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Aging Nov 2020Radiation-induced skin injury (RSI) refers to a frequently occurring complication of radiation therapy. Nearly 90% of patients having received radiation therapy... (Review)
Review
Radiation-induced skin injury (RSI) refers to a frequently occurring complication of radiation therapy. Nearly 90% of patients having received radiation therapy underwent moderate-to-severe skin reactions, severely reducing patients' quality of life and adversely affecting their disease treatment. No gold standard has been formulated for RSIs. In the present study, the mechanism of RSI and topical medications was discussed. Besides, this study can be referenced for clinicians to treat RSIs to guide subsequent clinical medicine.
Topics: Administration, Cutaneous; Animals; Apoptosis; Dermatologic Agents; Fibrosis; Humans; Occupational Exposure; Radiation Exposure; Radiodermatitis; Radiotherapy; Severity of Illness Index; Skin; Treatment Outcome
PubMed: 33202382
DOI: 10.18632/aging.103932 -
Radiation-Induced Skin Fibrosis: Pathogenesis, Current Treatment Options, and Emerging Therapeutics.Annals of Plastic Surgery Oct 2019Radiotherapy (RT) has become an indispensable part of oncologic treatment protocols for a range of malignancies. However, a serious adverse effect of RT is... (Review)
Review
Radiotherapy (RT) has become an indispensable part of oncologic treatment protocols for a range of malignancies. However, a serious adverse effect of RT is radiodermatitis; almost 95% of patients develop moderate to severe skin reactions following radiation treatment. In the acute setting, these can be erythema, desquamation, ulceration, and pain. Chronically, soft tissue atrophy, alopecia, and stiffness can be noted. Radiodermatitis can delay oncologic treatment protocols and significantly impair quality of life. There is currently a paucity of effective treatment options and prevention strategies for radiodermatitis. Importantly, recent preclinical and clinical studies have suggested that fat grafting may be of therapeutic benefit, reversing detrimental changes to soft tissue following RT. This review outlines the damaging effects of RT on the skin and soft tissue as well as discusses available treatment options for radiodermatitis. Emerging strategies to mitigate detrimental, chronic radiation-induced changes are also presented.
Topics: Fibrosis; Humans; Neoplasms; Quality of Life; Radiodermatitis; Radiotherapy
PubMed: 31513068
DOI: 10.1097/SAP.0000000000002098 -
EMBO Molecular Medicine Aug 2022Irradiation-induced alopecia and dermatitis (IRIAD) are two of the most visually recognized complications of radiotherapy, of which the molecular and cellular basis...
Irradiation-induced alopecia and dermatitis (IRIAD) are two of the most visually recognized complications of radiotherapy, of which the molecular and cellular basis remains largely unclear. By combining scRNA-seq analysis of whole skin-derived irradiated cells with genetic ablation and molecular inhibition studies, we show that senescence-associated IL-6 and IL-1 signaling, together with IL-17 upregulation and CCR6 -mediated immune cell migration, are crucial drivers of IRIAD. Bioinformatics analysis colocalized irradiation-induced IL-6 signaling with senescence pathway upregulation largely within epidermal hair follicles, basal keratinocytes, and dermal fibroblasts. Loss of cytokine signaling by genetic ablation in IL-6 or IL-1R mice, or by molecular blockade, strongly ameliorated IRIAD, as did deficiency of CCL20/CCR6-mediated immune cell migration in CCR6 mice. Moreover, IL-6 deficiency strongly reduced IL-17, IL-22, CCL20, and CCR6 upregulation, whereas CCR6 deficiency reciprocally diminished IL-6, IL-17, CCL3, and MHC upregulation, suggesting that proximity-dependent cellular cross talk promotes IRIAD. Therapeutically, topical application of Janus kinase blockers or inhibition of T-cell activation by cyclosporine effectively reduced IRIAD, suggesting the potential of targeted approaches for the treatment of dermal side effects in radiotherapy patients.
Topics: Animals; Interleukin-17; Interleukin-6; Mice; Radiodermatitis; Receptors, CCR6; Transcriptome
PubMed: 35785521
DOI: 10.15252/emmm.202115653 -
Frontiers in Oncology 2022This article is based on recommendations from the 12 WALT Congress, Nice, October 3-6, 2018, and a follow-up review of the existing data and the clinical observations of...
