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.

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.

Decrease of radiation-induced skin reactions in breast cancer patients by preventive application of film dressings-a systematic review.

PURPOSE: Radiation-induced skin reactions remain one of the most frequent side effects of adjuvant radiotherapy for breast cancer, which is the most common global malignancy. In individual cases, we observed a decrease in radiation dermatitis under film dressings used for skin marking purposes. Therefore, we decided to revise the available evidence regarding the prophylactic use of film dressings to reduce radiation dermatitis in breast cancer patients. METHODS: On 20 March 2023, we conducted a systematic review of literature for randomized controlled trials published in the English, German, French, or Spanish language, available in the PubMed database. RESULTS: Of 82 publications, 9 full texts were assessed and 6 randomized controlled trials were included in the final synthesis. Two trials analyzed the application of polyurethane film (Hydrofilm, Paul Hartmann AG, Heidenheim, Germany), the other four of silicone-based polyurethane film (Mepitel film, Molnlycke Health Care Limited, Milton Keynes, United Kingdom). The evaluation scales Common Terminology Criteria for Adverse Events (CTCAE), Radiation Therapy Oncology Group (RTOG), and the Radiation-Induced Skin Reaction Assessment Scale (RISRAS) were used for assessment. All six trials, with a total of 788 patients yielding data for analysis, demonstrate a significant decrease in radiation-induced skin reactions by use of the film (mainly p < 0.001). CONCLUSION: Our analysis demonstrates a significant decrease in radiation-induced skin reactions by prophylactically applied film dressings in breast cancer patients. Consequent preventive use of film dressings might systematically reduce acute radiation-induced skin reactions in these patients.

Homologous platelet gel on radiation-induced dermatitis in a patient receiving head and neck radiotherapy plus cetuximab: A case report.

INTRODUCTION: Acute radiodermatitis is a significant complication of cancer radiotherapy, and platelet-based therapies are emerging as potential new treatments. MAIN SYMPTOMS AND IMPORTANT CLINICAL FINDINGS: In this report, we present the case of a patient with head and neck cancer undergoing radiotherapy combined with the monoclonal antibody cetuximab. After 4 weeks of this treatment, the patient developed cutaneous radiation dermatitis. Despite receiving standard treatment with corticosteroids and emollient cream, the lesion did not improve. MAIN DIAGNOSIS: cutaneous radiation dermatitis on head and neck cancer patient. THERAPEUTIC INTERVENTIONS: Topical application of platelet gel was initiated on the wound. From the second week of radiotherapy to the 4th week, homologous platelet-rich plasma was applied on the dermatitis using a bandage, 4 times a day. OUTCOMES: The topical treatment with homologous platelet gel resulted in complete healing of the radiodermatitis, including restoration of the epidermis, reepithelialization, and reduction in associated pain. CONCLUSION: homologous platelet gel might be an alternative to standard treatment of radiation dermatitis.

Efficacy of sesame oil versus placebo in the management of acute radiation-induced dermatitis in breast cancer patients: A double-blind randomized clinical trial.

AIM: Considering the anti-inflammatory and positive effects of sesame oil in treating skin diseases, the present research aimed to study its therapeutic effects on acute radiotherapy dermatitis in such patients. METHODS: Forty women with breast cancer during radiotherapy (for 5 weeks) were randomly grouped into two categories: sesame oil (20 patients) and placebo (20 patients). After each radiotherapy session, they were asked to use 3cc of the ointment on the treating field and continue the treatment until the end. They were examined weekly according to the staging criteria of the radiation therapy oncology group. RESULTS: No significant difference was observed in the first 3 weeks. In the fourth week, dermatitis grade 0 was 35%, grade 1 was 65%, and grade 2 was 0% in the intervention (case) group, while in the control group, they were 10%, 75%, and 15%, respectively. This difference was statistically significant (p = 0.046). Also, in the fifth week in the case group, dermatitis grade 0 was 25%, grade 1 was 70%, and grade 2 was 5%, while in the control group, they were 0%, 80%, and 20%, respectively. This difference was also statistically significant (p = 0.032). CONCLUSION: Based on the findings, sesame oil, as a cheap and available herbal treatment, may be utilized in treating acute dermatitis caused by radiotherapy. However, an investigation with a larger sample size in several centers should be conducted to examine sesame oil effects in treating acute radio dermatitis more comprehensively.

