Computational Model Based on Optical Coherence Tomography (OCT) Skin Scanning to Identify and Quantify Acute Radiation Dermatitis (ARD): A Prospective Diagnostic Study.

BACKGROUND: acute radiation dermatitis (ARD) is the most widely reported radiotherapy-induced adverse event. Currently, there is no objective or reliable method to measure ARD. OBJECTIVE: our main objective was to identify and quantify the effects of radiotherapy with a computational model using optical coherence tomography (OCT) skin scanning. Secondary objectives included determining the ARD impact of different radiotherapeutic schemes and adjuvant topical therapies. METHODS: we conducted a prospective, single-center case series study in a tertiary referral center of patients with breast cancer who were eligible for whole breast radiotherapy (WBRT). RESULTS: a total of 39 women were included and distributed according to the radiotherapeutic schemes (15, 20, and 25 fractions). A computational model was designed to quantitatively analyze OCT findings. After radiotherapy, OCT scanning was more sensitive revealing vascularization changes in 84.6% of the patients (vs 69.2% of the patients with ARD by clinical examination). OCT quantified an increased vascularization at the end of WBRT (P < .05) and a decrease after 3 months (P = .032). Erythematous skin changes by OCT were more pronounced in the 25-fraction regime. CONCLUSION: an OCT computational model allowed for the identification and quantification of vascularization changes on irradiated skin, even in the absence of clinical ARD. This may allow the design of standardized protocols for ARD beyond the skin color of the patients involved.

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.

The effect of various interventions on the prevention of radiation dermatitis: a network meta-analysis.

OBJECTIVE: High doses of radiation, while effective at destroying tumor tissues, also result in radiation dermatitis (RD) at irradiated sites, which is one of the most common complications in cancer radiotherapy. Currently, no standardized protocols for the prevention and treatment of RD have been established in clinical practices, and severe RD can compromise treatment efficacy and reduce patients' quality of life. This systematic review and network meta-analysis (NMA) aims to compare the effectiveness of various interventions in preventing RD in patients. METHODS: As of June 2023, four databases, including PubMed, Embase, Web of Science, and the Cochrane Library, were searched, with a total of 19 interventions obtained for comparative analysis of their effectiveness in preventing RD. The Cochrane risk-of-bias tool was employed to screen literature, extract data, and appraise the quality of the studies by two researchers. Bayesian network meta-analysis (NMA) was conducted utilizing StataSE 15 and R 4.2.3. RESULTS: A total of 33 studies involving 4307 patients were included in this analysis. From the 33 studies, 19 interventions, encompassing Barrier Films and Dressings (BFD), Boron_Gel, Best supportive care, Corticosteroids_cream, Doxepin_cream, Eau Thermale Avèn_gel, Epidermal Growth Factor_cream, Hyaluronan_cream, Medicinal_Plants, Mineral_Oil, Olive oil and calcium hydroxide (OOCH), Photobiomodulation therapy, Recove_cream, Silicone_gel, Silver sulfadiazine (SSD), Timolol_Gel, Trolamine, VitD_Gel, and VitE_Gel, were retrieved and compared. The NMA results indicated that Hyaluronan_cream (SUCRA: 94.9%) was highly effective in preventing Grade 0/1 RD. Meanwhile, OOCH (SUCRA: 95.7%) demonstrated the most prominent effect in preventing ≥ Grade 2 RD. CONCLUSION: The study reveals that Hyaluronan_cream and OOCH are two promising treatments for the prevention of RD in patients undergoing radiotherapy. Future research might focus on validating the efficacy of these two therapies with large sample sizes and on identifying an optimal intervention strategy.

The need for a holistic guide to prevent and manage radiation dermatitis in patients' with breast cancer: a case report.

Background: Radiation therapy (RT) is often indicated in the treatment of breast cancer following breast conserving surgery or mastectomy, yet carries a 95% risk of radiation dermatitis (RD) of varying severity within 1 to 4 weeks of treatment. The burdens of RT include skin breakdown, pain, psychological distress, and functional challenges. Given limited patient education regarding the prevention and management of RD, a Clinician Guide and Evidence-based Skin Care Plan were developed to offer a holistic, patient-centered approach to care, with optimal RD prevention and management strategies to enhance patients' quality of life and survival. Case Description: M.R. (a pseudonym) was a 64-year-old Caucasian woman, diagnosed with invasive adenocarcinoma of the left breast, underwent a lumpectomy with a positive sentinel node biopsy. Within 4 weeks of surgery, she received RT, 5 days a week for 6 weeks. Within 1 week, the skin of her breast and axilla was red and hyperpigmented with skin damage progressing to dryness, itching and flaking. At this point, she asked the Radiology team for a skin care protocol to prevent or reduce RD, but limited information was provided. Ultimately, her skin cracked, blistered and crusted, with the development of a skin infection. She expressed the significant impact on her physical, emotional and functional well-being, and lamented about the shortfalls in her care, specifically the limited availability of information to prevent and reduce RD. Conclusions: In order to prevent and minimize RD and to promote health, this case study highlights the need for an all-encompassing, patient-centered approach to care, which may be achievable by implementation of a Clinician Guide and an Evidence-based Skin Care Plan. Highlighted in the Clinician Guide are the importance of developing a trustworthy patient-clinician relationship, emotional support, social support, education, weekly physical assessments, assessment of overall adjustment to a cancer diagnosis and treatment, promotion of patient engagement and self-care, reinforcement of healthy lifestyles, and patient adherence to the Evidence-based Skin Care Plan during RT. These strategies are expected to decrease the physical, mental, and functional difficulties associated with RT, avoid treatment delays or discontinuation, and increase the likelihood of disease-free survival and quality of life.

