Cultured Human Foreskin as a Model System for Evaluating Ionizing Radiation-Induced Skin Injury.

PURPOSE: Precise molecular and cellular mechanisms of radiation-induced dermatitis are incompletely understood. Histone variant H2A.J is associated with cellular senescence and modulates senescence-associated secretory phenotype (SASP) after DNA-damaging insults, such as ionizing radiation (IR). Using ex vivo irradiated cultured foreskin, H2A.J was analyzed as a biomarker of radiation-induced senescence, potentially initiating the inflammatory cascade of radiation-induced skin injury. METHODS: Human foreskin explants were collected from young donors, irradiated ex vivo with 10 Gy, and cultured in air-liquid interphase for up to 72 h. At different time-points after ex vivo IR exposure, the foreskin epidermis was analyzed for proliferation and senescence markers by immunofluorescence and immunohistochemical staining of sectioned tissue. Secretion of cytokines was measured in supernatants by ELISA. Using our mouse model with fractionated in vivo irradiation, H2A.J expression was analyzed in epidermal stem/progenitor cell populations localized in different regions of murine hair follicles (HF). RESULTS: Non-vascularized foreskin explants preserved their tissue homeostasis up to 72 h (even after IR exposure), but already non-irradiated foreskin epithelium expressed high levels of H2A.J in all epidermal layers and secreted high amounts of cytokines. Unexpectedly, no further increase in H2A.J expression and no obvious upregulation of cytokine secretion was observed in the foreskin epidermis after ex vivo IR. Undifferentiated keratinocytes in murine HF regions, by contrast, revealed low H2A.J expression in non-irradiated skin and significant radiation-induced H2A.J upregulations at different time-points after IR exposure. Based on its staining characteristics, we presume that H2A.J may have previously underestimated the importance of the epigenetic regulation of keratinocyte maturation. CONCLUSIONS: Cultured foreskin characterized by highly keratinized epithelium and specific immunological features is not an appropriate model for studying H2A.J-associated tissue reactions during radiation-induced dermatitis.

Establishment and characterization of a radiation-induced dermatitis rat model.

Radiation-induced dermatitis is a common and serious side effect after radiotherapy. Current clinical treatments cannot efficiently or fully prevent the occurrence of post-irradiation dermatitis, which remains a significant clinical problem. Resolving this challenge requires gaining a better understanding of the precise pathophysiology, which in turn requires establishment of a suitable animal model that mimics the clinical condition, and can also be used to investigate the mechanism and explore effective treatment options. In this study, a single dose of 90 Gy irradiation to rats resulted in ulceration, dermal thickening, inflammation, hair follicle loss, and sebaceous glands loss, indicating successful establishment of the model. Few hair follicle cells migrated to form epidermal cells, and both the severity of skin fibrosis and hydroxyproline levels increased with time post-irradiation. Radiation damaged the mitochondria and induced both apoptosis and autophagy of the skin cells. Therefore, irradiation of 90 Gy can be used to successfully establish a rat model of radiation-induced dermatitis. This model will be helpful for developing new treatments and gaining a better understanding of the pathological mechanism of radiation-induced dermatitis. Specifically, our results suggest autophagy regulation as a potentially effective therapeutic target.

Patient preference study comparing hypofractionated versus conventionally fractionated whole-breast irradiation after breast-conserving surgery.

