Factors affecting acute skin toxicity in patients having breast irradiation after conservative surgery: A prospective study of treatment practice at the Royal Marsden Hospital

Fernando, Indrajit; Ford, H. T.; Powles, T. J.; Ashley, S.; Glees, J.P.; Torr, M.; Grafton, D.; Harmer, C.

doi:10.1016/s0936-6555(05)80657-0

Cited by 106 publications

(76 citation statements)

References 20 publications

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“…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].…”

Section: Introductionmentioning

confidence: 99%

“…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 women. Other factors associated with late adverse effects, including age [20], scar visibility, large excision volume, post-operative complications [12], smoking and adjuvant chemotherapy [11,21], appear unlikely to provide an adequate alternative explanation, since they are not all associated with breast size. Against this background, a retrospective analysis has been undertaken to test the hypothesis that residual dose inhomogeneity of whole breast radiotherapy delivered in conformity with ICRU recommendations (95-107% of reference) [22,23] accounts for a significant part of the association between breast size and risk of late adverse effects.…”

Section: Introductionmentioning

confidence: 99%

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Large breast size as a risk factor for late adverse effects of breast radiotherapy: Is residual dose inhomogeneity, despite 3D treatment planning and delivery, the main explanation?

Goldsmith

Haviland

Tsang

et al. 2011

Radiotherapy and Oncology

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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...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Large breast size as a risk factor for late adverse effects of breast radiotherapy: Is residual dose inhomogeneity, despite 3D treatment planning and delivery, the main explanation?

Goldsmith

Haviland

Tsang

et al. 2011

Radiotherapy and Oncology

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“…The film outlines were drawn on the phantom to permit accurate placements of further film as required (for each tangential beam). The points for film dosimetry were chosen as they are reported sites of skin toxicity for breast irradiation and as such are of clinical interest (Donovan et al 2007, Fernando et al 1996.…”

Section: Film Dosimetrymentioning

confidence: 99%

Surface dosimetry for breast radiotherapy in the presence of immobilization cast material

Kelly¹,

Hardcastle²,

Metcalfe³

et al. 2011

Phys. Med. Biol.

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Curative breast radiotherapy typically leaves patients with varying degrees of cosmetic damage. One problem interfering with cosmetically acceptable breast radiotherapy is the external contour for large pendulous breasts which often results in high doses to skin folds. Thermoplastic casts are often employed to secure the breasts to maintain setup reproducibility and limit the presence of skin folds. This paper aims to determine changes in surface dose that can be attributed to the use of thermoplastic immobilization casts. Skin dose for a clinical hybrid conformal/IMRT breast plan was measured using radiochromic film and MOSFET detectors at a range of water equivalent depths representative of the different skin layers. The radiochromic film was used as an integrating dosimeter, while the MOSFETs were used for real-time dosimetry to isolate the contribution of skin dose from individual IMRT segments. Strips of film were placed at various locations on the breast and the MOSFETs were used to measure skin dose at 16 positions spaced along the film strips for comparison of data. The results showed an increase in skin dose in the presence of the immobilization cast of up to 45.7% and 62.3% of the skin dose without the immobilization cast present as measured with Gafchromic EBT film and MOSFETs, respectively. The increase in skin dose due to the immobilization cast varied with the angle of beam incidence and was greatest when the beam was normally incident on the phantom. The increase in surface dose with the immobilization cast was greater under entrance dose conditions compared to exit dose conditions.

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“…[3][4][5][6] The discrepancy in patient radiosensitivity is attributed then to patient genetic backgrounds and/or predispositions to adverse reactions. Previously, others group have attempted to correlate radiosensitivity in patient populations with in vitro assessments of patient initial DNA damage and repair efficacies, single nucleotide polymorphism (SNPs) in DNA repair genes, lymphocyte apoptosis efficiencies, fibroblast clonogenic survival, and chromosomal aberrations in response to RT.…”

Section: Introductionmentioning

confidence: 99%

“…Previously, others group have attempted to correlate radiosensitivity in patient populations with in vitro assessments of patient initial DNA damage and repair efficacies, single nucleotide polymorphism (SNPs) in DNA repair genes, lymphocyte apoptosis efficiencies, fibroblast clonogenic survival, and chromosomal aberrations in response to RT. [3][4][5][6] Even with large patient cohorts and multiple studies, these reports have failed to validate any potential predictive biomarkers for RT-induced skin toxicities. RT inadvertently affects immune cells and triggers a pro-inflammatory response leading to various immune responses with a different extent for the wound healing response, which may account for the onset of acute skin toxicities following radiation tissue damage.…”

Section: Introductionmentioning

confidence: 99%

ElevatedARG1expression in primary monocytes-derived macrophages as a predictor of radiation-induced acute skin toxicities in early breast cancer patients

Jung

Sabri

Hanson

et al. 2015

Cancer Biology & Therapy

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Radiation therapy (RT) the front-line treatment after surgery for early breast cancer patients is associated with acute skin toxicities in at least 40% of treated patients. Monocyte-derived macrophages are polarized into functionally distinct (M1 or M2) activated phenotypes at injury sites by specific systemic cytokines known to play a key role in the transition between damage and repair in irradiated tissues. The role of M1 and M2 macrophages in RT-induced acute skin toxicities remains to be defined. We investigated the potential value of M1 and M2 macrophages as predictive factors of RT-induced skin toxicities in early breast cancer patients treated with adjuvant RT after lumpectomy. Blood samples collected from patients enrolled in a prospective clinical study (n D 49) were analyzed at baseline and after the first delivered 2Gy RT dose. We designed an ex vivo culture system to differentiate patient blood monocytes into macrophages and treated them with M1 or M2-inducing cytokines before quantitative analysis of their "M1/M2" activation markers, iNOS, Arg1, and TGFß1. Statistical analysis was performed to correlate experimental data to clinical assessment of acute skin toxicity using Common Toxicity Criteria (CTC) grade for objective evaluation of skin reactions. Increased ARG1 mRNA significantly correlated with higher grades of erythema, moist desquamation, and CTC grade. Multivariate analysis revealed that increased ARG1 expression in macrophages after a single RT dose was an independent prognostic factor of erythema (p D 0 .032), moist desquamation (p D 0 .027), and CTC grade (p D 0 .056). Interestingly, multivariate analysis of ARG1 mRNA expression in macrophages stimulated with IL-4 also revealed independent prognostic value for predicting acute RT-induced toxicity factors, erythema (p D 0 .069), moist desquamation (p D 0 .037), and CTC grade (p D 0 .046). To conclude, our findings underline for the first time the biological significance of increased ARG1 mRNA levels as an early independent predictive biomarker of RT-induced acute skin toxicities.

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Factors affecting acute skin toxicity in patients having breast irradiation after conservative surgery: A prospective study of treatment practice at the Royal Marsden Hospital

Cited by 106 publications

References 20 publications

Large breast size as a risk factor for late adverse effects of breast radiotherapy: Is residual dose inhomogeneity, despite 3D treatment planning and delivery, the main explanation?

Large breast size as a risk factor for late adverse effects of breast radiotherapy: Is residual dose inhomogeneity, despite 3D treatment planning and delivery, the main explanation?

Surface dosimetry for breast radiotherapy in the presence of immobilization cast material

ElevatedARG1expression in primary monocytes-derived macrophages as a predictor of radiation-induced acute skin toxicities in early breast cancer patients

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