Preventive versus curative photobiomodulation for oral mucositis in patients with multiple myeloma undergoing hematopoietic stem cell transplantation: which approach is more effective?

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.

Impact of photobiomodulation for prevention of oral mucositis on the quality of life of patients with head and neck cancer: a systematic review.

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.

Monte Carlo based dosimetry of extraoral photobiomodulation for prevention of oral mucositis.

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/cm2 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/cm2 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.

Development and Application of Prototype System Based on Light-Emitting Diode Arrays (660 nm) with a Top Hat Beam Profile in Order to Optimize Photobiomodulation Protocols for Treatment of Radiation-Induced Oral Mucositis in Rats.

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/cm2 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/cm2 (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.

Management of Cancer Therapy-Induced Oral Mucositis Using Photobiomodulation Therapy: An Overview of Systematic Reviews.

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.

Low-Level Laser Therapy for the Treatment of Oral Mucositis Induced by Hematopoietic Stem Cell Transplantation: A Systematic Review with Meta-Analysis.

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.

Photobiomodulation for the management of xerostomia and oral mucositis in patients with cancer: a randomized clinical trial.

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.

Twenty-year analysis of photobiomodulation clinical studies for oral mucositis: a scoping review.

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.

Photobiomodulation in the management of oral mucositis for adult head and neck cancer patients receiving irradiation: the LiTEFORM RCT.

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 cm2, irradiance 50 mW/cm2, exposure time 60 seconds and fluence 3 J/cm2. 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.

Around 9 out of 10 head and neck cancer patients undergoing treatment experience pain, swelling and sores in their mouth (oral mucositis). This can lead to weight loss, painful ulcers, difficulty talking, eating and drinking, and even hospitalisation. Current care includes helping patients to keep their mouth and teeth clean, encouraging them to have a healthy diet and prescribing mouthwashes, painkillers and mouth-coating gels. However, these treatments give limited help in preventing or treating this condition. The LiTEFORM trial looked at whether or not low-level laser therapy could be used to prevent and treat oral mucositis. Patients were allocated to one of two arms at random: active laser or fake (sham) laser. Neither the patients nor the hospital staff knew which laser was being used. Eighty-seven people joined the study during the time allowed (44 received low-level laser therapy and 43 received sham treatment); however, this was a smaller number than the planned target of 380 people. As a result, no meaningful conclusion can be drawn from the results about whether the therapy is beneficial or cost-effective. People receiving the low-level laser therapy reported slightly more soreness in their mouth than those receiving the sham laser, but this could be down to chance. The number of participants is too small to draw conclusions about whether or not the low-level laser is helpful. Some patients found the laser treatment sessions to be difficult. Setting up a new service delivering laser therapy at the same time as cancer treatments was more complicated than originally anticipated. Problems included the scheduling of appointments, finding suitable rooms and having enough trained staff with time to deliver laser therapy. However, this study has provided us with knowledge on how best to set up a laser therapy service in the NHS as part of the cancer treatment pathway and the costs involved. These findings could help future studies looking into low-level laser therapy for those with head and neck cancer.

Diode Laser as an Adjunctive Treatment for Peri-implant Mucositis: A Systematic Review and Meta-analysis.

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.

Photobiomodulation Therapy in the Treatment of Oral Mucositis-A Case Report.

In 2021, our group published a laboratory study on the impact of PBM on human gingival fibroblasts. The in vitro results confirmed the fact that the appropriately selected wavelength and properly selected parameters of the laser settings can increase cell proliferation, modulate inflammatory markers, and decrease the susceptibility of human gingival fibroblasts to apoptosis. Therefore, this case report was aimed at the clinical evaluation of the proposed settings and treatment regimen in a very difficult situation of an immunocompromised patient with extensive changes and stagnation of symptoms for many weeks. A 65-year-old man, during his oncological treatment, was diagnosed with oral mucositis grade 3 according to the World Health Organization and National Cancer Institute scales. Due to pain sensation, long-lasting and not healing oral lesions, and problems with solid food intake, he was qualified for laser photobiomodulation therapy. For the management of oral lesions, a diode laser 635 nm (SmartMPro, Lasotronix, Poland) was intraorally applied at an energy density of 4 J/cm2, the 20 s of irradiation, the output power of 100 mW, and in continuous wave mode. Seven treatment procedures were performed two times a week using the spot technique in contact and non-contact mode. Within 21 days of monotherapy, all ailments disappeared. The patient was also able to reuse dental dentures and return to a solid diet. The obtained results confirm the efficiency of at least 3 PBM protocols. Our case shows that the use of PMB therapy contributes to faster healing of painful oral lesions in oncological patients, and thus the treatment time and return to the appropriate quality of life is shorter.