OBJECTIVE: To compare patient preferences and acute adverse events of hypofractionated (HF) and conventionally fractionated (CF) whole-breast irradiation (WBI) after breast-conserving surgery in our institution. METHODS: We conducted a patient preference study comparing CF-WBI (50 Gy/25 fractions) and HF-WBI (41.6 Gy/16 fractions) after breast-conserving surgery. Eligible patients selected either type of fractionation following an explanation from the radiation oncologist. In this report, we analyzed the selection rate and acute toxicities. RESULTS: Between June 2009 and December 2013, 348 patients (349 breasts) were identified as eligible for the study. Among them, 259 patients (260 breasts [74.5%]) selected CF-WBI and 89 patients (89 breasts [25.5%]) selected HF-WBI. Factors significantly associated with the selection of HF-WBI were older age (P = 0.028) and no adjuvant chemotherapy (P = 0.041). Regarding acute adverse events, Grade 2 (G2) or higher radiation dermatitis was less frequently observed in HF-WBI than in CF-WBI (13.8% vs. 29.4%; P = 0.004). In addition, G2 or higher breast pain was only observed in the CF-WBI group (6.9%; P = 0.012). There were no significant differences in the presence of fatigue, wound pain or radiation pneumonitis of G2 or higher between the groups. CONCLUSIONS: In this study, in which patients themselves selected the irradiation method, more patients tended to select CF-WBI. The frequency of G2 or higher dermatitis and breast pain was significantly lower in the HF-WBI group than in the CF-WBI group. Our results support the evidence for recommending HF-WBI after breast-conserving surgery while presenting aspects of patient preferences.

Preemptive treatment with Xonrid®, a medical device to reduce radiation induced dermatitis in head and neck cancer patients receiving curative treatment: a pilot study.

PURPOSE: The purpose of this study was to investigate efficacy, safety and tolerability of Xonrid®, a new medical device, in preventing radiation dermatitis associated with head and neck cancer (HNC) radiotherapy (RT). METHODS: In this monocentric, prospective pilot study, adult consecutive HNC patients who were planned to receive curative RT with or without chemotherapy were enrolled. Patients were instructed to apply Xonrid® on the irradiated area during treatment continuing until 2 weeks after the completion of RT or the development of severe skin toxicity. Toxicity was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 scale. The patient reported outcome measures included the Skindex-16 questionnaire and patient satisfaction. Skin reflectance spectra were analyzed to objectively evaluate dermatitis. RESULTS: In total, 41 subjects were enrolled (30 males, median age 60 years). No skin adverse events were recorded either in the skin area where the product was applied or in the nearby skin over the entire period of administration. At the end of RT, nine patients (22%) presented G1, 31 (76%) G2, and one patient (2%) G3 skin toxicity (after 5 weeks). Seven and 20 patients reached skin maximum toxicity at the fourth week and after the seventh week, respectively. An increasing trend of median spectrophotometry scores along with skin toxicity grades was observed. A correlation between Skindex-16 scores and skin toxicity grade during treatment was found. CONCLUSIONS: Our study results suggest that Xonrid® is well tolerated, safe, and effective in minimizing and delaying high-grade radiation dermatitis in HNC patients.

Subacute radiation dermatitis following an interventional cardiology procedure.

Although radiation dermatitis is a widely known complication of radiotherapy, its association with fluoroscopy-guided interventional procedures is yet under recognized. We present a case of a 66-year-old man with a left scapular cutaneous lesion, initially diagnosed as a fixed drug eruption. The subsequent knowledge of a previous percutaneous aortic paravalvular leak closure procedure allowed a correct clinicopathological correlation and the final diagnosis of subacute radiodermatitis associated with fluoroscopy. Many of the patients with skin injury associated with fluoroscopic procedures do not associate both and seek physicians other than the one who performed the procedure. Besides interventional physicians, dermatologists and other physicians should be aware of this form of radiation injury and its manifestations. Suspicion and active search for a history of previous fluoroscopic procedures in patients with figurate cutaneous lesions in allusive locations may allow the diagnosis of this potentially serious complication that should have long follow-up due to the possibility of long-term side effects.

No Sting Barrier Film to Protect Skin in Adult Patients: Findings From a Scoping Review With Implications for Evidence-Based Practice.

