Drains in Breast Reduction: How Good is the Recommendation Not to Use Them?

A clinical practice guideline (CPG) recommended not to use drains in breast reduction. This CPG was based on 3 randomized controlled trials (RCTs). The objective of this review was to double-check the methodological quality of the three RCTs. These RCTs were critically appraised using a) the Users' guide to RCT assessment for methodological quality, b) the CONSORT guideline for reporting quality, and c) the Cochrane risk of bias tool 2 (RoB 2) for risk of bias. Weaknesses were identified in all assessments for the three RCTs. Items with the poorest adherence in the User's guide to RCT included: "Were patients stratified?", "Was follow-up complete?", and "Were all clinically important outcomes considered?". The overall adherence to the CONSORT Reporting Checklist across all studies was moderate with 40.0%, 62.1% and 48.3% adherence. All 3 RCTs had a similar low to moderate risk of bias, with no areas with a high risk of bias. None of the studies took into consideration a single critical outcome (such as major hematoma) and the outcome's minimally important difference as the basis for the sample size and power calculation of the study. All three RCTs additionally lacked clear reporting of treatment effect sizes or precision of estimates. Our re-examination of the evidence questions the recommendation of the CPG. We believe that the recommendation should have been "we remain uncertain whether drains in breast reduction have a salutary effect". As such, we recommend that a methodologically robust RCTs be conducted to answer this question.

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

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

Perceptions of healthcare professionals on the use of Mepitel Film for the prevention of acute radiation dermatitis in breast cancer.

INTRODUCTION: Randomized clinical trials support Mepitel Film (MF) as a prophylactic treatment for radiation dermatitis (RD) in patients undergoing breast radiotherapy. Although several studies have canvassed the opinion of patients on using MF, no such studies have been done to investigate the perception of healthcare professionals (HCPs). The objective of this study was therefore to investigate the perceptions of HCPs on MF as a treatment option for RD. METHODS: Anonymized responses to a web-based survey sent to HCPs at a single institution managing patients using MF during breast radiotherapy were analyzed. RESULTS: Of the 28 HCPs contacted, 22 completed the survey, including 6 radiation oncologists (ROs), 11 radiation therapists (RTTs), and 5 nurses. Most HCPs reported MF was better at preventing severe RD than the standard of care and improved radiation-induced skin reactions (n = 20/22, 91%, and n = 19/22, 86%, respectively). MF was recommended for mastectomy patients without reconstruction (n = 15/21, 71%). The majority of HCPs believed that patients' families could be trained to apply and remove MF (n = 19/22, 86%). Many HCPs perceived that implementation of MF would be difficult in terms of maintaining patient flow and wide-scale implementation within their institution (n = 11/22, 50%, and n = 10/22, 46%, respectively). Most HCPs perceived that fewer than 50% of their patients could afford MF if priced at $100 CAD (n = 15/20, 75%). CONCLUSION: These findings provide insights into the possibility of MF to be incorporated into standard practice of care for RD. Although most HCPs were satisfied with MF as a prophylactic treatment for RD, there are concerns about its resource-intensive operationalization and financial accessibility to patients. Future research should focus on ways to improve HCP experience with MF and to improve its implementation into clinical settings as standard of care.

StrataXRT for the prevention and treatment of radiation dermatitis: a critical review.

PURPOSE: The primary objective is to systematically review primary studies, such as randomized control trials (RCTs), feasibility, exploratory, and case studies; and the secondary objective is to evaluate all secondary articles, such as reviews, guidelines, and editorials, relevant to the use of StrataXRT for the prevention and/or management of radiation dermatitis (RD) in cancer patients. METHODS: A literature search was conducted up to February 26, 2023, for articles investigating the use of StrataXRT for the prevention and treatment of RD, in the following databases: Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar. The keywords "StrataXRT", "dermatitis", "radiotherapy", and "radiation" were used to identify relevant articles. RESULTS: Twenty-seven articles from 2018 to 2022 were identified to fulfill the inclusion criteria of this review, of which nine are primary studies and 18 are secondary papers. Significant heterogeneity was observed in the current literature studying the effects of StrataXRT, making it difficult to make cross-trial comparisons. There is a suggestion of the efficacy of StrataXRT in the prevention and treatment of RD. CONCLUSION: The findings of this review recommend further adequately powered RCTs with robust methodology including patient and clinician assessments to determine the efficacy of StrataXRT in preventing and treating RD. This is essential to improve the quality of life of patients and identify which groups of patients would benefit most from StrataXRT.

