Radiation therapy dose escalation achieves high rates of local control with tolerable toxicity profile in pediatric and young adult patients with Ewing sarcoma.

BACKGROUND: Local control for patients with Ewing sarcoma (EWS) who present with large tumors are suboptimal when treated with standard radiation therapy (RT) doses of 54-55.8 Gy. The purpose of this study is to determine local control and toxicity of dose-escalated RT for tumors ≥8 cm (greatest diameter at diagnosis) in pediatric and young adult patients with EWS. METHODS: Eligible patients ≤30 years old with newly diagnosed EWS ≥8 cm treated with definitive conformal or intensity modulated photon, or proton radiation therapy techniques were included. All patients in the study received dose-escalated RT doses. Outcomes included overall survival (OS), event-free survival (EFS), local failure rates, and toxicity. RESULTS: Thirty-two patients were included, 20 patients presented with metastatic disease and 12 patients with localized disease. The median RT dose was 64.8 Gy (range, 59.4-69.4 Gy) with variability of doses to protect normal surrounding tissues. All patients received systemic chemotherapy. The 5-year OS and EFS for the cohort was 64.2% and 42%, respectively. The 5-year cumulative incidence of local failure was 6.6%. There were two combined local and distant failures with no isolated local failures. Twenty-nine patients experienced short term toxicity, 90% of those being radiation dermatitis. Twenty-seven patients experienced long-term toxicity, with only one experiencing grade 4 toxicity, a secondary malignancy after therapy. CONCLUSION: This study demonstrates that definitive RT for pediatric and young adult patients with EWS ≥8 cm provides high rates of local control, while maintaining a tolerable toxicity profile.

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

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

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.

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.

Spray skin protectant versus standard moisturiser in the prevention of radiodermatitis in patients with anal canal and rectal cancer: A randomised clinical trial.

The evidence on products for the prevention of radiodermatitis is limited. The primary objective was to analyse the effectiveness of the spray skin protectant 'non-burning barrier film' in the prevention of radiodermatitis with moist desquamation in patients with the anal canal and rectal cancer followed in nursing consultations compared to a standardised moisturiser based on Calendula officinalis and Aloe barbadensis. Single-blind randomised clinical trial. The study was performed in a hospital in Rio de Janeiro, Brazil, with 63 patients undergoing anal canal and rectal cancer treatment, randomised into one of the following two groups: an experimental group, which used a spray skin protectant and a control group, which used a moisturiser. Data were collected using an initial and subsequent evaluation form and were assessed using descriptive and inferential analyses. Participants who used the spray skin protectant had a lower chance of presenting radiodermatitis with moist desquamation and a longer time without this outcome when compared to the control group. The overall incidence of radiodermatitis was 100%, with 36.5% being severe. Furthermore, 17.5% of participants discontinued radiotherapy due to radiodermatitis. There were no differences between the groups regarding the severity of radiodermatitis and the number of patients who discontinued radiotherapy. The skin protectant was effective in preventing radiodermatitis with moist desquamation amongst patients with anal canal and rectal cancer.

The Assessment of the Long-Term Impact of Radiotherapy on Biophysical Skin Properties in Patients after Head and Neck Cancer.

Background and Objectives: Chronic radiotherapy-induced skin injury (cRISI) is an irreversible and progressive condition that can significantly impact a patient's quality of life. Despite the limited literature available on the assessment of the epidermal barrier in cRISI, there is a consensus that appropriate skincare, including the use of emollients, is the primary therapeutic approach for this group of patients. The aim of this study was to evaluate the biophysical properties of the skin during the late period (at least 90 days) following radiation therapy (RT) for head and neck cancer. Materials and Methods: This was a single-center prospective non-randomized study. It involved the analysis of 16 adult patients with head and neck cancer who underwent RT at the Greater Poland Cancer Center, along with 15 healthy volunteers. The study and control groups were matched for gender and age (p = 0.51). Clinical assessment, based on the LENT-SOMA scale, was conducted for all patients. Evaluation of the skin's biophysical properties included: an analysis of transepidermal water loss (TEWL), stratum corneum hydration (SCH), and skin visualization using high-frequency ultrasonography (HF-USG). Results: A significantly higher TEWL was observed in the irradiated area compared to the control area in the study group (p = 0.004). However, there was no statistically significant difference in SCH (p = 0.073). Additionally, no significant difference was observed in the values of TEWL and SCH in the irradiated area between the group of patients with and without clinically obvious RISI (p = 0.192 and p = 0.415, respectively). The skin thickness of the irradiated area, assessed by HF-USG, did not differ significantly from the skin thickness of the control area (p = 0.638). Furthermore, no difference in skin thickness was observed in patients with clinical features of cRISI in the irradiated and control areas (p = 0.345). The mean time after RT was 6.1 years. Conclusions: This study marks the first demonstration of epidermal barrier damage in patients in the long term following RT for head and neck cancer. The impairment of the epidermal barrier was observed independently of evident cRISI features. This observation underscores the necessity to recommend appropriate skin care, including the use of emollients, for all patients following RT. We also suggest that HF-USG examination is generally inconclusive in determining the degree of skin damage in the late period after RT.