BACKGROUND: In the industrialized world, approximately 1-1.5% of the population has received treatments for skin lesions. In the 1990s, a polymeric barrier film called the No Sting Barrier Film (NSBF) was developed as an alternative to petrolatum-based ointments and zinc oxide formulas. To date, few studies have explored the effectiveness of NSBF in protecting skin integrity. AIMS: To map the methods, fields and outcomes used to produce evidence on NSBF effectiveness. METHODS: A scoping review was performed in 2015. A search strategy for identifying relevant studies was designed and performed. Systematic reviews, meta-analyses, randomized controlled trials, controlled clinical trials, and comparative studies for all types of interventions were included; research conducted in any clinical context was eligible for inclusion. Studies were selected by two reviewers; data extraction and analysis also was performed by two reviewers and disagreements were discussed. RESULTS: Six studies were included. NSBF's potential as a skin protector was investigated with respect to (a) chronic wounds (pressure ulcers or vascular leg ulcers); (b) urinary or fecal incontinence; and (c) post-mastectomy irradiation. The principal clinical outcomes investigated were, respectively: (a) wound healing, wound exudates and erythema control; (b) incidence of incontinence-associated dermatitis and skin reactions; and (c) intensity of pruritus and skin reactions. Pain and comfort were measured in all clinical applications. The main process outcomes investigated were: (a) ease of application, (b) application and removal time, and (c) costs. Zinc oxide and petroleum formulations were the most common comparison interventions in research on chronic ulcers and incontinence; sorbolene cream and topical corticosteroids were the most frequent comparisons in the context of post-mastectomy irradiation. LINKING EVIDENCE TO ACTION: NBSF may be used for peri-wound skin protection in patients with chronic wounds, with urinary or fecal incontinence and for women undergoing post-mastectomy irradiation. However, more robust experimental studies are needed in all clinical fields where NBSF is applied.

3M Cavilon No-Sting Barrier Film or topical corticosteroid (mometasone furoate) for protection against radiation dermatitis: A clinical trial.

BACKGROUND/PURPOSE: Evidence on the prevention of radiation dermatitis is lacking. The aim of this study was to investigate the effect of 3M Cavilon No Sting Barrier Film and topical corticosteroids on irradiated skin. METHODS: Thirty-nine postoperative breast cancer patients were randomized into three groups for intraindividual comparison (skin to be irradiated was divided into 2 parts): (1) 3M No Sting Barrier Film versus no treatment; (2) corticosteroid versus no treatment; and (3) corticosteroid versus 3M No Sting Barrier Film. The primary end points monitored were the time to first occurrence of grade 1 pruritus, pain score of 3 and grade 2 radiation dermatitis. The secondary end points studied were the incidence of grade 3 radiation dermatitis and total pain scores. Data analysis was done using the SPSS software version 10. RESULTS: Skin given the 3M barrier film experienced a later occurrence of pruritus compared to both corticosteroids and untreated, although this was statistically insignificant. Corticosteroids delayed the time to occurrence of grade 2 dermatitis compared to both untreated skin and 3M barrier film, (mean day of onset = corticosteroid: 52 vs. untreated: 43, p = 0.092; corticosteroid: 53.4 vs. 3M barrier film: 44.5, p = 0.002, t test). Skin given corticosteroids had the lowest incidence of grade 3 dermatitis among all three conditions, although the differences were statistically insignificant. No statistically significant differences were noted in total pain scores. CONCLUSION: The 3M barrier film may be helpful against dermatitis associated pruritus. Corticosteroids may delay the time of onset of severe skin reactions and also reduce the incidence of severe radiation dermatitis.

Dermoscopy of Chronic Radiation-Induced Dermatitis in Patients with Head and Neck Cancers Treated with Radiotherapy.

