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This review aimed to determine whether photobiomodulation therapy (PBMT) is a safe and effective alternative for treating and preventing OM in children. The database search was carried out on PubMed, Embase, and Cochrane. Gray literature was also consulted through Google Scholar. Among 20 studies included, no adverse effect was reported, and only one study did not show any evidence of benefit from the use of PBMT. The analgesic effect of PBMT was emphasized and its action in accelerating the healing process and reducing the severity, duration and even incidence of OM was also noted. Evidence was found to encourage the use of PBMT to treat OM in pediatric patients. Higher quality studies must be developed in order to clarify the PBMT prophylactic effect and the best protocols for each clinical situation.The protocol of this review was registered on PROSPERO (CRD42023418109)., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Objective: This study aimed to review the current body of literature on underexplored areas of photobiomodulation (PBM) for preventing and/or treating oral adverse events. Background: Recent studies suggest that PBM may offer potential benefits in managing cancer-related toxicities other than oral mucositis. Nevertheless, further research to establish conclusive evidence is still missing. Methods: A panel of specialists conducted a narrative review to evaluate the evidence on PBM therapy for oral mucositis, xerostomia, dysgeusia, dysphagia, and trismus/fibrosis. Each topic was reviewed by two specialists who discussed treatment rationale, summarized current evidence, evaluated risk/benefit ratio, and identified future research directions. Results: The current evidence suggests promising outcomes in nonroutine uses of PBM for xerostomia, dysgeusia, odynophagia, oral mucositis (extraoral PBM and the pediatric population), and trismus/fibrosis. However, the primary studies are often small and may have biases that require further evaluation, particularly regarding treatment safety. Conclusion: Despite the overall positive impression of PBM therapy for oral adverse events of cancer treatment, robust evidence from large multicentered studies is necessary to support its widespread clinical use.

Objectives: To assess the predictive value of different dosimetric parameters for acute radiation oral mucositis (ROM) in head and neck cancer (HNCs) patients treated with carbon-ion radiotherapy (CIRT)., Methods: 44 patients with HNCs treated with CIRT were evaluated for acute ROM which was defined as severe when the score ≥3 (acute ROM was scored prospectively using the Radiation Therapy Oncology Group (RTOG) score system). Predictive dosimetric factors were identified by using univariate and multivariate analysis., Results: Male gender, weight loss >5%, and total dose/fractions were related factors to severe ROM. In multivariate analysis, grade ≥3 ROM was significantly related to the Dmax, D10, D15, and D20 (P < 0.05, respectively). As the receiver operating characteristics (ROC) curve shows, the area under the curve (AUC) for D10 was 0.77 (p = 0.003), and the cutoff value was 51.06 Gy (RBE); The AUC for D15 was 0.75 (p = 0.006), and the cutoff value was 42.82 Gy (RBE); The AUC for D20 was 0.74 (p = 0.009), and the cutoff value was 30.45 Gy (RBE); The AUC for Dmax was 0.81 (p < 0.001), and the cutoff value was 69.33 Gy (RBE)., Conclusion: Male gender, weight loss, and total dose/fractions were significantly association with ROM. Dmax, D10, D15 and D20 were identified as the most valuable predictor and we suggest a Dmax limit of 69.33 Gy (RBE), D10 limit of 51.06 Gy (RBE), D15 limit of 42.82 Gy (RBE), and D20 limit of 30.45 Gy (RBE) and for oral mucosa., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Photobiomodulation (PBM) is a laser-based therapy used to promote tissue repair, reduce inflammation and pain, and has been extensively studied in chemo- and radiotherapy-induced oral mucositis (OM). This review examines the level of evidence of systematic reviews (SRs) that have investigated PBM in such cases of OM., Materials and Methods: SRs evaluating PBM for both the treatment and prevention of OM in patients undergoing chemotherapy and/or radiotherapy and published before November 30, 2023, on PubMed, Cochrane, Embase, Web of Science, LILACS, TRIP and Open Grey databases were eligible for inclusion. We assessed the level of methodological and meta-analytic procedures., Results: Of the 1201 SRs, 21 that met the inclusion criteria were included. The quality of evidence was assessed using the Assessing the Measurement Tool to Assess Systematic Reviews (AMSTAR2), and the majority was of critically low quality (n = 15, 71.4%) with only 28.5% of low quality. A total of 40 meta-analytic estimates were obtained and analyzed. Approximately 87.5% of the meta-analysis were significant (n = 33), but only one meta-analyses had a strength of "highly suggestive", while the rest were classified as "weak". When analyzing the overlap values, the covered area was 12.14% and the corrected covered area was 7.75%, indicating a moderate overlap. Only 4 SRs had a very high overlap and one had a high overlap., Conclusion: The efficacy of PBM in the treatment of chemotherapy-induced OM is supported by low to critically low quality SRs and meta-analysis of low strength. This review highlights important areas that need to be addressed in future research on this topic., Registration: CRD42023484013 (PROSPERO)., (© 2024. The Author(s).)

