Mechanisms of radiation-induced skin injury and implications for future clinical trials

Kim, Jae Ho; Kolozsvary, Andrew; Jenrow, Kenneth A.; Brown, Stephen L.

doi:10.3109/09553002.2013.765055

Cited by 72 publications

(49 citation statements)

References 67 publications

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“…It is interesting that PR‐negative status predicted for higher skin toxicity grade in this series, whereas in our series evaluating risk factors for skin toxicity in the setting of PMRT, PR‐negative status was protective. There is no clear explanation for these findings; we are not aware of any literature that identifies hormone receptors as a predictor of RT‐induced skin reaction . The fact that PR status emerged as a significant predictor in both series, but in opposite directions, suggests that it is possible that these relationships are treatment specific or related to the statistical limitations of these relatively small series.…”

Section: Discussionmentioning

confidence: 79%

Prospective evaluation of radiation‐induced skin toxicity in a race/ethnically diverse breast cancer population

et al. 2016

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We evaluated predictors of radiation‐induced skin toxicity in a prospective study of a tri‐racial/ethnic breast cancer population. We evaluated patient demographics, tumor characteristics, and treatment variables in the first 392 patients in a prospective study assessing radiation‐induced skin toxicity. Logistic regression analyses were conducted to evaluate potential predictors of skin toxicity. The study consists of 59 non‐Hispanic whites (NHW; 15%), 241 Hispanic Whites (HW; 62%), 79 black or African Americans (AA; 20%), and 13 others (3%). Overall, 48% developed grade 0–1 skin toxicity, 49.8% grade 2, and 2.2% grade 3 by the National Cancer Institute's Common Toxicity Criteria for Adverse Events (CTCAE) scale. Twenty‐one percent developed moist desquamation. In multivariate analysis, higher body mass index (BMI; OR = 2.09; 95%CI = 1.15, 3.82), higher disease stage (OR = 1.82; 95%CI = 1.06, 3.11), ER‐positive/PR‐negative status (OR = 2.74; 95%CI = 1.26, 5.98), and conventionally fractionated regimens (OR = 3.25; 95%CI = 1.76, 6.01) were significantly associated with higher skin toxicity grade after adjustment for age, race, ethnicity, ER status, and breast volume. BMI specifically predicted for moist desquamation, but not degree of erythema. In this racially and ethnically diverse cohort of breast cancer patients receiving radiation to the intact breast, risk factors including BMI, disease stage, and conventionally fractionated radiation predicted for higher skin toxicity grade, whereas age, race, ethnicity, and breast volume did not. BMI specifically predicted for moist desquamation, suggesting that preventive measures to address this particular outcome should be investigated.

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Section: Discussionmentioning

confidence: 79%

Prospective evaluation of radiation‐induced skin toxicity in a race/ethnically diverse breast cancer population

et al. 2016

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“…Irradiation of the skin leads to direct tissue injury and inflammatory cell recruitment, involving damage to epidermal basal cells and connective tissue including endothelial cells and vascular components [19]. Radiation-induced generation of free radicals induces DNA injury and release of inflammatory cytokines [mainly interleukin (IL)-1 and IL-6] [20, 21]. This process leads to the development of erythema, edema, and possible ulceration.…”

Section: Pbm For the Management Of Orofacial And Neck Complications Omentioning

confidence: 99%

Low-level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 2: proposed applications and treatment protocols

Zecha

Raber-Durlacher

Nair

et al. 2016

Support Care Cancer

196

138

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Purpose There is a large body of evidence supporting the efficacy of low-level laser therapy (LLLT), more recently termed photobiomodulation (PBM) for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved and dosimetric parameters may lead to the management of a broader range of complications associated with HNC treatment. This could enhance patient adherence to cancer therapy, and improve quality of life and treatment outcomes. The mechanisms of action, dosimetric, and safety considerations for PBM have been reviewed in part 1. Part 2 discusses the head and neck treatment side effects for which PBM may prove to be effective. In addition, PBM parameters for each of these complications are suggested and future research directions are discussed. Methods Narrative review and presentation of PBM parameters are based on current evidence and expert opinion. Results PBM may have potential applications in the management of a broad range of side effects of (chemo)radiation therapy (CRT) in patients being treated for HNC. For OM management, optimal PBM parameters identified were as follows: wavelength, typically between 633 and 685 nm or 780–830 nm; energy density, laser or light-emitting diode (LED) output between 10 and 150 mW; dose, 2–3 J (J/cm2), and no more than 6 J/cm2 on the tissue surface treated; treatment schedule, two to three times a week up to daily; emission type, pulsed (<100 Hz); and route of delivery, intraorally and/or transcutaneously. To facilitate further studies, we propose potentially effective PBM parameters for prophylactic and therapeutic use in supportive care for dermatitis, dysphagia, dry mouth, dysgeusia, trismus, necrosis, lymphedema, and voice/speech alterations. Conclusion PBM may have a role in supportive care for a broad range of complications associated with the treatment of HNC with CRT. The suggested PBM irradiation and dosimetric parameters, which are potentially effective for these complications, are intended to provide guidance for well-designed future studies. It is imperative that such studies include elucidating the effects of PBM on oncology treatment outcomes.