Computational Model Based on Optical Coherence Tomography (OCT) Skin Scanning to Identify and Quantify Acute Radiation Dermatitis (ARD): A Prospective Diagnostic Study. / Modelo computacional basado en la tomografía de coherencia óptica (TCO) para identificar y cuantificar la radiodermatitis aguda (RA): estudio observacional prospectivo.

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.

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.

Radiation-induced skin injury in the head and neck region: pathogenesis, clinics, prevention, treatment considerations and proposal for management algorithm.

Worldwide increase of head and neck cancers ranks these malignancies among top causes of cancer in human population. Radiation induced skin injury (RISI) is one of the major side effects of radiotherapy (RT). Skin of the neck is exposed to radiation due to necessity of therapeutic or prophylactic (elective) irradiation of neck lymph nodes and target organs, including the larynx and hypopharynx. The location of the neck exposes these regions of the skin to various additional exposomes such as ultraviolet radiation (UVR), pollution and cigarette smoke. There are many controversies or inconsistencies regarding RISI, from molecular aspects and therapy to terminology. There is lack of high-quality and large-sample studies in both forms of RISI: acute (aRISI) and chronic (cRISI). Finally, no gold standards in the management of aRISI and cRISI have been established yet. In this article, the authors discuss the pathogenesis, clinical picture, prevention and clinical interventions and present a proposed treatment algorithm.

Experimental investigation of skin toxicity after immune checkpoint inhibition in combination with radiation therapy.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. However, structured knowledge to mitigate a patient's specific risk of developing adverse events are limited. Nevertheless, there is an exponential growth of clinical studies combining conventional therapies such as radiation therapy (RT) with ICIs. Cutaneous reactions are among the most common adverse events after monotherapy with either ICIs or RT. So far, little is known about interindividual differences for the risk of developing severe tissue toxicity after the combination of RT with ICIs, and the underlying biological mechanisms are ill defined. We used experimental models of RT-induced skin injury to analyze skin toxicity after simultaneous application of ICIs. We compared different RT regimens such as fractionated or stereotactic RT with varying dose intensity. Strikingly, we found that simultaneous application of RT and ICIs did not significantly aggravate acute skin injury in two different mouse strains. Detailed examination of long-term tissue damage of the skin revealed similar signs of epidermal hyperplasia, dermal fibrosis, and adnexal atrophy. In summary, we here present the first experimental study demonstrating the excellent safety profiles of concurrent treatment with RT and ICIs. These findings will help to interpret the development of adverse events of the skin after radioimmunotherapy and guide the design of new clinical trials and clinical decision-making in individual cases. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Effects of oral supplementation to manage radiation dermatitis in cancer patients: a systematic review.

PURPOSE: To evaluate the effectiveness and safety of oral supplementation as a radioprotective intervention in the management of radiation dermatitis (RD). METHODS: Systematic review and meta-analysis. Six databases and the gray literature were searched for randomized controlled clinical trials (RCTs). Meta-analysis was performed only with studies that evaluated the same intervention. Methodology of included studies was evaluated by the Cochrane risk-of-bias tool for randomized trials (RoB 2.0), and the certainty of evidence was assessed by the GRADE instrument. RESULTS: Seventeen RCTs were included in this review. These evaluated different types of oral supplementations. Findings from three meta-analyses demonstrated no significant benefits to the more severe grades of RD, as oral curcuminoids (RR, 0.59; 95% CI, 0.27 to 1.29; P = 0.19; I2 = 88%), glutamine (RR, 0.40; 95% CI, 0.15 to 1.03; P = 0.06; I2 = 78%) or Wobe-Mugos (RR, 0.57; 95% CI, 0.29 to 1.14; P = 0.11; I2 = 72%). Also, the certainty of the evidence of outcomes evaluated was moderate or low. Except for a few gastrointestinal adverse events, oral supplementation was well tolerated. CONCLUSION: Most oral supplements cannot yet be recommended to manage RD due to insufficient or conflicting evidence. However, despite no significant results, glutamine was shown to be a promising substance in terms of the potential radioprotective effect and may be well tolerated. These results suggest that more RCTs with larger samples are needed to evaluate the efficacy, safety, and tolerance of glutamine in the management of RD.