This network meta-analysis aims to compare the clinical efficacy of seven non-surgical therapies for peri-implant disease, including laser treatment, photobiomodulation therapy (PBMT), photodynamic therapy (PDT), systemic antibiotics (SA), probiotics, local antimicrobials (LA), and air-powder polishing (APP) combined with mechanical debridement (MD). We conducted searches in four electronic databases, namely PubMed, Embase, Web of Science, and The Cochrane Library, to identify randomized controlled trials of non-surgical treatments combined with MD for individuals (aged at least 18 years) diagnosed with peri-implantitis or peri-implant mucositis with a minimum of 3 months follow-up. The outcomes of the study were the reduction in pocket probing depth (PPD) and bleeding on probing (BoP), plaque index (PLI), clinical attachment level (CAL), and marginal bone loss (MBL). We employed a frequency random effects network meta-analysis model to combine the effect sizes of the trials using standardized mean difference (SMD) and 95% confidence intervals (CIs). Network meta-analyses include network plots, paired comparison forest plots, league tables, funnel plots, surface under the cumulative ranking area (SUCRA) plots, and sensitivity analysis plots. The results showed that, for peri-implantitis, PBMT +MD demonstrated the highest effect in improving PPD (SUCRA = 75.3%), SA +MD showed the highest effect in improving CAL (SUCRA = 87.4%, SMD = 2.20, and 95% CI: 0.38 to 4.02) and MBL (SUCRA = 99.9%, SMD = 3.92, and 95% CI. 2.90 to 4.93), compared to MD alone. For peri-implant mucositis, probiotics +MD demonstrated the highest effect in improving PPD (SUCRA = 100%) and PLI (SUCRA = 83.2%), SA +MD showed the highest effect in improving BoP (SUCRA = 88.1%, SMD = 0.77, and 95% CI: 0.27 to 1.28), compared to MD alone. Despite the ranking established by our study in the treatment of peri-implant disease, decisions should still be made with reference to the latest treatment guidelines. There is still a need for more high-quality studies to provide conclusive evidence and especially a need for studies regarding direct comparisons between multiple treatment options., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Photobiomodulation therapy (PBMT) has been employed for the prevention and treatment of oral mucositis in patients with head and neck cancer undergoing treatment. However, information about the survival of patients receiving PBMT is still lacking. Therefore, the aim of this study was to correlate the survival of patients who either received or did not receive PBMT, combined with cancer treatments, and to assess whether the number of PBMT sessions had a positive impact on survival., Methods: The records of 751 patients seen at Hospital de Caridade São Vicente de Paulo diagnosed with head and neck cancer, treated by D.L.P., the sole operator of PBMT, between 2000 and 2016, were analyzed. The median survival rates were compared by analyzing diagnostic staging, the combination of cancer treatments, and the number of PBMT sessions. Correlation analyses were performed to assess the interactions between the number of PBMT sessions and survival., Results: PBMT increased survival by 55.14 %, from 1.07 (Without PBMT) to 1.66 years (With PBMT) for the total population and more significantly in Group 41 (stages III and IV, radiation therapy/chemotherapy, with more than five PBMT sessions), the median survival value of 1.83 years, which represents a 66.36 % higher survival rate. In all the analyzed populations, the larger number of sessions was associated with better survival. In terms of survival, advanced stages III and IV almost equated with stages I and II in the absence of PBMT., Conclusions: PBMT seems to interfere with the survival of patients with head and neck cancer, corroborating its recommendation for the treatment of mucositis, but further research is needed to investigate possible synergistic effects between PBMT and cancer treatments., Competing Interests: Declaration of competing interest Declaration of Competing Interest None., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: Considering the tumor in the oral cavity or the oropharynx and nasopharynx region might be an aggravating factor for oral mucositis (OM) manifestation, the present study aimed to evaluate whether the location of the tumor and the use of photobiomodulation therapy (PBMT) might affect the frequency of oral candidiasis (OC) during radiotherapy (RT) and/or chemotherapy (CT) treatments., Methods: The medial records of seventy-four patients with head and neck cancer treated in a public service from 2016 to 2019 were evaluated. All these patients were submitted to RT in an accumulated dose of 48 to 70 Gy of radiation. Data about OM and OC were collected and presented according to the application of a therapeutic protocol with laser photobiomodulation (PBMT) to control oral mucositis, or not (No-PBM), and the location of tumor (head and neck or oral cavity). In the PBMT group patients, a low-power laser device composed of InGaAlP diode (maximum output power of 86.7 mW, active tip area of 0.1256 cm 2 , and continuous wavelength of 660 nm), was applied to the lips (three points each), right and left jugal mucosa (three points each), the limit between hard and soft palate (three points), buccal floor/sublingual gland (one point), lateral edge of the tongue (three points on each side), and back of the tongue (six points), three times weekly, for 5 weeks. The dosimetry used in each application was 2 J for 3 s, thus totaling 56 J. The correlation between clinical characteristics such as age, tumor size (T), metastatic lymph node (N), number of RT and CT sessions, candidiasis, and OM were analyzed., Results: Mucositis grades 1 and 2 were the most common among all patients, especially before the 12th radiotherapy session, regardless of the treatment with PBM (p > 0.05). Additionally, no difference in the grade of OM and OC was significantly observed when comparing the two laser therapy groups. OC was more frequent after the 12th radiotherapy session in all groups. Nonetheless, OM and OC had a different correlation regarding to tumor location (head and neck and oral cavity) being PBMT a positive therapy to delay OM. It was observed a positive and statistically significant correlation between tumors at oral cavity and OM, regardless PBMT (R = 0.84, p < 0.05 to PBMT and R = 0.13, p < 0.05 to No-PBM). Otherwise, OC was positively correlated to local metastasis in patients with oral tumors undergoing PBMT (R = 0.84, p < 0.05)., Conclusion: Patients with oral cavity tumor presented more OM, especially high grades, then patients with tumors in other regions of the head and neck, which seems to be related to the irradiation parameters of radiotherapy and/or with the limitation of conduction of PBMT in tumor areas. OM and OC were not changed by PBMT, although it helped to reduce the incidence of severe cases of OM., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Photobiomodulation therapy is recommended by multiple international societies for managing oral mucositis. These recommendations are based on extensive evidence. However, the search for an optimal photobiomodulation protocol continues. This mapping review focuses on a novel aspect of photobiomodulation therapy which is the immediate effect on pain levels associated with oral ulcerative conditions., Data Sources: This literature review systematically compiles and evaluates the evidence about oral mucositis, alongside other oral ulcerative conditions, as the protocols that achieved pain relief for these oral conditions may have potential applicability to oral mucositis management. The scientific database used was PubMed., Conclusion: Whereas most of the randomized controlled trials about photobiomodulation therapy for oral mucositis and other ulcerative oral diseases reported delayed pain relief, certain photobiomodulation therapy protocols reported immediate pain relief. The results of this review highlight the concept of preemptive photobiomodulation therapy, in which photobiomodulation therapy is delivered early in the development of oral mucositis throughout the oncotherapy and may achieve immediate pain relief consistently in most of the patients and close to a negligible pain level. Photobiomodulation therapy, as a powerful nonpharmacologic tool for immediate pain relief, has a great beneficial value in patients suffering from oral mucositis and other painful oral ulcerative diseases such as recurrent aphthous stomatitis and chronic graft-versus-host disease.

Background/aim: Aiming to resolve debates on honey's efficacy for radiotherapy-induced severe oral mucositis in head and neck cancer, we conducted a meta-analysis focused on randomized trials, primarily assessing severe mucositis incidence. Secondary outcomes included weight loss, pain management, and honey types., Materials and Methods: A comprehensive literature search was conducted in PubMed, Embase, WOS, and the Cochrane Library up to December 2023. The analysis concentrated on randomized controlled trials that assessed the efficacy of honey, targeting the incidence of mucositis as the main outcome. Additional outcomes explored were weight loss, intolerable pain, and the specific types of honey used in interventions. Data analysis was performed using CMA software, and a funnel plot was employed to identify publication bias., Results: The analysis of 176 records resulted in the inclusion of 10 studies with 599 patients receiving radiotherapy. The research showed that honey significantly reduced the occurrence of grade 3-4 mucositis (severe mucositis), provided significant pain relief, and had a positive effect on reducing weight loss. Regarding the type of honey used, no significant differences were found in their effectiveness in alleviating severe mucositis., Conclusion: Honey serves as an effective intervention for individuals with oral mucositis. It can be considered as an adjuvant in the management of clinical radiotherapy-associated oral mucositis, particularly for patients requiring prolonged use of anti-analgesic or antifungal medications., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: We aimed to evaluate the efficacy of high-power (class IV) laser photobiomodulation (PBM) therapy for immediate pain relief due to oral mucositis (OM) refractory to recommended first-line therapy., Methods: This retrospective study included 25 cancer patients with refractory chemotherapy- or radiotherapy-induced OM (16 and 9 patients, respectively) that were treated for pain relief with an intraoral InGaAsP diode laser (power density = 1.4 W/cm 2 ). Pain was self-assessed immediately before and after laser treatment using a 0-to-10 numeric rating scale ([NRS], "0" = no pain, "10" = intolerable pain)., Results: Patients reported an immediate decrease in pain following 94% (74 of 79) of the PBM sessions, in 61% (48 sessions) the pain reduction was over 50%, and in 35% (28 sessions) the initial pain was completely eliminated. There were no reports of increased pain post-PBM. For chemotherapy and radiotherapy-treated patients, mean reduction in pain NRS post-PBM was 4.8 ± 2.5 (p < 0.001) and 4.5 ± 2.8 (p = 0.001), indicating a post-PBM reduction of 72% and 60% of the initial pain level, respectively. The analgesic benefit of PBM remained for a mean of 6.0 ± 5.1 days. One patient reported a transient burning sensation after one PBM session., Conclusions: High-power laser PBM may provide nonpharmacologic, patient-friendly, long-lasting, rapid pain relief for refractory OM., (© 2023 The Authors. Oral Diseases published by Wiley Periodicals LLC.)

Purpose: There is increasing evidence that photobiomodulation (PBM) therapy is both an effective and safe approach in hematopoietic stem cell transplantation (HSCT) for both prevention and management of oral mucositis (OM), but its use in clinical practice is still limited and the timing of application is under discussion. The aim of this retrospective study was to evaluate possible differences between patients treated either with preventive or curative PBM therapy., Methods: The retrospective case series included 24 patients suffering from multiple myeloma who underwent the same conditioning and transplantation protocol. Patients were treated either with preventive PBM starting from the first day of conditioning up to two days post-HSCT or with curative PBM (starting at OM onset for four consecutive days). OM score, pain, and functional parameters were recorded., Results: All patients developed OM. Preventive PBM was significantly more effective in reducing OM severity (p < 0.0001) and pain (p < 0.0001) post-HSCT than curative PBM. Furthermore, we found a lower number of patients reporting discomfort in all subjective parameters (pain during swallowing, chewing, and speaking) in the preventive PBM group. No adverse events related to PBM therapy were recorded in both groups., Conclusion: The timing for PBM therapy in patients undergoing HSCT is crucial: when started on the first day of conditioning, it significantly reduces both pain and OM severity, providing an important benefit also in subjective oral functions such as speaking, swallowing, and chewing, thus increasing the overall adherence to the oncological therapies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aim of this study was to perform a systematic review to evaluate the impact of photobiomodulation therapy (PBMT) for the prevention of oral mucositis (OM) on the quality of life (QoL) of patients with head and neck cancer (HNC) undergoing radiation therapy. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The search strategy was performed in five electronic databases (Cochrane, Embase, PubMed, Scopus, and Web of Science). The included studies assessed the QoL of patients undergoing radiation therapy (RT) for HNC and undergoing PBMT for the management of OM. Seven articles met the eligibility criteria. Data extraction was performed in the selected studies including the PBMT parameters (active medium, application procedure, wavelength, fluence, power, irradiance, irradiation time, spot size, energy per point, schedule of irradiation, and total energy). The included studies were qualitatively analyzed, and descriptive analyses were performed. Also, summary results were evaluated for group comparison analysis. All included studies confirmed a decrease in the QoL of the patients that developed OM throughout the RT progress when compared to baseline. Of the informed cases, most of the patients who received PBMT showed grades 1 and 2 OM, while the control group showed more individuals with severe forms of OM (grades 3 and 4). In this sense, patients submitted to PBMT reported better QoL at the end of the treatment compared with the control group. PBMT used for the management of OM preserves the QoL of patients with head and neck cancer., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Photobiomodulation therapy (PBMT) is recommended for prevention and treatment of oral mucositis, a painful condition that occurs in cancer patients. Intraoral PBMT is limited to treating distal oral mucosa and oropharynx. Extraoral PBMT may provide a more efficient intervention. The goal of this study was to develop a clinically viable protocol for extraoral PBMT. Monte Carlo modeling was used to predict the distribution of 850 nm light for four treatment sites, using anatomical data obtained from MRI and optical properties from the literature. Simulated incident light power density was limited to 399 mW/cm 2 to ensure treatment safety and to prevent tissue temperature increase. The results reveal that total tissue thickness determines fluence rate at the oral mucosa, whereas the thickness of individual tissue layers and melanin content are of minor importance. Due to anatomical differences, the fluence rate varied greatly among patients. Despite these variations, a universal protocol was established using a median treatment time methodology. The determined median treatment times required to deliver efficacious dose between 1 and 6 J/cm 2 were within 15 min. The developed PBMT protocol can be further refined using the combination of pretreatment imaging and the Monte Carlo simulation approach implemented in this study., (© 2023. The Author(s).)

