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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 -
European Journal of Dermatology : EJD Oct 2016Taxanes (docetaxel and paclitaxel) are among the most commonly prescribed anticancer drugs approved for the treatment of metastatic or locally advanced breast, non-small... (Review)
Review
Taxanes (docetaxel and paclitaxel) are among the most commonly prescribed anticancer drugs approved for the treatment of metastatic or locally advanced breast, non-small cell lung, prostate, gastric, head and neck, and ovarian cancers, as well as in the adjuvant setting for operable node-positive breast cancers. Although the true incidence of dermatological adverse events (AEs) in patients receiving taxanes is not known, and has never been prospectively analysed, they clearly represent one of the major AEs associated with these agents. With an increase in the occurrence of cutaneous AEs during treatment with novel targeted and immunological therapies when used in combination with taxanes, a thorough understanding of reactions attributable to this class is imperative. Moreover, identification and management of dermatological AEs is critical for maintaining the quality of life in cancer patients and for minimizing dose modifications of their antineoplastic regimen. This analysis represents a systematic review of the dermatological conditions reported with the use of these drugs, complemented by experience at comprehensive cancer centres. The conditions reported herein include skin, hair, and nail toxicities. Lastly, we describe the dermatological data available for the new, recently FDA-and EMA- approved, solvent-free nab-paclitaxel.
Topics: Alopecia; Antineoplastic Agents; Docetaxel; Drug Eruptions; Edema; Humans; Lupus Erythematosus, Cutaneous; Nail Diseases; Paclitaxel; Pigmentation Disorders; Radiodermatitis; Taxoids
PubMed: 27550571
DOI: 10.1684/ejd.2016.2833 -
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 -
Oral Oncology Jan 2019Radiation therapy plays an integral role in the management of head and neck cancers (HNCs). While most HNC patients have historically been treated with photon-based... (Review)
Review
Radiation therapy plays an integral role in the management of head and neck cancers (HNCs). While most HNC patients have historically been treated with photon-based radiation techniques such as intensity modulated radiation therapy (IMRT), there is a growing awareness of the potential clinical benefits of proton therapy over IMRT in the definitive, postoperative and reirradiation settings given the unique physical properties of protons. Intensity modulated proton therapy (IMPT), also known as "pencil beam proton therapy," is a sophisticated mode of proton therapy that is analogous to IMRT and an active area of investigation in cancer care. Multifield optimization IMPT allows for high quality plans that can target superficially located HNCs as well as large neck volumes while significantly reducing integral doses. Several dosimetric studies have demonstrated the superiority of IMPT over IMRT to improve dose sparing of nearby organs such as the larynx, salivary glands, and esophagus. Evidence of the clinical translation of these dosimetric advantages has been demonstrated with documented toxicity reductions (such as decreased feeding tube dependency) after IMPT for patients with HNCs. While there are relative challenges to IMPT planning that exist today such as particle range uncertainties and high sensitivity to anatomical changes, ongoing investigations in image-guidance techniques and robust optimization methods are promising. A systematic approach towards utilizing IMPT and additional prospective studies are necessary in order to more accurately estimate the clinical benefit of IMPT over IMRT and passive proton therapy on a case-by-case basis for patients with sub-site specific HNCs.
Topics: Head and Neck Neoplasms; Humans; Photons; Proton Therapy; Radiodermatitis; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated; Retreatment; Stomatitis; Survival Rate; Treatment Outcome
PubMed: 30616799
DOI: 10.1016/j.oraloncology.2018.11.015 -
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 -
CMAJ : Canadian Medical Association... May 2023
Topics: Humans; Carcinoma; Liver Neoplasms; Radiodermatitis
PubMed: 37156558
DOI: 10.1503/cmaj.221122-f -
Blood May 2021Plasminogen is an abundant plasma protein that exists in various zymogenic forms. Plasmin, the proteolytically active form of plasminogen, is known for its essential... (Review)
Review
Plasminogen is an abundant plasma protein that exists in various zymogenic forms. Plasmin, the proteolytically active form of plasminogen, is known for its essential role in fibrinolysis. To date, therapeutic targeting of the fibrinolytic system has been for 2 purposes: to promote plasmin generation for thromboembolic conditions or to stop plasmin to reduce bleeding. However, plasmin and plasminogen serve other important functions, some of which are unrelated to fibrin removal. Indeed, for >40 years, the antifibrinolytic agent tranexamic acid has been administered for its serendipitously discovered skin-whitening properties. Plasmin also plays an important role in the removal of misfolded/aggregated proteins and can trigger other enzymatic cascades, including complement. In addition, plasminogen, via binding to one of its dozen cell surface receptors, can modulate cell behavior and further influence immune and inflammatory processes. Plasminogen administration itself has been reported to improve thrombolysis and to accelerate wound repair. Although many of these more recent findings have been derived from in vitro or animal studies, the use of antifibrinolytic agents to reduce bleeding in humans has revealed additional clinically relevant consequences, particularly in relation to reducing infection risk that is independent of its hemostatic effects. The finding that many viruses harness the host plasminogen to aid infectivity has suggested that antifibrinolytic agents may have antiviral benefits. Here, we review the broadening role of the plasminogen-activating system in physiology and pathophysiology and how manipulation of this system may be harnessed for benefits unrelated to its conventional application in thrombosis and hemostasis.