A systematic review of the use of the then-test for evaluating health-related quality of life in cancer patients.

BACKGROUND: The then-test, also known as the retrospective pre- and post-test design method, is a measurement used to evaluate response shift. The method requires patients to assess their previous health-related quality of life (HRQoL) and provide a retrospective judgement based on their current perspectives. The then-test, however, has been criticized for its reliability and validity. The objective of this systematic review is to summarize the current literature for the use of the then-test for evaluating HRQoL in cancer patients and account for potential response shift effects. METHODS: A literature search was conducted in May 2022 using MEDLINE, PubMed, and PsychINFO dated from 2005 to the time of the search. Studies were included if they (I) used the then-test and (II) involved a population of cancer patients (any cancer site). RESULTS: The literature search resulted in 16 studies, published between 2005 and 2020. All studies used the then-test to detect response shifts. The EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires were the most common assessments used to evaluate HRQoL. Of the 16 articles, 5 exclusively reported on breast cancer, 5 reported on prostate cancer, and the remaining included all cancer sites. Most studies looked at patients undergoing a combination of chemotherapy, radiotherapy, and hormonal therapy. The mean differences between the retrospective assessment at both 3 and 6 months were significant for various quality of life (QoL) dimensions. Patients in some studies recalled their pretreatment HRQoL (then-score) as better than the pretreatment baseline scores and others reported them as worse, both confirming the existence of a response shift. CONCLUSIONS: Our review demonstrates that the then-test measurement tool has been commonly used for the detection of response shift. Newer measures for response shift have become more accepted; the then-test, if used, should be used with caution considering its limitations and the emergence of more advanced methods.

Mepitel Film for the prevention of acute radiation dermatitis in head and neck cancer: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: This systematic review and meta-analysis evaluates the efficacy of Mepitel Film in preventing acute radiation dermatitis (RD) in patients with head and neck cancer (HNC) across randomized controlled trials (RCTs). METHODS: Embase, MEDLINE, and Cochrane Central Register of Controlled Trials were searched on 5 March 2023 to identify relevant RCTs. RD assessment tools and outcomes were compared across studies. Pooled effect sizes and 95% confidence intervals (CI) were estimated based on random-effects analysis using RevMan 5.4. RESULTS: Three RCTs conducted between 2018 and 2020 were included. Mepitel Film decreased RD severity when compared to Sorbolene or Biafine but not when compared to mometasone. A per-protocol analysis of two of the trials revealed that, overall, Mepitel Film significantly reduced the incidence of grade 2-3 RD (odds ratio (OR), 0.24; 95% CI, 0.09-0.65; p = 0.005) and moist desquamation (OR, 0.21; 95% CI, 0.10-0.46; p < 0.0001) and decreased average patient, researcher, and combined components of the Radiation-Induced Skin Reaction Assessment Scale (the standardized mean difference (SMD) for patient ratings, - 2.56; 95% CI, - 3.15 to - 1.96, p < 0.00001; SMD for researcher ratings, - 3.47; 95% CI, - 6.63 to - 0.31, p = 0.03; SMD for combined scores, - 3.68; 95% CI, - 6.43 to - 0.92, p = 0.009). Noted issues with Mepitel Film included itchiness and poor adherence. CONCLUSION: While there were discrepancies across studies, Mepitel Film demonstrated a decrease in the incidence of grade 2-3 RD and moist desquamation. These findings emphasize the need for further examining Mepitel Film's efficacy across diverse patient groups and the importance of standardizing RD severity assessment methodologies and control arms.