Background: Oral mucositis (OM) is a common adverse effect of radiation to the head and neck. Recent research has shown that extra oral photobiomodulation (EO-PBM) reduces the severity of OM. However, appropriate EO-PBM therapy parameters for OM severity reduction have not been documented. Objective: This work aims to optimize EO-PBM radiation parameters for lowering the severity of radiation-induced OM in rats by establishing a photobiomodulation (PBM) treatment system based on light-emitting diode arrays with top-hat beam profile. Methods: The 36 rats are separated into 2 control groups and 4 groups receiving PBM treatment. The PBM groups are exposed to irradiance between 4 and 24 J/cm 2 at 660 nm. The cheek pouch mucosa is removed after scarification for biochemical and histological examination. Student's t -test, and one-way analysis of variance (ANOVA) followed by Tukey's Multiple were applied to compare the statistical significance of differences between control groups and PBM treatment groups. Results: Statistical analysis reveals that PBM irradiation at 12 J/cm 2 (200 sec) with a flatness of 0.8 and a diameter of 3 cm substantially decreased the level of inflammatory cytokines compared with the positive control group. Conclusions: Our results indicate that the designed treatment PBM system is capable of delivering the optical parameters necessary for therapeutic treatment.

Objective: To systematically summarize the evidence for photobiomodulation therapy (PBMT) in the prevention and treatment of oral mucositis (OM) in patients undergoing cancer treatment. An electronic search was conducted in 8 databases and grey literature. Background: PBMT is recommended for the management of OM resulting from cancer treatment, with several systematic reviews (SRs) being published in recent years on this topic. Methods: Only SRs with outcomes from clinical trials were included, with no language or year restriction. The AMSTAR 2 tool was used to assess the methodological quality of the SRs. Results: Five thousand eight hundred fifty-six references were found, and 16 were selected for this review. OM prevention and treatment were favorable for PBMT in most studies, with a significant reduction in OM severity. Most studies obtained moderate confidence. Conclusions: PBMT represents an effective strategy in the management of OM, and this evidence is supported by studies with acceptable methodological quality.

Oral mucositis is a common and debilitating side effect induced by stem cell transplantation that is experienced by cancer patients undergoing chemotherapy or radiation therapy. This condition involves inflammation and ulceration of the oral mucosa, leading to pain, difficulty with eating and speaking, and an increased risk of infections. Mucositis not only compromises the quality of life for cancer patients, but also affects treatment outcomes and may necessitate dose reductions or treatment delays. This scientific article provides a comprehensive overview of mucositis. The purpose of this literature review with a meta-analysis is to evaluate the efficacy of laser therapy in treating post-transplant mucositis. Materials and methods : A search of the literature from 3 May 2023 was carried out on three online databases, PubMed, Scopus, and Web of Science. Only studies that treated patients with laser therapy were considered; only studies with the placebo-treated control group were considered. Review Manager version 5.2.8 (Cochrane Collaboration) was used for the pooled analysis. We measured the std. mean difference between the two groups (laser and placebo). Results : There were 230 papers included in this review. Two hundred twenty-seven were excluded. Furthermore, a manual search was performed. After the search phase, three articles were considered in the study. The overall effect showed differences in the degree of mucositis in the laser-treated patients compared with the placebo group. The meta-analysis shows a reduction in the degree of mucositis in the patients treated with laser therapy (std. mean difference -1.34 [-1.98; -0.98]; C.I. 95%). Conclusions : The application of laser therapy results in decreased severity of oral mucositis from radiation and chemotherapy. Our study shows that the application of low-level laser therapy in the treatment of transplant mucositis has excellent efficacy in relieving the symptoms and severity of mucositis.

Objective: Our objective was to review the first 20 years of photobiomodulation (PBM) clinical studies for oral mucositis (OM) mitigation., Study Design: A scoping review screened controlled clinical studies. The PBM devices, protocols, and clinical outcomes were analyzed., Results: Seventy-five studies met the inclusion criteria. The first study dated from 1992, and the term "PBM" was first published in 2017. Public services, placebo-controlled randomized trials, and patients with head and neck chemoradiation were predominant among included studies. Prophylactic red intraoral laser protocols were mostly used. Comparing the outcomes of all protocols was unfeasible due to missing treatment parameters and nonhomogeneous measurements., Conclusions: The main barrier to optimizing clinical protocols of PBM for OM was the lack of standardization in clinical studies. Although PBM use is now globally present in oncology settings and generally marked by good outcomes reported, additional randomized clinical trials with well-described methods are necessary., (Copyright © 2022 Elsevier Inc. All rights reserved.)

To evaluate the applicability of photobiomodulation therapy (PBM-T) in the management of xerostomia and OM. Fifty-three patients with head and neck squamous cell carcinoma were randomized into two groups: Sham and PBM-T. The Sham group received artificial saliva and laser simulation, while the PBM-T group received artificial saliva and PBM-T. Xerostomia-related quality of life (QoL), the presence or absence of OM lesions, the decayed-missing-filled teeth (DMFT) index, and periodontal charts were evaluated. The results of the QoL questionnaire, DMFT index, and periodontal chart were analyzed with the Kruskal-Wallis test, followed by the Student-Newman-Keuls test, while OM findings were compared using the Mann-Whitney test. QoL scores significantly increased in the Sham group (p < 0.0001), denoting more severe xerostomia symptoms (p = 0.0074), and decreased in the PBM-T group, indicating no or very mild xerostomia. Higher grades of OM were found in the Sham group than the PBM-T group (p = 0.0001). There was no significant difference in DMFT index or periodontal charts between the groups (p > 0.05). PBM-T improved QoL in patients with head and neck cancer treated with radiotherapy, whether as radiation alone or as an adjunct to chemotherapy and surgery., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

