In vitro cytoprotective and in vivo anti-oral mucositis effects of melatonin and its derivatives.

According to our preliminary study, melatonin and its N-amide derivatives (N-(2-(1-4-bromobenzoyl-5-methoxy-1H-indol-3-yl)ethyl)acetamide (BBM) and 4-bromo-N-(2-(5-methoxy-1H-indol-3-yl)ethyl)benzamide (EBM)) inhibited the marker of acute inflammation in tests in vitro and in vivo. The anti-inflammatory agent is intended for the prevention and treatment of chemotherapy-induced toxicity. In this study aimed to evaluate the effect of melatonin and its derivatives on mechanisms related to chemotherapy-induced oral mucositis by in vitro ROS and 5-FU-induced human keratinocyte cells as well as in vivo oral mucositis model. In in vitro H2O2-induced HaCaT cells, BBM had the highest level of protection (34.57%) at a concentration 50 µM, followed by EBM (26.41%), and melatonin (7.9%). BBM also protected cells against 5-FU-induced to 37.69-27.25% at 12.5-100 µM while EBM was 36.93-29.33% and melatonin was 22.5-11.39%. In in vivo 5-FU-induced oral mucositis in mice, melatonin, BBM, and EBM gel formulations protected tissue damage from 5-FU similar to the standard compound, benzydamine. Moreover, the weight of mice and food consumption recovered more quickly in the BBM group. These findings suggested that it was possible to develop BBM and EBM as new therapeutic agents for the treatment of oral mucositis.

Oral Mucositis and Nutritional Status in Children Who Underwent Hematopoietic Cell Transplantation: A Comparison Between Nonmalignant and Malignant Primary Diseases.

BACKGROUND: There is a lack of studies analyzing the association between oral mucositis (OM) and nutritional imbalance in children during hematopoietic stem cell transplantation (HSCT). The aim of this study was to compare the risk factors for OM and nutritional imbalance during HSCT in pediatric patients with nonmalignant diseases (NMD) and malignant diseases (MD). METHODS: Data on age, sex, primary disease, transplantation type, conditioning regimen, GVHD prophylaxis, gastrointestinal toxicity, OM, percent body weight loss or gain, nutritional repositioning, and overall survival (OS) were retrospectively collected from the 132 medical records. The data were then compared between patients with NMD (n = 70) and MD (n = 62). RESULTS: OM had a similar severity between the groups. The primary risk factor for OM in the NMD group was the conditioning regimen with busulfan, while in the MD group it was GVHD prophylaxis with cyclosporin and methotrexate. OM did not have an impact on body weight loss or gain in any of the groups. In the NMD, body weight gain due to fluid overload was more pronounced and associated with a lower age range. OS was similar between the groups and was not affected by OM. CONCLUSIONS: OM pattern was similar in pediatric patients with or without MD, but the factors that determined these oral lesions were different. There were disparities in body weight changes between the two groups, and these changes were not associated to OM.

Might photobiomodulation therapy interfere with the frequency of severe mucositis and oral candidiasis? A retrospective analysis in patients with head and neck carcinoma.

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 cm2, 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.

Recent advances in cancer therapy-associated oral mucositis.

Oral mucositis (OM) is a common and debilitating toxicity of cancer treatments - chemotherapy, radiotherapy, hematopoietic cell transplant, or combinations. OM is associated with severe oral pain and has negative impacts on patient function and quality of life. Additionally, OM has accompanying systemic complications that may have critical implications. These local and systemic consequences can alter cancer treatment, and add an economic burden. This review covers the clinical presentation and course of OM, differential diagnosis, clinical and economic impacts, pathogenesis, risk factors, assessment measures, biomarkers and prediction of OM, management, research advances in the development of new drugs and treatments, and big data.

Chemotherapy-induced oral mucositis: hierarchical analysis of recurrence factors.

