Validation of the Skin Symptom Assessment (SSA) questionnaire for the evaluation of radiation dermatitis in breast cancer patients.

PURPOSE: Radiation dermatitis (RD) is a painful side effect of radiation therapy (RT). The objective of this analysis was to investigate the validity and reliability of the Skin Symptom Assessment (SSA) questionnaire in evaluating the severity of patient- and clinician-reported outcomes for RD in breast cancer patients by comparing it to a validated assessment tool, the Radiation-Induced Skin Reaction Assessment Scale (RISRAS) questionnaire. METHODS: This study compared patient and clinician-reported outcomes for RD from previous clinical trials conducted in a Canadian cancer centre. The analysis included 376 and 38 patients in the two trials using Mepitel Film (doi.org/10.1200) and StrataXRT (clinicaltrials.gov identifier: NCT05594498), respectively. Patients in both studies completed the SSA and RISRAS questionnaires at baseline, 2-weeks post-RT, and 3 months after completion of RT. Clinician SSA and RISRAS assessments were collected at baseline and 2-weeks post-RT. These time points were analyzed longitudinally to investigate the SSA's validity in RD symptom assessment. RESULTS: The majority of patient-reported items on the SSA and RISRAS assessments demonstrated positive significant associations between symptoms of itchiness, between pain/soreness and pain/discomfort, and between blistering or erythema with burning sensation items. All items in the clinician-reported SSA and clinician component of RISRAS showed positive statistical significance between items measuring erythema, pigmentation or edema with dry desquamation, and blistering/peeling with moist desquamation. CONCLUSIONS: The SSA has been validated for assessing patient- and clinician-reported symptoms of RD accurately as outcomes correlate well with the previously validated RISRAS assessment.

Acute radiation skin injury in stage III-IV head and neck cancer: scale correlates and predictive model.

PURPOSE: Active radiation skin injury (ARSI) has the highest incidence of acute adverse reactions caused by radiotherapy (RT) in patients with head and neck cancer (HNC). This study aimed to screen risk factors that can facilitate the identification of HNC patients at high risk of ARSI. METHODS: Data from 255 stage III-IV HNC patients who underwent intensity-modulated radiation therapy (IMRT) were collected. The data from our medical records, including clinical characteristics and hematological indices before RT, were retrospectively collected and arranged. The Common Terminology Criteria for Adverse Events Criteria (CTCAE), Radiation Therapy Oncology Group Criteria (RTOG), World Health Organization Criteria (WHO), Oncology Nursing Society (ONS), Acute Radiation Dermatitis Graduation Scale, Douglas & Fowler and Radiation Dermatitis Severity Scale (RDSS) were used to assess ARSI. Of these, CTCAE was used for further analysis. Binary logistic regression analyses were used to identity risk factors. To establish the correction between each risk factor and the ARSI score, the odds ratio (OR) and 95% confidence interval (CI) were computed. RESULTS: The assessment results of the CTCAE with RTOG, WHO, ONS, Graduation Scale, Douglas & Fowler and RDSS have good consistency. After radiotherapy, 18.4% of patients had at least 3 (3 +) grade ARSI. Multivariate logistic regression analysis revealed that the KPS score, blood glucose level, white blood cell count, and plasma free thyroxine (FT4) concentration were independent risk factors for 3 + grade ARSI. A nomogram was constructed on the basis of these risk factors, which demonstrated good predictive power according to the area under the ROC curve (AUC). The satisfactory consistency and clinical efficacy of the nomogram were confirmed by calibration curves and decision curve analysis (DCA). CONCLUSION: A low KPS score, high blood glucose level, high white blood cell count, and high thyroid hormone prior to radiotherapy for stage III-IV HNC are independent risk factors for grade 3 + RSI.

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.

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.

Efficacy of an aloe vera, chamomile, and thyme cosmetic cream for the prophylaxis and treatment of mild dermatitis induced by radiation therapy in breast cancer patients: a controlled clinical trial (Alantel Trials).