Mepitel film for the prevention and treatment of acute radiation dermatitis in breast cancer: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: This systematic review and meta-analysis aimed to evaluate the efficacy of Mepitel film in preventing or treating acute radiation dermatitis (RD) in patients with breast cancer in randomized controlled trials (RCTs). METHODS: Embase, APA PsychInfo, Journals@Ovid Full Text, Ovid MEDLINE, PubMed, and Cochrane Trials were searched until December 12, 2022, to identify RCTs on the use of Mepitel film for preventing or treating acute RD from breast cancer radiotherapy. Per-protocol analysis was used to compare outcomes, calculate pooled effect sizes, odds ratio (OR), and 95% confidence intervals (CI), and to create forest plots using random effects analysis in RevMan 5.4. RESULTS: Three RCTs were included in this review. Mepitel film significantly reduced the incidence of grade 3 RD (OR 0.15 95% CI 0.06, 0.37, p<0.0001) and grade 2 or 3 RD (OR 0.16 95% CI 0.04, 0.65, p=0.01) as scored on either the CTCAE or the RTOG scale. Additionally, Mepitel film significantly reduced RISRAS mean scores assessed by patients and combined researcher and patient (standardized mean difference (SMD) -7.59, 95% CI -14.42, -0.76, p=0.03; SMD -15.36, 95% CI -30.01, -0.71 p=0.04) but not the researcher component of the assessment tool (SMD -17.55, 95% CI -36.94, 1.84, p=0.08). CONCLUSION: Mepitel film reduced the incidence of acute RD and improved patient-reported outcomes with minimal side effects, the main one being itchiness. Future research should assess the feasibility of Mepitel film with respect to specific patient-reported outcomes such as health-related quality of life issues associated with its use.

StrataXRT for the prevention of acute radiation dermatitis in breast cancer: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: To evaluate the overall efficacy of StrataXRT, a topical gel dressing, in preventing acute radiation dermatitis (RD) in breast cancer patients undergoing radiotherapy (RT). METHODS: A systematic search was conducted on April 25, 2023 in Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. Randomized controlled trials (RCTs) assessing the effectiveness of StrataXRT in preventing acute RD in breast cancer patients undergoing adjuvant RT to the breast or chest wall with or without regional nodes were included. Pooled incidence odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effects model, with analysis and forest plots generated in RevMan v5.4. RESULTS: The analysis included three RCTs with a total of 189 patients assessed using per-protocol analysis. Two RCTs compared StrataXRT to standard of care, while the third compared it with Mepitel film and was reported separately. In the former RCTs, the odds ratio (OR) for developing acute grade 3 RD favored StrataXRT at 0.05 (95% CI, 0.01-0.22; P < 0.0001). The OR for developing acute grades 2-3 RD was 0.32 (95% CI, 0.03-3.18; P = 0.33). The RCT comparing StrataXRT with Mepitel film showed insignificant ORs for grade 3 and grades 2-3 RD. One RCT reported significantly lower erythema index (P = 0.008) and melanin index (P = 0.015) in StrataXRT patients. The use of StrataXRT did not raise additional safety concerns. CONCLUSION: StrataXRT may help prevent severe acute RD in breast cancer RT patients. Further high quality, large-scale studies are needed to confirm these findings.

Topical corticosteroids for the prevention of severe radiation dermatitis: a systematic review and meta-analysis.