PURPOSE: This study aimed to analyze, through a hierarchical model, the risk factors associated with the recurrence of chemo-induced oral mucositis (OM) in children and adolescents. METHODS: A retrospective cohort with 31 individuals of both sexes, aged 1-18 years, who were undergoing chemotherapy, and presented OM lesions was conducted. Data collection included analysis of medical records, interviews, and intraoral examination. Information regarding patients' socioeconomic and demographic profile, underlying disease, antineoplastic regimen, hematological condition, and oral health status were collected. To assess the association of independent variables with the outcome, the Chi-square, Fisher's Exact, and Mann-Whitney tests were used, in addition to a binary logistic regression model, with a maximum error of 5% and a 95% confidence interval. RESULTS: Significant associations were observed between the history of OM and the diagnosis of the child/adolescent, neutrophil count, previous cancer treatments and the chemotherapy scheme in use (p < 0.05). Binary logistic regression revealed a 13.69 higher risk of developing OM recurrence in individuals who received high-dose methotrexate (MTX) therapy. CONCLUSION: Socioeconomic and demographic factors did not influence OM recurrence. However, clinical variables, such as neutropenia, diagnosis of leukemia, and high-dose MTX protocols increase the chance of OM new cases.

Application of In Situ Mucoadhesive Hydrogel with Anti-Inflammatory and Pro-Repairing Dual Properties for the Treatment of Chemotherapy-Induced Oral Mucositis.

Chemotherapy-induced oral mucositis (CIOM) is a prevalent complication of chemotherapy and significantly affects the treatment process. However, effective treatment for CIOM is lacking due to the unique environment of the oral cavity and the single effect of current drug delivery systems. In this present study, we propose an innovative approach by combining a methacrylate-modified human recombinant collagen III (rhCol3MA) hydrogel system with hyaluronic acid-epigallocatechin gallate (HA-E) and dopamine-modified methacrylate-alginate (AlgDA-MA). HA-E is used as an antioxidant and anti-inflammatory agent and synergizes with AlgDA-MA to improve the wet adhesion of hydrogel. The results of rhCol3MA/HA-E/AlgDA-MA (Col/HA-E/Alg) hydrogel demonstrate suitable physicochemical properties, excellent wet adhesive capacity, and biocompatibility. Notably, the hydrogel could promote macrophage polarization from M1 to M2 and redress human oral keratinocyte (HOK) inflammation by inhibiting NF-κB activation. Wound healing evaluations in vivo demonstrate that the Col/HA-E/Alg hydrogel exhibits a pro-repair effect by mitigating inflammatory imbalances, fostering early angiogenesis, and facilitating collagen repair. In summary, the Col/HA-E/Alg hydrogel could serve as a promising multifunctional dressing for the treatment of CIOM.

Efficacy of probiotics in the treatment of oral mucositis in head and neck cancer patients: a systematic review and meta-analysis.

OBJECTIVES: To assess the effect of probiotics in oral mucositis induced by chemotherapy or radiotherapy on patients with head and neck cancer (HNC). METHODS: The PubMed, Embase, Cochrane Library, Clinical trials were screened from January 2010 to April 2024. Randomized clinical trials (RCTs) comparing the efficacy of probiotics in treatment of oral mucositis in HNC were eligible. Outcomes of interest were incidence of oral mucositis and severe oral mucositis. The PROSPERO registration number was 42022384685. The Cochrane risk-of-bias tool (RoB2) was used to assess methodological quality of studies and GRADE criteria (GRADEpro) was applied for rating the certainty of evidence. Meta-analysis was performed by using RevMan 5.4. RESULTS: A total of eight RCTs comprising 691 patients with HNC were included in this meta-analysis. Probiotics administration significantly reduced the incidence of SOM (RR = 0.60, 95%CI: 0.46-0.78, P = 0.0002). However, it showed no distinct advantage in reducing the overall incidence of oral mucositis (RR = 0.88, 95%CI: 0.76-1.02, P = 0.08). Subgroup analysis found more benefit for reducing SOM in multi-bacterial treated group (RR = 0.35, 95%CI: 0.17-0.73, P = 0.005) than mono-bacterial treated group (RR = 0.69, 95%CI: 0.58-0.82, P < 0.0001). In Addition, probiotics could reduce the incidence of SOM in nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (RR = 0.43, 95%CI: 0.26-0.70, P = 0.0006). CONCLUSION: Probiotics reduced the incidence of SOM caused by chemotherapy or radiotherapy for HNC. The multi-bacterial combination therapy was more efficacious than the mono-bacterial therapy. Moreover, probiotics also reduced the incidence of SOM in nasopharyngeal carcinoma. However, the advantage of probiotics had not been established in the overall incidence of OM.