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).

Head and neck cancer patients under radiotherapy undergoing skin application of hydrogel dressing or hyaluronic acid: results from a prospective, randomized study.

PURPOSE: Acute radiodermatitis (ARD) is a frequent side effect of radiotherapy, a therapeutic option for head and neck squamous cell carcinoma (HNSCC). It is responsible for pain, quality of life (QoL) impairment, and increased risk of treatment discontinuation, which may compromise the prognosis for patients. Local therapies to prevent or alleviate ARD have been proposed without providing any high level of evidence to establish recommendations. METHODS: We implemented a prospective multicenter randomized study on patients with HNSCC treated with definitive radiotherapy to assess the impact on ear, nose, and throat (ENT) pain of the application of a hydrogel-based skin dressing (HydroTac®) compared with the application of hyaluronic acid (Ialuset®) during radiotherapy. RESULTS: Out of 130 enrolled patients, 48 patients per group were assessable for the main endpoint. No difference between groups was found: a worsening of ENT pain of 3 points or more on a visual analog scale from the initiation to 1 month after the end of the radiotherapy was observed for 8 patients (16.7%) who received HydroTac® compared to 13 patients (27%) who received Ialuset® (p = 0.342). The proportion of patients who experienced ARD and grades of ARD (CTCAE v4.0 criteria) were similar between groups. Patient compliance with radiodermatitis treatment was poor, with 56.1% of patients in the HydroTac® group having their treatment temporarily stopped. CONCLUSION: The application of a hydrogel dressing to prevent ARD during radiotherapy for HNSCC patients has failed to demonstrate a benefit. These results may be limited by the difficulties of applying the dressing.

Autophagy gene Atg7 regulates the development of radiation-induced skin injury and fibrosis of skin.

BACKGROUND: Radiation-induced skin injury, which may progress to fibrosis, is a severe side effect of radiotherapy in patients with cancer. However, currently, there is a lack of preventive or curative treatments for this injury. Meanwhile, the mechanisms underlying this injury remain poorly understood. Here, we elucidated whether autophagy is essential for the development of radiation-induced skin injury and the potential molecular pathways and mechanisms involved. METHODS AND RESULTS: We used the myofibroblast-specific Atg7 knockout (namely, conditional Atg7 knockout) mice irradiated with a single electron beam irradiation dose of 30 Gy. Vaseline-based 0.2% rapamycin ointment was topically applied once daily from the day of irradiation for 30 days. On day 30 post irradiation, skin tissues were harvested for further analysis. In vitro, human foreskin fibroblast cells were treated with rapamycin (100 nM) for 24 h and pretreated with 3-MA (5 mM) for 12 h. Macroscopic skin manifestations, histological changes, and fibrosis markers at the mRNA and protein expression levels were measured. Post irradiation, the myofibroblast-specific autophagy-deficient (Atg7Flox/Flox Cre+ ) mice had increased fibrosis marker (COL1A1, CTGF, TGF-ß1, and α-SMA) levels in the irradiated area and had more severe macroscopic skin manifestations than the control group (Atg7Flox/Flox Cre- ) mice. Treatment with an autophagy agonist rapamycin attenuated macroscopic skin injury scores and skin fibrosis marker levels with decreased epidermal thickness and dermal collagen deposition in Atg7Flox/Flox Cre+ mice compared with the vehicle control. Moreover, in vitro experiment results were consistent with the in vivo results. Together with studies at the molecular level, we found that these changes involved the Akt/mTOR pathway. In addition, this phenomenon might also relate to Nrf2-autophagy signaling pathway under oxidative stress conditions. CONCLUSION: In conclusion, Atg7 and autophagy-related mechanisms confer radioprotection, and reactivation of the autophagy process can be a novel therapeutic strategy to reduce and prevent the occurrence of radiodermatitis, particularly skin fibrosis, in patients with cancer.