Topics: Animals; Antifibrinolytic Agents; Brain; Conjunctivitis; Enzyme Activation; Fibrin; Fibrinolysin; Fibrinolysis; Fibrinolytic Agents; Humans; Immunity; Infections; Inflammation; Mice; Plasminogen; Radiodermatitis; Receptors, Cell Surface; Skin Diseases, Genetic; Thrombosis; Tranexamic Acid; Wound Healing; Wounds and Injuries
PubMed: 33735914
DOI: 10.1182/blood.2020008951 -
Actas Dermo-sifiliograficas Apr 2017Radiotherapy for cancer is used increasingly. Because skin cells undergo rapid turnover, the ionizing radiation of radiotherapy has collateral effects that are often... (Review)
Review
Radiotherapy for cancer is used increasingly. Because skin cells undergo rapid turnover, the ionizing radiation of radiotherapy has collateral effects that are often expressed in inflammatory reactions. Some of these reactions-radiodermatitis and recall phenomenon, for example-are very familiar to dermatologists. Other, less common radiotherapy-associated skin conditions are often underdiagnosed but must also be recognized.
Topics: Humans; Radiation Dosage; Radiodermatitis
PubMed: 28010872
DOI: 10.1016/j.ad.2016.09.011 -
Frontiers in Pharmacology 2022Topical Chinese herbal medicine (TCHM) is widely used to prevent radiodermatitis in patients who receive radiation therapy in China. However, evidence regarding its...
Topical Chinese herbal medicine (TCHM) is widely used to prevent radiodermatitis in patients who receive radiation therapy in China. However, evidence regarding its efficacy remains limited. The purpose of the review is to evaluate the effects of TCHM in preventing radiodermatitis. The protocol of this review was registered in PROSPERO (CRD42020220620). Relevant clinical trials were identified (from January 1, 2010, to April 24, 2022) through 11 electronic databases, including PubMed, SpringerLink, Proquest, the Cochrane Central Register of Controlled Trials, Scopus, the ProQuest Dissertation & Theses Global, PsycINFO, Applied Social Sciences Index and Abstracts, the Chinese National Knowledge Infrastructure Databases, Wangfang Data Knowledge Service Platform, and the Chongqing VIP Chinese Science and Technology Periodical Database. The quality of the included trials was assessed through a risk of bias assessment using Version 2 of the Cochrane risk-of-bias tool (RoB 2.0). We included RCTs that compared TCHM single used or as adjunctive treatment with routine drugs, conventional therapy, or placebo for cancer patients who are about to start radiation therapy and do not possess any type of dermatitis or skin lesions at that time. Primary outcomes of interest were the incidence of radiodermatitis and the grade of radiodermatitis according to the RTOG (Radiation Therapy Oncology Group). Secondary outcomes included the recovery time of skin and mucosa, the occurrence time of radiodermatitis, the radiation dose, quality of life, and adverse events. Data were summarized using risk ratio (RR) calculations and 95% confidence intervals (CI) for binary outcomes or mean difference (MD) with 95% CI for continuous outcomes. Certainty of the evidence was assessed according to the GRADE criteria. In this review, 38 randomized controlled trials (RCTs) were included. Risk of bias assessment through RoB 2.0 showed that two studies were rated as low risk, two studies were rated as high risk, and the rest were rated as having some concerns. Compared with routine drugs, TCHM may have an advantage in reducing RTOG grading (RR = 0.46, 95%CI 0.35-0.60), decreasing the recovery time of radiodermatitis (MD = -2.35, 95%CI 3.58 to -1.12 days), delaying the occurrence of radiodermatitis (MD = 2.36, 95%CI 1.74-2.98), and improving the quality of life of patients (RR = 1.46, 95%CI 1.03-2.06). Compared with conventional therapy, TCHM may also have an advantage in decreasing the grade of RTOG (RR = 0.28, 95%CI 0.21-0.38). Current low evidence revealed that TCHM may have better efficacy in the prevention of radiodermatitis; however, more high-quality RCTs are still warranted to testify this conclusion. (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020220620), identifier (PROSPERO 2020 CRD42020220620).
PubMed: 35814240
DOI: 10.3389/fphar.2022.819733