PURPOSE: Radiation dermatitis (RD) is a frequently occurring adverse reaction during radiotherapy in cancer patients. While the use of topical corticosteroids (TCs) is common for the treatment of RD, its role in preventing severe reactions remains unclear. This systematic review and meta-analysis aim to evaluate the evidence on the use of TCs as prophylaxis of RD. METHODS: A systematic search was conducted using OVID MedLine, Embase, and Cochrane databases (between 1946 and 2023) to identify studies examining TC use in the prevention of severe RD. Statistical analysis was completed using RevMan 5.4 to calculate pooled effect sizes and 95% confidence intervals. Forest plots were then developed using a random effects model. RESULTS: Ten RCTs with a total of 1041 patients met the inclusion criteria. Six studies reported on mometasone furoate (MF) and four studies reported on betamethasone. Both TCs were associated with a significant improvement in the prevention of moist desquamation [OR = 0.34, 95% CI [0.25, 0.47], p < 0.00001], but betamethasone was found to be more effective than MF [OR = 0.29, 95% CI [0.18, 0.46], p < 0.00001 and OR = 0.39, 95% CI [0.25, 0.61], p < 0.0001, respectively]. A similar finding was seen in reducing the development of grade 2 or higher RD according to the Radiation Therapy Oncology Group scale. CONCLUSIONS: The current evidence supports the use of TCs in preventing severe reactions of RD. Both MF and betamethasone were found to be effective; however, betamethasone, a higher potency TC, is more effective despite MF being more commonly reported in literature.

MASCC clinical practice guidelines for the prevention and management of acute radiation dermatitis: part 1) systematic review.

Acute radiation dermatitis (ARD) commonly develops in cancer patients undergoing radiotherapy and is often characterized by erythema, desquamation, and pain. A systematic review was conducted to summarize the current evidence on interventions for the prevention and management of ARD. Databases were searched from 1946 to September 2020 to identify all original studies that evaluated an intervention for the prevention or management of ARD, with an updated search conducted in January 2023. A total of 235 original studies were included in this review, including 149 randomized controlled trials (RCTs). Most interventions could not be recommended due to a low quality of evidence, lack of supporting evidence, or conflicting findings across multiple trials. Photobiomodulation therapy, Mepitel® film, mometasone furoate, betamethasone, olive oil, and oral enzyme mixtures showed promising results across multiple RCTs. Recommendations could not be made solely based on the published evidence due to limited high-quality evidence. As such, Delphi consensus recommendations will be reported in a separate publication.

Appropriateness of the 30-day expected mortality metric in palliative radiation treatment: a narrative review.

BACKGROUND AND OBJECTIVE: The 30-day expected mortality rate is frequently used as a metric to determine which patients benefit from palliative radiation treatment (RT). We conducted a narrative review to examine whether its use as a metric might be appropriate for patient selection. METHODS: A literature review was conducted to identify relevant studies that highlight the benefits of palliative RT in timely symptom management among patients with a poor performance status, the accuracy of predicting survival near the end of life and ways to speed up the process of RT administration through rapid response clinics. KEY CONTENT AND FINDINGS: Several trials have demonstrated substantial response rates for pain and/or bleeding by four weeks and sometimes within the first two weeks after RT. Models of patient survival have limited accuracy, particularly for predicting whether patients will die within the next 30 days. Dedicated Rapid Access Palliative RT (RAPRT) clinics, in which patients are assessed, simulated and treated on the same day, reduce the number of patient visits to the radiation oncology department and hence the burden on the patient as well as costs. CONCLUSIONS: Single-fraction palliative RT should be offered to eligible patients if they are able to attend treatment and could potentially benefit from symptom palliation, irrespective of predicted life expectancy. We discourage the routine use of the 30-day mortality as the only metric to decide whether to offer RT. More common implementation of RAPRT clinics could result in a significant benefit for patients of all life expectancies, but particularly those having short ones.

