tissue toxicity is not increased when the increase in fraction size is the modest and the total dose is reduced (7). Similar models also suggest that rapid schedules may be equally efficacious if the reduction in total dose is accompanied by a shorter overall treatment time or if the tumor is more sensitive to a larger daily dose. This approach is supported by data from randomized trials that compared hypofractionated radiation therapy with more conventional radiation therapy in women with early breast cancer (6). In these three trials, no difference was detected in late radiation morbidity or local recurrence. In this study, radiation therapy was delivered by a modern approach. All patients received radiotherapy at a total tumor dose of 53 Gy (EQD2 60 Gy), 265cGy per fraction, in 20 fractions, over 25 days. Acute and late effects as well as cosmetic results were assessed using the European Organisation for Research and Treatment of cancer (RTOG-EORTC) Cosmetic Rating System. For follow-up purposes, mammograms were performed before radiotherapy, six months after the end of treatment and yearly thereafter. The recovery from the acute radiation toxicity is shown in Table 1. A total of 90.7% of women presented grade 0 side effects in 6 months, and the 100% of women recovered completely 2 years after radiotherapy. The mammograms indicated that changes were more prominent in periareolar and the inferior portions of breast. We noticed increased density and thickening of trabecula and skin 6 months after RT. Changes usually resolved within 1–2 years. Approximately, 20% of women had a grade 1 residual skin thickening 2 years after radiotherapy. Skin thickening is a factor in the overall increased density of breast after radiotherapy. Address correspondence and reprint requests to: Anna G. Zygogianni, MD, Aretaieion Hospital, University of Athens – Radiology, Radiation Oncology Section, Vas. Sophias 76, Athens 11528, Greece, or e-mail: annaz1@otenet.gr.