Impact of Curcumin Supplementation on Radiation Dermatitis Severity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Radiation dermatitis (RD) is a common side effect of radiotherapy in most breast cancer patients. Curcumin has recently attracted more attention for managing the side effects of breast cancer treatments. This review study aimed to investigate the effect of curcumin on the severity of radiation dermatitis in patients with breast cancer.   Methods: All eligible randomized controlled trials (RCTs) were collected by searching PubMed, Scopus, Cochrane, and Web of Science. The effect size was expressed as weighted mean difference (WMD) and 95% confidence interval (CI). Study heterogeneity was assessed through Q statistics and I-squared. RESULTS: Four RCTs with 882 patients were included in the final analysis. The results of the meta-analysis indicated that curcumin supplementation significantly reduced radiation dermatitis severity (RDS) score in the intervention group compared to the control group (WMD=-0.50; 95% CI -0.72 to -0.27, P <0.001). A significant heterogeneity was observed between the studies (I2 = 95.7%, P < 0.001). CONCLUSION: Based on the results of the present study, curcumin has significant effects in reducing the severity of radiation dermatitis in breast cancer patients receiving radiotherapy. Further well-designed longitudinal studies are recommended to confirm these results and to discover the underlying mechanisms of the effects of curcumin on the severity of radiation dermatitis in patients with cancer.

Efficacy of Epigallocatechin-3-Gallate in Preventing Dermatitis in Patients With Breast Cancer Receiving Postoperative Radiotherapy: A Double-Blind, Placebo-Controlled, Phase 2 Randomized Clinical Trial.

Importance: Safe and effective prophylactic therapies for radiation-induced dermatitis (RID) remain an unmet need. Objective: To determine if epigallocatechin-3-gallate (EGCG) solution reduces the incidence of RID in patients undergoing radiotherapy after breast cancer surgery. Design, Setting, and Participants: This phase 2 double-blind, placebo-controlled randomized clinical trial enrolled 180 patients with breast cancer receiving postoperative radiotherapy at Shandong Cancer Hospital and Institute in Shandong, China, between November 2014 and June 2019. Data analysis was performed from September 2019 to January 2020. Interventions: Participants were randomly assigned (2:1) to receive either EGCG solution (660 µmol/L) or placebo (0.9% NaCl saline) sprayed to the whole radiation field from day 1 of the radiation until 2 weeks after radiation completion. Main Outcomes and Measures: The primary end point was incidence of grade 2 or worse RID, defined by the Radiation Therapy Oncology Group scale. The secondary end points included RID index (RIDI), symptom index, changes in the skin temperature measured by infrared thermal images, and safety. Results: A total of 180 eligible patients were enrolled, of whom 165 (EGCG, n = 111; placebo, n = 54) were evaluable for efficacy (median [range] age, 46 [26-67] years). The occurrence of grade 2 or worse RID was significantly lower (50.5%; 95% CI, 41.2%-59.8%) in the EGCG group than in the placebo group (72.2%; 95% CI, 60.3%-84.1%) (P = .008). The mean RIDI in the EGCG group was significantly lower than that in the placebo group. Furthermore, symptom indexes were significantly lower in patients receiving EGCG. Four patients (3.6%) had adverse events related to the EGCG treatment, including grade 1 pricking skin sensation (3 [2.7%]) and pruritus (1 [0.9%]). Conclusions and Relevance: In this randomized clinical trial, prophylactic use of EGCG solution significantly reduced the incidence and severity of RID in patients receiving adjuvant radiotherapy for breast cancer. It has the potential to become a new choice of skin care for patients receiving radiotherapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02580279.

Reduction in severity of radiation-induced dermatitis in head and neck cancer patients treated with topical aloe vera gel: A randomized multicenter double-blind placebo-controlled trial.