The efficacy of medicinal plant preparations in the alleviation of radiodermatitis in patients with breast cancer: A systematic review of clinical trials.

Radiodermatitis in breast cancer patients varies from mild irritation to life-threatening lesions. Several studies suggest a role for topical corticosteroid ointments in the treatment of radiodermatitis. Yet, to avoid the adverse effects of corticosteroids, many authors recommend the use of topical herbal products instead. The therapeutic role of herbal treatments has yet to be fully understood. This systematic review evaluates the role of topical or oral herbal medicines in radiodermatitis prevention and treatment. A systematic search of four databases (Embase, PubMed, Web of Science, and Scopus) was performed without language and time restrictions from their inception until April 2023. The bibliographies of potential articles were also searched manually. Studies evaluated and compared the effects of herbal preparations with the control group, on dermatitis induced by radiotherapy for breast cancer. The Cochrane risk of bias tool was used to assess the included studies. Thirty-five studies were included in the systematic review. Studies which used herbal drugs including topical and oral formulations were evaluated. Herbal monotherapy and combination therapy were reported, and their effects on radiodermatitis were explained in the systematic review. In conclusion, henna ointments, silymarin gel, and Juango cream were reported to reduce the severity of radiodermatitis. These agents should be considered for radiodermatitis prophylaxis and treatment. The data on aloe gel and calendula ointment were conflicting. Further randomized controlled trials of herbal medications and new herbal formulations are required to determine their effects on breast cancer radiodermatitis.

The action of topical application of Vitamin B12 ointment on radiodermatitis in a porcine model.

Radiodermatitis is an inevitable side effect of radiotherapy in cancer treatment and there is currently no consensus on effective drugs for treating the condition. Vitamin B12 is known to be effective for repairing and regenerating damaged skin. However, there are few studies on the use of Vitamin B12 for treating radiodermatitis. This study explored the therapeutic efficacy and mechanism of action of Vitamin B12 ointment on radiodermatitis. A porcine model of grade IV radiodermatitis was established. The ointment was applied for 12 weeks after which histological staining, transmission electron microscopy, RT-qPCR, western blotting, and gene sequencing were performed for the evaluation of specific indicators in skin samples. After 12 weeks of observation, the Vitamin B12 treatment was found to have significantly alleviated radiodermatitis. The treatment also significantly reduced the expression levels of NF-κB, COX-2, IL-6, and TGF-ß in the skin samples. The pathways involved in the effects of the treatment were identified by analysing gene expression. In conclusion, Vitamin B12 ointment was found to be highly effective for treating radiodermatitis, with strong anti-radiation, anti-inflammatory, and anti-fibrosis effects. It is thus a promising drug candidate for the treatment of severe radiodermatitis.

Effects of topical timolol for the prevention of radiation-induced dermatitis in breast cancer: a pilot triple-blind, placebo-controlled trial.

INTRODUCTION: Radiation therapy is one of the standard methods in the treatment of breast cancer. Radiotherapy-induced dermatitis (RID) is a common complication of radiotherapy (RT) resulting in less tolerance in RT and even discontinuation of treatment. Timolol is a ß-adrenergic receptor antagonist that presents the best wound healing effects on both chronic and incurable wound healing. Topical forms of timolol could be effective in the prevention of RID due to the role of ß-adrenergic receptors in skin cells and keratinocyte migration, as well as the anti-inflammatory effect of timolol. However, no placebo-controlled randomized trial is available to confirm its role. The current trial aimed to evaluate the efficacy of topical timolol 0.5% (w/w) on the RID severity and patients' quality of life (QOL). METHOD: Patients aged older than 18 years with positive histology confirmed the diagnosis of invasive and localized breast cancer were included. Patients were randomized based on the random number table to receive each of the interventions of timolol 0.5% (w/w) or placebo topical gels from the first day of initiation of RT and for 6 weeks, a thin layer of gel twice daily. Patients were asked to use a thin layer of gel for at least two hours before and after radiation therapy. Primary outcomes were acute radiation dermatitis (ARD) grade using Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer (RTOG/EORTC) scale and severity of desquamation based on Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Secondary outcomes were QOL based on Skindex16 (SD-16), maximum grade of ARD, and time of initial RD occurrence. RESULTS: A total of 64 female patients with an age range of 33 to 79 years were included. The means (SD) of age were 53.88 (11.02) and 54.88 (12.48) in the control and timolol groups, respectively. Considering the RTOG/EORTC and CTCAE scores the difference between groups was insignificant (P-Value = 0.182 and P-Value = 0.182, respectively). In addition, the mean (SD) of time of initial RID occurrence in placebo and timolol groups were 4.09 (0.588) and 4.53 (0.983) weeks, respectively (P-Value = 0.035). The maximum grade of RID over time was significantly lower in the timolol group. During the study period, 75.0% of patients in placebo groups had grade 2 of ARD while in the timolol group it was 31.3% (P-Value = 0.002). QoL was not significantly different between groups (P-Value = 0.148). CONCLUSION: Although the topical formulation of timolol, 0.5% (w/w), was found to reduce the average maximum grade of ARD and increase the mean (SD) time of initial RID occurrence, it showed no effect on ARD, severity, and QOL. However, future clinical trials should be performed to assess timolol gel formulation in larger study populations. TRIAL REGISTRATION: https://irct.ir/ IRCT20190810044500N11 (17/03/2021).