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“…The real-time PCR cycling conditions were 95°C for 10 minutes, followed by 50 cycles of 95°C for 20 sec, 55°C for 30 sec, and 72°C for 20 sec. The sequences of the mouse primers were as follows : IL-1b (FW 5'-TGGTGTGTGACGTTCCCATT-3'; RW 5'-CAGCACGAGGCTTTTTTGTTG-3'), IL- 6 (FW 5'-ACAAGTCGGAGGCTTAATTACACAT-3'; RW 5'-TTGCCATTGCACAACTCTTTTC-3'), IL- 8 (FW 5'-CTCCAGCCACACTCCAACAGA-3'; RW 5'-CACCTAACACACCCACGAT-3'), TGFβ (FW 5'-GCAACATGTGGAACTCTACCAGAA-3'; RW 5'-GACGTCAAAAGACAGCCACTC-3'), CCL2 (FW 5'-GCTGACCCCAAGAAGGAATG-3'; RW 5'-GTGCTTGAGGTGGTTGTGGA-3'), CCL4 (FW 5'-CCAGGGTTCTCAGCACCAA-3'; RW 5'-GCTCACTGGGGTTAGCACAGA-3'), CXCL10 (FW 5'-CCTCATCCTGCTGGGTCTG-3'; RW 5'-CTCAACACGTGGGCAGGA-3'). All experiments were performed in triplicate and were normalized to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression.…”

Section: Quantitative Real-time Polymerase Chain Reaction (Pcr)mentioning

confidence: 99%

Metformin Alleviates Radiation-Induced Skin Fibrosis via the Downregulation of FOXO3

Kim

Yoo

Kim

et al. 2018

Cell Physiol Biochem

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Background/Aims: Radiation-induced skin fibrosis is a common side effect of clinical radiotherapy. Our previous next-generation sequencing (NGS) study demonstrated the reduced expression of the regulatory α subunit of phosphatidylinositol 3-kinase (PIK3r1) in irradiated murine skin. Metformin has been reported to target the PIK3-FOXO3 pathway. In this study, we investigated the effects of metformin on radiation-induced skin fibrosis. Methods: Metformin was orally administered to irradiated mice. Skin fibrosis was analyzed by staining with H&E and Masson’s trichrome stain. The levels of cytokines and chemokines associated with fibrosis were analyzed by immunohistochemistry and quantitative RT-PCR. The roles of PIK3rl and FOXO3 in radiation-induced skin fibrosis were studied by overexpressing PIK3rl and transfecting FOXO3 siRNA in NIH3T3 cells and mouse-derived dermal fibroblasts (MDF). Results: The oral administration of metformin significantly reduced radiation-induced skin thickening and collagen accumulation and significantly reduced the radiation-induced expression of FOXO3 in murine skin. Additionally, the overexpression of PIK3r1 reduced the radiation-induced expression of FOXO3, while FOXO3 silencing decreased the radiation-induced expression of TGFβ in vitro. Conclusions: The results indicated that metformin suppresses radiation-induced skin injuries by modulating the expression of FOXO3 through PIK3r1. Collectively, the data obtained in this study suggested that metformin could be a potent therapeutic agent for alleviating radiation-induced skin fibrosis.

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Mechanisms of radiation-induced skin injury and implications for future clinical trials

Abstract: As pathways underlying the cellular and molecular mechanisms of radiation-induced skin injury are becoming better understood, novel approaches are being developed for mitigating or treating the associated pathogenesis.

Cited by 72 publications

References 67 publications

Prospective evaluation of radiation‐induced skin toxicity in a race/ethnically diverse breast cancer population

Prospective evaluation of radiation‐induced skin toxicity in a race/ethnically diverse breast cancer population

Low-level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 2: proposed applications and treatment protocols

Metformin Alleviates Radiation-Induced Skin Fibrosis via the Downregulation of FOXO3

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