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.

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.

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.

Comparison of the efficacy among different interventions for radiodermatitis: A Bayesian network meta­analysis of randomized controlled trials.

BACKGROUND: Radiation dermatitis (RD) is a prevalent and difficult-to-manage consequence of radiation therapy (RT). A variety of interventions have been proven effective in preventing and treating RD. However, the optimal approach remains unclear. This network meta-analysis (NMA) conducted a comparison and ranking of the effectiveness and patient-reported outcomes (PROs) of the interventions currently utilized in RD. METHODS: PubMed, Web of Science, Embase, and Cochrane Library were searched to identify pertinent randomized controlled trials (RCTs) focused on the prevention and treatment of RD. The primary outcome measures included the incidence of grade≥2 RD (i.e., percentage of moist desquamation) and RD score. The secondary outcome measures encompassed patients' subjective assessment scores of pains, itching and burning sensations. RESULTS: Our meta-analysis encompassed 42 studies and 4884 participants. Regarding the primary outcomes, photobiomodulation treatment (PBMT) ranked first in surface under curve cumulative ranking area (SUCRA:0.92) for reducing the incidence of grade≥2 RD. It demonstrated a significant difference when compared to Trolamine (OR 0.18,95%CrI 0.09-0.33) and Xonrid® (OR 0.28,95%CrI 0.12-0.66). Mepitelfilm (SUCRA: 0.98) achieved the highest rank in reducing the RD score, demonstrating superiority over StrataXRT® (MD -0.89, 95% CrI -1.49, -0.29). Henna (SUCRA: 0.89) demonstrated the highest effectiveness in providing pain relief, with a significant difference compared to Hydrofilm (MD -0.44, 95% CrI -0.84, -0.04) and Mepitelfilm (MD -0.55, 95% CrI -0.91, -0.19). Hydrofilm (SUCRA: 0.84) exhibited the fewest itching sensations, demonstrating superiority over Mepitelfilm (MD -0.50, 95% CrI -0.84, -0.17). No statistically significant difference was observed among various interventions in the assessment of burning sensations. CONCLUSION: PBMT and Mepitelfilm demonstrated better efficacy in reducing the incidence of grade≥2 RD and RD score, respectively. In terms of PROs, Henna and Hydrofilm had fewer complaints in pain and itching sensations, respectively. However, studies with larger sample size on different interventions are warranted in the future. TRIAL REGISTRATION: PROSPERO registration number CRD42023428598.

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 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.

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.

CSMed® wound dressing for prophylaxis and management of radiation dermatitis in breast and head-neck cancer patients: a single hospital prospective clinical trial.

PURPOSE: CSMed® wound dressing, a dressing with various herb extracts, was tested for its therapeutic effect in radiation dermatitis of breast and head-and-neck cancer patients. METHODS: This study included 20 breast cancer patients and 10 head-and-neck cancer patients. Half of the irradiated area was covered with CSMed® and the other half was under routine treatment. The severity of radiation dermatitis was evaluated with radiation therapy oncology group (RTOG) grade throughout the treatment and the follow-up period. The RTOG grade between the dressed and undressed area were compared to illustrate the therapeutic effect of CSMed® dressing. RESULTS: The results showed that CSMed® dressed area had significant lower RTOG score at 3-7 weeks and final record during the treatment, and 1-3 weeks during follow-up than undressed area. CONCLUSIONS: This indicated that CSMed® can delay the onset, reduce the severity, and enhance healing of radiation dermatitis. CSMed® can be used for prophylaxis and management of radiation dermatitis.

Association of Skin Microbiome Dynamics With Radiodermatitis in Patients With Breast Cancer.

Importance: The interindividual differences in severity of acute radiation dermatitis are not well understood. To date, the pathomechanism and interplay of microbiome and radiodermatitis before and during treatment remain largely unknown. Objective: To assess the association of skin microbiome baseline composition and dynamics with severity of radiodermatitis in patients undergoing adjuvant radiotherapy for breast cancer. Design, Setting, and Participants: A longitudinal prospective pilot observational study was conducted between January 2017 and January 2019. Sequencing results were received in March 2021, and the data were analyzed from August 2021 to March 2023. This study was performed at an urban academic university cancer center. A total of 21 female patients with breast cancer after surgery were consecutively approached, of which 1 patient withdrew consent before the study started. Exposure: Adjuvant radiotherapy for breast cancer for 7 weeks. Main Outcomes and Measures: The main outcome was the association of baseline skin microbiome composition and its dynamics with the severity of radiodermatitis. A total of 360 skin microbiome samples from patients were analyzed, taken before, during, and after radiotherapy, from both the treated and contralateral healthy sides. The skin microbiome samples were analyzed using 16S (V1-V3) amplicon sequencing and quantitative polymerase chain reaction bacterial enumeration. Results: Twenty female patients with breast cancer after surgery who underwent radiotherapy enrolled in the study had a median (range) age of 61 (37-81) years. The median (range) body mass index of the patients was 24.2 (17.6-38.4). The 16S sequencing revealed that low (<5%) relative abundance of commensal skin bacteria (Staphylococcus epidermidis, Staphylococcus hominis, Cutibacterium acnes) at baseline composition was associated with the development of severe radiodermatitis with an accuracy of 100% (sensitivity and specificity of 100%, P < .001). Furthermore, in patients with severe radiodermatitis, quantitative polymerase chain reaction bacterial enumeration revealed a general non-species-specific overgrowth of skin bacterial load before the onset of severe symptoms. Subsequently, the abundance of commensal bacteria increased in severe radiodermatitis, coinciding with a decline in total bacterial load. Conclusions and Relevance: The findings of this observational study indicated a potential mechanism associated with the skin microbiome for the pathogenesis of severe radiodermatitis, which may be a useful biomarker for personalized prevention of radiodermatitis in patients undergoing adjuvant radiotherapy for breast cancer.

