Association of Transforming Growth Factor β Polymorphism C−509T With Radiation-Induced Fibrosis Among Patients With Early-Stage Breast Cancer

Grossberg, Aaron J.; Lei, Xiudong; Xu, Ting; Shaitelman, Simona F.; Hoffman, Karen E.; Bloom, Elizabeth Stroh; Stauder, Michael C.; Tereffe, Welela; Schlembach, Pamela J.; Woodward, Wendy A.; Buchholz, Thomas A.; Smith, Benjamin D.

doi:10.1001/jamaoncol.2018.2583

Cited by 35 publications

(30 citation statements)

References 35 publications

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“…The survival fraction of cultured fibroblast at 2 Gy was reported to be associated with late fibrosis in the same patients [ 35 , 36 ]. In addition, genetic studies identified an association between late radiation-induced fibrosis and polymorphisms in the ATM, TGFB, ERCC1, and ERCC5 genes for cancer patients who had been treated with radiotherapy [ 37 – 40 ]. The development of late fibrosis involves a cytokine cascade and a variety of different pathological processes, of which fibroblast, genetic polymorphisms, or NF- κ B is only one of the many elements.…”

Section: Discussionmentioning

confidence: 99%

Association between NF-κB Activation in Peripheral Blood Mononuclear Cells and Late Skin and Subcutaneous Fibrosis following Radiotherapy

Zhang

Sun

et al. 2020

BioMed Research International

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Background. This study aimed at evaluating the association between the speed of nuclear factor-kappa B (NF-κB) activation in peripheral blood mononuclear cells (PBMCs) and late skin and subcutaneous fibrosis in patients with head and neck squamous cell carcinoma (HNSCC) after radiotherapy. Methods. The speed of NF-κB activation was represented by the nuclear p65 expression ratio before and after irradiation. The optimal time point to measure the ratio was determined by Western blot in the PBMCs from healthy outpatients ranging from 0 to 12 hours after ex vivo irradiation. We recruited patients with HNSCC who had received ratiotherapy and who were under regular follow-up care. We assessed the association between the risk of developing ≥grade 2 late fibrosis and the nuclear p65 expression ratio in the PBMCs after ex vivo irradiation in these patients. Results. The maximum nuclear p65 ratio was observed at 1 hour after ex vivo irradiation in the PBMCs from the healthy outpatients. The speed of NF-κB activation was then represented by the nuclear p65 ratio in the PBMCs before and 1 hour after ex vivo irradiation. A total of 200 patients with HNSCC were recruited, 32.50% (n=65) of which presented with ≥grade 2 late fibrosis. There was a significant association between the speed of NF-κB activation in the PBMCs and an increased risk of developing ≥grade 2 late fibrosis in these patients (P=0.004). Subgroup analysis suggested that this finding was independent of the known clinical characteristics. Conclusions. The speed of NF-κB activation might be a potential predictor of late toxicity in cancer patients after radiotherapy. Prospective studies are needed for validation.

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Section: Discussionmentioning

confidence: 99%

Association between NF-κB Activation in Peripheral Blood Mononuclear Cells and Late Skin and Subcutaneous Fibrosis following Radiotherapy

Zhang

Sun

et al. 2020

BioMed Research International

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“…DNA extraction and polymerase chain reaction methods have been previously described. 10 The presence of at least one C-to-T single-nucleotide polymorphism at the first major transcription start site, position −509, of the TGFβ1 gene, was defined as a genomic marker for breast fibrosis risk.…”

Section: Methodsmentioning

confidence: 99%

“…Additionally, we sought to evaluate whether 3D measurements of cosmesis varied by radiation treatment arm or by transforming growth factor β 1( TGFβ1 ) polymorphism status, a potential genomic marker for radiation-related fibrosis. 10 …”

Section: Introductionmentioning

confidence: 99%

Quantitative 3-Dimensional Photographic Assessment of Breast Cosmesis After Whole Breast Irradiation for Early Stage Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial

Chapman

Lei

Patil

et al. 2020

Advances in Radiation Oncology

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Purpose Our purpose was to use 3-dimensional (3D) surface photography to quantitatively measure breast cosmesis within the framework of a randomized clinical trial of conventionally fractionated (CF) and hypofractionated (HF) whole breast irradiation (WBI); to identify how 3D measurements are associated with patient- and physician-reported cosmesis; and to determine whether objective measures of breast symmetry varied by WBI treatment arm or transforming growth factor β 1 ( TGFβ1 ) status. Methods and Materials From 2011 to 2014, 287 women age ≥40 with ductal carcinoma in situ or early-stage invasive breast cancer were enrolled in a multicenter trial and randomized to HF-WBI or CF-WBI with a boost. Three-dimensional surface photography was performed at 3 years posttreatment. Patient-reported cosmetic outcomes were recorded with the Breast Cancer Treatment Outcome Scale. Physician-reported cosmetic outcomes were assessed by the Radiation Therapy Oncology Group scale. Volume ratios and 6 quantitative measures of breast symmetry, termed F1-6C, were calculated using the breast contour and fiducial points assessed on 3D surface images. Associations between all metrics, patient- and physician-reported cosmesis, treatment arm, and TGFβ1 genotype were performed using the Kruskal-Wallis test and multivariable logistic regression models. Results Among 77 (39 CF-WBI and 38 HF-WBI) evaluable patients, both patient- and physician-reported cosmetic outcomes were significantly associated with the F1C vertical symmetry measure (both P < .05). Higher dichotomized F1C and volumetric symmetry measures were associated with improved patient- and physician-reported cosmesis on multivariable logistic regression (both P ≤ .05). There were no statistically significant differences in vertical symmetry or volume measures between treatment arms. Increased F6C horizontal symmetry was observed in the CF-WBI arm ( P = .05). Patients with the TGFβ1 C-509T variant allele had lower F2C vertical symmetry measures ( P = .02). Conclusions Quantitative 3D image-derived measures revealed comparable cosmetic outcomes with HF-WBI compared with CF-WBI. Our findings suggest that 3D surface imaging may be a more sensitive method for measuring subtle cosmetic changes than global patient- or physician-reported assessments.

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“…RgC members performed an individual‐patient meta‐analysis of 2782 patients from 11 cohorts to assess for association of rs1800469 with late fibrosis or late overall toxicity (using a harmonized average score) in breast radiotherapy and found no association with multivariable odds ratio 0.98 (95% confidence interval 0.85–1.11) . However, Grossberg et al report a positive association following breast radiotherapy with odds ratio 4.47 (95% confidence interval 1.22–15.99) as assessed with the Late Effects Normal Tissue/Subjective, Objective, Medical Management, Analytic scale …”

Section: Normal Tissue Radiosensitivitymentioning

confidence: 99%

Genomics models in radiotherapy: From mechanistic to machine learning

et al. 2020

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Machine learning (ML) provides a broad framework for addressing high‐dimensional prediction problems in classification and regression. While ML is often applied for imaging problems in medical physics, there are many efforts to apply these principles to biological data toward questions of radiation biology. Here, we provide a review of radiogenomics modeling frameworks and efforts toward genomically guided radiotherapy. We first discuss medical oncology efforts to develop precision biomarkers. We next discuss similar efforts to create clinical assays for normal tissue or tumor radiosensitivity. We then discuss modeling frameworks for radiosensitivity and the evolution of ML to create predictive models for radiogenomics.

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Association of Transforming Growth Factor β Polymorphism C−509T With Radiation-Induced Fibrosis Among Patients With Early-Stage Breast Cancer

Abstract: ClinicalTrials.gov identifier: NCT01266642.

Cited by 35 publications

References 35 publications

Association between NF-κB Activation in Peripheral Blood Mononuclear Cells and Late Skin and Subcutaneous Fibrosis following Radiotherapy

Association between NF-κB Activation in Peripheral Blood Mononuclear Cells and Late Skin and Subcutaneous Fibrosis following Radiotherapy

Quantitative 3-Dimensional Photographic Assessment of Breast Cosmesis After Whole Breast Irradiation for Early Stage Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial

Genomics models in radiotherapy: From mechanistic to machine learning

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