BACKGROUND: Dermatitis is a skin condition caused by multiple causes, including radiotherapy treatment. Pharmacological treatments can become chronic and are not exempt from side effects. The latest recommendations of the American Academy of Dermatology establish the use of natural, nourishing, and moisturizing cosmetic products as prevention and the first therapeutic step for dermatitis. Alantel® is a cream developed to reduce redness and irritation, promote the local immune system, combat immunosenescence, and promote the healing of epidermal lesions. The objective was to evaluate the effect of a cream (Alantel) based on natural products at high concentrations for the preventive and curative treatment (at early stages) of radiation-induced dermatitis in patients with breast cancer. METHODS: Our protocol is an experimental, prospective, triple-blind, multicenter, controlled clinical trial with two parallel arms. The experimental group will be treated with Alantel, while the control group will receive another moisturizing cream. Radiotherapy oncology professionals will recruit a total of 88 patients (44 per comparison group) with breast cancer who will receive radiotherapy oncology treatment for 15 days, and they will be randomly allocated to the experimental or control group. Selected patients will be followed up for four visits by primary care physicians for up to 1 week after completion of radiotherapy. The main study variable will be the incidence rate of mild post-radiation dermatitis. An intention-to-treat analysis will be performed, applying a comparison test for independent means and proportions. A bivariate and multivariate analysis will also be developed to check the treatment effect, adjusting for predictive sociodemographic and clinical variables. DISCUSSION: By carrying out this clinical trial, it is expected to verify that Alantel cream, based on natural products at high concentrations, has advantages over a moisturizing cream for the preventive and curative treatment of RD in patients with breast cancer. The COVID-19 pandemic has been influenced by delaying the start of the study. One of the main limitations of this study will be the time required to recruit the patients from the planned sample, given that the selection criteria are restrictive and, although the study is multicenter, recruitment will be coordinated through a single service on radiotherapy oncology. TRIAL REGISTRATION: ClinicalTrials.gov NCT04116151 . Registered on 4 October 2019.

Radiation Dermatitis and Pneumonitis in Patients Irradiated for Breast Cancer.

BACKGROUND/AIM: Adjuvant radiotherapy (RT) for breast cancer can be associated with acute dermatitis (ARD) and pneumonitis (RP). Prevalence and risk factors were characterized. PATIENTS AND METHODS: This study included 489 breast cancer patients receiving adjuvant RT with conventional fractionation (CF) ± sequential or simultaneous integrated boost, or hypo-fractionation ± sequential boost. RT-regimen and 15 characteristics were investigated for grade ≥2 ARD and RP. RESULTS: Prevalence of grade ≥2 ARD and RP was 25.3% and 2.5%, respectively. On univariate analyses, ARD was significantly associated with CF and radiation boost (p<0.0001), age ≤60 years (p=0.008), Ki-67 ≥15% (p=0.012), and systemic treatment (p=0.002). On multivariate analysis, RT-regimen (p<0.0001) and age (p=0.009) were associated with ARD. Chronic inflammatory disease was significantly associated with RP on univariate (p=0.007) and multivariate (p=0.016) analyses. CONCLUSION: Risk factors for grade ≥2 ARD and RP were determined that may help identify patients who require closer monitoring during and after RT.

Clinical Effect of Moisturized Skin Care on Radiation Dermatitis of Head and Neck Cancer.

BACKGROUND/AIM: Radiation therapy (RT) for head and neck cancer may cause severe radiation dermatitis (RD) resulting in RT interruption and affecting disease control. A few studies address skin moisture changes during RT for head and neck cancer. The purpose of this study was to explore the effect of moisturized skin care (MSC) on severity of RD. PATIENTS AND METHODS: The study includes newly diagnosed head and neck cancer patients undergoing RT. Participants were divided into MSC group and routine skin care (RSC) group based on patient's preferred decision. Skin moisture in the four quadrants of the neck was measured weekly before and after RT. RD was assessed with the Radiation Induced Skin Reaction Assessment Scale (RISRAS) and the Radiation Therapy Oncology Group (RTOG) acute skin toxicity grading criteria. RESULTS: A total of 54 patients were enrolled, of which 49 patients were suitable for the statistical analysis. There was a statistically significant difference in the RISRAS total score since the 5th week after RT between the groups. The severity of RD was less (B=0.814, p=0.021) and the onset was later (B=-0.384, p=0.006) in the MSC group when compared to the RSC group. Skin moisture decreased with cumulative radiation dose. In the upper neck, the MSC group had a slower rate of skin moisture decrease compared to the RSC group (right upper neck: B=0.935, p=0.007; left upper neck: B=0.93, p=0.018). CONCLUSION: MSC can effectively reduce the severity and delay the onset of RD, while slows down skin moisture decrease during RT.

A novel, multi-active emollient for the prevention of acute radiation dermatitis in breast cancer patients: a randomized clinical trial.