The early detection and management of peri-implant mucositis may help in reducing inflammatory parameters and arrest disease progression to peri-implantitis. The potential therapeutic benefits of different adjunctive therapies, such as the diode laser, are still not completely understood. The objective of this systematic review and meta-analyses was to assess the outcomes of using diode laser on the management of peri-implant mucositis in terms of changes in periodontal parameters. Electronic databases were searched to identify randomised controlled trials (RCTs) that compared the combined use of mechanical debridement and diode laser with mechanical debridement alone. A specific risk-of-bias tool was used to assess the risk of bias. Data were analysed using a statistical software programme. In total, 149 studies were found. A meta-analysis of 3 RCTs showed no statistically significant differences in probing pocket depths (mean difference [MD], -0.36; 95% confidence interval [CI], -0.88 to 0.16; P = .18) or bleeding on probing (MD, -0.71; 95% CI, 1.58-0.16; P = .11) between the 2 groups at 3 months. In the management of peri-implant mucositis, the combined use of diode laser and mechanical debridement did not provide any additional clinical advantage over mechanical debridement alone. Long-term, well-designed RCTs are still needed., Competing Interests: Conflict of interest None disclosed., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Oral mucositis is a debilitating and painful complication of head and neck cancer irradiation that is characterised by inflammation of the mucous membranes, erythema and ulceration. Oral mucositis affects 6000 head and neck cancer patients per year in England and Wales. Current treatments have not proven to be effective. International studies suggest that low-level laser therapy may be an effective treatment., Objectives: To assess the clinical effectiveness and cost-effectiveness of low-level laser therapy in the management of oral mucositis in head and neck cancer irradiation. To identify barriers to and facilitators of implementing low-level laser therapy in routine care., Design: Placebo-controlled, individually randomised, multicentre Phase III superiority trial, with an internal pilot and health economic and qualitative process evaluations. The participants, outcome assessors and therapists were blinded., Setting: Nine NHS head and neck cancer sites in England and Wales., Participants: A total of 87 out of 380 participants were recruited who were aged ≥ 18 years and were undergoing head and neck cancer irradiation with ≥ 60 Gy., Intervention: Random allocation (1 : 1 ratio) to either low-level laser therapy or sham low-level laser therapy three times per week for the duration of irradiation. The diode laser had the following specifications: wavelength 660 nm, power output 75 mW, beam area 1.5 cm 2 , irradiance 50 mW/cm 2 , exposure time 60 seconds and fluence 3 J/cm 2 . There were 20-30 spots per session. Sham low-level laser therapy was delivered in an identical manner., Main Outcome Measure: The mean Oral Mucositis Weekly Questionnaire-Head and Neck Cancer score at 6 weeks following the start of irradiation. Higher scores indicate a worse outcome., Results: A total of 231 patients were screened and, of these, 87 were randomised (low-level laser therapy arm, n  = 44; sham arm, n  = 43). The mean age was 59.4 years (standard deviation 8.8 years) and 69 participants (79%) were male. The mean Oral Mucositis Weekly Questionnaire-Head and Neck Cancer score at 6 weeks was 33.2 (standard deviation 10) in the low-level laser therapy arm and 27.4 (standard deviation 13.8) in the sham arm., Limitations: The trial lacked statistical power because it did not meet the recruitment target. Staff and patients willingly participated in the trial and worked hard to make the LiTEFORM trial succeed. However, the task of introducing, embedding and sustaining new low-level laser therapy services into a complex care pathway proved challenging. Sites could deliver low-level laser therapy to only a small number of patients at a time. The administration of low-level laser therapy was viewed as straightforward, but also time-consuming and sometimes uncomfortable for both patients and staff, particularly those staff who were not used to working in a patient's mouth., Conclusions: This trial had a robust design but lacked power to be definitive. Low-level laser therapy is relatively inexpensive. In contrast with previous trials, some patients found low-level laser therapy sessions to be difficult. The duration of low-level laser therapy sessions is, therefore, an important consideration. Clinicians experienced in oral cavity work most readily adapt to delivering low-level laser therapy, although other allied health professionals can be trained. Blinding the clinicians delivering low-level laser therapy is feasible. There are important human resource, real estate and logistical considerations for those setting up low-level laser therapy services., Future Work: Further well-designed randomised controlled trials investigating low-level laser therapy in head and neck cancer irradiation are needed, with similar powered recruitment targets but addressing the recruitment challenges and logistical findings from this research., Trial Registration: This trial is registered as ISRCTN14224600., Funding: This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 26, No. 46. See the NIHR Journals Library website for further project information.

Purpose: To evaluate the impact of photobiomodulation for oral mucositis on body weight and body mass index (BMI) in head and neck cancer patients., Methods: Patients were separated into two groups: photobiomodulation (PBM) (n = 17) and SHAM (n = 19). Participants assigned to the PBM group received the photobiomodulation therapy on alternate days at 33 different sites of the oral mucosa (1 J for 10 s per application point) using a low-power aluminum gallium arsenide (AsGaAl) laser device with a maximum output power of 86.7 mW and a wavelength of 660 nm (red). The same protocol was performed in patients allocated in the SHAM group but with the device turned off. At the first and twenty-fourth radiotherapy sessions, participants from both groups underwent an intraoral examination to assess the presence or absence of mucositis using the WHO scale, and measurements of weight and height for BMI calculation were undertaken., Results: All patients had significant differences in weight and BMI throughout the study period. Patients in the PBM group lost less weight (p < 0.01) and had a reduced BMI loss (p < 0.01) in comparison to patients in the SHAM group. Although PBM did not prevent oral mucositis, it decreased its severity (p < 0.01)., Conclusion: Photobiomodulation for oral mucositis reduced weight loss and prevented a reduction in BMI in patients who underwent chemoradiotherapy for head and neck cancer. Retrospectively registered at https://data.mendeley.com//datasets/4kd7s49wk4/1 ., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Healthcare professionals require effective treatment options for managing the complications that may arise during cancer treatment. The Multinational Association of Supportive Care in Cancer (MASCC) and the International Society of Oral Oncology (ISOO) work together to reduce oral complications secondary to cancer, including difficulties associated with oral mucositis (OM). The present article is intended to summarize the MASCC/ISOO guidelines, which are updated periodically based on the most recent evidence supporting the multiple treatment options for OM caused by chemotherapy and radiotherapy used to treat head and neck tumors. The Mucositis Study Group (MSG) of MASCC/ ISOO conducted systematic reviews of the current literature pertaining to several interventions, including anti-inflammatory agents; basic oral care; vitamins, minerals, and nutritional supplements; and photobiomodulation. The MSG then categorized the effectiveness of each treatment for preventing OM or reducing the severity, duration, and reported pain of patients with OM based on the type of cancer being treated, the cancer treatment modality (chemotherapy, radiotherapy, or combination therapy), and the goals of the OM treatment (preventive or therapeutic). The present article also describes a case demonstrating the positive effects of using various laser devices to heal the symptoms of OM in a patient undergoing radiotherapy and chemotherapy for a squamous cell carcinoma at the base of the tongue., Competing Interests: Dr Walinski is a consultant for Biolase, one of the devices used in this article. The patient was treated with a Biolase laser at a different institution by a different author who has no relationship with Biolase. The other authors report no conflicts of interest pertaining to any of the products or companies discussed in this article.

Objective: To assess the efficacy of oral low-level laser therapy (LLLT) - also known as photobiomodulation - in the reduction of oral mucositis experienced by children and young people with cancer undergoing chemotherapy., Design: A systematic review to evaluate the efficacy of oral LLLT for oral mucositis in children with cancer and the safety of oral LLLT in any age with cancer (International Prospective Register of Systematic Reviews/PROSPERO registration: CRD42018099772). Multiple databases and grey literature were screened. Randomised controlled trials were considered for assessing efficacy, and all studies were considered for assessing safety. Primary outcomes included severity of oral mucositis, oral pain and adverse events. Where results were compatible, meta-analysis was performed using a random-effects model. A narrative synthesis considered other outcome measures., Results: 14 studies (n>416 children) were included in the narrative synthesis of LLLT efficacy. 5 studies (n=380 children and young people) were included in the meta-analyses. Results demonstrate that LLLT may reduce the severity of oral mucositis and the level of oral pain, but further randomised controlled trials are needed to confirm or deny this. There is vast variation in different trial protocols. Insufficient blinding between LLLT or sham therapy/control led to a strong risk of performance bias. 75 studies (encompassing 2712 patients of all ages who had undergone LLLT) demonstrated minor and infrequent adverse reactions, but most studies had significant areas of weakness in quality., Conclusion: LLLT appears to be a safe therapy, but further evidence is needed to assess its efficacy as a prevention or treatment tool for oral mucositis in children with cancer., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Photobiomodulation (PBM) consists of a photon energy transfer to the cell, employing non-ionizing light sources belonging to the visible and infrared spectrum. PBM acts on some intrinsic properties of molecules, energizing them through specific light wavelengths. During the evolution of life, semiconducting minerals were energized by sun radiation. The molecules that followed became photoacceptors and were expressed into the first proto-cells and prokaryote membranes. Afterward, the components of the mitochondria electron transport chain influenced the eukaryotic cell physiology. Therefore, although many organisms have not utilized light as an energy source, many of the molecules involved in their physiology have retained their primordial photoacceptive properties. Thus, in this review, we discuss how PBM can affect the oral microbiota through photo-energization and the non-thermal effect of light on photoacceptors (i.e., cytochromes, flavins, and iron-proteins). Sometimes, the interaction of photons with pigments of an endogenous nature is followed by thermal or photodynamic-like effects. However, the preliminary data do not allow determining reliable therapies but stress the need for further knowledge on light-bacteria interactions and microbiota management in the health and illness of patients through PBM.