PURPOSE: To assess the efficacy of topical aloe vera gel on radiation induced dermatitis (RID) in head and neck cancer (HNC) patients. METHOD: In this multicenter randomized double-blind controlled study, HNC patients treated with concurrent chemoradiation (CCRT) received either aloe vera gel or placebo gel. Adverse skin toxicity levels were evaluated with the radiation-induced skin reaction assessment scale (RISRAS). RESULTS: One hundred-twenty patients were enrolled in this study. Analysis of the baseline characteristics did not reveal any differences between the groups. The median RISRAS values from the 1st to the 8th week of the CCRT course were not statistically different between the two groups. In the 5th and 6th weeks of treatment, moderate to severe grades of skin erythematous were observed at values of 13.6% and 24.1% versus 27.8 and 42.6% for members of the aloe vera gel group and the placebo group, respectively (p = 0.05 for the 5th week and p = 0.038 for the 6th week). In the 7th week, moderate to severe instances of moist desquamation were observed in eight patients (19.0%) in the placebo group (p = 0.001). Subjects experienced a burning sensation with RISRAS scores of 3-4 in the 7th week representing only 11.9% of patients in the placebo group (p = 0.016). CONCLUSION: Topical applications of aloe vera gel significantly reduced moderate to severe grades of skin erythematous and instances of moist desquamation in HNC patients receiving CCRT. In this study, there was no prophylactic efficacy for RID in the aloe vera gel group when compared to the placebo group.

A Chitosan-Coated Chamomile Microparticles Formulation to Prevent Radiodermatitis in Breast: A Double-blinded, Controlled, Randomized, Phase II Clinical Trial.

PURPOSE: The aim was to evaluate the effect of a topical formulation containing chitosan-coated Chamomilla recutita (L.) rauschert microparticles regarding the incidence, grade, and days for the appearance of radiodermatitis (RD) in women with breast cancer. METHODS: A double-blinded, controlled, randomized, phase II clinical trial developed with women diagnosed with breast cancer who will receive radiation therapy. The participants were randomly divided into 2 groups: control and treatment. They were followed up until the end of the treatment or the appearance of grade III RD. RESULTS: Fifty-four women were included in the study. There is no significant difference between the groups in the incidence (88.9% vs. 88.9%, P=1.0) or time to develop any grade of RD (3 days of difference, P=0.300). A significant reduction was observed in the incidence (P=0.03) and in the time to appearance (7 d of difference, P=0.01) grade 2 or >RD. In the follow-up evaluation (15 d after the end of treatment), the Chamomile group presented a superior skin recovery than the control group (P=0.0343). High-intensity local symptoms as pain, and pruritus were significantly reduced in the Chamomile group. CONCLUSIONS: Although no effect was observed with chamomile to reduce any grade of RD, it was effective to reduce grade 2 or >toxicity, to improve skin recovery and to diminish high-intensity local symptoms. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials (ReBEC): RBR-9hnftg, April 29, 2019.

Serum zinc status and the development of mucositis and dermatitis in head-and-neck cancer patients undergoing curative radiotherapy: A pilot study.

Background: Radiation-induced mucositis and dermatitis are severe side effects and compromise the health of the head-and-neck cancer patient undergoing treatment. Zinc supplementation during the course of the treatment is shown to have protective effects against both radiation-induced mucositis and dermatitis. The aim of this study was to understand whether the level of serum zinc has an effect on the development of mucositis and dermatitis. Materials and Methods: This was noninterventional study where the levels of serum zinc were ascertained before the start of treatment by spectrophotometric methods. The patients were treated every day with no more than one fraction of 2 Gy per day, five times a week without any intended gaps for a planned target dose of 60-70 Gy (6-7 consecutive weeks). The patients were assessed for radiation-induced dermatitis and mucositis in accordance with the standard guidelines. The association between the levels of serum zinc with the development of different grades of mucositis and dermatitis (on the day of development) was ascertained using the Pearson correlation coefficient (r). A statistical value of P < 0.05 was considered to be statistically significant. Results: A total of 52 consecutive patients satisfying the inclusion criteria were enrolled. The results indicate that serum zinc levels showed a significant correlation (r = 0.29; P < 0.038) for Grade 1, while it was insignificant for Grades 2 and 3. For dermatitis, a significant correlation for all the grades (Grade 1 [r = 0.28; P < 0.043]; Grade 2 [r = 0.39; P < 0.006]; and Grade 3 [r = 0.49; P < 0.047]) was observed. Conclusions: For the first time, the results of this pilot study indicate that the serum level of zinc had an inverse association with the early development of mucositis and dermatitis, with better effects seen in dermatitis where it was also effective in Grades 2 and 3.

