Topical agents for the prevention ofradiodermatitis in cancer patients: A systematic review / Agentes tópicos para prevenção de radiodermatiteem pacientes com câncer: revisão sistemática

Objetivo: Analisar as evidências sobre o efeito dos agentes tópicos empregados para a prevenção da radiodermatite em pacientes com câncer. Método: Revisão sistemática de estudos clínicos randomizados duplos-cegos construída conforme recomendações do Joanna Briggs Institute e busca nas bases de dados MEDLINE/PubMed, CINAHL, LILACS, Web of Science, Embase, Scopus, além da literatura cinzenta. Utilizaram-se a ferramenta de avaliação crítica do JBI para ensaios clínicos randomizados para avaliar a possibilidade de viés, o Grading of Recommendations, Assessment, Development and Evaluation para a qualidade das evidências e o Gradepro® para recomendá-las. Resultados: Selecionaram-se 13 estudos que avaliaram diferentes agentes tópicos para prevenir a radiodermatite, a saber: corticosteroides, de ação antioxidante e fitoterápicos. A qualidade metodológica de cada estudo foi apropriada, mas a qualidade da evidência gerada pela reunião deles foi baixa, independentemente do tipo de agente tópico empregado, sugerindo que a confiança no seu efeito é limitada e tornando a força de recomendação fraca. Conclusão: Alguns agentes tópicos mostraram-se promissores para a prevenção de radiodermatite, mas as evidências aqui reunidas sobre a eficácia deles não permitem indicar seu uso para a prevenção de radiodermatite em pacientes com câncer. (AU)

Objective: To analyze the evidence on the effect of topical agents to prevent radiodermatitis in cancer patients. Methods: Systematic review of double-blind randomized clinical studies built according to JBI recommendations and search in the databases MEDLINE/PubMed, CINAHL, LILACS, Web of Science, Embase and Scopus, in addition to the Gray Literature. The JBI critical assessment tool for randomized clinical trials was used to assess the possibility of bias, GRADE for the quality of evidence, and Gradepro® to recommend them. Results: Thirteen studies were selected that evaluated different topical agents to prevent radiodermatitis, namely: corticosteroids, with antioxidant action and herbal medicines. The methodological quality of each study was appropriate. Still, the quality of evidence generated by pooling them was low, regardless of the type of topical agent employed, suggesting that confidence in its effect is limited and weakening the strength of the recommendation. Conclusions: Some topical agents have shown promise for the prevention of radiodermatitis, but the evidence gathered here about their effectiveness does not indicate their use for the prevention of radiodermatitis in cancer patients. (AU)

Objetivo: Analizar la evidencia sobre el efecto de los agentes tópicos utilizados para la prevención de la radiodermatitis en pacientes con cáncer. Método: Revisión sistemática de estudios clínicos aleatorizados, doble ciego, elaborados según las recomendaciones del JBI y buscados en MEDLINE/PubMed, CINAHL, LILACS, Web of Science, Embase y Scopus, además de literatura gris. Se utilizó la herramienta de evaluación crítica JBI para ensayos clínicos aleatorios para evaluar la posibilidad de sesgo, GRADE para la calidad de la evidencia y Gradepro® para recomendarla. Resultados: Se seleccionaron trece estudios que evaluaron diferentes agentes tópicos para prevenir la radiodermatitis, a saber: corticosteroides, con acción antioxidante y fitoterapia. La calidad metodológica de cada estudio fue apropiada, pero la calidad de la evidencia generada al combinarlos fue baja, independientemente del tipo de agente tópico empleado, lo que sugiere que la confianza en su efecto es limitada y debilita la fuerza de la recomendación. Conclusión: Algunos agentes tópicos se han mostrado prometedores para la prevención de la radiodermatitis, pero la evidencia aquí reunida sobre su eficacia no nos permite indicar su uso para la prevención de la radiodermatitis en pacientes con cáncer. (AU)

Development of a risk prediction model for radiation dermatitis following proton radiotherapy in head and neck cancer using ensemble machine learning.