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.

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.

18ß-glycyrrhetinic acid alleviates radiation-induced skin injury by activating the Nrf2/HO-1 signaling pathway.

Radiation-induced skin injury is a common side effect of radiotherapy, but there are few therapeutic drugs available for prevention or treatment. In this study, we demonstrate that 18ß-Glycyrrhetinic acid (18ß-GA), a bioactive component derived from Glycyrrhiza glabra, substantially reduces the accumulation of reactive oxygen species (ROS) and inhibits apoptosis in HaCaT cells after ionizing radiation (IR), thereby mitigating radiation-induced skin injury. Mechanistically, 18ß-GA promotes the nuclear import of Nrf2, leading to activation of the Nrf2/HO-1 signaling pathway in response to IR. Importantly, Nrf2 silencing increases cell apoptosis and reverse the protective effect of 18ß-GA on radiation-induced skin injury. Furthermore, 18ß-GA preserves skin tissue structure after irradiation, inhibits inflammatory cell infiltration, and alleviates radiation dermatitis. In conclusion, our results suggest that 18ß-GA reduces intracellular ROS production and apoptosis by activating the Nrf2/HO-1 signaling pathway, leading to amelioration of radiation dermatitis.

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.

Computational Model Based on Optical Coherence Tomography (OCT) Skin Scanning to Identify and Quantify Acute Radiation Dermatitis (ARD): A Prospective Diagnostic Study.

BACKGROUND: Acute radiation dermatitis (ARD) is the most widely reported radiotherapy-induced adverse event. Currently, there is no objective or reliable method to measure ARD. OBJECTIVE: Our main objective was to identify and quantify the effects of radiotherapy with a computational model using optical coherence tomography (OCT) skin scanning. Secondary objectives included determining the ARD impact of different radiotherapeutic schemes and adjuvant topical therapies. METHODS: We conducted a prospective, single-center case series study in a tertiary referral center of patients with breast cancer who were eligible for whole breast radiotherapy (WBRT). RESULTS: A total of 39 women were included and distributed according to the radiotherapeutic schemes (15, 20, and 25 fractions). A computational model was designed to quantitatively analyze OCT findings. After radiotherapy, OCT scanning was more sensitive revealing vascularization changes in 84.6% of the patients (vs 69.2% of the patients with ARD by clinical examination). OCT quantified an increased vascularization at the end of WBRT (P<.05) and a decrease after 3 months (P=.032). Erythematous skin changes by OCT were more pronounced in the 25-fraction regime. CONCLUSION: An OCT computational model allowed for the identification and quantification of vascularization changes on irradiated skin, even in the absence of clinical ARD. This may allow the design of standardized protocols for ARD beyond the skin color of the patients involved.

A topical BRAF inhibitor (LUT-014) for treatment of radiodermatitis among women with breast cancer.

Background: Modern radiotherapy is associated with dermatitis (RD) in approximately one-third of patients treated for breast cancer. There is currently no standard for treating RD. Objective: The objective of this study was to determine whether LUT014, a topical BRAF inhibitor which paradoxically activates mitogen-activated protein kinase, can safely improve RD. Methods: A phase I/II study was designed to first follow a small cohort of women with grade 2 RD regarding toxicity and response. Then, 20 patients were randomized to compare LUT014 to "vehicle" relative to safety and response (measured with common terminology criteria for adverse events, Dermatology Life Quality Index). Results: No substantial toxicity (eg, 0 serious adverse event) was associated with LUT014. All 8 women receiving LUT014 achieved treatment success (5-point Dermatology Life Quality Index reduction at day 14) compared to 73% (8/11) on the placebo arm (P = .591). The time to complete recovery was shorter in the treatment arm. Limitations: The sample size was limited. Only 2 hospitals were included. Conclusions: Topical LU014 is tolerable and may be efficacious for grade 2 RD.

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.

Analysis of Individualized Silicone Rubber Bolus Using Fan Beam Computed Tomography in Postmastectomy Radiotherapy: A Dosimetric Evaluation and Skin Acute Radiation Dermatitis Survey.