Prevention of radiation dermatitis with skin hygiene and washing: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aims to evaluate the effects of washing in patients receiving radiotherapy (RT) on radiation dermatitis (RD) severity. METHODS: A literature search was performed using Ovid MEDLINE, Embase, and Cochrane databases between January 1, 1946, and January 31, 2023. Four randomized controlled trials (RCTs) studying the effects of washing with or without soap on RD were identified. A meta-analysis was conducted for clinician-reported outcomes using RevMan 5.4 and a narrative synthesis for patient-reported outcomes due to a lack of reported data amenable to quantitative comparison in accordance with the Synthesis Without Meta-analysis (SWiM) guidelines. The Cochrane Risk of bias (RoB2) and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria were used to assess risk of bias and certainty of evidence, respectively. RESULTS: Two RCTs met the inclusion criteria for meta-analysis. Washing with or without soap significantly reduced the incidence of severe RD (OR: 0.32, 95% CI: 0.19-0.55, p < 0.01) and moist desquamation (OR: 0.25, 95% CI: 0.12-0.52, p < 0.01). Two of four trials found an association between washing and reduced itching score (p = 0.38). Pain score was not found to be significantly different with or without washing in any of the four studies (p = 0.07). The two studies that assessed burn scores did not detect any difference between the washing group versus no washing group (p = 0.25). Washing was associated with improved quality of life (QoL) measures in one study. CONCLUSION: Washing with or without soap during RT resulted in less severe RD and less moist desquamation. Given the QoL benefits of washing, it should be advocated as part of routine skin care during RT.

A comparison of acute patient-reported outcomes in breast cancer patients with and without regional nodal irradiation using the ESAS and PRFS tool.

BACKGROUND AND PURPOSE: Regional nodal irradiation (RNI) is commonly administered in patients with breast cancer with node-positive disease to prevent cancer recurrence. The purpose of this study is to identify whether RNI is associated with greater acute symptom burden from baseline to 1 to 3 months post completion of radiotherapy (RT) when compared to localized RT. MATERIALS AND METHODS: Patient and treatment characteristics were collected prospectively for breast cancer patients with and without RNI from February 2018 to September 2020. The Edmonton Symptom Assessment System (ESAS) and Patient-Reported Functional Status (PRFS) tool were completed by patients at baseline, weekly during RT, and at a 1- to 3-month follow-up visit. The Wilcoxon rank-sum or Fisher exact tests were used to compare variables between patients with or without RNI. RESULTS: A total of 781 patients were included in the analysis. Baseline symptom reporting was similar between cohorts, with the exception of PRFS scores (p = 0.0023), which were worse in patients receiving RNI. Across all time points, differences in outcomes between cohorts were minimal, except for lack of appetite (p = 0.03) and PRFS scores (p = 0.049), which were significantly aggravated in patients treated with RNI. CONCLUSION: There is insufficient evidence to suggest that RNI is associated with greater symptom burden as assessed with the ESAS. Further research should be conducted over a longer time period to determine the impact of late effects of RNI on patient-reported symptoms.

Systematic review and meta-analysis on interventions for radiation dermatitis prevention and management: an overview of the methods.

Over several decades, research on the prevention and management of acute radiation dermatitis (RD) has continued to emerge, yet there remains no "gold standard" treatment for RD care. Recent guidelines on RD prevention and management were published in 2022 by the Oncodermatology Study Group of the Multinational Association of Supportive Care in Cancer (MASCC). As part of this guideline process, a collaborative effort was undertaken by international RD experts to quantitatively compare commonly studied RD skin interventions through meta-analyses and discern superiority of interventional treatments over another intervention, standard-of-care, or placebo in RD prevention and management. This paper summarizes the materials and methodology used in a set of meta-analysis studies that supplement the 2022 MASCC Clinical Practice Guidelines on RD Prevention and Management.

Natural and miscellaneous agents for the prevention of acute radiation dermatitis: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to evaluate the available literature describing the efficacy of natural and miscellaneous agents in preventing acute radiation dermatitis (RD) in cancer patients. METHODS: OVID MedLine, Embase, and Cochrane literature databases were searched from 1946 to January 2023 for randomized controlled trials studying the use of natural and miscellaneous agents to prevent RD. RevMan 5.4 was used for the meta-analysis to calculate the pooled effect sizes and 95% confidence intervals (CI) using the random effects analysis. RESULTS: For the systematic review and meta-analysis, 19 and 16 studies were included, respectively. Of the five studied natural products (aloe vera, oral enzymes, olive oil, calendula, and curcumin), only oral enzymes and olive oil significantly reduced the incidence of Radiation Therapy Oncology Group grade 2+ (RR: 0.42, 95%CI 0.30-0.58, p < 0.00001, RR: 0.66, 95% CI 0.51-0.85, p = 0.001, resp.). The oral enzymes also reduced the grade 3+ RD incidence (RR: 0.18, 95%CI 0.06-0.55, p = 0.003). The other agents demonstrated no significant effect. CONCLUSION: This review and meta-analysis on natural and miscellaneous agents in preventing RD in cancer patients demonstrated that oral enzymes and olive oil prevented RD severity. However, evidence supporting natural agents to prevent RD is inconsistent, mainly because of low studies numbers, low-quality study designs, and small sample sizes. Therefore, concrete conclusions cannot be made. Research on (new) natural or miscellaneous agents should focus on a randomized controlled double-blinded study design with a large patient population, a higher consistency in research methods, and clinician- and patient-reported outcomes.

