a b s t r a c tBackground and Purpose: Large breast size is associated with an increased risk of late adverse effects after breast conservation surgery and radiotherapy, even when 3D dosimetry is used. The purpose of this study is to test the hypothesis that residual dose inhomogeneity is sufficient to explain the association. Methods: Patients previously treated after breast conservation surgery with whole breast radiotherapy using 3D dosimetry and followed up in the UK FAST hypofractionation trial were selected for this analysis. The residual level of dose inhomogeneity across the whole breast treatment volume was used to test for association between residual dosimetry and post-treatment change in breast appearance at 2 years post-radiotherapy. Results: At 2 years, 201/279 (72%) of women had no change in photographic breast appearance, 61 (22%) had mild change and 17 (6%) had marked change. Breast size and dosimetry were both significantly associated with late effects in univariate analyses, but only breast size remained an independent significant risk factor for change in breast appearance when included in a multiple regression model together with other prognostic factors (p = 0.006 for trend). Conclusion: Large-breasted women are more likely to suffer change in breast size and shape after whole breast radiotherapy delivered using 3D dosimetry, but residual dose inhomogeneity is insufficient to explain the association.Ó 2011 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology xxx (2011) xxx-xxxThere is retrospective evidence that breast size is a risk factor for late adverse effects following breast conservation surgery and adjuvant radiotherapy for early breast cancer [1][2][3][4][5][6][7][8][9]. Body mass index, correlated to breast size and brassiere size, has also been linked to the risk of acute skin reactions and to late cosmesis [10][11][12]. Not all studies are confirmatory, but the weight of evidence suggests that the association between the size of the breast and the risk of early and late adverse effects in the breast is real [13][14][15][16]. Analyses are based on assessments of late adverse effects made in clinic or from photographs, focusing on changes in breast size and shape, breast oedema and telangiectasia. Marked acute skin reactions in the inframammary fold of heavy-breasted patients may explain part of the association via an increased risk of consequential late effects.Suboptimal dosimetry is thought to explain at least part of the association between breast size and risk of late normal tissue damage after radiotherapy delivered using 2D techniques [1,2,4,6,17]. A cause and effect relationship is supported by the 5-year results of a randomised trial (N = 306) comparing 2D and 3D radiation dosimetry [18], but not so far by the 2-year results of a larger confirmatory study [19]. Assuming dose distribution matters, it is not known if residual dose inhomogeneity in patients treated using 3D dosimetry explains a significant component of late adverse effects in large breasted w...

CYP3A enzymes metabolize endogenous hormones and chemotherapeutic agents used to treat cancer, thereby potentially affecting drug effectiveness. Here, we refined the genetic basis underlying the functional effects of a CYP3A haplotype on urinary estrone glucuronide (E1G) levels and tested for an association between CYP3A genotype and outcome in patients with chronic lymphocytic leukemia (CLL), breast, or lung cancers. The most significantly associated SNP was rs45446698, an SNP that tags the CYP3A7 Ã 1C allele; this SNP was associated with a 54% decrease in urinary E1G levels. Genotyping this SNP in 1,008 breast cancer, 1,128 lung cancer, and 347 CLL patients, we found that rs45446698 was associated with breast cancer mortality (HR, 1.74; P ¼ 0.03), all-cause mortality in lung cancer patients (HR, 1.43; P ¼ 0.009), and CLL progression (HR, 1.62; P ¼ 0.03). We also found borderline evidence of a statistical interaction between the CYP3A7 Ã 1C allele, treatment of patients with a cytotoxic agent that is a CYP3A substrate, and clinical outcome (P interaction ¼ 0.06). The CYP3A7 Ã 1C allele, which results in adult expression of the fetal CYP3A7 gene, is likely to be the functional allele influencing levels of circulating endogenous sex hormones and outcome in these various malignancies. Further studies confirming these associations and determining the mechanism by which CYP3A7 Ã 1C influences outcome are required. One possibility is that standard chemotherapy regimens that include CYP3A substrates may not be optimal for the approximately 8% of cancer patients who are CYP3A7 Ã 1C carriers.

BackgroundWe developed, applied, and prospectively evaluated a novel deep-inspiration breath-hold (DIBH) screening and delivery technique to optimize cardiac sparing in left-breast radiotherapy (RT) at our clinic. The impact of set-up and dose variables upon organs at risk (OAR) dose in DIBH RT was investigated.Methods and materialsAll patients with left-breast cancer referred between 2011 and 2014 – of all disease stages, set-up variations, and dose prescriptions – were included. Radiographers used simple screening criteria at CT simulation, to systematically assess patients for obvious DIBH benefit and capability. Selected patients received forward-planned intensity-modulated RT (IMRT) based on a DIBH CT scan. A 3D-surface monitoring system with visual feedback assured reproducible DIBH positioning during gated radiation delivery. Patient, target set-up, and OAR dose information were collected at treatment.ResultsOf 272 patients who were screened, 4 withdrew, 56 showed no obvious advantage, and 56 showed benefit but had suitability issues; 156 patients were selected and successfully completed DIBH treatment. The technique was compatible with complex set-up and optimal target coverage was maintained. Comparison of free-breathing (FB) and DIBH treatment plans in the first five patients enrolled confirmed DIBH reduced heart radiation by ~80% (p = 0.032). Low OAR doses were achieved overall: the mean (95% confidence interval [CI]) heart dose was 1.17 (1.12–1.22) Gy, and the mean ipsilateral lung dose was 5.26 (5.01–5.52) Gy. Patients who underwent a standard radiation schedule (40 Gy/15#) after breast-conserving surgery had the lowest OAR doses: post-mastectomy treatment, simultaneous supraclavicular (SCV) node coverage, and alternative dose schedule (50 Gy/25#) were interrelated variables associated with increased OAR risk and compromised ipsilateral lung dose constraints.ConclusionThe DIBH technique was successfully implemented and resulted in optimally low heart radiation. All patients who demonstrate sufficient DIBH technique at planning CT are now offered DIBH RT at our clinic. Patients with more advanced disease, particularly those with additional pulmonary risk factors, warrant additional focus to improve lung sparing.

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