Objective: To investigate the dosimetric effects of using individualized silicone rubber (SR) bolus on the target area and organs at risk (OARs) during postmastectomy radiotherapy (PMRT), as well as evaluate skin acute radiation dermatitis (ARD). Methods: A retrospective study was performed on 30 patients with breast cancer. Each patient was prepared with an individualized SR bolus of 3 mm thickness. Fan-beam computed tomography (FBCT) was performed at the first and second fractions, and then once a week for a total of 5 times. Dosimetric metrics such as homogeneity index (HI), conformity index (CI), skin dose (SD), and OARs including the heart, lungs, and spinal cord were compared between the original plan and the FBCTs. The acute side effects were recorded. Results: In targets' dosimetric metrics, there were no significant differences in Dmean and V105% between planning computed tomography (CT) and actual treatments (P > .05), while the differences in D95%, V95%, HI, and CI were statistically significant (P < .05). In OARs, there were no significant differences between the Dmean, V5, and V20 of the affected lung, V5 of the heart and Dmax of the spinal cord (P > .05) except the V30 of affected lung, which was slightly lower than the planning CT (P < .05). In SD, both Dmax and Dmean in actual treatments were increased than plan A, and the difference was statistically significant (P < .05), while the skin-V20 and skin-V30 has no difference. Among the 30 patients, only one patient had no skin ARD, and 5 patients developed ARD of grade 2, while the remaining 24 patients were grade 1. Conclusion: The OR bolus showed good anastomoses and high interfraction reproducibility with the chest wall, and did not cause deformation during irradiation. It ensured accurate dose delivery of the target and OARs during the treatment, which may increase SD by over 101%. In this study, no cases of grade 3 skin ARD were observed. However, the potential of using OR bolus to reduce grade 1 and 2 skin ARD warrants further investigation with a larger sample size.

Photobiomodulation CME part II: Clinical applications in dermatology.

Photobiomodulation (PBM) is an emerging treatment modality in dermatology with increasing office and home-based use. PBM is the use of various light sources in the red light (620-700 nm) and near-infrared (700-1440 nm) spectrum as a form of light therapy. PBM is often administered through low-level lasers or light-emitting diodes. Studies show that PBM can be used effectively to treat conditions secondary to cancer therapies, alopecia, ulcers, herpes simplex virus, acne, skin rejuvenation, wounds, and scars. PBM offers patients many benefits compared to other treatments. It is noninvasive, cost-effective, convenient for patients, and offers a favorable safety profile. PBM can be used as an alternative or adjuvant to other treatment modalities including pharmacotherapy. It is important for dermatologists to gain a better clinical understanding of PBM for in-office administration and to counsel patients on proper application for home-use devices to best manage safety and expectations as this technology develops. PBM wavelengths can induce varied biological effects in diverse skin types, races, and ethnicities; therefore, it is also important for dermatologists to properly counsel their skin of color patients who undergo PBM treatments. Future clinical trials are necessary to produce standardized recommendations across conditions and skin types.

Vitamin D3 and its Potential to Ameliorate Chemical and Radiation-Induced Skin Injury During Cancer Therapy.

Skin injury and dermatitis are common complications following chemotherapy and radiation administration for cancer treatment. Symptomatic relief of these complications is limited to slow-acting therapies and often results in holding or modifying cancer therapy that may impact patient outcomes. The off-label use of oral high dose vitamin D3 has demonstrated rapid clinical improvement in skin inflammation and swelling in both chemotherapy and radiation-induced injury. Furthermore, vitamin D3 has been shown to downregulate pro-inflammatory pathways and cytokines, including NFkB, and CCL2, as well as CCL20, which are not only involved in tissue injury, but may confer resistance to cancer treatment. In this paper, we discuss 2 patients with acute radiation dermatitis and acute radiation recall dermatitis following chemotherapy who received 50 000 - 100 000 IU of oral high dose vitamin D3 with improvement in their symptoms. These findings may indicate the potential use of vitamin D as a therapeutic intervention and future target for studying skin healing following chemotherapy and/ or radiation-induced cutaneous toxicity.

Patient-reported experience with the use of Mepitel Film for prevention of acute radiation dermatitis in breast cancer.

BACKGROUND AND PURPOSE: Mepitel Film (MF) has been demonstrated to reduce the severity of radiation dermatitis (RD) in patients receiving breast cancer radiotherapy (RT). The objective of this study was to characterize patient-reported experience with MF use, including its impact on daily activities and wellbeing. MATERIALS AND METHODS: This single-institution study analyzed anonymized responses to a questionnaire completed by patients who used MF for the prevention of RD during breast cancer RT. RESULTS: Of the 254 patients contacted, 192 patients completed the survey. Most patients disagreed or strongly disagreed that MF limited their ability to perform their daily activities, including household chores (88%, n = 169/191), their ability to work (83%, n = 157/189), or their ability to sleep (85%, n = 163/191). Furthermore, patients agreed or strongly agreed MF was comfortable on their skin (67%, n = 126/189) and protected their skin from rubbing against clothing (86%, n = 161/188). Some patients agreed or strongly agreed that MF affected their ability to shower (31%, n = 50/162), wear bras (28%, n = 51/185), and impacted their level of pruritus (35%, n = 67/189). However, most patients agreed or strongly agreed that their overall experience with MF was positive (92%, n = 173/189) and would recommend MF to a friend undergoing breast cancer RT (88%, n = 166/188). CONCLUSION: MF use is associated with positive patient-reported experience during breast RT with minimal impact on daily activities.

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.