Effectiveness and Tolerability of Natural Herbal Formulations in the Prevention of Radiation-Induced Skin Toxicity in Patients Undergoing Radiotherapy.

The aim of this study is to investigate the preventive role of 3 herbal formulation products on reducing the incidence of radiation-induced dermatitis in patients undergoing radiotherapy for either breast or head and neck cancer. A total of 59 patients participated in the study. The novel herbal products, a combination of beeswax, olive oil, Calendula and Hypericum oils and Aloe gel, were daily and regularly being used by the patients during radiotherapy and 2 weeks after treatment end. Acute skin toxicity was scored weekly during radiotherapy and after treatment for a further 4-week follow-up period. Demographic data were analyzed by descriptive statistics. Statistical analyses of the study objectives were based on an intent-to-treat principle. Most of the patients presented with grade I (RTOG/EORTC) toxicity in the first weeks of radiotherapy, progressed to grade II but reverted to grade I toxicity up until the study end. A total of 94.9% of the patients had Dermatology Life Quality Index up to 1, and 66.1% remained in this scale. The application of the novel natural product combinations proved to be statistically significantly effective in reducing the intensity of radiation dermatitis, positively affecting the quality of life of the patients.

New photobiomodulation device for prevention and cure of radiotherapy-induced oral mucositis and dermatitis: results of the prospective Safe PBM study.

PURPOSE: The study aims to assess the feasibility, safety, and tolerability of CareMin650, a new photobiomodulation device, in patients treated by radiotherapy (RT) and to collect preliminary data on efficacy for prevention and treatment of oral mucositis (OM) and radiation dermatitis (RD). METHODS: Safe PBM is a French, multicentric, prospective, non-comparative study which include patients with head and neck cancer (H&NC, cohort A) or breast cancer (BC, cohort B) treated in prophylactic (cohorts A1 and B1) or curative setting (cohort A2 and B2). Prophylactic treatment was administered from D1 to end of RT, at a dose of 3 J/cm2. Curative treatment started when a grade 1 to grade 3 lesion had occurred and was pursued until end of RT. Primary endpoint was incidence of device-related adverse events (AEs). OM and RD lesions were graded according to CTCAE V3. RESULTS: Overall, 72 patients were included (22, 9, 23, and 18 in cohorts A1, A2, B1, and B2, respectively). No device-related AE was reported after 1312 CareMin650 sessions. In cohorts A1 and B1, median time to first OM or RD lesion was 20 days. One BC patient developed G3 RD after completion of RT and discontinuation of CareMin650. Four H&NC patients developed G3 OM. In cohorts A2 and B2, lesions improved or stabilized in 71% of patients. Rates of satisfaction were high among patients and users. CONCLUSION: CareMin650 is feasible, safe, and well tolerated for preventive or curative treatment of OM and RD in cancer patients treated with RT. Preliminary efficacy results are promising.

Photobiomodulation therapy for the prevention of acute radiation dermatitis in breast cancer patients undergoing hypofractioned whole-breast irradiation (LABRA trial).

OBJECTIVES: To evaluate the efficacy of photobiomodulation therapy in breast cancer patients post-lumpectomy undergoing hypofractionated whole-breast irradiation (HF-WBI) for the prevention and management of acute radiodermatitis (ARD). MATERIALS AND METHODS: A randomized, multicentric clinical trial (LABRA trial, NCT03924011) was set up at the Limburg Oncology Center, including the Jessa Hospital (Hasselt, BE) and Ziekenhuis Oost-Limburg (Genk, BE). A total of 71 breast cancer patients planned to undergo HF-WBI were randomized to one of the two study arms: the control group (n = 32) or the PBM group (n = 39). The PBM group received the standard institutional skincare combined with PBM (2×/week) during the complete radiotherapy (RT) course. Patients in the control group received the standard skincare combined with placebo treatment (2x/week). Patients' skin reactions were evaluated weekly during the RT treatment by using the modified version of the Radiation Therapy Oncology Group (RTOG) criteria. RESULTS: At week 3 of RT, one patient presented a grade 2 and one patient a grade 3 skin reaction in the control group, while in the PBM group, all patients still presented grade 1 ARD. At the final RT session 28% of the patients presenting grade 2-3 ARD, while in the PBM group 10% presented grade 2 and no grade 3 ARD. PBM reduced the incidence of severe ARD by 18%. However, the difference was not significant (p = 0.053). CONCLUSION: Based on the LABRA trial results, PBM seems not able to reduce the incidence of severe ARD in breast cancer patients undergoing HF-WBI. Research in a larger patient population is recommended.