Background and Aim: Oral mucositis (OM) is a common side effect of systemic chemotherapy (CT) in cancer patients. The aim was to evaluate the effect of low-level laser therapy (LLLT) for the treatment of CT-induced OM children., Patients and Methods: The study was carried out in 40 pediatric patients 3 to 18 years of age, who were hospitalized for the diagnosis of leukemia and underwent CT between June 1, 2019, and December 31, 2019. They were randomly divided into 2 groups with 20 cases in each group. The LLLT group was treated with GaAlAs diode laser (l): 830 nm (infrared), power: 150 mW, dose: 4.5 J/cm2 and the control group underwent bicarbonate treatment. Patients received intervention for 3 days. The grade of OM was clinically assessed by the World Health Organization (WHO) Common Toxicity Criteria Scale. Visual Analog Scale was used on the same days with OM grade to evaluate the pain status., Results: While there was no significant difference between the groups in terms of OM grade at the beginning of the treatment and on the first, second, fourth, and 11th days of the treatment, the average OM grade of the LLLT group was found to be statistically significantly lower on the third, fifth, sixth, and seventh days of the treatment. The Visual Analog Scale score of the LLLT group was statistically significantly lower compared with the control group at all examinations starting from the first day of treatment (P<0.05)., Conclusion: In the treatment of oral OM that occurs in children after CT, both standard care and LLLT treatment improve the grade and pain of OM., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate the current and potential indications of photobiomodulation (PBM) and their level of evidence in the prevention or management of radiation therapy-related side effects., Materials and Methods: The Embase, Medline/PubMed, Cochrane, EBSCO, Scopus, and LILACS databases were systematically reviewed to include and analyze publications of clinical studies that have assessed PBM in the prevention or management of radiotherapy-related side effects. The keywords used were "photobiomodulation"; "low level laser therapy"; "acute oral mucositis"; "acute dysphagia"; "acute radiation dermatitis"; "lymphedema"; "xerostomia"; "hyposalivation"; "trismus"; "bone necrosis"; "osteoradionecrosis"; and "radiation induced fibrosis". Prospective studies were included, whereas retrospective cohorts and non-original articles were excluded from the analysis., Results: PBM in the red or infrared spectrum has demonstrated efficacy in randomized controlled trials in the prevention and management of radiotherapy-related side effects, especially acute oral mucositis, acute radiation dermatitis, and upper extremity lymphedema. The level of evidence associated with PBM was heterogeneous, but overall was still moderate. The main shortcomings were the diversity and lack of detail in treatment protocols, which could have compromised efficiency and reproducibility of PBM results., Conclusion: The published data suggest that PBM may be considered as a full-fledged supportive care for patients treated with radiotherapy, or at least in the setting of a therapeutic clinical trial. However, until strong evidence has been published on its long-term safety, the use of PBM should be considered with caution, specifically when applied near areas with proven or potential tumors. The patient should be informed of the theoretical benefits and risks of PBM in order to obtain his informed consent before treatment., (Copyright © 2021. Published by Elsevier Masson SAS.)

To assess the effectiveness of photobiomodulation therapy (PBMT) in the oral health-related quality of life (OHRQoL) of patients with head and neck cancer undergoing radiotherapy (RT), using the Oral Health Impact Profile-14 (OHIP-14) and the Patient-Reported Oral Mucositis (OM) Symptoms Scale (PROMS), and to correlate OM degree with the PROMS and OHIP-14 scores. Forty-eight patients undergoing RT for head and neck cancer were randomly assigned into two groups: PBMT group (n = 25)-daily PBMT associated with a preventive oral care program (POCP); and control group (n = 23)-receiving POCP exclusively. OHRQoL was assessed using the PROMS and OHIP-14 questionnaires. OM degrees were classified according to the World Health Organization and the National Cancer Institute scales. Assessments were performed at the 1st, 7th, 14th, 21st, and 30th RT sessions. PBMT was effective in preventing and treating severe OM. Both groups showed increased OHRQoL impacts throughout the RT sessions; however, higher impacts were observed in the control group, mainly at the final stage of treatment (21st and 30th RT sessions). Significant correlations were found between the severity of OM and PROMS scores in the total sample and the control group at all RT periods. PROMS and OM scores were positive correlated at 14th, 21st, and 30th RT sessions in the control group, suggesting that this instrument is useful in classifying OM. PBMT was effective in treating and preventing severe OM and OM-related symptoms, and with consequent positive impacts in OHRQoL in head and neck patients undergoing RT. The PROMS scale was helpful instrument for assessment of the severity of OM. Brazilian Clinical Trials database (ReBEC - RBR-5h4y4n), registered in Aug, 24th 2017.

Introduction: Oral mucositis (OM) is a severe side effect in patients undergoing anticancer therapies, which negatively impacts on their quality of life often leading to either the interruption of the therapy. Photobiomodulation (PBM) is emerging as an effective strategy allowing a faster wound healing., Objectives: This pilot study aims at verifying whether PBM modulates the inflammatory response in patients and its effect on the oral microbiome composition., Materials and Methods: Buccal swabs were collected from four patients affected by OM, both on ulcerated and clinically healthy areas, before and on the last day of PBM therapy, as well as on the first day after treatment discontinuation. The concentration of 38 cytokines and the composition of oral microbiome were measured., Results: Most of the pro-inflammatory cytokines were reduced, whereas anti-inflammatory cytokines resulted up-regulated by PBM. In addition, PBM influenced the composition of oral microbiome, by decreasing the amount of pathogenic species and promoting the growth of commensal bacteria. These changes were even more evident when separately analysing patients who clinically responded to PBM and the only patient who did not respond., Conclusions: PBM reduces inflammatory burden in patients affected by OM and positively influences the composition of the oral microbiome.

Oral complications of cancer therapy, such as oral dryness, dysphagia, and taste alteration, are associated with a negative impact in the quality of life of the patients. Few supportive care measures are available for such complications. This case series reveals the effectiveness of the photobiomodulation (PBM) therapy when used in a specific protocol and parameters, in the management of oral complications related to cancer therapy. Dysphagia was measured using the functional outcome swallowing scale for staging oropharyngeal dysphagia (FOSS). Oral mucositis was measured according to the National Cancer Institute scale. The quantity of the whole resting and stimulated saliva was measured in order to assess the oral dryness. In addition, the taste alteration was measured according to a protocol suggested by the International Standards organization (ISO). Sensation of burning mouth was measured using a visual analogue scale. These measurements were made before treatment, during, and at the end of the treatment. Diode laser 635 nm was used in 3 J/cm 2 . Five sessions interleaved with 24 h breaks were conducted for the dysphagia and oral dryness, and 10 sessions were conducted for the taste alteration and burning mouth sensation. Regardless of the limitations of this case series, PBM can be considered safe, time saving, and a promising approach for the management of the oral complications due to cancer therapy and the quality of life of cancer patients.

Cancer treatment with chemotherapy or radiotherapy is associated with some side effects including in the oral cavity. One of the more significant oral complications is oral mucositis (OM) which induces severe pain and limits fundamental life behaviors such as eating, drinking, and talking. Although advancements in cancer treatment improved the survival rate, severe OM and opportunistic infection affect treatment adversely. Therefore, the control of OM is important for oral health quality of life and prognosis. Low-level laser therapy (LLLT) and photodynamic therapy (PT) are noninvasive methods that reduce inflammation and pain during wound healing. The aim of this study is to evaluate immunohistochemical and histological examination of the OM region of the PT comparing LLLT. In this study, 24 Sprague-Dawley rats were divided into three groups as control, LLLT, and PT groups. All groups received 5-fluorouracil intraperitoneally and a linear trauma to the mouth pouch with a needle. After the formation of OM in the mouth, the control group had no treatment; the LLLT group was administered LLLT, and the PT group had LLLT after indocyanine green application. Then all groups were sacrificed, and histological analyses and protein level detection of basic fibroblast growth factor (bFGF), transforming growth factor (TGF-β), and platelet-derived growth factor (PDGF-BB) were evaluated in all groups. PT was determined to be more statistically significantly than LLLT with bFGF and PDGF-BB. However, regarding TGF-β, no statistically significant difference was observed between the groups. Within the limitations of this study, indocyanine green may accelerate the LLLT effect. However, further studies on this subject are required.