PURPOSE: This study aims to develop an ensemble machine learning-based (EML-based) risk prediction model for radiation dermatitis (RD) in patients with head and neck cancer undergoing proton radiotherapy, with the goal of achieving superior predictive performance compared to traditional models. MATERIALS AND METHODS: Data from 57 head and neck cancer patients treated with intensity-modulated proton therapy at Kaohsiung Chang Gung Memorial Hospital were analyzed. The study incorporated 11 clinical and 9 dosimetric parameters. Pearson's correlation was used to eliminate highly correlated variables, followed by feature selection via LASSO to focus on potential RD predictors. Model training involved traditional logistic regression (LR) and advanced ensemble methods such as Random Forest and XGBoost, which were optimized through hyperparameter tuning. RESULTS: Feature selection identified six key predictors, including smoking history and specific dosimetric parameters. Ensemble machine learning models, particularly XGBoost, demonstrated superior performance, achieving the highest AUC of 0.890. Feature importance was assessed using SHAP (SHapley Additive exPlanations) values, which underscored the relevance of various clinical and dosimetric factors in predicting RD. CONCLUSION: The study confirms that EML methods, especially XGBoost with its boosting algorithm, provide superior predictive accuracy, enhanced feature selection, and improved data handling compared to traditional LR. While LR offers greater interpretability, the precision and broader applicability of EML make it more suitable for complex medical prediction tasks, such as predicting radiation dermatitis. Given these advantages, EML is highly recommended for further research and application in clinical settings.

Highly efficient prevention of radiation dermatitis using a PEGylated superoxide dismutase dissolving microneedle patch.

PEGylated superoxide dismutase (PEG-SOD) is commonly used as a cytoprotective agent in radiotherapy. However, its effectiveness in preventing radiation dermatitis is limited owing to its poor skin permeability. To address this issue, a PEG-SOD-loaded dissolving microneedle (PSMN) patch was developed to effectively prevent radiation dermatitis. Initially, PSMN patches were fabricated using a template mold method with polyvinylpyrrolidone K90 as the matrix material. PSMNs exhibited a conical shape with adequate mechanical strength to penetrate the stratum corneum. More than 90 % of PEG-SOD was released from the PSMN patches within 30 min. Notably, the PSMN patches showed a significantly higher drug skin permeation than the PEG-SOD solutions, with a 500-fold increase. In silico simulations and experiments on skin pharmacokinetics confirmed that PSMN patches enhanced drug permeation and skin absorption, in contrast to PEG-SOD solutions. More importantly, PSMN patches efficiently mitigated ionizing radiation-induced skin damage, accelerated the healing process of radiation-affected skin tissues, and exhibited highly effective radioprotective activity for DNA in the skin tissue. Therefore, PSMN patches are promising topical remedy for the prevention of radiation dermatitis.

Composite hydrogels with antioxidant and robust adhesive properties for the prevention of radiation-induced dermatitis.

Radiotherapy is a pivotal means of cancer treatment, but it often leads to radiation dermatitis, a skin injury caused by radiation-induced excess reactive oxygen species (ROS). Scavenging free radicals in the course of radiation therapy will be an effective means to prevent radiation dermatitis. This study demonstrates a novel double network hydrogel doped with MoS2 nanosheets for the prevention of radiation-induced dermatitis. The resultant SPM hydrogel constructed from polyacrylamide (PAM) and sodium alginate (SA) nanofiber presented favorable mechanical and adhesion properties. It could conform well to the human body's irregular contours without secondary dressing fixation, making it suitable for skin protection applications. The in vitro and in vivo experiments showed that the antioxidant properties conferred by MoS2 nanosheets enable SPM to effectively mitigate excessive ROS and reduce oxidative stress, thereby preventing radiation dermatitis caused by oxidative damage. Biosafety assessments indicated good biocompatibility of the composite hydrogel, suggesting SPM's practicality and potential as an external dressing for skin radiation protection.

Acute skin toxicity and self-management ability among Chinese breast cancer radiotherapy patients: a qualitative study.