Radiotherapy (RT) is an integral part of many cancer treatment protocols. Chronic radiation-induced dermatitis (CRD) is a cutaneous toxicity that occurs in one-third of all patients treated with this method. CRD is usually observed several months after completion of treatment. Typical symptoms of CRD are telangiectasia, skin discoloration, atrophy, thickening, and cutaneous fibrosis. There are currently no data in the literature on the evaluation of the dermoscopic features of CRD. The aim of this prospective study was the identification of clinical and dermoscopic features in a group of 32 patients with head and neck cancer (HNC) in whom CRD developed after RT. CRD was assessed at 3, 6, and 12 months after RT in 16, 10, and 10 patients, respectively. CRD was assessed at one time point and two time points in 28 and 4 patients, respectively. The control included skin areas of the same patient not exposed to RT. The dataset consisted of 36 clinical and 216 dermoscopic photos. Clinical evaluation was performed according to the RTOG/EORTC radiation-induced dermatitis scale. The highest score was grade 2 observed in 21 patients. Clinical observations revealed the presence of slight and patchy atrophy, pigmentation change, moderate telangiectasias, and some and total hair loss. Dotted vessels, clustered vessel distribution, white patchy scale, perifollicular white color, white structureless areas, brown dots and globules, and white lines were the most frequently noted features in dermoscopy. Three independent risk factors for chronic toxicity, such as age, gender, and surgery before RT, were identified. The dermoscopic features that had been shown in our study reflect the biological reaction of the skin towards radiation and may be used for the parametrization of CRD regarding its intensity and any other clinical consequences in the future.

Aloe vera for prevention of radiation-induced dermatitis: a self-controlled clinical trial.

To evaluate an Aloe vera lotion for prevention of radiation-induced dermatitis, all patients with a prescription of radiotherapy to a minimum dose of 40 Gy were eligible provided that their treatment area could be divided into two symmetrical halves. Patients were given a lotion of Aloe vera to use on one half of the irradiated area, with no medication to be used on the other half. The grade of dermatitis in each half was recorded weekly until 4 weeks after the end of radiotherapy. The trial enrolled 60 patients (mean age: 52 years; 67% women). Most patients had breast cancer (38%), followed by pelvic (32%), head-and-neck (22%), and other cancers (8%). Field size was 80-320 cm(2) (mean: 177 cm(2)), and the dose of radiotherapy was 40-70 Gy (mean: 54 Gy). Concurrent chemotherapy was administered in 20 patients. From week 4 to week 6 of radiotherapy and then at weeks 2 and 4 after radiotherapy, the mean grade of dermatitis with and without Aloe vera was 0.81 and 1.10 (p < 0.001), 0.96 and 1.28 (p < 0.001), 1.00 and 1.57 (p = 0.006), 0.59 and 0.79 (p = 0.003), and 0.05 and 0.21 (p = 0.002) respectively. Age and radiation field size had a significant effect on the grade of dermatitis. Based on these results, we conclude that the prophylactic use of Aloe vera reduces the intensity of radiationinduced dermatitis.

Efficacy of topical alpha ointment (containing natural henna) compared to topical hydrocortisone (1%) in the healing of radiation-induced dermatitis in patients with breast cancer: a randomized controlled clinical trial.

BACKGROUND: This two-arm, randomized clinical study aimed to compare efficacy between topical Alpha ointment and topical hydrocortisone cream (1%) in the healing of radiation-induced dermatitis in breast cancer patients. METHODS: The inclusion criteria comprised newly pathologically proven, locally advanced breast cancer (treated with modified radical mastectomy followed by sequential adjuvant treatments, including chest wall radiotherapy [45-50.4 Gy]) and grade 2 and/or 3 chest wall dermatitis. The exclusion criteria were comprised of any underlying disease or medications interfering with the wound healing process, previous history of chest wall radiotherapy, and concurrent use of chemotherapy. Sixty eligible patients were randomly assigned to use either topical Alpha ointment (study arm, n=30) or topical hydrocortisone cream (1%) (control arm, n=30) immediately after receiving a total dose of 45-50 Gy chest wall radiotherapy. RESULTS: The mean radiation dose was 49.1 Gy in the control arm and 48.8 Gy in the study arm. The mean dermatitis area was 13.54 cm(2) in the control arm and 17.02 cm(2) in the study arm. Topical Alpha ointment was more effective on the healing of radiation-induced dermatitis than was topical hydrocortisone cream (1%) (P=0.001). This effect was significant in the second week (P=0.007). In addition, Alpha ointment decreased the patients' complaints such as pain (P<0.001), pruritus (P=0.009), and discharge (P=0.010) effectively and meaningfully. CONCLUSION: Topical Alpha ointment was more effective on the healing of radiation-induced dermatitis than was topical hydrocortisone cream (1%) in our patients with breast cancer. TRIAL REGISTRATION NUMBERS: IRCT201206099979N1, ACTRN12612000837820.