PURPOSE: To investigate the efficacy of a novel, multi-active emollient in preventing and managing acute radiation dermatitis (ARD) in breast cancer patients undergoing moderate hypofractionated (HF) radiotherapy (RT) compared to standard of care. METHODSA: A monocentric, open-label, randomized clinical trial (RCT) with breast cancer patients receiving moderate HF (dose: 40.05-55.86 Gy, fractions: 15-21) was conducted between January 2022 and May 2023. The experimental group received the novel emollient, while the control group received the standard skin care. Patients applied the skin care products twice daily during the complete RT course. The primary outcome was the severity of ARD at the final RT session measured by the modified Radiation Therapy Oncology Group (RTOG) criteria. Secondary outcomes included patient symptoms, quality of life (QoL), and treatment satisfaction. RESULTS: A total of 100 patients with 50 patients per group were enrolled. In the control group, 50% of the patients developed RTOG grade 1 ARD and 48% grade 2 or higher, while in the experimental group, the severity of ARD was significantly lower with 82% grade 1 and 16% grade 2 ARD (P = .013, χ2-test). The frequency and severity of xerosis were significantly lower in the experimental compared to the control group (Ps ≤ .036, Mann Whiney U test). The impact of ARD on the QoL was low, and treatment satisfaction was high in both groups, with no significant difference. CONCLUSION: This RCT shows that the novel, multi-active emollient significantly reduced the ARD RTOG grade. Research in a more diverse patient population is warranted. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04929808 (11/06/2021).

A New Approach to Quantify and Grade Radiation Dermatitis Using Deep-Learning Segmentation in Skin Photographs.

AIMS: Objective evaluation of radiation dermatitis is important for analysing the correlation between the severity of radiation dermatitis and dose distribution in clinical practice and for reliable reporting in clinical trials. We developed a novel radiation dermatitis segmentation system based on convolutional neural networks (CNNs) to consistently evaluate radiation dermatitis. MATERIALS AND METHODS: The radiation dermatitis segmentation system is designed to segment the radiation dermatitis occurrence area using skin photographs and skin-dose distribution. A CNN architecture with a dilated convolution layer and skip connection was designed to estimate the radiation dermatitis area. Seventy-three skin photographs obtained from patients undergoing radiotherapy were collected for training and testing. The ground truth of radiation dermatitis segmentation is manually delineated from the skin photograph by an experienced radiation oncologist and medical physicist. We converted the skin photographs to RGB (red-green-blue) and CIELAB (lightness (L∗), red-green (a∗) and blue-yellow (b∗)) colour information and trained the network to segment faint and severe radiation dermatitis using three different input combinations: RGB, RGB + CIELAB (RGBLAB) and RGB + CIELAB + skin-dose distribution (RGBLAB_D). The proposed system was evaluated using the Dice similarity coefficient (DSC), sensitivity, specificity and normalised Matthews correlation coefficient (nMCC). A paired t-test was used to compare the results of different segmentation performances. RESULTS: Optimal data composition was observed in the network trained for radiation dermatitis segmentation using skin photographs and skin-dose distribution. The average DSC, sensitivity, specificity and nMCC values of RGBLAB_D were 0.62, 0.61, 0.91 and 0.77, respectively, in faint radiation dermatitis, and 0.69, 0.78, 0.96 and 0.83, respectively, in severe radiation dermatitis. CONCLUSION: Our study showed that CNN-based radiation dermatitis segmentation in skin photographs of patients undergoing radiotherapy can describe radiation dermatitis severity and pattern. Our study could aid in objectifying the radiation dermatitis grading and analysing the reliable correlation between dosimetric factors and the morphology of radiation dermatitis.

Chronic radiation dermatitis induced by cardiac catheterization: a case report and literature review.

Fluoroscopy-induced chronic radiation dermatitis (FICRD) is an uncommon but increasing complication that is challenging to diagnose due to its varied symptoms and delayed onset, usually from months to years after radiation exposure. For patients undergoing cardiac catheterization, high-risk factors for radiodermatitis include obesity, the presence of complex or chronic total occlusion lesions, the use of a fixed large beam angulation, and a procedure time of more than 2 hours. We present an individual with FICRD that had an indurated plaque on his back for 7 years to familiarize physicians with high-risk groups and early recognition of the disease.

Radiation recall dermatitis: A review of the literature.