DISCLAIMER
This article is based on recommendations from the 12 WALT Congress, Nice, October 3-6, 2018, and a follow-up review of the existing data and the clinical observations of an international multidisciplinary panel of clinicians and researchers with expertise in the area of supportive care in cancer and/or PBM clinical application and dosimetry. This article is informational in nature. As with all clinical materials, this paper should be used with a clear understanding that continued research and practice could result in new insights and recommendations. The review reflects the collective opinion and, as such, does not necessarily represent the opinion of any individual author. In no event shall the authors be liable for any decision made or action taken in reliance on the proposed protocols.
OBJECTIVE
This position paper reviews the potential prophylactic and therapeutic effects of photobiomodulation (PBM) on side effects of cancer therapy, including chemotherapy (CT), radiation therapy (RT), and hematopoietic stem cell transplantation (HSCT).
BACKGROUND
There is a considerable body of evidence supporting the efficacy of PBM for preventing oral mucositis (OM) in patients undergoing RT for head and neck cancer (HNC), CT, or HSCT. This could enhance patients' quality of life, adherence to the prescribed cancer therapy, and treatment outcomes while reducing the cost of cancer care.
METHODS
A literature review on PBM effectiveness and dosimetry considerations for managing certain complications of cancer therapy were conducted. A systematic review was conducted when numerous randomized controlled trials were available. Results were presented and discussed at an international consensus meeting at the World Association of photobiomoduLation Therapy (WALT) meeting in 2018 that included world expert oncologists, radiation oncologists, oral oncologists, and oral medicine professionals, physicists, engineers, and oncology researchers. The potential mechanism of action of PBM and evidence of PBM efficacy through reported outcomes for individual indications were assessed.
RESULTS
There is a large body of evidence demonstrating the efficacy of PBM for preventing OM in certain cancer patient populations, as recently outlined by the Multinational Association for Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). Building on these, the WALT group outlines evidence and prescribed PBM treatment parameters for prophylactic and therapeutic use in supportive care for radiodermatitis, dysphagia, xerostomia, dysgeusia, trismus, mucosal and bone necrosis, lymphedema, hand-foot syndrome, alopecia, oral and dermatologic chronic graft-versus-host disease, voice/speech alterations, peripheral neuropathy, and late fibrosis amongst cancer survivors.
CONCLUSIONS
There is robust evidence for using PBM to prevent and treat a broad range of complications in cancer care. Specific clinical practice guidelines or evidence-based expert consensus recommendations are provided. These recommendations are aimed at improving the clinical utilization of PBM therapy in supportive cancer care and promoting research in this field. It is anticipated these guidelines will be revised periodically.
PubMed: 36110957
DOI: 10.3389/fonc.2022.927685 -
JAMA Oncology Jul 2023Evidence-based approaches for the prevention of acute radiation dermatitis (ARD) are limited, and additional strategies are necessary to optimize care. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Evidence-based approaches for the prevention of acute radiation dermatitis (ARD) are limited, and additional strategies are necessary to optimize care.
OBJECTIVE
To determine the efficacy of bacterial decolonization (BD) to reduce ARD severity compared with standard of care.
DESIGN, SETTING, AND PARTICIPANTS
This phase 2/3 randomized clinical trial was conducted from June 2019 to August 2021 with investigator blinding at an urban academic cancer center and enrolled patients with breast cancer or head and neck cancer receiving radiation therapy (RT) with curative intent. Analysis was performed on January 7, 2022.
INTERVENTIONS
Intranasal mupirocin ointment twice daily and chlorhexidine body cleanser once daily for 5 days prior to RT and repeated for 5 days every 2 weeks through RT.
MAIN OUTCOMES AND MEASURES
The primary outcome as planned prior to data collection was the development of grade 2 or higher ARD. Based on wide clinical variability of grade 2 ARD, this was refined to grade 2 ARD with moist desquamation (grade 2-MD).
