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).

The use of photobiomodulation therapy for the management of chemotherapy-induced alopecia: a randomized, controlled trial (HAIRLASER trial).

PURPOSE: The purpose of this trial was to evaluate if photobiomodulation (PBM) can accelerate hair regrowth after chemotherapy in breast cancer patients and if this is correlated with a better quality of life (QoL). METHODS: A randomized controlled trial with breast cancer patients that underwent an anthracycline and taxane-containing chemotherapy regimen was set up at the Jessa Hospital (Hasselt, Belgium). Patients were randomized into the control group (no intervention) or the PBM group (three PBM sessions each week for 12 weeks, starting the last day of their chemotherapy). Hair regrowth was evaluated based on photographic assessments. Two blinded researchers independently scored the hair regrowth using a numerical rating scale (NRS). In addition, the QoL was measured using the European Organization for Research and Treatment-QOL questionnaire and Breast Cancer-specific module (EORTC QLQ-C30 and QLQ-BR23). Data were collected on the day of their last chemotherapy session and 1, 2, and 3 months post-chemotherapy. RESULTS: A total of 32 breast cancer patients were included in the trial between June 2020 and February 2022. Significantly higher NRS scores were observed in the PBM group at 1-month post-chemotherapy compared to baseline, whereas they remained constant in the control group. Patients allocated to the PBM group scored their global health significantly higher at all time points compared to the control. CONCLUSION: Based on the results of the HAIRLASER trial, PBM seems to accelerate hair regrowth after chemotherapy in breast cancer patients resulting in an improved global health status and better body image. The study was registered in July 2019 at ClinicalTrials.gov (NCT04036994).

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.

Evaluation of a novel skin care product for the management of chemotherapy-related dermatologic toxicities: A quasi-experimental study.

PURPOSE: Evaluate the efficacy of a novel skincare product for the management of chemotherapy-related dermatological toxicities. METHODS: A monocentric, prospective, interventional, open-label, pretest-posttest, single-group study with cancer patients receiving chemotherapy (n = 100) was set up. All enrolled patients applied the emollient daily to their face and body for three weeks. The severity of the skin reactions was evaluated by a researcher using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 at baseline and end of the trial. Patient-reported outcomes (PROs) included the frequency and severity of skin symptoms (Numerical rating scale, NRS), quality of life (QoL; Skindex-16 and Dermatology Life Quality Index), Patient Benefit Index (PBI), and treatment satisfaction. PROs were collected at baseline, weekly, and at the end of the trial. RESULTS: According to the CTCAE and NRS, the novel emollient significantly improved the severity and frequency of xerosis and pruritus (Ps ≤ .001). A significant reduction in the NRS score for frequency of erythema was measured (p < .001). The frequency and severity of burning and pain did not change. Regarding the patients' QoL, no beneficial effect of the skin care product was measurable. 44% of the patients experienced at least one patient-relevant treatment benefit. 87% of the patients were satisfied with the emollient and would recommend it. CONCLUSIONS: This study shows that the novel emollient significantly reduced chemotherapy-induced skin toxicity, more specifically xerosis and pruritus without hampering patient's QoL. Future research is needed to make definite conclusions using a study design including a control group and a long-term follow-up.

Barrier Films and Dressings for the Prevention of Acute Radiation Dermatitis: A Systematic Review and Meta-Analysis.

PURPOSE: This systematic review and meta-analysis aimed to evaluate the efficacy of barrier films and dressings in preventing acute radiation dermatitis (RD). METHODS: OVID Medline, Embase, and Cochrane databases were searched from 1946 to September 2020 to identify randomized controlled trials on the use of barrier films or dressings to prevent RD. For comparable outcomes between studies, pooled effect sizes and 95% confidence intervals (CI) were calculated using the random effects analysis in RevMan 5.4. RESULTS: Fourteen and 11 studies were included in the qualitative and quantitative analyses, respectively. Five types of barrier films used for RD were identified: Hydrofilm, StrataXRT®, Mepitel® Film, 3 M™ Cavilon™ No-Sting Barrier Film, and silver leaf nylon dressing. Hydrofilm and Mepitel Film significantly reduced the development of RD grade ≥ 2 in breast and head and neck cancer patients (RR 0.32, 95%CI 0.19, 0.56, p < 0.0001; RR 0.21, 95%CI 0.05, 0.89, p = 0.03, resp.). Moreover, Hydrofilm had a beneficial effect on patient-reported outcomes (PROs) (SMD -0.75, 95%CI -1.2, -0.29, p = 0.001). The meta-analyses on the other barrier films did not show any significant effect. CONCLUSION: This review and meta-analysis demonstrated that Hydrofilm and Mepitel Film could effectively reduce RD severity and improve PROs. The evidence is generally weak for all the studies on barrier films and dressings due to a limited study number, high risk of bias, small sample sizes, and minimal comparable outcome measures. It's potential has been proven, but future research in this field is recommended to confirm the efficacy of these products and assess real-world feasibility.

