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

DisclaimerThis article is based on recommendations from the 12(th) 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.Peer reviewe

Swallowing dysfunction in cancer patients

Purpose Dysphagia (swallowing dysfunction) is a debilitating, depressing, and potentially life-threatening complication in cancer patients that is likely underreported. The present paper is aimed to review relevant dysphagia literature between 1990 and 2010 with a focus on assessment tools, prevalence, complications, and impact on quality of life in patients with a variety of different cancers, particularly in those treated with curative chemoradiation for head and neck cancer. Methods The literature search was limited to the English language and included both MEDLINE/PubMed and EMBASE. The search focused on papers reporting dysphagia as a side effect of cancer and cancer therapy. We identified relevant literature through the primary literature search and by articles identified in references. Results A wide range of assessment tools for dysphagia was identified. Dysphagia is related to a number of factors such as direct impact of the tumor, cancer resection, chemotherapy, and radiotherapy and to newer therapies such as epidermal growth factor receptor inhibitors. Concomitant oral complications such as xerostomia may exacerbate subjective dysphagia. Most literature focuses on head and neck cancer, but dysphagia is also common in other types of cancer. Conclusions Swallowing impairment is a clinically relevant acute and long-term complication in patients with a wide variety of cancers. More prospective studies on the course of dysphagia and impact on quality of life from baseline to long-term follow-up after various treatment modalities, including targeted therapies, are needed

The role of benzydamine in prevention and treatment of chemoradiotherapy-induced mucositis

Purpose: To discuss the role of benzydamine in the prevention and treatment of radiation-induced oral mucositis (OM) in head and neck (H&N) cancer patients. This document represents an expert opinion paper on indications and key-role aspects in OM pathogenesis, prevention and treatment. Oral mucositis: OM represents a common side effect of chemotherapy (CHT) and radiotherapy (RT). It consists in a painful erythema involving the oral cavity mucosa, which may progress to ulceration. Five biologically dynamic phases are considered crucial in mucositis: “initiation, signalling, amplification, ulceration and healing”. Oral environment and microbiota are fundamental in mucositis development being involved in susceptibility to infections and in ulceration consequences. Different agents against mucositis have been studied and the use of benzydamine is strongly supported in literature. The Multinational Association of Supportive Care in Cancer and International Society for Oral Oncology (MASCC/ISOO) guidelines recommend its use for the prevention of OM in H&N patients undergoing RT and RT/CHT. Benzydamine: Benzydamine is a local anti-inflammatory drug with analgesic properties. It can decrease TNF-α, IL-1β and prostaglandin synthesis, also inhibiting leukocyte-endothelial interactions, neutrophil degranulation, vasodilation and vascular permeability. Literature agrees on the beneficial effects of benzydamine in preventing and reducing oral mucositis severity in H&N cancer patients undergoing RT/CHT. Conclusions: Mucositis represents a major concern in H&N cancer patients and a clinical and economical issue. A multimodal and multidisciplinary approach is needed for its management. International guidelines recommend benzydamine for OM prevention and treatment in H&N cancer patients, but further “real world” trials should be designed

Role of photobiomodulation therapy in neurological primary burning mouth syndrome. A systematic review and meta-analysis of human randomised controlled clinical trials

Mitochondrial homeostasis is crucial for energy production and neuronal survival in neurological primary burning mouth syndrome (npBMS). Photobiomodulation therapy (PBMT) has been utilised in npBMS management, however, its role of intervention remains controversial. The aim of this systematic review and meta-analysis of CRD 42020198921 PROSPERO registration reference was to oversee and determine the efficacy of PBMT in patients with npBMS, identifying the gaps and bridge them by proposing recommendations for future studies purposes. PRISMA guidelines and Cochrane Collaboration recommendations followed. Various search engines employed to analyse a total of 351 studies of which 12 were included. A wide range of utilised PBM wavelengths was between 635–980 nm and the power output ranged between 30 mW and 4000 mW. A high risk of bias (RoB) was noted in 7 out of 12 included studies (58.3%), as results of qualitative analysis. Meta-analysis findings of 4 out of 12 studies showed statistically significant intergroup differences (SSID) for visual analogue scale (VAS) values (MD = −1.47; 95% CI = −2.40 to −0.53; Z = 3.07 (p = 0.002) whereas meta-analysis on 5 out of 12 studies revealed SSID for anxiety/depression and quality of life (MD = −1.47; 95% CI = −2.40 to −0.53; Z = 3.07 (p = 0.002), favouring PBMT group to the control treatment strategies. Despite the inconsistency and diversity in PBM parameters (wavelength, power, light source, spot size, emission mode, energy per point, total energy) and treatment protocols (exposure time, number of sessions, time interval between sessions, treatment duration)—majority of the included studies showed positive PBM results. The high RoB and metaanalytical heterogeneity in the eligible studies warrant the necessity to perform well-designed and robust RCTs after acknowledging the drawbacks of the available scientific literature and addressing our suggested recommendations highlighted in our review

Role of Photobiomodulation Therapy in Neurological Primary Burning Mouth Syndrome. A Systematic Review and Meta-Analysis of Human Randomised Controlled Clinical Trials