OBJECTIVES: Radiation dermatitis is the most common reaction to radiotherapy, almost all breast cancer patients receive radiotherapy on an outpatient basis. Currently, there are no studies on the experience of radiation dermatitis and the ability to self-manage it. Therefore, we aimed to use qualitative approaches to gain a deeper understanding of the actual experiences and self-management ability in order to provide a reference for further improving the effectiveness of self-management and to optimize symptom management strategies. METHODS: A descriptive qualitative study was conducted using purposive sampling to select 17 breast cancer patients undergoing radiotherapy. Semi-structured interviews were conducted from September to November 2023. The Colaizzi seven-step analysis method was used to classify the data into summarized themes. RESULTS: Four themes were identified from the interview responses: (1) multiple self-reported skin symptoms in breast cancer patients with radiation dermatitis; (2) the multidimensional impact on patient's quality of life, especially pruritus, ulceration; (3) the ability to self-manage radiation dermatitis: strong mental toughness, positive response, and self-doubt; (4) challenges faced: concerns about radiotherapy side effects and recurrence, targeted symptom management and continuity of care after the radiotherapy. CONCLUSIONS: Healthcare professionals should consider patients' self-reported symptoms when assessing radiation dermatitis. For pruritus and pain, we can enhance precision symptom management to improve patients' quality of life. By utilizing information technology tools, we can increase breast cancer patients' ability and confidence in managing radiation dermatitis effectively while enhancing accurate symptom management during radiotherapy.

Seasonal Impact on Grade ≥2 Dermatitis in Patients With Breast Cancer Undergoing Radiotherapy: A Supplementary Analysis.

BACKGROUND/AIM: We investigated grade ≥2 dermatitis in patients irradiated for breast cancer. This study evaluated associations between dermatitis and the season during which radiotherapy took place. PATIENTS AND METHODS: Associations between the season and grade ≥2 dermatitis were retrospectively evaluated in 327 breast cancer patients. Seasons were March to May (spring), June to August (summer), September to November (autumn), and December to February (winter). Subgroup analyses were performed considering fractionation, radiation technique, treatment volume, radiation boost, and deep-inspiration breath-hold technique. Furthermore, warmer and cooler months were compared. RESULTS: The season had no significant impact on the rate of grade ≥2 dermatitis in the entire cohort (p=0.63) nor in the subgroup analyses (p-values between 0.17 and 0.82). No significant difference in rate was found between warm and cool months. CONCLUSION: Grade ≥2 dermatitis was not associated with the season during which radiotherapy was performed. This factor may not be important for stratification in prospective trials.

Dose-toxicity surface histogram-based prediction of radiation dermatitis severity and shape.

Objective.This study aimed to develop a new approach to predict radiation dermatitis (RD) by using the skin dose distribution in the actual area of RD occurrence to determine the predictive dose by grade.Approach.Twenty-three patients with head and neck cancer treated with volumetric modulated arc therapy were prospectively and retrospectively enrolled. A framework was developed to segment the RD occurrence area in skin photography by matching the skin surface image obtained using a 3D camera with the skin dose distribution. RD predictive doses were generated using the dose-toxicity surface histogram (DTH) calculated from the skin dose distribution within the segmented RD regions classified by severity. We then evaluated whether the developed DTH-based framework could visually predict RD grades and their occurrence areas and shapes according to severity.Main results.The developed framework successfully generated the DTH for three different RD severities: faint erythema (grade 1), dry desquamation (grade 2), and moist desquamation (grade 3); 48 DTHs were obtained from 23 patients: 23, 22, and 3 DTHs for grades 1, 2, and 3, respectively. The RD predictive doses determined using DTHs were 28.9 Gy, 38.1 Gy, and 54.3 Gy for grades 1, 2, and 3, respectively. The estimated RD occurrence area visualized by the DTH-based RD predictive dose showed acceptable agreement for all grades compared with the actual RD region in the patient. The predicted RD grade was accurate, except in two patients.Significance. The developed DTH-based framework can classify and determine RD predictive doses according to severity and visually predict the occurrence area and shape of different RD severities. The proposed approach can be used to predict the severity and shape of potential RD in patients and thus aid physicians in decision making.

Risk Prediction Model for Radiation-induced Dermatitis in Patients with Cervical Carcinoma Undergoing Chemoradiotherapy.