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 in management of cancer therapy-induced side effects: WALT position paper 2022.

Disclaimer: This article is based on recommendations from the 12th WALT Congress, Nice, October 3-6, 2018, and a follow-up review of the existing data and the clinical observations of an international multidisciplinary panel of clinicians and researchers with expertise in the area of supportive care in cancer and/or PBM clinical application and dosimetry. This article is informational in nature. As with all clinical materials, this paper should be used with a clear understanding that continued research and practice could result in new insights and recommendations. The review reflects the collective opinion and, as such, does not necessarily represent the opinion of any individual author. In no event shall the authors be liable for any decision made or action taken in reliance on the proposed protocols. Objective: This position paper reviews the potential prophylactic and therapeutic effects of photobiomodulation (PBM) on side effects of cancer therapy, including chemotherapy (CT), radiation therapy (RT), and hematopoietic stem cell transplantation (HSCT). Background: There is a considerable body of evidence supporting the efficacy of PBM for preventing oral mucositis (OM) in patients undergoing RT for head and neck cancer (HNC), CT, or HSCT. This could enhance patients' quality of life, adherence to the prescribed cancer therapy, and treatment outcomes while reducing the cost of cancer care. Methods: A literature review on PBM effectiveness and dosimetry considerations for managing certain complications of cancer therapy were conducted. A systematic review was conducted when numerous randomized controlled trials were available. Results were presented and discussed at an international consensus meeting at the World Association of photobiomoduLation Therapy (WALT) meeting in 2018 that included world expert oncologists, radiation oncologists, oral oncologists, and oral medicine professionals, physicists, engineers, and oncology researchers. The potential mechanism of action of PBM and evidence of PBM efficacy through reported outcomes for individual indications were assessed. Results: There is a large body of evidence demonstrating the efficacy of PBM for preventing OM in certain cancer patient populations, as recently outlined by the Multinational Association for Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). Building on these, the WALT group outlines evidence and prescribed PBM treatment parameters for prophylactic and therapeutic use in supportive care for radiodermatitis, dysphagia, xerostomia, dysgeusia, trismus, mucosal and bone necrosis, lymphedema, hand-foot syndrome, alopecia, oral and dermatologic chronic graft-versus-host disease, voice/speech alterations, peripheral neuropathy, and late fibrosis amongst cancer survivors. Conclusions: There is robust evidence for using PBM to prevent and treat a broad range of complications in cancer care. Specific clinical practice guidelines or evidence-based expert consensus recommendations are provided. These recommendations are aimed at improving the clinical utilization of PBM therapy in supportive cancer care and promoting research in this field. It is anticipated these guidelines will be revised periodically.

The Effectiveness of a Novel Skin Barrier Protectant in the Management of Acute Radiation Dermatitis: A Case Series.

OBJECTIVE: Acute radiation dermatitis (ARD) is a frequent adverse effect in patients with cancer undergoing radiotherapy (RT). The aim of this case series is to evaluate the effect of a novel skin barrier protectant in patients with ARD. METHODS: The skin barrier protectant was used in four patients with different cancer types undergoing RT at two clinical sites. All patients received the standard institutional skincare alongside the novel skin barrier protectant. The skin reactions were evaluated by an RT nurse using the modified version of the Radiation Therapy Oncology Group criteria. RESULTS: At the final RT session, three of four patients developed erythema with or without dry desquamation. One patient presented only a minor patchy moist wound. Overall, the pain and pruritus due to ARD was low or nonexistent. No adverse events related to the skin barrier protectant were reported. CONCLUSIONS: This case series demonstrates the beneficial effects and safety of the novel skin barrier protectant in the management of ARD in patients with cancer of different etiologies. These results lay the foundation for future studies with larger, more homogeneous patient populations; a well-defined application scheme; and a stricter study design.