Comparative efficacy of Jaungo, a traditional herbal ointment, and a water-in-oil type non-steroidal moisturizer for radiation-induced dermatitis in patients with breast cancer: a prospective, randomized, single-blind, pilot study.

Background: Radiation-induced dermatitis (RID) is one of the most prevalent side-effects of conventional cancer therapies; however, there is no standard treatment for its prevention. Therefore, this study aimed to evaluate the comparative efficacy and safety of Jaungo (mainly composed of Lithospermum erythrorhizon Siebold & Zucc. and Angelica sinensis (Oliv.) Diel) and the water-in-oil-type non-steroidal moisturizer for the prevention of RID in patients with breast cancer (BC). Methods: This is a prospective, single-blind, pilot randomized controlled trial. Between March 2021 and July 2022, 50 patients were randomly selected to use Jaungo or the moisturizer while undergoing postoperative radiation therapy (RT). Assessments were conducted nine times-every week while the patients underwent RT and 2 weeks after the end of therapy. The primary outcome was the incidence rate of RID grade ≥2. The secondary outcomes were the incidence rate of maximum grade RID, time to RID onset, RID-related quality of life (QOL) score, pain intensity, and adverse events. Results: The incidence rate of RID grade ≥2 was 24.0% and 20.0% in the Jaungo and the moisturizer groups, respectively, with no significant difference between the groups (p = 0.733). Regarding the secondary outcomes, the incidence rate of maximum grade RID (p = 0.890), mean time to RID onset (p = 0.092), cumulative incidence rate of RID (p = 0.280), RID-related QOL score, and maximum pain intensity (p = 0.844) also did not differ significantly between the groups. None of the subjects in either group experienced severe adverse effects, although one participant in the moisturizer group had mild fever and insomnia. Conclusion: These findings suggest that Jaungo has preventive efficacy without severe side-effects against RID in patients with BC that is comparable to that of the water-in-oil type non-steroidal moisturizer. Further extensive randomized controlled trials with larger sample sizes are warranted to validate our findings. Clinical Trial Registration: Clinical Research Information Service (CRIS), https://cris.nih.go.kr, identifier KCT0005971.

A Bayesian optimization tunning integrated multi-stacking classifier framework for the prediction of radiodermatitis from 4D-CT of patients underwent breast cancer radiotherapy.

Purpose: In this study, we aimed to develop a novel Bayesian optimization based multi-stacking deep learning platform for the prediction of radiation-induced dermatitis (grade ≥ two) (RD 2+) before radiotherapy, by using multi-region dose-gradient-related radiomics features extracted from pre-treatment planning four-dimensional computed tomography (4D-CT) images, as well as clinical and dosimetric characteristics of breast cancer patients who underwent radiotherapy. Materials and methods: The study retrospectively included 214 patients with breast cancer who received radiotherapy after breast surgeries. Six regions of interest (ROIs) were delineated based on three PTV dose -gradient-related and three skin dose-gradient-related parameters (i.e., isodose). A total of 4309 radiomics features extracted from these six ROIs, as well as clinical and dosimetric characteristics, were used to train and validate the prediction model using nine mainstream deep machine learning algorithms and three stacking classifiers (i.e., meta-learners). To achieve the best prediction performance, a Bayesian optimization based multi-parameter tuning technology was adopted for the AdaBoost, random forest (RF), decision tree (DT), gradient boosting (GB) and extra tree (XTree) five machine learning models. The five parameter -tuned learners and the other four learners (i.e., logistic regression (LR), K-nearest neighbors (KNN), linear discriminant analysis (LDA), Bagging) whose parameters cannot be tuned, all as the primary week learners, were fed into the subsequent meta-learners for training and learning the final prediction model. Results: The final prediction model included 20 radiomics features and eight clinical and dosimetric characteristics. At the primary learner level, on base of Bayesian parameter tuning optimization, the RF, XGBoost, AdaBoost, GBDT, and LGBM models with the best parameter combinations achieved AUC of 0.82, 0.82, 0.77, 0.80, and 0.80 prediction performance in the verification data set, respectively. In the secondary meta-learner lever, compared with LR and MLP meta-learner, the best predictor of symptomatic RD 2+ for stacked classifiers was the GB meta-learner with an area under the curve (AUC) of 0.97 [95% CI: 0.91-1.0] and an AUC of 0.93 [95% CI: 0.87-0.97] in the training and validation datasets, respectively and the 10 top predictive characteristics were identified. Conclusion: A novel multi-region dose-gradient-based Bayesian optimization tunning integrated multi-stacking classifier framework can achieve a high-accuracy prediction of symptomatic RD 2+ in breast cancer patients than any other single deep machine learning algorithm.