Review effectiveness of low-level laser therapy (LLLT) in the curative treatment of oral mucositis (OM) in patients receiving cancer therapy. A systematic review with meta-analysis was performed using Medline, Embase, and Cochrane Library databases according to PRISMA guidelines, to identify randomized controlled trials (RCT) on OM in patients during and/or after cancer therapy and in which the therapeutic approach was LLLT, with wavelengths between 632 and 970 nm. We considered grade of OM as a dichotomous variable (such as an improvement or not in severe OM on the seventh day of therapy), with the analysis of subgroups of adult patients or children and adolescents and as a continuous variable with determination of the time for the complete resolution and the subgroup analysis occurred with the strata of the samples by treatment only with chemotherapy or chemotherapy and radiotherapy. This paper's protocol was registered a priori at https://www.crd.york.ac.uk/PROSPERO . We found five RCT (total of 315 patients) with adequate methodology. LLLT was effective, presenting a 62% risk reduction of severe mucositis on the seventh day of evaluation (RR = 0.38 [95% CI, 0.19-0.75]). When we analyzed subgroups, RR was 0.28 (95% CI 0.17-0.46) in the adult studies and 0.90 (95% CI, 0.46-1.78) in the studies with children and adolescents. We demonstrated a mean reduction of 4.21 days in the time of complete resolution of OM (CI - 5.65 to - 2.76) in favor of LLLT. There is moderate evidence that LLLT is effective in resolving OM lesions in adult patients undergoing cancer therapy. LLLT demonstrates potential for decreasing the resolution time of OM lesions by approximately 4.21 days.

Photobiomodulation is recommended in adults for the prevention of mucositis induced by cervicofacial irradiation or pre-transplant chemotherapy. The results of pediatric studies are promising but this support treatment is still underused. The objective was to conduct a feasibility study in the pediatric hematology-oncology unit at X Children's Hospital. Extra- and intraoral scans were performed a minimum of three times every 2 days for grade 2 or higher mucositis in children (median age, 8.6 years) using the Oncolase laser (Biophoton, Saint Alban, France), with a combination of two wavelengths (635 and 815nm). The effect of the laser on mucositis grade, pain, the child's tolerance, and the time dedicated to this care were also evaluated. The success of the procedure was 77% in 1 year, with the inclusion of 84% of the patients (n=22) and 146 laser treatment sessions (median of four per episode of mucositis). We observed excellent tolerance and pain relief with a gain of two points on the VAS and the HEDEN mucositis scale. This study shows that photobiomodulation that incorporates two application modes (intra- and extraoral) through the combination of two wavelengths is feasible when integrated into the care of a pediatric hematology-oncology department and is perfectly tolerated, even by young children. Along with oral hygiene and analgesic management, it alleviates pain associated with oral mucositis., (Copyright © 2019 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Dosimetry for low-level laser therapy (LLLT) depends on several parameters, such as target tissue type, lesion type and laser equipment used. This study aimed to determine the most used LLLT dosimetry for the treatment and prevention of oral mucositis (OM) resulting from radiation therapy (RT) in head and neck cancer patients (HNCP). This research was conducted according to the PRISMA guidelines using the PICO framework. After extensively searching PubMed, Web of Science, Embase, Scopus, BVS and Cochrane Library databases, we found 130 records and selected 7 studies, involving 363 HNCP with an average age of 60.6 years who received RT. Briefly, sites affected by tumors were the following: oral cavity (170), oropharynx (91), throat (42), larynx (32), nasopharynx (11), hypopharynx (9), and in 8 cases, sites were not reported. These studies used several classifications for OM (RTOG/EORTC, WHO, NCI-CTC) and pain (NRS, VAS and modified VAS). These various researchers performed the LLLT punctual application of different forms using several protocols making analysis difficult. However, LLLT was effective regardless of the parameters used (632.8 nm to 685 nm, 1.8 J/cm 2 to 3.0 J/cm 2 , 10 mW to 60 Mw, 0.8 J to 3.0 J). The meta-analysis showed a better results with preventive LLLT 660 nm, 3.8 J/cm 2 , 15 mW; 0.15 J compared to preventive LLLT 660 nm, 1.3 J/cm 2 , 5 mW; 0.05 J (OMS: p = 0.03; NCI-CTC: p = 0.027). We conclude that there is, as of yet, no evidence of better laser dosimetry being more effective. Thus, randomized clinical trials to determine which doses of LLLT are most appropriate for treating and preventing OM due to RT are lacking and should be further investigated., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Photobiomodulation therapy (PBMT), also known as low-level laser therapy (LLLT), has been increasingly used for the treatment of toxicities related to cancer treatment. One of the challenges for the universal acceptance of PBMT use in cancer patients is whether or not there is a potential for the light to stimulate the growth of residual malignant cells that evaded oncologic treatment, increasing the risk for tumor recurrences and development of a second primary tumor. Current science suggests promising effects of PBMT in the prevention and treatment of breast cancer-related lymphedema and oral mucositis, among other cancer treatment toxicities. Nevertheless, this seems to be the first systematic review to analyze the safety of the use of PBMT for the management of cancer-related toxicities. Scopus, MEDLINE/PubMed, and Embase were searched electronically. A total of 27 articles met the search criteria. Selected studies included the use of PBMT for prevention and treatment of oral mucositis, lymphedema, radiodermatitis, and peripheral neuropathy. Most studies showed that no side effects were observed with the use of PBMT. The results of this systematic review, based on current literature, suggest that the use of PBMT in the prevention and management of cancer treatment toxicities does not lead to the development of tumor safety issues., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Low-level laser therapy (LLLT) also called Photobiomodulation therapy (PBMT) could reduce oral mucositis (OM) incidence and severity in head and neck cancer patients treated by chemoradiotherapy, however randomised data about efficacy and safety are missing with curative dose 4 J/cm 2 ., Methods: This phase III trial was conducted in patients with oral cavity, or oro/hypopharyngeal cancers (stage III or IV). Patients were treated by lasertherapy on OM lesions grade ≥ 2 (4 J/cm 2 or placebo), during chemoradiotherapy and until recovery. Severity of OM (incidence and duration of grades ≥3) was used as primary endpoint and blindly assessed., Results: Among 97 randomised patients, 83 patients (85.6%) could be assessed finally (erroneous inclusions, chemoradiotherapy interruptions) and 32 patients had no lasertherapy because of unreachable OM lesions. Randomisation and population characteristics (sex ratio, age, chemoradiotherapy procedures, toxicities incidence) were still comparable between the two LLLT/PBMT groups. An acute OM (grade ≥ 3) was observed in 41 patients (49.4%): 23 patients (54.8%) of the active laser group versus 18 (43.9%) in the control group (modified intend to treat, p = 0.32). Median time before occurrence of OM ≥ grade 3 in half of the patients was 8 weeks in active laser group (vs. 9 weeks in control group). However, 95% of patients exhibited a very good tolerance of LLLT/PBMT., Conclusions: This study assessed LLLT/PBMT according to the Multinational Association of Supportive care in Cancer recommendations but lacked power. LLLT/PBMT was well tolerated with a good safety profile, which promotes its use in clinical routine for severe OM treatment., Trial Registration: ClinicalTrials.gov Identifier: NCT01772706 ., Title: Laser Mucite ORL: Effectiveness of Laser Therapy for Mucositis Induced by a Radio-chemotherapy in Head and Neck Cancer (LaserMucite). Study Start Date: October 2008. Primary Completion Date: October 2016. Responsible Party: Institut de Cancérologie de l'Ouest - Paul Papin. Principal Investigator: Eric Jadaud, M.D., Institut de Cancérologie de l'Ouest - Paul Papin., Funding: French Ministry of Health, French national funding scheme (PHRC 2008).