Vaginal mucositis in patients with gynaecological cancer undergoing (chemo-)radiotherapy: a retrospective analysis.

The objective of this retrospective analysis was to determine the incidence and extent of vaginal mucositis (VM) in women with gynaecological cancer undergoing external (chemo)radiation therapy (CRT). A retrospective analysis was set up to collect data on the incidence and severity of VM in women treated with external pelvic RT for gynaecological cancer at the Jessa Hospital, Hasselt and ZOL, Genk, BE between January 2017 and June 2018. At the start and end of their external (C)RT, they rated the frequency and intensity of five common symptoms of VM. Thirty-three patients treated with RT for gynaecological cancer met the inclusion criteria. A non-negligible proportion of patients already experienced at least one VM symptom to any degree before the start of RT, a proportion that further increased towards the end of the RT (73%). At the end of RT, on average, about 25% of these patients reported moderate-to-severe symptoms (against about 7% before the (C)RT). These results suggest that VM is a rather frequent side effect in gynaecological cancer patients that aggravates during treatment up to a moderate severity level. Although the small sample size, these data highlight the need for attention to VM.Impact StatementWhat is already known about this topic? Radiotherapy plays an important role in the treatment of gynaecological malignancies. A debilitating complication in patients undergoing pelvic radiotherapy is vaginal mucositis, an inflammation of the vaginal mucosal lining. To date, the incidence of vaginal mucositis is still not well documented.What this paper adds? A non-negligible proportion of patients already experienced at least one symptom related to vaginal mucositis before the start of radiotherapy. Most patients presented mild to moderate vaginal mucositis symptoms at the end of external pelvic radiotherapy. Burning sensation, pruritus, and pain were the most frequently documented radiotherapy-induced complications.The implications of this paper: Vaginal mucositis is an underrated side effect of pelvic radiotherapy that needs to be tackled multidisciplinary by a team of nurses, radiotherapists, oncologists, and gynaecologists. The team should tackle the complication from the start of radiotherapy by using the most appropriate measures. Due to a possible link between acute vaginal mucositis and late vaginal toxicity, the team needs to follow-up patient's post-radiotherapy to support patients in late complications and advise/encourage patients in performing vaginal dilatation to prevent vaginal stenosis.

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.

Evaluating the Effectiveness of a Novel Skin Barrier Protectant in a Patient with Acute Radiodermatitis of the Vulva: A Case Report.

OBJECTIVE: To evaluate the use of a novel skin barrier protectant in a patient treated with radiotherapy for vulvar cancer. METHODS: This case report was conducted in a radiotherapy department with two women undergoing radiotherapy for vulvar carcinoma. A novel skin barrier protectant was evaluated in one patient; the other underwent the institutional standard skin care protocol. Skin reactions and pain were evaluated using the Radiotherapy Oncology Group Criteria. MAIN RESULTS: The patient who was treated with the skin protectant showed accelerated healing toward the end of radiotherapy, and this was accompanied with a decrease in pain (maximum pain score 6/10). In comparison, the patient treated with the standard skin care protocol had an extended healing process, experienced a higher pain level (maximum pain score 9/10), and required more nursing care. CONCLUSIONS: This case report is the first to suggest that this novel skin barrier protectant could effectively manage acute radiodermatitis in patients with cancer. This case report hopes to lay the foundation for future randomized controlled trials with a larger and broader patient population.

Safety and efficacy of photobiomodulation therapy in oncology: A systematic review.