A Narrative Review on Oral and Periodontal Bacteria Microbiota Photobiomodulation, through Visible and Near-Infrared Light: From the Origins to Modern Therapies.

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.

Impact of photobiomodulation for oral mucositis on body weight and BMI of patients with head and neck cancer.

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 .

Review of oral mucositis treatment guidelines with an emphasis on laser therapy.

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.

Is Low-level Laser Therapy a Candidate to Be a Good Alternative in the Treatment of Mucositis in Childhood Leukemia?

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.

Low-level laser therapy for oral mucositis in children with cancer.

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.

[State of art of photobiomodulation in the management of radiotherapy adverse events: Indications and level of evidence]. / État de l'art de la photobiomodulation dans la prise en charge des effets secondaires de la radiothérapie : indications et niveaux de preuve.

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.

Photobiomodulation therapy for oral mucositis management in head and neck cancer patients undergoing radiotherapy: case reports

Introduction: Photobiomodulation therapy (PBM) has been recommended for the prevention of oral mucositis (OM). Objective: to evaluate the use of PBM to prevent and control the severity of oral mucositis lesions and painful sensitivity in patients undergoing radiotherapy for head and neck cancer (HNC) treatment. Case reports: Eight patients with HNC attended for radiotherapy treatment, either associated with chemotherapy, or not were followed up. Clinical evaluation was performed, including meticulous anamnesis. The patients were followed up throughout the entire period of radiotherapy treatment. For the protocol of prophylaxis of OM, low level laser equipment was used, with a wavelength in the range of 660nm, in a contact mode, 30 mW of continuous emission 4J/cm² three times per week and for the therapeutic protocol wavelength in the range of 660nm, in a contact mode, 30 mW of continuous emission 8 J/cm², in the respective areas compromised by oral mucositis, 3 times per week till the complete remission of the lesions. All the patients were clinically followed up from the beginning of the antineoplastic therapy up to the conclusion of the medical treatment or total remission of the oral lesion, involving post radiotherapy control. A visual analog scale (VAS) was used to measure pain every week. Results: A progressive development of the lesions was observed from the 1st to the 5th week. Remission of OM was observed from the 7th week up to the conclusion of treatment. There is a continuous increase in the pain process, attaining the maximum level in the 6th week, with decline occurring up to the 7th week. Conclusion: Photobiomodulation therapy was able to control the severity of OM lesions and painful sensitivity in patients undergoing radiotherapy for head and neck cancer treatment, avoiding the interruption of the cancer therapy.

Introdução: A terapia com fotobiomodulação (FBM) tem sido recomendada para a prevenção da mucosite oral (MO). Objetivo: avaliar o uso de FBM para prevenir e controlar a gravidade das lesões da mucosite oral e a sensibilidade dolorosa em pacientes submetidos à radioterapia para tratamento de câncer de cabeça e pescoço (CCP). Relato dos casos: Oito pacientes com CCP atendidos para tratamento radioterápico, associado ou não à quimioterapia, foram acompanhados. Foi realizada avaliação clínica, incluindo anamnese meticulosa. Os pacientes foram acompanhados durante todo o período de tratamento radioterápico. Para o protocolo de profilaxia de MO, foi utilizado um equipamento laser de baixa potência, com comprimento de onda na faixa de 660nm, em modo de contato e 30 mW de emissão contínua com 4J/cm2. Para o protocolo terapêutico, e para comprimento de onda na faixa de 660nm, em modo de contato e 30 mW de emissão contínua com 8J/cm2 na área da lesão, até sua completa remissão. Todos os pacientes foram acompanhados clinicamente desde o início da terapia antineoplásica até a conclusão do tratamento médico ou remissão total da lesão oral, envolvendo o controle pós-radioterapia. Uma escala visual analógica (EVA) foi usada para medir a dor semanalmente. Resultados: Observou-se um desenvolvimento progressivo das lesões da 1ª à 5ª semana. A remissão da mucosite oral foi observada a partir da 7ª semana até o final do tratamento. Houve um aumento contínuo do processo doloroso, atingindo o nível máximo na 6ª semana, com declínio ocorrendo até a 7ª semana. Conclusão: A terapia de fotobiomodulação foi capaz de controlar a gravidade das lesões de MO e a sensibilidade dolorosa em pacientes submetidos à radioterapia para tratamento do câncer de cabeça e pescoço, evitando a interrupção da terapia oncológica.

Photobiomodulation reduces the impact of radiotherapy on oral health-related quality of life due to mucositis-related symptoms in head and neck cancer patients.

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.