RESULTS
Of 123 patients assessed for eligibility via convenience sampling, 3 were excluded, and 40 refused to participate, with 80 patients in our final volunteer sample. Of 77 patients with cancer (75 patients with breast cancer [97.4%] and 2 patients with head and neck cancer [2.6%]) who completed RT, 39 were randomly assigned BC, and 38 were randomly assigned standard of care; the mean (SD) age of the patients was 59.9 (11.9) years, and 75 (97.4%) were female. Most patients were Black (33.7% [n = 26]) or Hispanic (32.5% [n = 25]). Among patients with breast cancer and patients with head and neck cancer (N = 77), none of the 39 patients treated with BD and 9 of the 38 patients (23.7%) treated with standard of care developed ARD grade 2-MD or higher (P = .001). Similar results were observed among the 75 patients with breast cancer (ie, none treated with BD and 8 [21.6%] receiving standard of care developed ARD grade ≥2-MD; P = .002). The mean (SD) ARD grade was significantly lower for patients treated with BD (1.2 [0.7]) compared with patients receiving standard of care (1.6 [0.8]) (P = .02). Of the 39 patients randomly assigned to BD, 27 (69.2%) reported regimen adherence, and only 1 patient (2.5%) experienced an adverse event related to BD (ie, itch).
CONCLUSIONS AND RELEVANCE
The results of this randomized clinical trial suggest that BD is effective for ARD prophylaxis, specifically for patients with breast cancer.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03883828.
Topics: Humans; Female; Middle Aged; Male; Radiodermatitis; Chlorhexidine; Mupirocin; Breast Neoplasms; Head and Neck Neoplasms
PubMed: 37140904
DOI: 10.1001/jamaoncol.2023.0444 -
Actas Dermo-sifiliograficas 2023
Topics: Humans; Radiodermatitis; Fluoroscopy
PubMed: 36370832
DOI: 10.1016/j.ad.2022.09.017 -
Wounds : a Compendium of Clinical... Feb 2020Radiation therapy (RT) following breast-conserving surgical excision of cancer reduces cancer-related mortality and recurrence.1 However, most patients experience acute...
Radiation therapy (RT) following breast-conserving surgical excision of cancer reduces cancer-related mortality and recurrence.1 However, most patients experience acute radiation dermatitis (ARD) within weeks after beginning RT2; symptoms of ARD, including severe skin erythema, dryness, moist or dry desquamation, and/or ulceration, may interrupt radiotherapy. This can negatively affect patient quality of life (QoL) and cancer outcomes. Acute radiation dermatitis is not to be confused with chronic radiation dermatitis, which can lead to fibrosis, skin atrophy, pigmentation, and telangiectasia months to years after RT.3 Evidence-based guidelines4 to both prevent and treat ARD recommend the application of 1 of 2 topical interventions during and/or after RT: (1) corticosteroids to improve ARD-related discomfort and itching5 or (2) 1% silver sulfadiazine (SSD) cream to reduce ARD-related dermatitis scores.6 This Evidence Corner reviews evidence supporting the 2 aforementioned topical interventions for patients undergoing RT for breast cancer.
Topics: Adrenal Cortex Hormones; Dermatologic Agents; Humans; Radiodermatitis; Silver Sulfadiazine
PubMed: 32155122
DOI: No ID Found -
CMAJ : Canadian Medical Association... May 2023
Topics: Humans; Carcinoma; Liver Neoplasms; Radiodermatitis
PubMed: 37156558
DOI: 10.1503/cmaj.221122-f -
Annals of Oncology : Official Journal... Jan 2023To evaluate potential synergistic effect of pembrolizumab with radiotherapy (RT) compared with a standard-of-care (SOC) cetuximab-RT in patients with locally... (Randomized Controlled Trial)
Randomized Controlled Trial
Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial.
BACKGROUND
To evaluate potential synergistic effect of pembrolizumab with radiotherapy (RT) compared with a standard-of-care (SOC) cetuximab-RT in patients with locally advanced-squamous cell carcinoma of head and neck (LA-SCCHN).