PURPOSE/OBJECTIVES: Radiation recall dermatitis (RRD) is a skin reaction limited to an area of prior radiation triggered by the subsequent introduction of systemic therapy. To characterize RRD, we conducted a literature search, summarized RRD features, and compared the most common drug classes implicated in this phenomenon. MATERIALS/METHODS: PubMed, Embase, Scopus, Web of Science, and Cochrane DBSR databases were queried through July 1, 2019 using key words: radiation recall, RRD, and radiodermatitis (limited to humans and English language). Studies included case reports in which patients treated with radiotherapy were initiated on a new line of systemic therapy and subsequently developed a skin reaction in the irradiated area. RRD cases were organized by whether RRD occurred after a single drug or multiple drug administration. RESULTS: One-hundred fifteen studies representing 129 RRD cases (96 single-drug RRD, 33 multi-drug) were included. Sixty-three drugs were associated with RRD. Docetaxel (22) and gemcitabine (18) were the two drugs most commonly associated with RRD. Breast cancer (69 cases) was the most commonly associated tumor type. For single-drug RRD, the median radiotherapy dose was 45.0 Gy (range, 30.0-63.2 Gy). The median time from radiotherapy to drug exposure, time from drug exposure to RRD and time to significant improvement was 8 weeks (range, 2-132 weeks), 5 days (range, 2-56 days), and 14 days (range, 7-49 days), respectively. Variables significantly associated with grade ≥2 toxicity were docetaxel (P = 0.04) and non-antifolate antimetabolite (P = 0.05). The only variable significantly associated with grade ≥3 toxicity was capecitabine (P = 0.04). CONCLUSIONS: RRD is a complex toxicity that can occur after a wide range of radiotherapy doses and many different systemic agents. Most commonly, it presents in patients diagnosed with breast cancer and after administration of a taxane or antimetabolite medication. RRD treatment generally consists of corticosteroids with consideration of antibiotics if superinfection is suspected. Drug re-challenge may be considered after RRD if the initial reaction was of mild intensity.

Deep Learning-Based Automatic Assessment of Radiation Dermatitis in Patients With Nasopharyngeal Carcinoma.

PURPOSE: Radiation dermatitis (RD) is a common, unpleasant side effect of patients receiving radiation therapy. In clinical practice, the severity of RD is graded manually through visual inspection, which is labor intensive and often leads to large interrater variations. To overcome these shortcomings, this study aimed to develop an automatic RD assessment based on deep learning (DL) techniques that could efficiently assist the RD severity classification in clinical application. METHODS AND MATERIALS: A total of 1205 photographs of the head and neck region were collected from patients with nasopharyngeal carcinoma (NPC) undergoing radiation therapy. The severity of RD in these photographs was graded by 5 qualified assessors based on the Radiation Therapy Oncology Group guidance. An end-to-end RD grading framework was developed by combining a DL-based segmentation network and a DL-based RD severity classifier, which are used for segmenting the neck region from the camera-captured photographs and grading, respectively. U-Net was used for segmentation and another convolutional neural network classifier (DenseNet-121) was applied to RD severity classification. Dice similarity coefficient was used to evaluate the performance of segmentation. Severity classification was evaluated by several metrics, including overall accuracy, precision, recall, and F1 score. RESULTS: Results of segmentation showed that the averaged dice similarity coefficients were 91.2% and 90.8% for front and side view, respectively. For RD severity classification, the overall accuracy of test photographs was 83.0%. Our method accurately classified 90.5% of grade 0, 67.2% of grade 1, 93.8% of grade 2, and 100% of above grade 2 cases. The overall prediction performance was comparable with human assessors. There was no significant difference in accuracy when using manually or automatically segmented regions (P = .683). CONCLUSIONS: We have successfully demonstrated a DL-based method for automatic assessment of RD severity in patients with NPC. This method holds great potential for efficient and effective assessing and monitoring of RD in patients with NPC.

Quantitative evaluation of radiodermatitis following whole-breast radiotherapy with various color space models: A feasibility study.