Background/aim: The aim of this retrospective cohort study was to investigate the association between renal dysfunction (RD) and the development of oral mucositis (OM) in patients undergoing concurrent chemoradiotherapy (CCRT) for pharyngeal cancer including radiation to the oral cavity., Patients and Methods: Of 130 patients diagnosed as having pharyngeal cancer who received CCRT at the Okayama University Hospital Head and Neck Cancer Center, 44 were finally selected., Results: During the observation period, 24 (54.5%) patients experienced severe OM (grade 3). The Cox proportional hazards regression model demonstrated that RD (hazard ratio(HR)=2.45, 95% confidence interval(CI)=1.067-6.116, p=0.035) and nasopharynx/oropharynx as center of the irradiated area (HR=2.56, 95% CI=1.072-5.604, p=0.034) were significantly associated with the incidence of severe OM (grade 3)., Conclusion: In patients with pharyngeal cancer treated with CCRT including radiation to the oral cavity, RD at baseline can be a risk factor for developing severe OM., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Photobiomodulation (PBM) is emerging as an effective strategy for the management of multiple inflammatory conditions, including oral mucositis (OM) in cancer patients who receive chemotherapy or radiotherapy. Still, the poor understanding of the mechanisms by which the light interacts with biological tissues and the heterogeneity of light sources and protocols employed worldwide significantly limits its applicability. Reactive oxygen species (ROS) are massively generated during the early phases of OM and play a major role in the pathogenesis of inflammation in general. Here, we report the results of a clinical and experimental study, aimed at evaluating the effect of laser light at different wavelengths on oxidative stress in vivo in oncologic patients suffering from OM and in vitro in two cell types abundantly present within the inflamed oral mucosa, neutrophil polymorphonuclear (PMN) granulocytes, and keratinocytes. In addition to standard ROS detection methods, we exploited a roGFP2-Orp1 genetically encoded sensor, allowing specific, quantitative, and dynamic imaging of redox events in living cells in response to oxidative stress and PBM. We found that the various wavelengths differentially modulate ROS production. In particular, the 660 nm laser light increases ROS production when applied either before or after an oxidative stimulus. In contrast, the 970 nm laser light exerted a moderate antioxidant activity both in the saliva of OM patients and in both cell types. The most marked reduction in the levels of ROS was detected in cells exposed either to the 800 nm laser light or to the combination of the three wavelengths. Overall, our study demonstrates that PBM exerts different effects on the redox state of both PMNs and keratinocytes depending on the used wavelength and prompts the validation of a multiwavelength protocol in the clinical settings.

Oral squamous cell carcinoma (OSCC) is the most frequent oral malignant neoplasia. As consequence of OSCC treatment, oral mucositis (OM) is one of the most common adverse effects of OSCC treatment. Currently, there is no consensus for OM treatment. The purpose of the current study was to test the combination of red and infrared low-level laser therapy (LLLT) for OM treatment. Primary culture of human fibroblast was performed to identify LLLT dose. After laboratory tests, a two-arm parallel, single-blind, controlled study was conducted. The two arms were group 1, both 660- and 808-nm wavelengths (300 J/cm 2 , 9 J of total energy, 100 mW, spot size 3 mm 2 ), and group 2, only 660-nm wavelength (300 J/cm 2 , 9 J of total energy, 100 mW, spot size 3 mm 2 ). Both treatments were performed twice a week. Group 1 presented a reduction of mucositis grade in comparison to group 2. Group 1 also presented reduction of analgesics prescription. But no significant differences between groups 1 and 2 were observed according to the pain scale. In conclusion, the current study demonstrated that a combination of red and infrared at a higher dose (300 J/cm 2 ) reduced both oral mucositis grade and analgesics prescription. The effects of the combination of RT and LLLT are unclear and need more studies.

Objectives: To demonstrate the efficacy of laser photobiomodulation (PBM) compared to that of placebo on severe oral mucositis (OM) in pediatric oncology patients. The primary objective was the reduction of OM grade (World Health Organization [WHO] scale) 7 days after starting PBM. Secondary objectives were reduction of pain, analgesic consumption, and incidence of side effects., Methods: One hundred and one children with WHO grade > 2 chemotherapy-induced OM were enrolled in eight Italian hospitals. Patients were randomized to either PBM or sham treatment for four consecutive days (days +1 to +4). On days +4, +7, and +11, OM grade, pain (following a 0-10 numeric pain rating scale, NRS) and need for analgesics were evaluated by an operator blinded to treatment., Results: Fifty-one patients were allocated to the PBM group, and 50 were allocated to the sham group. In total, 93.7% of PBM patients and 72% of sham patients had OM grade < 3 WHO on day +7 (P = 0.01). A significant reduction of pain was registered on day +7 in the PBM versus sham group (NRS 1 [0-3] vs. 2.5 [1-5], P < 0.006). Reduced use of analgesics was reported in the PBM group, although it was not statistically significant. No significant adverse events attributable to treatment were recorded., Conclusions: PBM is a safe, feasible, and effective treatment for children affected by chemotherapy-induced OM, as it accelerates mucosal recovery and reduces pain., (© 2018 Wiley Periodicals, Inc.)

Oral mucositis is one of the most frequent complications after chemotherapy, occurring in approximately 52 to 80% of children receiving treatment for cancer. Recently, it has been suggested that the use of low-energy laser could reduce the grade of oral mucositis and alleviate the symptoms. In 2014, Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology has recommended low-level laser therapy in prevention of mucositis for hematopoietic stem cell transplantation patients because of its beneficial effects in majority of recent studies. However, the recommendation was made for adult patients, not pediatric patients. Data about the effect of low-level laser therapy in pediatric patients is limited. This study aims to synthesize the available clinical evidences on the effects of low-level laser therapy (LLLT) in the prevention and treatment of chemotherapy-induced oral mucositis (OM). A meta-analysis was performed using trials identified through the Cochrane Central Register of Controlled Trials, Embase, MEDLINE, Web of Science, China Biology Medicine (CBM), Wanfang Database, and China National Knowledge Infrastructure (CNKI). Data on occurrence, duration, and severity of oral mucositis were collected. All randomized controlled studies and clinical controlled studies comparing LLLT to routine qualified prevention or treatment during or after chemotherapy were critically appraised and analyzed. We found 8 qualified clinical trials with a total of 373 pediatric patients; the methodological quality was acceptable. After prophylactic LLLT, the odds ratio for developing OM was significantly lower compared with placebo(OR = 0.50, 95% CI 0.29 to 0.87, P = 0.01), the odds ratio for developing grade III OM or worse was statistically significantly lower compared with placebo (OR = 0.30, 95% CI (0.10, 0.90), P = 0.03), and the OM severity was statistically significantly lower compared with placebo (SMD = - 0.56, 95% CI (- 0.98, - 0.14), P = 0.009). For therapeutic LLLT, the OM severity was significantly reduced compared to routine care (SMD = - 1.18, 95% CI (- 1.52, - 0.84), P < 0.00001). Oral pain was also reduced after LLLT over routine care (MD = - 0.73, 95% CI (- 1.36, - 0.11), P = 0.02)., Conclusion: Prophylactic LLLT reduces mucositis and severe mucositis and decreases the average severity of oral mucositis in pediatric and young patients with cancer. Therapeutic LLLT also reduces the average severity of oral mucositis and oral pain. Further research should investigate the optimal parameter of LLLT in pediatric and young patients, and studies with higher methodological quality should be performed. What is known: • Low-level laser therapy (LLLT) was recommended by Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology; however, evidences about LLLT on oral mucositis in pediatric and young patients were insufficient and lack supportive synthesized data. • Recently, there have been several new RCTs or CCTs for pediatric patients or young adults. What is new: • Prophylactic LLLT reduces the occurrence of mucositis and severe mucositis and decreases the average severity of oral mucositis in pediatric and young patients. • Therapeutic LLLT reduces the average severity of oral mucositis and oral pain.

Oral mucositis (OM) is an adverse side effect among hematopoietic stem cell transplantation (HSCT) recipients. The objective of this retrospective study was to evaluate the preventive effect of photobiomodulation (PBM) applied three times per week versus seven times per week in patients undergoing HSCT. The risk factors related to the incidence and severity of OM were also assessed. This was a retrospective study that evaluated 99 HSCT recipients who received different PBM protocols. Group I received three sessions per week, and group II received daily treatment. PBM was applied using a continuous-wave diode laser (InGaAlP; MM Optics, São Carlos, SP, Brazil) at a wavelength of 660 nm (visible-red) and a total radiant energy of 0.24 J per point. The baseline disease, type of transplant, type of conditioning, prophylaxis against graft-versus-host disease, OM grade, absolute leukocyte and platelet counts, and levels of liver and renal function markers were collected from medical records. The patients' age ranged from 13 to 71 years (mean/SD, 40.54 ± 16.45). No significant difference was observed between groups I and II regarding sex, age, ethnic, diagnosis, donor type, and conditioning treatment. Both PBM protocols were equally efficient in preventing OM (p = 0.34, ANOVA). Independent of the PBM protocol used, patients who received allogeneic transplant (p < 0.01-Fischer's exact test), total body irradiation (TBI-12Gy) (p = 0.01-chi-square test), busulfan + cyclophosphamide (p < 0.01-chi-square test), or methotrexate-containing regimens (p < 0.01-Fischer's exact test) demonstrated higher OM incidence and severity. Myelosuppression (p < 0.01-Mann-Whitney test) and impaired renal function (p = 0.02-Mann-Whitney test) were also considered risk factors for OM. Based on this retrospective data, PBM was effective in preventing OM in patients undergoing HSCT even when it was applied three times a week. A prospective study might be necessary to confirm these findings.