Mitochondrial homeostasis is crucial for energy production and neuronal survival in neurological primary burning mouth syndrome (npBMS). Photobiomodulation therapy (PBMT) has been utilised in npBMS management, however, its role of intervention remains controversial. The aim of this systematic review and meta-analysis of CRD 42020198921 PROSPERO registration reference was to oversee and determine the efficacy of PBMT in patients with npBMS, identifying the gaps and bridge them by proposing recommendations for future studies purposes. PRISMA guidelines and Cochrane Collaboration recommendations followed. Various search engines employed to analyse a total of 351 studies of which 12 were included. A wide range of utilised PBM wavelengths was between 635–980 nm and the power output ranged between 30 mW and 4000 mW. A high risk of bias (RoB) was noted in 7 out of 12 included studies (58.3%), as results of qualitative analysis. Meta-analysis findings of 4 out of 12 studies showed statistically significant intergroup differences (SSID) for visual analogue scale (VAS) values (MD = −1.47; 95% CI = −2.40 to −0.53; Z = 3.07 (p = 0.002) whereas meta-analysis on 5 out of 12 studies revealed SSID for anxiety/depression and quality of life (MD = −1.47; 95% CI = −2.40 to −0.53; Z = 3.07 (p = 0.002), favouring PBMT group to the control treatment strategies. Despite the inconsistency and diversity in PBM parameters (wavelength, power, light source, spot size, emission mode, energy per point, total energy) and treatment protocols (exposure time, number of sessions, time interval between sessions, treatment duration)—majority of the included studies showed positive PBM results. The high RoB and meta-analytical heterogeneity in the eligible studies warrant the necessity to perform well-designed and robust RCTs after acknowledging the drawbacks of the available scientific literature and addressing our suggested recommendations highlighted in our review

Photobiomodulation therapy in the management of oral mucositis: search for the optimal clinical treatment parameters

This commentary attempts to clarify the setting of photobiomodulation (BPM) therapy in the management of oral mucositis. The suggested dose range balances efficacy data with our current understanding about PBM safety. The literature about the molecular basis of photobiomodulation and its controversial relationship to malignant transformation is briefly presented

Emerging potential of phototherapy in management of symptomatic oral lichen planus: A systematic review of randomised controlled clinical trials

Phototherapy incorporating photobiomodulation therapy and antimicrobial photodynamic therapy has been utilised as antioxidants in symptomatic oral lichen planus (OLP) management; however, its role of intervention remains controversial. The aim of this systematic review of CRD42021227788 PROSPERO (an international prospective register of systematic reviews in health and social care) registration number was to oversee and determine phototherapy efficacy in patients with symptomatic OLP, identifying and bridging the literature gaps by proposing recommendations for future studies. A search strategy was developed in consistent with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Various electronic databases were exercised to search for randomised controlled clinical trials (RCTs). Several search engines were employed to analyse a total of 177 studies of which nine included. A wide range of utilised laser and light-emitted diode wavelengths between 630 and 808 nm and irradiance ranged between 10 and 13 mW/cm2 were noted. 67% of studies reported a high risk of bias and a high heterogeneity obtained from numerical data for quantitative analysis, therefore meta-analysis was impossible to conduct. Despite inconsistency and diversity in phototherapy parameters, treatment protocols, photosensitiser (type, concentration and method of application) and outcome assessment tools, the majority of the studies showed positive results compared with standard care treatments. Hence, a necessity to perform well-designed RCTs with robust methodology is warranted, after acknowledging the current drawbacks and addressing the suggested recommendations highlighted in our review. Moreover, advanced knowledge in understanding further phototherapy-antioxidants molecular mechanistic in symptomatic OLP is required

A systematic review of trismus induced by cancer therapies in head and neck cancer patients

This systematic review represents a thorough evaluation of the literature to clarify the impact of cancer therapies on the prevalence, quality of life and economic impact, and management strategies for cancer-therapy-induced trismus. A systematic literature search was conducted with assistance from a research librarian in the databases MEDLINE/PubMed and EMBASE for articles published between January 1, 1990 and December 31, 2008. Each study was independently assessed by two reviewers. Taking into account predetermined quality measures, a weighted prevalence was calculated for the prevalence of trismus. The level of evidence, recommendation grade, and guideline (if possible) were given for published preventive and management strategies for trismus. We reviewed a total of 22 published studies between 1990 and 2008. Most of them assessed the prevalence of this complication, and few focused on management. The weighted prevalence for trismus was 25.4% in patients who received conventional radiotherapy and 5% for the few intensity-modulated radiation therapy studies. No clear guideline recommendations could be made for the prevention or management of trismus. Newer radiation modalities may decrease the prevalence of trismus compared to conventional radiotherapy. Few studies have addressed the quality of life impact of trismus, and no studies were identified to assess the economic impact of trismus. The few preventive and management trials identified in the literature showed some promise, although larger, well-designed studies are required to appropriately assess these therapies before recommendations can be provided

Photobiomodulation Therapy Alleviates Tissue Fibroses Associated with Chronic Graft-Versus-Host Disease: Two Case Reports and Putative Anti-Fibrotic Roles of TGF-beta

Objective: Patients who receive allogeneic hematopoietic stem cell transplantation may experience oral complications due to chronic graft-versus-host disease (cGVHD). The manifestations may include progressive sclerosis-like changes that may involve various body sites, including the oropharynx. Methods and results: We present two cGVHD cases of oropharyngeal fibrotic changes that affected functions that were treated with photobiomodulation (PBM) therapy. These case reports suggest that PBM therapy represents an additional, innovative approach affecting discrete phases in cGVHD-associated fibrotic changes. Conclusions: We discuss these observations in the context of currently understood molecular mechanisms, especially induction of transforming growth factor beta and NFB that appear to be counter-intuitive to their known roles in matrix synthesis and inflammation that contribute to tissue fibroses. The clinical benefit noted in the two cases presented clearly indicates that there are distinct mechanistic and biological insights in the regulation of these molecular pathways in determining therapeutic efficacy with PBM therap