Photobiomodulation therapy for the prevention of acute radiation dermatitis in head and neck cancer patients (DERMISHEAD trial).

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the effectiveness of photobiomodulation therapy (PBMT) for the prevention of acute radiation dermatitis (ARD) in head and neck cancer (HNC) patients. MATERIALS AND METHODS: A randomised, placebo-controlled trial (RCT) with 46 HNC patients who underwent radiotherapy (RT) with or without concomitant chemotherapy was set up (DERMISHEAD trial). Patients were randomised to receive PBM or placebo treatments from the first day of RT (2×/week) alongside the institutional skincare. The severity of skin reactions was assessed by the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.03 (NCI-CTCAE v4.03) and the Radiotherapy-Induced Skin Reaction Assessment Scale (RISRAS). Quality of life (QoL) was evaluated using the Skindex-16 questionnaire. RESULTS: PBMT significantly reduced NCI-CTCAE grade 2-3 ARD with 49% at the end of RT. CONCLUSION: The results of the first RCT in HNC patients showed that PBMT is an effective method to prevent the development of severe ARD. These results support the implementation of PBM in the clinical oncology - radiotherapy practice.

Topical use of Jiawei Simiao Yongan Gao to prevent radiodermatitis in patients with head and neck cancer: A retrospective cohort study.

Radiodermatitis is a common side effect of radiotherapy, but currently there is no standard treatment for its prevention. This study aimed to observe the effect of topical application of a paste based on traditional Chinese medicine, Jiawei Simiao Yongan Gao, on radiodermatitis caused by radiotherapy for patients with head and neck cancer.This was a retrospective cohort study of 40 patients with head and neck cancer evaluated during their radiotherapy. Of these, 20 patients were treated with Jiawei Simiao Yongan Gao on the irradiated skin from the beginning of radiotherapy (JSY group). The other 20 patients were given standard nursing (standard group). Acute skin reactions were classified according to the radiation-induced skin reaction assessment scale (RISRAS) and American radiation therapy oncology group (RTOG) acute toxicity grading criteria every 2 weeks, and adverse effects were recorded until the end of the radiotherapy.The two groups showed differences in severity of radiodermatitis. At 0 to 30 Gy, the skin reactions were similar in the two groups, while above 40 Gy the skin reactions were significantly lower grade in the JSY group (P < .05). At 0 to 20 Gy, there was no statistical significance (P > .05); but above 30 Gy they were lower in the JSY group (P < .05).Jiawei Simiao Yongan Gao effectively alleviated acute radiodermatitis caused by radiotherapy of head and neck cancer patients compared with standard nursing.

ONS Guidelines™ for Cancer Treatment-Related Radiodermatitis.

PURPOSE: Radiodermatitis is a side effect of radiation therapy. Evidence-based interventions to minimize severity or delay progression are important for clinical care. This guideline intends to support individuals with cancer, clinicians, and others in decisions regarding radiodermatitis treatment. METHODOLOGIC APPROACH: A panel of healthcare professionals with patient representation was convened to develop a national clinical practice guideline for the management of radiodermatitis. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology and the National Academies of Sciences, Engineering, and Medicine criteria for trustworthy guidelines were followed. The Cochrane Collaboration risk-of-bias tool was used, and certainty of the evidence was assessed using the GRADE approach. A quantitative and narrative synthesis of the evidence was completed. FINDINGS: The panel agreed on eight recommendations and made a conditional recommendation for deodorant/antiperspirant. Aloe vera and oral curcumin had knowledge gaps and were recommended only in the context of a clinical trial. The panel suggested against emu oil, calendula, and nonsteroidal interventions. IMPLICATIONS FOR NURSING: This guideline summarizes evidence-based interventions for the management of radiodermatitis to guide clinical care. SUPPLEMENTARY MATERIAL CAN BE FOUND AT&NBSP;HTTPS: //bit.ly/2GEwJtT.