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Purpose: Radiation-induced fibrosis is a common late reaction of radiation therapy. Due to a lack of feasible noninvasive techniques to assess this reaction, the long-term development of radiation fibrosis is not well described. In order to develop quantitative means for the purpose, subcutaneous fibrosis of breast cancer patients after postmastectomy radiotherapy was evaluated by clinical scoring and a new technique based on dielectric properties of the skin. Methods and Materials: Dielectric properties of biological tissues at radiofrequencies are principally determined by tissue water content. The major skin components are proteins, proteoglycans, and water either free or bound to the surface of proteins and proteoglycans. Since the MR studies have shown that bound water is tightly attached onto the surface of collagen, a dielectric measurement sensitive to bound water could be related to the protein content. Therefore, the dielectric constant of human skin was measured in vivo with an open-ended coaxial probe at electromagnetic (EM) frequencies in the range of δ-dispersion. Since the in vitro experiments with protein–water solutions have indicated that the slope of the dielectric constant vs. the EM frequency is a measure of the protein concentration, a respective slope was determined with irradiated skin of 14 breast cancer patients 2 years after postmastectomy radiotherapy at 63, 100, 300, and 500 MHz. Irradiated skin sites were clinically scored for subcutaneous fibrosis using a scale: none, slight, moderate, or severe fibrosis. Results: A statistically significant correlation was found between the slope and the clinical score of subcutaneous fibrosis at 63, 100, and 300 MHz but not at 500 MHz. The correlation was best at 100 and 300 MHz. Conclusions: Considerable changes in the dielectric constant of the irradiated skin were found. The correlation between the dielectric constant and clinical score suggests that this novel technique is a potential tool for the follow-up and quantitative assessment of radiation-induced subcutaneous fibrosis.

Standard adjuvant chemotherapy regimens for patients with moderate-to-high-risk early breast cancer typically contain a taxane, an anthracycline, and cyclophosphamide. We aimed to investigate whether integration of capecitabine into such a regimen enhances outcome.In this open-label trial, we randomly assigned (centrally by computer; stratified by node status, HER2 status, and centre) 1500 women with axillary node-positive or high-risk node-negative breast cancer to either three cycles of capecitabine and docetaxel followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (capecitabine group, n=753), or to three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (control group, n=747). The primary endpoint was recurrence-free survival. A planned interim analysis was done after 3 years' median follow-up. Efficacy analyses were by modified intention to treat. The study is registered with ClinicalTrials.gov, number NCT00114816.Two patients in each group were excluded from efficacy analyses because of withdrawal of consent or distant metastases. After a median follow-up of 35 months (IQR 25.5-43.6), recurrence-free survival at 3 years was better with the capecitabine regimen than with control (93%vs 89%; hazard ratio 0.66, 95% CI 0.47-0.94; p=0.020). The capecitabine regimen was associated with more cases of grade 3 or 4 diarrhoea (46/740 [6%] vs 25/741 [3%]) and hand-foot syndrome (83/741 [11%] vs 2/741 [1%]) and the control regimen with more occurrences of grade 3 or 4 neutropenia (368/375 [98%] vs 325/378 [86%]) and febrile neutropenia (65/741 [9%] vs 33/742 [4%]). More patients discontinued planned treatment in the capecitabine group than in the control group (178/744 [24%] vs 23/741 [3%]). Four patients in the capecitabine group and two in the control group died from potentially treatment-related causes.The capecitabine-containing chemotherapy regimen reduced breast cancer recurrence compared with a control schedule of standard agents. Capecitabine administration was frequently discontinued because of adverse effects.Roche, Sanofi-Aventis, AstraZeneca, Cancer Society of Finland.