Corrigendum: Comparative efficacy of Jaungo, a traditional herbal ointment, and a water-in-oil type non-steroidal moisturizer for radiation-induced dermatitis in patients with breast cancer: a prospective, randomized, single-blind, pilot study.

[This corrects the article DOI: 10.3389/fphar.2023.1216668.].

Radiotherapy-induced Pathology of the Ear.

Acute radiotherapy (RT)-induced external ear soft tissue changes start with erythema and dry desquamation and may progress to moist desquamation and epidermal ulceration. Chronic RT-induced changes include epithelial atrophy and subcutaneous fibrosis. Although RT-induced radiation dermatitis has been well studied, interventions for soft tissue disease involving the external auditory canal (EAC) warrant investigation. Medical management includes topical steroid treatment for EAC radiation dermatitis and topical antibiotic therapy for suppurative otitis externa. Hyperbaric oxygen and pentoxifylline-vitamin E therapy have shown promise for other applications, but their clinical effect on soft tissue EAC disease is currently undefined.

Aloe vera for prevention of radiation-induced dermatitis: A systematic review and cumulative analysis of randomized controlled trials.

Background: Aloe vera were frequently reported to reduce the risk of radiation-induced dermatitis (RID), but the quantitative results from all the relevant studies were not presently available. This study sought to conduct a cumulative analysis to better clarify the preventive effects of aloe vera in RID. Methods: MEDLINE (PubMed), Cochrane, EMBASE, PsychINFO, Web of Science, China National Knowledge Infrastructure (CNKI), and Wan Fang Database were utilized for identifying the eligible randomized controlled trials (RCTs) without language restrictions, up to March 2022. The pooled incidence of RID was conducted by the Relative risk (RR) with its 95% confidence interval (CI) through the STATA software under a random-effects model. This systematic review and cumulative analysis were registered on PROSPERO (ID: CRD42022335188). Results: Fourteen RCTs met our predefined inclusion criteria, enrolling 1,572 participants (mean age: 46.5-56 years). The cumulative results revealed that patients pretreated with aloe vera were associated with a significantly lower risk of RID compared to those without aloe vera usage (RR = 0.76, 95% CI: 0.67-0.88, p < 0.001; heterogeneity: I 2 = 79.8%, p < 0.001). In the subgroup analysis, the pooled incidence of Grade 2-4, Grade 2, and Grade 3 RID was also dramatically lower in the group of aloe vera as compared to the placebo group [RR = 0.44 (0.27, 0.74), 0.58 (0.36, 0.94), and 0.27 (0.12, 0.59) in Grade 2-4, Grade 2, and Grade 3, respectively]. However, in regard to Grade 4 RID, the combined RR indicated that the incidence of RID was comparable between aloe vera and the control group (RR = 0.13, 95% CI: 0.02-1.01, p = 0.051; heterogeneity: I 2 = 0.0%, p = 0.741). The sensitivity analyses showed that there was no substantial change in the new pooled RR after eliminating anyone of the included study. Conclusion: The current cumulative analysis revealed that patients pretreated with aloe vera were less likely to suffer from RID than the controls without using aloe vera. Based on this finding, the prophylactic application of aloe vera might significantly reduce the incidence of RID, especially in Grade 2 and Grade 3 RID. Further large-sample multicenter RCTs are still warranted to confirm these findings and for better clinical application.