PURPOSE: Radiation-induced dermatitis (RD) is a common side-effect of therapeutic ionizing radiation that can severely affect patient quality of life. This study aimed to develop a risk prediction model for the occurrence of RD in patients with cervical carcinoma undergoing chemoradiotherapy using electronic medical records (EMRs). METHODS: Using EMRs, the clinical data of patients who underwent simultaneous radiotherapy and chemotherapy at a tertiary cancer hospital between 2017 and 2022 were retrospectively collected, and the patients were divided into two groups: a training group and a validation group. A predictive model was constructed to predict the development of RD in patients who underwent concurrent radiotherapy and chemotherapy for cervical cancer. Finally, the model's efficacy was validated using a receiver operating characteristic curve. RESULTS: The incidence of radiation dermatitis was 89.5% (560/626) in the entire cohort, 88.6% (388/438) in the training group, and 91.5% (172/188) in the experimental group. The nomogram was established based on the following factors: age, the days between the beginning and conclusion of radiotherapy, the serum albumin after chemoradiotherapy, the use of single or multiple drugs for concurrent chemotherapy, and the total dose of afterloading radiotherapy. Internal and external verification indicated that the model had good discriminatory ability. Overall, the model achieved an area under the receiver operating characteristic curve of .66. CONCLUSIONS: The risk of RD in patients with cervical carcinoma undergoing chemoradiotherapy is high. A risk prediction model can be developed for RD in cervical carcinoma patients undergoing chemoradiotherapy, based on over 5 years of EMR data from a tertiary cancer hospital.

Potential Single Nucleotide Polymorphisms markers for radiation dermatitis in head and neck cancer patients: a meta-analysis.

PURPOSE: To identify potential Single Nucleotide Polymorphisms (SNPs) of susceptibility for the development of acute radiation dermatitis in head and neck cancer patients, and also to verify the association between SNPs and the severity of RD. METHODS: This systematic review was reported according to the PRISMA guideline. The proportion meta-analysis was performed to identify the prevalence of genetic markers by geographical region and radiation dermatitis severity. The meta-analysis was performed to verify the association between genetic markers and RD severity. The certainty of the evidence was assessed by GRADE. RESULTS: Thirteen studies were included. The most prevalent SNPs were XRCC3 (rs861639) (36%), TGFß1 (rs1800469) (35%), and RAD51 (rs1801321) (34%). There are prevalence studies in Europe and Asia, with a similar prevalence for all SNPs (29-40%). The prevalence was higher in patients who developed radiation dermatitis ≤2 for any subtype of genes (75-76%). No SNP showed a statistically significant association with very low certainty of evidence. CONCLUSION: The most prevalent SNPs may be predictors of acute RD. The analysis of SNP before starting radiation therapy may be a promising method to predict the risk of developing radiation dermatitis and allow radiosensitive patients to have a customized treatment. This current review provides new research directions.

Understanding therapeutic radiographers' confidence in assessing, managing & teaching radiation induced skin reactions (RISR): A national survey in the UK.

INTRODUCTION: The standard toxicity tools adopted for assessing Radiation Induced Skin Reactions (RISR) do not currently reflect how skin changes occur across all skin tones. A one size fits all approach is adopted currently for RISR assessment. The aim of this study was to understand what evidence-based practice and RISR tools are being used across the therapeutic radiography workforce and the levels of confidence in using these tools. METHODS: A survey using Likert scales to assess confidence in RISR assessment and management was made available to 77 departments in the UK between August-November 2021. Descriptive statistics were used to understand respondents' confidence in assessing, managing, and teaching RISR between white, brown, and black skin tones; Fisher's exact test was used to assess the significance of differences between groups. RESULTS: Complete responses were received from 406 therapeutic radiographers. Radiation Therapy Oncology Group (RTOG) was the most used RISR assessment tool (58% of respondents n = 237). Most respondents (74.2% n = 303) reported use of locally produced patient information on skin care, rather than the Society and College of Radiographers evidence-based patient leaflets. Confidence in assessing and managing RISR in white skin was higher than that in brown and black skin. Similarly, confidence was higher in teaching of appropriate RISR assessment and management in white skin tones when compared to brown and black skin. CONCLUSION: White skin tones appear to be more confidently assessed and managed for RISR along with taught appropriate assessment and management, than brown and black skin tones in the sample of the workforce that responded. IMPLICATIONS FOR PRACTICE: A greater understanding of the reasons for these differences is required but this study aims to instigate change and positive growth within this area.

Clinically Significant Dermatitis During Adjuvant Radiotherapy for Invasive Breast Cancer.