PATIENTS AND METHODS
Patients with nonoperated stage III-IV SCC of oral cavity, oropharynx, hypopharynx, and larynx and unfit for receiving high-dose cisplatin were enrolled. Patients received once-daily RT up to 69.96 Gy in 33 fractions with weekly cetuximab (cetuximab-RT arm) or 200 mg Q3W pembrolizumab during RT (pembrolizumab-RT arm). The primary endpoint was locoregional control (LRC) rate 15 months after RT. To detect a difference between arms of 60%-80% in 15-month LRC, inclusion of 66 patients per arm was required to achieve a power of at least 0.85 at two-sided significance level of 0.20.
RESULTS
Between May 2016 and October 2017, 133 patients were randomized to cetuximab-RT (n = 66) and pembrolizumab-RT (n = 67). Two patients (one in each arm) were not included in the analysis (a consent withdrawal and a progression before treatment start). The median age was 65 years (interquartile range 60-70 years), 92% were smokers, 60% were oropharynx (46% of oropharynx with p16+) and 75% were stage IV. Median follow-up was 25 months in both arms. The 15-month LRC rate was 59% with cetuximab-RT and 60% with pembrolizumab-RT ]odds ratio 1.05, 95% confidence interval (CI) 0.43-2.59; P = 0.91]. There was no significant difference between arms for progression-free survival (hazard ratio 0.85, 95% CI 0.55-1.32; P = 0.47) and for overall survival (hazard ratio 0.83, 95% CI 0.49-1.40; P = 0.49). Toxicity was lower in the pembrolizumab-RT arm than in the cetuximab-RT arm: 74% versus 92% patients with at least one grade ≥3 adverse events (P = 0.006), mainly due to mucositis, radiodermatitis, and rash.
CONCLUSION
Compared with the SOC cetuximab-RT, pembrolizumab concomitant with RT did not improve the tumor control and survival but appeared less toxic in unfit patients with LA-SCCHN.
Topics: Aged; Humans; Middle Aged; Cetuximab; Chemoradiotherapy; Cisplatin; Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck
PubMed: 36522816
DOI: 10.1016/j.annonc.2022.10.006 -
International Journal of Molecular... Mar 2024An important hallmark of radiation dermatitis is the impairment of the mitotic ability of the stem/progenitor cells in the basal cell layers due to radiation-induced DNA... (Review)
Review
An important hallmark of radiation dermatitis is the impairment of the mitotic ability of the stem/progenitor cells in the basal cell layers due to radiation-induced DNA damage, leading to suppressed cell renewal in the epidermis. However, this mechanism alone does not adequately explain the complex pathogenesis of radiation-induced skin injury. In this review, we summarize the latest findings on the complex pathogenesis of radiation dermatitis and correlate these with the clinical features of radiation-induced skin reactions. The current studies show that skin exposure to ionizing radiation induces cellular senescence in the epidermal keratinocytes. As part of their epithelial stress response, these senescent keratinocytes secrete pro-inflammatory mediators, thereby triggering skin inflammation. Keratinocyte-derived cytokines and chemokines modulate intercellular communication with the immune cells, activating skin-resident and recruiting skin-infiltrating immune cells within the epidermis and dermis, thereby orchestrating the inflammatory response to radiation-induced tissue damage. The increased expression of specific chemoattractant chemokines leads to increased recruitment of neutrophils into the irradiated skin, where they release cytotoxic granules that are responsible for the exacerbation of an inflammatory state. Moreover, the importance of IL-17-expressing γδ-T cells to the radiation-induced hyperproliferation of keratinocytes was demonstrated, leading to reactive hyperplasia of the epidermis. Radiation-induced, reactive hyperproliferation of the keratinocytes disturbs the fine-tuned keratinization and cornification processes, leading to structural dysfunction of the epidermal barrier. In summary, in response to ionizing radiation, epidermal keratinocytes have important structural and immunoregulatory barrier functions in the skin, coordinating interacting immune responses to eliminate radiation-induced damage and to initiate the healing process.
Topics: Humans; Epidermis; Keratinocytes; Skin; Radiodermatitis; Dermatitis; Skin Neoplasms; Chemokines
PubMed: 38542294
DOI: 10.3390/ijms25063320