Smoking and Radiation-induced Skin Injury: Analysis of a Multiracial, Multiethnic Prospective Clinical Trial.

INTRODUCTION: Smoking during breast radiotherapy (RT) may be associated with radiation-induced skin injury (RISI). We aimed to determine if a urinary biomarker of tobacco smoke exposure is associated with increased rates of RISI during and after breast RT. PATIENTS AND METHODS: Women with Stage 0-IIIA breast cancer treated with breast-conserving surgery or mastectomy followed by RT to the breast or chest wall with or without regional nodal irradiation were prospectively enrolled on a multicenter study assessing acute/late RISI. 980 patients with urinary cotinine (UCot) measurements (baseline and end-RT) were categorized into three groups. Acute and late RISI was assessed using the ONS Acute Skin Reaction scale and the LENT-SOMA Criteria. RESULTS: Late Grade 2+ and Grade 3+ RISI occurred in 18.2% and 1.9% of patients, respectively-primarily fibrosis, pain, edema, and hyperpigmentation. Grade 2+ late RISI was associated with UCot group (P= 006). Multivariable analysis identified UCot-based light smoker/secondhand smoke exposure (HR 1.79, P= .10) and smoking (HR 1.60, p = .06) as non-significantly associated with an increased risk of late RISI. Hypofractionated breast RT was associated with decreased risk of late RISI (HR 0.51, P=.03). UCot was not associated with acute RISI, multivariable analysis identified race, obesity, RT site/fractionation, and bra size to be associated with acute RISI. CONCLUSIONS: Tobacco exposure during breast RT may be associated with an increased risk of late RISI without an effect on acute toxicity. Smoking cessation should be encouraged prior to radiotherapy to minimize these and other ill effects of smoking.

Potential Benefits of Aloe vera and Raphanus sativus var. longipinnatus Gel for Prevention of Radiation-Induced Dermatitis in Head and Neck Cancer Patients.

Background: The main therapy for head and neck cancer is radiation, and one of the toxic effects of radiation is radiation dermatitis. Aloe vera is a species of succulent plant of the genus Aloe, widely used in cosmetic and skin care products, as well as daikon (Raphanus sativus var. longipinnatus), which is high in antioxidants. Objectives: The present study aims to evaluate the potential benefits of Aloe vera and daikon gel combination in head and neck cancer patients to prevent radiation-induced dermatitis. Methods: A cohort study was conducted with eligible subjects, all head and neck cancer patients receiving radiation therapy selected in consecutive sampling. Samples were divided into two groups; either received Aloe vera and daikon combination gel (study group) or baby oil (control induced dermatitis (RID) were observed. Results: A total of 44 patients were grouped into intervention (Aloe vera-daikon gel) and control (baby oil) groups. After ten radiotherapies (RT) sessions, the intervention group had a lower percentage of grade 1 RID (35% vs. 91.7%, control: 65% grade 2 RID, P < 0.001). After 20 RT sessions, 40% had no dermatitis, while all patients had RID in the control group (P = 0.061). After 30 RT sessions, the intervention group had a lower RID grade overall (gr 0: 5%, gr 1: 85%, gr 2: 10%) compared to the control group (gr 1: 33.3%, gr 2: 54.3%, gr 3: 8.3%, P = 0.002). After 35 RT sessions, the intervention group also had a lower RID grade overall (gr 0: 5%, gr 1: 65%, gr 2: 20%, gr 3: 10%) compared to the control group (gr 1: 8.3%, gr 2: 37.5%, gr 3: 45.8%, gr 4: 8.3%, P < 0.001). Conclusions: The combination of Aloe vera and daikon gel showed promising results in reducing the severity of radiation-induced dermatitis for head and neck cancer patients.

Opium poisoning following self-medication of radiation-induced dermatitis with topical use of opium latex traditional extract; a teaching case.