Effect of hyaluronic acid on radiodermatitis in patients with breast cancer: a meta-analysis of randomized controlled trials.

BACKGROUND: Radiodermatitis is commonly experienced by patients with breast cancer undergoing radiotherapy, affecting their quality of life and potentially leading to cancer treatment postponement. Recently, people who use natural substances to treat radiodermatitis have attracted more and more attention. However, there is no unanimous conclusion to follow. OBJECTIVE: We conducted a meta-analysis of randomized controlled trials (RCTs) that compared hyaluronic acid with other topical agents in patients with breast cancer. METHODS: PubMed, Cochrane Library, and Embase databases were searched for eligible articles. The primary outcome indicating symptom relief was a decreased radiodermatitis grade. The secondary outcome indicating symptom relief was preference and desquamation. The study is registered with PROSPERO (number: CRD42021237793). RESULTS: Eight RCTs that together enrolled 500 patients were analyzed. Six studies assessed the radiodermatitis grade and found significant differences in three of eight subgroups. The subgroups comparing hyaluronic acid with phytosterol, omega-3, 6, 9, and vitamin E showed significantly lower risk ratios. In two subgroups, the effect of hyaluronic acid was not significantly different from that of grapevine extract and Avene thermal water. The remaining three studies reported that other topical agents exerted a nonsignificantly better effect than hyaluronic acid did. Physicians' preference was better for the control group, while the patients' preference for hyaluronic acid was better, and there was no statistical difference. In addition, our study showed that desquamation events were few in the hyaluronic group. CONCLUSIONS: Hyaluronic acid can show a better effect than other topical drugs and the lower incidence in desquamation events. Since hyaluronic acid has no obvious side effects, we recommend it as one of the alternative options. Further research is required to evaluate this effect comprehensively.

A long-term follow-up of early breast cancer patients treated with photobiomodulation during conventional fractionation radiotherapy in the prevention of acute radiation dermatitis.

OBJECTIVES: The evidence demonstrating the efficacy of photobiomodulation (PBM) therapy for preventing and managing acute radiation dermatitis (ARD) is growing steadily. The question that arises from many clinicians is, if PBM is safe for oncologic patients. This study aimed to evaluate the disease-free survival (DFS), cancer-free survival (CFS), and overall survival (OS) of breast cancer patients treated with PBM for ARD. METHODS: Clinical data of 120 breast cancer patients treated with prophylactic PBM (n = 60, 2x/week, 808-905 nm, 4 J/cm2 ) or placebo (n = 60) during conventional fractionation (CF) radiotherapy (RT) between April 2015 and June 2017 were retrospectively analyzed (TRANSDERMIS trial). During follow-up (April 2015 to May 2022), patients underwent a complete clinical evaluation every 6 months and blood analysis and mammography yearly in the first 5 years after the end of RT. The DFS, CFS, and OS were estimated. RESULTS: At a median follow-up time of 66 months (range 4-81), there was no significant difference in DFS (73.7% vs. 98.3%, resp., p = 0.54), CFS (68.4% vs. 77.8%, resp., p = 0.79), and OS (87.9% vs. 98.3%, resp., p = 0.30) between the placebo and PBM group. CONCLUSIONS: This paper is the first to describe the results of a long-term follow-up in early-stage breast cancer patients who underwent PBM for ARD. Results suggest that using PBM in breast cancer patients undergoing CF RT does not influence the locoregional recurrence, the development of new primary tumors, or OS.

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.