BACKGROUND/AIM: Patients with breast cancer receiving adjuvant radiotherapy may experience grade ≥2 dermatitis. In the Interreg-project HeAT, a mobile application (app) reminding patients to perform skin care will be prospectively tested with the goal of decreasing clinically significant radiation dermatitis. This study aimed to identify the prevalence of grade ≥2 dermatitis and risk factors, required for designing the prospective trial. PATIENTS AND METHODS: In a retrospective study of 327 patients with breast cancer irradiated during 2022-2023, the prevalence of grade ≥2 dermatitis and 23 potential risk factors were investigated. RESULTS: The prevalence of grade ≥2 dermatitis was 31.2%. On multivariate analysis, it was significantly associated with chronic inflammatory disease (p=0.001), significant cardiovascular disease (p<0.001), smoking history >10 pack years (p<0.001), advanced T-stage (p=0.017), normo-fractionation (p<0.001), and radiation boost (p<0.001). CONCLUSION: The prevalence of grade ≥2 dermatitis and independent risk factors during adjuvant radiotherapy for invasive breast cancer were identified that contribute to improved patient care and the design of a prospective trial.

Radiation Recall Dermatitis With Bruton Tyrosine Kinase Inhibitor Therapy.

This case report describes a woman in her 70s with a history of breast cancer and chronic lymphocytic leukemia who presented with a painful rash of the bilateral chest extending onto the flanks.

Radiation Dermatitis: Radiation-Induced Effects on the Structural and Immunological Barrier Function of the Epidermis.

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.

Effectiveness of glutamine for the treatment of radiodermatitis in cancer patients: a meta-analysis of randomized controlled trials.

BACKGROUND: After receiving radiation therapy, 60%-95% of patients with cancer develop radiodermatitis, which causes pain, wound infection, and poor quality of life. Glutamine is a popular nutritional supplement for patients with cancer. Several studies examined the usefulness of glutamine for reducing radiodermatitis. However, there is still no consolidated evidence for clinical use. METHODS: We searched PubMed, Embase, Cochrane Library, CINAHL PLUS, and the China Knowledge Resource Integrated Database for the relevant literature published up to March 2023, without language restrictions. Two reviewers screened, filtered, and appraised these articles independently, and their data were pooled using a random-effects model. RESULTS: Five randomized controlled trials (RCTs) with 218 participants were analyzed. The incidence of radiodermatitis in the glutamine group (89/110) was significantly lower than in the placebo group (99/108; risk ratio [RR], 0.90; 95% CI, 0.81-1.00; p = 0.05; I2 = 7%). The incidence of moderate to severe radiodermatitis was significantly lower in the glutamine group than in the placebo group (RR, 0.49; 95% CI, 0.32-0.76; p = 0.001; I2 = 52%). Moreover, subgroup analysis demonstrated heterogeneity (I2 = 52%) for moderate to severe radiodermatitis, the risk of which might be significantly reduced by a glutamine dose of 20-30 g/day (RR, 0.60; 95% CI, 0.41-0.87; I2 = 0%). CONCLUSION: The meta-analysis indicate that glutamine might lead to a lower incidence of radiodermatitis, and that a glutamine dose of 20-30 g/day might decrease the incidence of moderate to severe dermatitis. Thus, the serious impact of radiodermatitis on treatment follow-up makes the clinical use of glutamine even more important. PROSPERO number: CRD42021254394.

Factors associated with the quality of life of women undergoing radiotherapy.

OBJECTIVE: To evaluate the skin characteristics and quality of life of patients with breast cancer undergoing radiotherapy. METHOD: Cross-sectional study conducted with 60 women. The classification scales of skin changes resulting from exposure to ionizing radiation (RTOG) and the validated versions in Portuguese of those that classified skin types (Fitzpatrick), symptoms (RISRAS) and quality of life (DLQI) were applied. in the period between December 2021 and October 2022. For data analysis, Fisher's Exact Test, Chi-Square and Asymptotic General Independence Test were used. RESULTS: 100% of patients had skin irritation. As the treatment progressed and the radiodermatitis appeared or worsened, there was a tendency for the intensity of signs and symptoms to increase, such as: sensitivity, discomfort or pain, itching, burning and heat, dry and wet desquamation, which may have impacted the quality of life and reflected in other aspects, such as: shopping activities or outings (p=0.0020), social activities or leisure activities (p=0.0420). CONCLUSION: Radiodermatitis is a common condition that affects women with breast cancer undergoing radiotherapy, skin characteristics and quality of life of patients affected during this treatment.