Despite Radiation-induced dermatitis is a self-limiting complication, it can be complicated if inappropriate self-medications have been used such as opium latex traditional extract.

Comparative Efficacy of Jaungo, A Traditional Herbal Ointment, and the Water-in-Oil Type Non-Steroidal Moisturizer for Radiation-Induced Dermatitis in Patients With Breast Cancer: A Study Protocol for a Prospective, Randomized, Single-Blinded, Pilot Study.

Background: Radiation-induced dermatitis (RID) is a common complication of radiation therapy (RT). Although it has a high prevalence and can even trigger the premature end of conventional cancer therapies, there is no standard management. This study aims to evaluate whether topical use of Jaungo (Shiunko), a traditional herbal ointment mainly composed of Lithospermi radix and Angelica sinensis, could reduce RID compared to the water-in-oil type non-steroidal moisturizer in patients with breast cancer. Methods: This is a prospective, single-blinded, randomized controlled pilot trial that investigates the effect of topical application of Jaungo for the prevention of RID in postoperative breast cancer patients scheduled for RT, in comparison with the non-steroidal moisturizer, with a random distribution of 50 patients across the two groups. RT will be administered for 5-7 weeks with a biological equivalent dose (BED10) of 60 Gy or more, and the interventions will be applied 3 times a day during RT duration. Participants will be assessed a total of nine times, including eight visits during the period of RT and one visit at a 2-week follow-up period after the end of treatment. The incidence and severity of RID, quality of life, skin reaction symptoms, and maximum pain related to RID will be measured. The incidence rate of grade 2 or higher RID using the Radiation Therapy Oncology Group (RTOG) in the two groups will be statistically compared as the primary outcome. The types and frequencies of adverse events will be also collected and evaluated. All assessments will be performed by independent radiology oncologists. Discussion: This trial is currently ongoing and is recruiting. This study will determine the preventive efficacy of Jaungo in RID with postoperative breast cancer patients and provide evidence in traditional Korean medicine clinical practice.

Adipose-derived stem cells alleviate radiation-induced dermatitis by suppressing apoptosis and downregulating cathepsin F expression.

BACKGROUND: Radiation-induced dermatitis is a serious side effect of radiotherapy, and very few effective treatments are currently available for this condition. We previously demonstrated that apoptosis is an important feature of radiation-induced dermatitis and adipose-derived stem cells (ADSCs) are one of the most promising types of stem cells that have a protective effect on acute radiation-induced dermatitis. Cathepsin F (CTSF) is a recently discovered protein that plays an important role in apoptosis. In this study, we investigated whether ADSCs affect chronic radiation-induced dermatitis, and the underlying mechanisms involved. METHODS: ADSCs were isolated from male Sprague-Dawley (SD) rats and characterized. For in vivo studies, rats were randomly divided into control and ADSC-treated groups, and cultured ADSCs were transplanted into radiation-induced dermatitis model rats. The effects of ADSC transplantation were determined by skin damage scoring, histopathological analysis, electron microscopy, immunohistochemical staining, and western blotting analysis of apoptosis-related proteins. To evaluate the effects of ADSCs in vitro, radiation-induced apoptotic cells were treated with ADSC culture supernatant, and apoptosis-related protein expression was investigated by TUNEL staining, flow cytometry, and western blotting. RESULTS: In the in vivo studies, skin damage, inflammation, fibrosis, and apoptosis were reduced and hair follicle and sebaceous gland regeneration were enhanced in the ADSC group compared with the control group. Further, CTSF and downstream pro-apoptotic proteins (Bid, BAX, and caspase 9) were downregulated, while anti-apoptotic proteins (Bcl-2 and Bcl-XL) were upregulated. In vitro, ADSCs markedly attenuated radiation-induced apoptosis, downregulated CTSF and downstream pro-apoptotic proteins, and upregulated anti-apoptotic proteins. CONCLUSION: ADSCs protect against radiation-induced dermatitis by exerting an anti-apoptotic effect through inhibition of CTSF expression. ADSCs may be a good therapeutic candidate to prevent the development of radiation-induced dermatitis.