We performed a systematic review of the current literature addressing the safety and efficacy of photobiomodulation therapy (PBMT) in cancer patients. In this systematic review, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. In vitro, in vivo, and clinical studies, which investigated the effect of PBMT on cell proliferation/differentiation, tumor growth, recurrence rate, and/or overall survival were included. The Medline/PubMed, EMBASE, and Scopus databases were searched through April 2020. A total of 67 studies met the inclusion criteria with 43 in vitro, 15 in vivo, and 9 clinical studies identified. In vitro studies investigating the effect of PBMT on a diverse range of cancer cell lines demonstrated conflicting results. This could be due to the differences in used parameters and the frequency of PBM applications. In vivo studies and clinical trials with a follow-up period demonstrated that PBMT is safe with regards to tumor growth and patient advantage in the prevention and treatment of specific cancer therapy-related complications. Current human studies, supported by most animal studies, show safety with PBMT using currently recommended clinical parameters, including in Head & Neck cancer (HNC) in the area of PBMT exposure. A significant and growing literature indicates that PBMT is safe and effective, and may even offer a benefit in patient overall survival. Nevertheless, continuing research is indicated to improve understanding and provide further elucidation of remaining questions regarding PBM use in oncology.

A Narrative Review on the Use of Photobiomodulation Therapy for the Prevention and Management of Acute Radiodermatitis: Proposed Mechanisms, Current Clinical Outcomes, and Preliminary Guidance for Clinical Studies.

Objective: A narrative review of the available scientific evidence to identify the current proposals relating the use of photobiomodulation (PBM) to treat acute radiodermatitis (ARD), to guide future research. Background data: A devastating side effect of radiotherapy (RT) is ARD, defined as an inflammatory skin reaction induced by RT. Currently, there is still no standard of care for ARD. PBM is a non-invasive light therapy that is a growing modality in the field of supportive cancer care. There is a need for identifying the therapeutic irradiation windows in this field, based on the available literature. Methods: An electronic search of original articles in the PubMed database was performed with the following keywords: "photobiomodulation therapy," "low-level light therapy," "low-level laser therapy," "acute radiodermatitis," and "radiotherapy" until December 2019. Randomized controlled trials, prospective non-randomized, case report, cohort, cross-over, and retrospective studies were selected for this review. Results: Nine clinical trials that investigated the use of photobiomodulation therapy (PBMT) in ARD were available for evaluation. Results demonstrate that PBMT could significantly reduce the severity of ARD and the accompanying discomfort and pain in patients with cancer. Conclusions: Based on the available evidence of the narrative review, PBM might be an effective therapy for the prevention and management of ARD in patients with cancer. More research is needed to confirm this finding.

Photobiomodulation Therapy to Mitigate Radiation Fibrosis Syndrome.

Objective: We evaluated the role of photobiomodulation (PBM) in radiation fibrosis syndrome (RFS). Background: Radiation therapy (RT) is an important treatment utilized in over half of newly diagnosed cancers. Despite its benefits, patients treated with RT may experience acute and chronic significant side effects depending on both treatment- and patient-related factors. RFS is an important long-term side effect of RT, which can adversely impact patient's quality of life and organ function. With improved oncologic outcomes and survival for cancer patients after radiation, there is an unmet need to address long-term side effects of RT, particularly RFS. Results: Photobiomodulation (PBM) using low energy, nonionizing light primarily in the visible (especially red) or near-infrared spectrum has been demonstrated to decrease acute side effects of radiation in rigorously conducted phase III randomized studies; however, its potential benefit in ameliorating chronic radiation side effects, particularly RFS remains to be investigated. Conclusions: This review summarizes the in vitro data, preclinical animal studies and clinical reports, which showcase the potential benefits of PBM treatments in preventing and reversing RFS.

Photobiomodulation Therapy for the Management of Chemotherapy-Induced Peripheral Neuropathy: An Overview.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy (CT), affecting 68% of patients. Current treatment strategies are based on pharmacological symptom management, but have limited results. Photobiomodulation therapy (PBMT) is a new and emerging therapeutic tool in the supportive care of cancer patients. In this overview, we explore the usability of PBMT for management of CIPN. Objective: To provide a comprehensive overview of management of CIPN with PBMT. Methods: Specific terms, including "Photobiomodulation Therapy," "Drug Therapy," and "Peripheral Nervous System Diseases," were identified for the literature research in PubMed. Results: Three articles were considered eligible for this review. Primary outcome measures were highly variable across the included studies. Conclusions: PBMT might be an effective treatment strategy to manage CIPN, with very encouraging reports from renowned teams, but evidence is limited. More methodologically uniform research (mainly regarding the parameters of PBMT) is needed to support the use of PBMT for this indication.