The effect of antiperspirant and deodorant use on acute radiation dermatitis in breast cancer patients during radiotherapy: a systematic review and meta-analysis.

PURPOSE: While some authors have investigated the impact of antiperspirant /deodorant on the development of acute radiation dermatitis (RD) among patients undergoing radiotherapy (RT) for breast cancer, recommendations supporting the use of antiperspirant/deodorant during breast RT remain highly variable. This systematic review and meta-analysis aims to evaluate the evidence investigating the effect of antiperspirant/deodorant on the development of acute RD during post-operative breast RT. METHODS: A literature search has been performed using OVID MedLine, Embase, and Cochrane databases (1946 to September 2020) to identify randomized controlled trials (RCTs) that have investigated deodorant/antiperspirant use during RT. The meta-analysis was conducted using RevMan 5.4 to calculate pooled effect sizes and 95% confidence intervals (CI). RESULTS: Five RCTs met the inclusion criteria. The use of antiperspirant/deodorant did not significantly affect the incidence of grade (G) 1 + RD (OR 0.81, 95% CI 0.54-1.21, p = 0.31). Prohibition of deodorant use did not significantly prevent the occurrence of G2 + acute RD (OR 0.90, 95%, CI 0.65-1.25, p = 0.53). No significant effect was reported in preventing G3 RD between the antiperspirant/deodorant and control groups (OR 0.54, 95%, CI 0.26-1.12, p = 0.10). There was no significant difference in pruritus and pain between patients undergoing skin care protocols with or without antiperspirant/deodorant (OR 0.73, 95% CI 0.29, 1.81, p = 0.50, and OR 1.05, 95% CI 0.43-2.52, p = 0.92, respectively). CONCLUSIONS: The use of antiperspirant/deodorant during breast RT does not significantly affect the incidence of acute RD, pruritus, and pain. As such, the current evidence does not support recommendation against antiperspirant/deodorant use during RT.

Topical non-steroidal agents for the prevention of radiation dermatitis: a systematic review and meta-analysis.

PURPOSE: Radiation dermatitis (RD) is a common side effect of radiation therapy, affecting a majority of breast and head and neck cancer patients with a negative impact on quality of life. Currently, no consensus exists regarding the prevention of RD. METHODS: PubMed, Embase and Cochrane databases (1946 to December 2022) were searched using PRISMA guidelines to identify randomized controlled trials (RCTs) that investigated the use of topical non-steroidal agents in the prevention of RD in patients undergoing radiotherapy. RESULTS: A total of six RCTs were included, comprising 627 patients. Among the topical non-steroidal agents analyzed, only the use of Biafine® in breast cancer patients was significant in preventing grade 4 and 3 + RD as classified by the Radiation Therapy Oncology group (RTOG) scale (OR = 0.07, 95% CI 0.01-0.63, p = 0.02, and OR 0.11, 95% CI 0.03-0.41, p < 0.01, respectively). The remaining agents (trolamine alone and hyaluronic acid/hyaluronan) did not significantly prevent the occurrence of RD. CONCLUSION: The results of this systematic review and meta-analysis indicate that Biafine® can prevent grade 3 + RD in breast cancer patients. The use of trolamine and hyaluronic acid does not significantly affect the incidence of RD.