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.

INFRARED THERMAL IMAGING CONTROL OF RADIATION DERMATITIS DYNAMICS.

BACKGROUND: Radiation-induced dermatitis impairs the quality of life of cancer patients and may lead to the need of interrupting radiotherapy. The grade of dermatitis is subjectively assessed by the visual examination. There is an urgent need for both objective and quantitative methods for assessing the current grade of dermatitis and predicting its severity at an early stage of radiotherapy. AIM: The aim of the study was to evaluate the advantages and limitations of infrared thermography for monitoring the current level of radiation-induced dermatitis and predicting its severity by quantitative analysis of the thermal field dynamics in the irradiated zone. MATERIALS AND METHODS: 30 adult patients were examined by infrared thermography during the course of 2D conventional radiotherapy for malignant tumors of various types and localizations. Our approach for quantifying the thermal field caused by dermatitis alone was applied. A statistical (correlation and ROC) analysis was performed. RESULTS: Dermatitis of varying severity was observed in 100% of the patients studied. The dynamics in the intensity of the anomalous thermal fields in the irradiated zone correlated with the dynamics of dermatitis grades, excluding the case of a radiosensitive tumor (correlation coefficient 0.74÷0.84). It was found that the maximum toxicity (dermatitis grade ≥ 3) develops in patients who how significant hyperthermia in the area of interest (≥ 0.7 °C) at an early stage of radiotherapy. The ROC analysis demonstrated the "good quality" of the prognosis method (AUC = 0.871). CONCLUSIONS: The non-invasive and cheap infrared thermography is a suitable tool for objective quantitative monitoring the current dermatitis grade during radiotherapy as well as predicting its severity for any tumor location.

Randomized Pilot Study of a Keratin-based Topical Cream for Radiation Dermatitis in Breast Cancer Patients.

Purpose: Radiotherapy (RT) is commonly used in the treatment of breast cancer and often, despite advances in fractionated dosing schedules, produces undesirable skin toxicity. The purpose of this study was to evaluate the feasibility of using a keratin-based topical cream, KeraStat® Cream (KC; KeraNetics, Inc., Winston Salem, NC, USA) to manage the symptoms of radiation dermatitis (RD) in breast cancer patients undergoing RT. Materials and Methods: A total of 24 subjects were enrolled on this single-center, randomized, open-label study. Participants were randomly assigned to KC or standard of care (SOC, patient's choice of a variety of readily available creams or moisturizers). Patients were asked to apply the assigned treatment to the irradiated area twice daily, beginning with day 1 of RT, through 30 days post-RT. The primary outcome was compliance of use. Secondary outcomes included safety and tolerability of KC, as well as RD severity assessed using the Radiation Therapy Oncology Group (RTOG) scale and the patient-reported Dermatology Life Quality Index (DLQI). Results: All subjects in the KC group were assessed as compliant with no adverse events. The rate of RTOG Grade 2 RD was lower in the KC group (30.8%) compared to the SOC group (54.5%, P = .408). At the final RT visit, the mean RTOG RD score was lower in the KC group (1.0) versus the SOC group (1.4). Similarly, patient-reported quality of life measured by the DLQI at the end of RT was improved in the KC group (mean 4.25, small effect) versus the SOC group (mean 6.18, moderate effect, P = .412). Conclusions: KC was safe and well tolerated with no adverse events. Though efficacy measures were not powered to draw definitive conclusions, trends and clinical assessments suggest that there is a benefit of using KC compared to SOC for breast cancer patients treated with RT, and a larger powered study for efficacy is warranted. Trial Registry: This clinical trial is registered as NCT03374995 titled KeraStat(R) Cream for Radiation Dermatitis.