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.

Impact of photobiomodulation in a patient-derived xenograft model of oral squamous cell carcinoma.

BACKGROUND: Photobiomodulation therapy (PBMT) is an effective method for the prevention of oral mucositis. However, the effects of PBMT on oral squamous cell carcinoma (OSCC) have not yet been fully elucidated. This study aimed to evaluate the impact of PBMT in an OSCC-patient-derived xenograft (OSCC-PDX) model. METHODS: BALB/c nude mice with OSCC-PDX models were divided into Control, without PBMT (n = 8); Immediate irradiation, PBMT since one week after tumor implantation (n = 6); and Late irradiation, PBMT after tumors reached 200 mm3 (n = 6). OSCC-PDX were daily irradiated (660 nm; 100 mW; 6 J/cm2 ; 0,2 J/point) for 12 weeks. The tumors were collected and submitted to volumetric, histological, immunohistochemistry, and cell cycle analysis. RESULTS: No significant differences in the volumetric measurements (p = 0.89) and in the histopathological grade (p > 0.05) were detected between the groups. The immunohistochemical analysis of Ki-67 (p = 0.9661); H3K9ac (p = 0.3794); and BMI1 (p = 0.5182), and the evaluation of the cell cycle phases (p > 0.05) by flow cytometry also did not demonstrate significant differences between the irradiated and non-irradiated groups. CONCLUSION: In this study, PBMT did not impact the behavior of OSCC-PDX models. This is an important preclinical outcome regarding safety concerns of the use of PBMT in cancer patients.

Comparative study of royal jelly, propolis, and photobiomodulation therapies in 5-fluorouracil-related oral mucositis in rats.

PURPOSE: This study aimed to evaluate the effects and mechanisms of action of royal jelly (RJ) and propolis compared to photobiomodulation therapy (PBMT) in an animal model of 5-fluorouracil-related oral mucositis (OM). METHODS: Seventy-two male Wistar rats were randomly allocated to four groups (n = 18 each): control (no treatment), PBMT (intraoral laser, 6 J/cm2), RJ, and propolis. On days 0 and 2, the animals received an injection of 5-fluorouracil (5-FU). The buccal mucosa was scratched (days 3 and 4) and the treatments were initiated on day 5. Six animals of each group were euthanized on days 8, 10, and 14. Phytochemical analysis (thin-layer chromatography, TLC) and clinical, histopathological, and immunohistochemical analysis of pS6, pAKT, and NF-κB were performed, and oxidative stress markers were also investigated. RESULTS: TLC revealed the presence of large amounts of sucrose (Rf 0.34) in RJ and of flavonoids in propolis. Lower clinical OM scores were observed on day 8, and improved morphological data were observed on day 10 in the PBMT, RJ, and propolis groups (p < 0.05). On day 8, immunoexpression of pS6, pAKT, and NF-κB was increased compared to control. On day 14, reduced glutathione (GSH) antioxidant levels were increased in the propolis group compared to control (p < 0.05). CONCLUSIONS: Our results showed that RJ and propolis, as well as PBMT, are effective in the treatment of OM. Considering that some patients who develop OM do not have access to PBMT, the present study demonstrated that topical application of RJ and propolis may be an important alternative for the treatment of OM.

Photobiomodulation therapy drives massive epigenetic histone modifications, stem cells mobilization and accelerated epithelial healing.

Emerging evidence indicates the clinical benefits of photobiomodulation therapy (PBMT) in the management of skin and mucosal wounds. Here, we decided to explore the effects of different regiments of PBMT on epithelial cells and stem cells, and the potential implications over the epigenetic circuitry during healing. Scratch-wound migration, immunofluorescence (anti-acetyl-Histone H3, anti-acetyl-CBP/p300 and anti-BMI1), nuclear morphometry and western blotting (anti-Phospho-S6, anti-methyl-CpG binding domain protein 2 [MBD2]) were performed. Epithelial stem cells were identified by the aldehyde dehydrogenase enzymatic levels and sphere-forming assay. We observed that PBMT-induced accelerated epithelial migration and chromatin relaxation along with increased levels of histones acetylation, the transcription cofactors CBP/p300 and mammalian target of rapamycin. We further observed a reduction of the transcription repression-associated protein MBD2 and a reduced number of epithelial stem cells and spheres. In this study, we showed that PBMT could induce epigenetic modifications of epithelial cells and control stem cell fate, leading to an accelerated healing phenotype.

The impact of photobiomodulation therapy on the biology and behavior of head and neck squamous cell carcinomas cell lines.

Photobiomodulation therapy (PBMT) is an emerging therapeutic modality designed to prevent and treat chemotherapy-driven oral mucositis (OM). However, the response of tumor cells to the effects of PBMT remains poorly understood. Our study explores the effects of PBMT in head and neck squamous cell carcinoma (HNSCC) based on cellular proliferation, migration, and survival of tumor cells and its population of cancer stem cells (CSC). We explored the behavior of two HNSCC cell lines (HN6 and HN13) under two distinct conditions, a physiological growing condition (10% FBS), and under stress growing condition (2% FBS) prior to irradiation using diode laser (InGaAlP; MM Optics, São Carlos, SP, Brazil). Diode laser (660 nm) was applied with a power of 100 mW delivering a total energy per point of 0.24 J. MTT and wound healing test (scratch assay) were performed to evaluate, respectively, proliferation and migration of tumor cells. Clonogenic and spheres formation assays were also performed to evaluate the survival and percentage of CSC upon irradiation. Overall, we observed that PBMT does not exacerbate the behavior of HNSCC. We could only observe a decrease in cellular proliferation of one cell line (HN6) when cultured under nutritional stress conditions (p < .05). There were no significant differences between the control and the PBMT groups regarding cell migration, survival and the percentage of CSC. Collectively, our results suggest that in vitro administration of PBMT to HNSCC does not modify the behavior of tumor cells.

Examining tumor modulating effects of photobiomodulation therapy on head and neck squamous cell carcinomas.

Photobiomodulation (PBM) therapy is an effective method for preventing and managing oral mucositis (OM) in head and neck squamous cell carcinoma (HNSCC) patients undergoing radiotherapy alone or in combination with chemotherapy. However, the potential effects of PBM therapy on premalignant and malignant cells eventually present in the treatment site are yet unknown. The aim of this systematic review was to analyze the effects of PBM therapy on HNSCC. A literature search was conducted in four indexed databases as follows: MEDLINE/PubMed, EMBASE, Web of Science, and Scopus. The databases were reviewed for papers published up to and including in October 2018. In vitro and in vivo studies that investigated the effects of PBM therapy on HNSCC were selected. From the 852 initially gathered studies, 15 met the inclusion criteria (13 in vitro and 2 in vivo). Only three in vitro studies were noted to have a low risk of bias. The included data demonstrated wide variations of study designs, PBM therapy protocols, and study outcomes. Cell proliferation and viability were the primary evaluation outcome in the in vitro studies. Of the 13 in vitro studies, seven noted a positive effect of PBM therapy on inhibiting or preventing an effect on HNSCC tumor cells, while six studies saw increased proliferation. One in vivo study reported increased oral SCC (OSCC) progression, while the other observed reduced tumor progression. Overall, the data from the studies included in the present systematic review do not support a clear conclusion about the effects of PBM therapy on HNSCC cells.

Tumor safety and side effects of photobiomodulation therapy used for prevention and management of cancer treatment toxicities. A systematic review.

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.