PURPOSE: We analyzed skin images with various color space models to objectively assess radiodermatitis severity in patients receiving whole-breast radiotherapy. METHODS: Twenty female patients diagnosed with breast cancer were enrolled prospectively. All patients received whole-breast radiotherapy without boost irradiation. Skin images for both irradiated and unirradiated breasts were recorded in red-green-blue (RGB) color space using a mobile skin analysis device. For longitudinal analysis, the images were acquired before radiotherapy (RTbefore), approximately 7 days after the first fraction of radiotherapy (RT7days), RT14days, and approximately 10 days after radiotherapy completion (RTafter). Four color space models (RGB, hue-saturation-value (HSV), L*a*b*, and YCbCr models) were employed to calculate twelve color space parameters for each skin image. Skin dose measurements for irradiated breasts were performed using nanoDot optically stimulated luminescent dosimeters on the first fraction of radiotherapy. Subsequently, acute radiation dermatitis in each patient was assessed according to the Radiation Therapy Oncology Group scoring criteria at both RT14days and RTafter. Finally, several statistical analysis methods were applied to investigate the performance of the color space parameters to objectively assess the radiodermatitis. RESULTS: Owing to radiation-induced skin damage, R value of RGB model as well as S and V values of the HSV model for irradiated breasts increased significantly, while those for unirradiated breasts showed smaller increases. These parameters showed the longitudinal changes in color space parameters within each group and between groups over time with statistical significance. Strong correlations of the parameters for irradiated breasts at RT7days with skin doses and those at RTafter were observed with statistical significance. CONCLUSION: The R value of RGB model as well as the S and V values of HSV model showed relatively better performance in evaluating the acute radiation dermatitis. These color space parameters could therefore serve as useful tools to assess radiodermatitis severity in a dose-dependent manner.

Symptom Burden Associated With Radiation Dermatitis in Breast Cancer Patients Undergoing Radiotherapy.

PURPOSE: Radiation dermatitis (RD) is a side effect experienced by many patients undergoing radiotherapy (RT) for breast cancer. In the present study, the Edmonton Symptom Assessment System (ESAS), a validated patient-reported symptom screening tool, was used to determine the impacts of RT-induced skin outcomes on ESAS items. Patient- and treatment-related factors and skin treatments to manage RD symptoms, were assessed for association with ESAS scores. METHODS: Patient and treatment characteristics were collected retrospectively for breast cancer patients treated with adjuvant RT between December 2013 and November 2015. Prospective data was collected through clinician-reported surveys. Linear regression analyses were performed to detect the relationship between patient-reported ESAS scores and clinician-reported RD symptoms. RESULTS: A total of 857 patients were included in the analysis. Moderate to severe scores were commonly reported for fatigue (n = 412, 48%), wellbeing (n = 386, 45%) and anxiety (n = 266, 31%). Oral analgesic use was associated with ESAS fatigue, drowsiness, pain, nausea, lack of appetite, shortness of breath, and wellbeing (P < .05), while dressings were only associated with anxiety (P = .02). No RD symptoms were found to be significantly associated with any ESAS items. CONCLUSIONS: The ESAS accurately reflects symptoms of fatigue, anxiety, and wellbeing for breast cancer patients undergoing RT. Our study, however, found no association between ESAS scores and RD severity, which may reflect the shortcomings of the ESAS in assessing symptom burden. Further research is necessary to warrant the development of a new site-specific symptom screening tool for use in RT for breast cancer.

Radiation recall reactions: An oncologic enigma.

Radiation recall reactions (RRR) are uncommon but are a well-known phenomenon to oncologists. Tissue damage in a prior irradiation portal is 'recalled' after the administration of a drug, historically cytotoxics, or more recently, targeted or immunotherapeutic agents. Even COVID-19 vaccines are a reported cause. RRR are enigmatic in that their cause is unknown, but they generally have the histopathological and clinical features of acute or chronic inflammation. They can occur in a variety of tissues, the commonest being skin, which accounts for two-thirds of reported cases. They are generally relatively mild and self-limiting once the trigger drug is stopped, although severe cases with tissue necrosis have occurred. Rechallenge with drug does not necessarily cause reactivation of the reaction. Symptomatic treatment with steroids and antihistamines are usually effective, but their impact on the clinical course is unclear. Various hypotheses have been proposed as to the mechanism of RRR; a non-immune fixed drug reaction-like condition, dysregulated release of reactive oxygen species, abnormalities of tissue vasculature and impaired DNA repair. All could lead to a characteristic inflammatory microenvironment, resulting in dysfunction of tissue stem cells, keratinocyte necrosis and dermal abnormalities. Alternatively or in addition, low levels of inflammatory tissue cytokines induced by previous irradiation might be further upregulated by drug exposure. Most information in this review refers to data derived from cutaneous RRR, since they are the most common form reported.