Chronic gingivostomatitis in dogs is an inflammatory syndrome of the oral cavity, which treatment and control of concomitant periodontitis allow healing in most of the cases. In the presence of recurrent lesions, invasive methods are necessary to treat lesions and pain. As a conservative adjuvant method, photobiomodulation (PBM) with low power laser is able to promote reduction of tissue pain and tissue inflammation besides increasing vascularization and healing, restoring the normal function of the irradiated organ in a shorter time. In veterinary medicine, there is no standardization of technique for its use in oral tissue for treating gingivostomatitis in dogs. In the present case, a dog was submitted to aPDT (7.2J/point, 3min/point, 180J/cm 2 ) and PBM (1.6J/point, 40s/point, 25J/cm 2 ), using a semiconductor diode laser, with wavelength of 660nm, spot size of ​​0.04cm 2 and output power of 40mW. The established protocol proved to be effective as coadjutant treatment for chronic gingivostomatitis, restoring the integrity of dog's affected mucosa and gingiva., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: The objective of this network meta-analysis is to optimize the prophylactic treatment for radiotherapy-induced oral mucositis in patients with head and neck cancer (HNSCC) receiving postoperative or definitive radiotherapy with or without chemotherapy., Materials and Methods: We searched electronic databases to identify all eligible randomized clinical trials on oral mucositis. The endpoint was grade 0-2 oral mucositis. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were extracted. Network meta-analysis was performed using the frequentist approach to conduct multiple treatment comparisons., Results: In total, 57 trials with 5261 patients were eligible for this study. Both direct and network meta-analysis revealed that low-level laser additional to standard oral care (SOC) was better than most of the other treatments and achieved the highest effect on grade 0-2 oral mucositis, with a surface under the cumulative ranking curve (SUCRA) of 95.8%; however, SOC with or without placebo had worse effect than most of the other treatments and was ranked worst (SUCRA = 0.4%). Moreover, sensitivity analysis performed after we had combined the SOC and placebo groups (non-medication treatment, NMT) yielded similar results, with SUCRA of 91.3% and 3.5% for low-level laser and NMT, respectively., Conclusions: Low-level laser additional to SOC may be a more effective prophylactic treatment for reducing severe radiotherapy-induced oral mucositis; SOC alone is insufficient for patients with HNSCC receiving postoperative or definitive radiotherapy with or without chemotherapy., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Oral mucositis (OM) induces severe pain and limits fundamental life behaviors such as eating, drinking, and talking for patients receiving chemotherapy or radiotherapy. In addition, through opportunistic microorganisms, OM frequently leads to systemic infection which then leads to prolonged hospitalization. Severe lesions often adversely affect curative effects in cancer cases. Therefore, the control of OM is important for oral health quality of life and prognosis. Low-level laser therapy (LLLT) and ozone may be useful to accelerate wound healing. In this study, 24 Sprague-Dawley rats were divided into three groups as control, ozone, and laser groups. All groups received 5-fluorouracil intraperitoneally and trauma to the mouth pouch with a needle. After the formation of OM in the mouth, the control group had no treatment; the ozone group was administered ozone, and the laser group, LLLT. Then, all groups were sacrificed and basic fibroblast growth factor (bFGF), transforming growth factor (TGF-β), and platelet-derived growth factor (PDGF) were evaluated in all groups. LLLT was determined to be statistically significantly more effective than ozone on FGF and PDGF. However, in respect of TGF-β, no statistically significant difference was observed between the groups. In conclusion, within the limitations of this study, LLLT is more effective than ozone. However, further studies on this subject are required.

In this study, clinical, biochemical and histological analysis were used to compare different phototherapies, including LED, low and high-power laser (HPL) for the treatment of chemotherapy (CT)-induced oral mucositis (OM). One-hundred-fifty hamsters were divided into five groups: C: control; CH: CT/OM induction; L: CT/OM induction and treatment with LED (635 nm, 1.2 J), HL: CT/OM induction and treatment with HPL (808 nm, 10 J), LL: CT/OM induction and treatment with low-level laser therapy (LLLT) (660 nm, 1.2 J). OM was induced by scratches performed on check pouch mucosa after two injections of 5-Fluorouracil. The experiment lasted 10 days and OM was analyzed by specific clinical scales on days 5, 7 and 10. The animals were euthanized and the cheek pouch mucosa removed for biochemical (TNF-α concentration) and histological (light microscopy) analysis. After statistical analysis, the authors' results showed LED and LLLT therapies were efficient treatments for OM, decreasing TNF-α concentration on day 7 (p < 0.05) and completely healing the mucosa on day 10. HPL showed no interference in final healing of OM. According to the methodology used and the results obtained in the present study, LLLT and LED therapies were the best choices to decrease the severity of OM, accelerating tissue repair and decreasing the inflammatory process. Clinical evaluation of OM in Groups CH, LL, L and HL and their respective arrangement of phototherapy treatments at different time intervals (5, 7 and 10 days)., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background and Objectives: Increased expression of inflammatory cytokines in the oral cavity has been related to the etiopathogenesis of oral mucositis and to delayed oral mucosal repair. Low-level laser therapy (LLLT) stimulates proliferation and migration of gingival fibroblasts, but the effects of specific inflammatory cytokines on oral mucosal cells and the modulation of these effects by LLLT have not been fully investigated. Therefore, this study investigated the effects of LLLT on oral fibroblasts after being challenged by oral-mucositis-related inflammatory cytokines., Methods: Human gingival fibroblasts were seeded in plain culture medium (DMEM) containing 10% fetal bovine serum (FBS) for 24 hours. Then, cells were kept in contact with inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-8) in serum-free DMEM for 24 hours. After this period, cells were subjected to LLLT with a diode laser device (LaserTABLE, InGaAsP, 780 nm, 25 mW) delivering energy doses from 0.5 to 3 J/cm 2 . Irradiation was repeated for 3 consecutive days. Twenty-four hours after the last irradiation, cell migration (wound-healing and transwell migration assays), cell proliferation (BrdU), gene expression of COL-I and growth factors (real-time PCR), and synthesis of COL-I (Sirius Red assay) and VEGF (ELISA) were assessed. Data were subjected to two-way ANOVA and Tukey's tests or Kruskall-Walis and Mann-Whitney tests (P < 0.05)., Results: The inflammatory cytokines decreased the migration capacity of gingival fibroblasts. However, a statistically significant difference was observed only for IL-6, detected by transwell assay, where 30% less cells migrated through the pores (P < 0.05) and IL-8, with an increased wound area (116%; P < 0.05), detected by the wound healing method. Cell proliferation was not affected by contact with cytokines, while growth factors and COL-I expression (approximately 80%; P < 0.05), as well as VEGF synthesis (approximately 20%; P < 0.05), were decreased after contact to all tested cytokines. The opposite was seen for total collagen synthesis. LLLT promoted an acceleration of fibroblast migration (30%; P < 0.05) and proliferation (112%; P < 0.05) when delivering 0.5 J/cm 2 to the cells previously in contact with the inflammatory cytokines. Gene expression of VEGF (approximately 30%; P < 0.05), and EGF (17%; P < 0.05), was stimulated by LLLT after contact with TNF-α and IL-6., Conclusion: LLLT can counteract the negative effects of high concentrations of inflammatory cytokines, especially IL-6 and IL-8 on gingival fibroblast functions directly related to the wound-healing process. Lasers Surg. Med. 48:1006-1014, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Due to its analgesic, anti-inflammatory, and biostimulating effects, low-level laser therapy (LLLT) has been widely used for oral disorders, such as oral lichen planus (OLP), xerostomia, recurrent aphthous stomatitis (RAS), herpes labialis, burning mouth syndrome (BMS), and oral mucositis (OM). The research team for the present study has reviewed the literature on the subject, with an emphasis on the applicability of LLLT in general and of its various clinical protocols for the management of those oral disorders. In lesions such as the ones occurring in OM, RAS, herpes labialis, and OLP, the course of wound healing and the pain have been shown to decrease, with a few, or most often, no adverse side effects. The literature shows that LLLT can also be effective in reducing symptoms in patients with BMS. For the treatment of hyposalivation and xerostomia, the use of LLLT has been described in the literature, but no consensus has resulted. Very few controlled clinical studies with well-established therapeutic protocols have occurred, except for OM, for which LLLT has been widely researched. Although information on the use of the laser for some lesions has already been consolidated, further research is needed, especially randomized, controlled clinical trials with long-term follow-up. Those studies will allow the safe use of LLLT, permitting the creation of care protocols for the management of oral disorders.