Dynamic change of gut microbiota in head and neck concurrent chemoradiotherapy patients and its potential value in the prediction of acute oral mucositis grade as well as quality of life.

PURPOSE: Radiotherapy is the major therapy for head and neck squamous cell carcinoma (HNSCC). However, whether gut microbiota changes in HNSCC patients who received concurrent chemoradiotherapy remains unclear. This study aimed to investigate the dynamic change of gut microbiota composition, construct the first radiotherapy-related gut microbiota database in these patients and identify the potential value of the gut microbiota changing in the prediction of acute oral mucositis grade as well as patients' life quality. METHODS: We enrolled 47 HNSCC patients who scheduled with concurrent chemoradiotherapy. The field was irradiated with a total dose of 66-70 Gy in 33-35 fractions. All the patients received 2-3 cycles of platinum-based chemotherapy. After feces specimens collected, bacterial genomic DNA was isolated using magnetic beads and then analyzed by the Illumina MiSeq Sequencing System based on the V3-V4 hypervariable regions of the 16S rRNA gene. RESULTS: 194 genera which belonged to 27 phyla were found in 141 samples. Increased abundance of microbiota in diversity and richness was observed in mid-radiotherapy group. Bacteroides, Blautia, Phascolarctobacterium were three main genera in all three groups and the mid-radiotherapy group had the highest relative abundance of Phascolarctobacterium. What is more, most significantly altered bacteria shared the same variation pattern which was increased in mid-radiotherapy while decreased to the almost same level of as pre-radiotherapy in post-radiotherapy group. Further analysis indicated that Bacteroidetes showing an upward trend while Proteobacteria declining in higher grade of acute mucositis. Moreover, relatively low abundant Proteobacteria was significantly correlated with high-grade acute oral mucositis. As for the quality of life, Lactobacillales and Actinomycetales were specifically found in better life quality group. However, Clostridia_UCG_014, Eubacteriaceae, UCG_010 and Moraxellaceae were unique abundantly present in worse life quality group. CONCLUSION: Chemoradiotherapy can affect the composition of the gut microbiota in HNSCC patients during the mid-term of treatment. Yet self-stabilized ability maintained the gut microbiota homeostasis. Dynamic change of specific species could help predict acute oral mucositis grade and characterize different quality of life group in these patients.

Rebamipide gargle and benzydamine gargle in prevention and management of chemo-radiotherapy and radiotherapy-induced oral mucositis in head and neck cancer patients (randomized clinical trial).

OBJECTIVES: This study aimed to evaluate the preventive and therapeutic effects of rebamipide gargle in comparison with benzydamine in head and neck cancer patients undergoing radiotherapy with or without chemotherapy. MATERIALS AND METHODS: Phase III randomized clinical trial was conducted from January 2021 till August 2022 on one hundred patients with head and neck cancer receiving high doses of radiotherapy. These patients were equally allocated into either rebamipide group or benzydamine group, The measured outcomes were the incidence of oral mucositis ≥ grade1, according to the WHO mucositis scale, in addition to the duration, and the onset of oral mucositis. RESULTS: There was no statistically significant difference between the two groups, regarding the incidence of a severe grade of oral mucositis (WHO grades 3), as well as the onset and duration of oral mucositis. Both gargles succeeded to prevent the development of WHO grade 4 oral mucositis. Side effects reported were mainly burning sensation in benzydamine group and nausea in rebamipide group. CONCLUSION: Rebamipide mouthwash was as beneficial as benzydamine mouthwash in minimizing the incidence of severe oral mucositis induced by treatment of head and neck cancer. However, rebamipide gargle proved to be superior to benzydamine in terms of reduction in the severity of the radiation-induced oral mucositis. TRIAL REGISTRATION: The trial was registered in the protocol Registration and Result system of Clinical Trials (Registration ID: NCT04685395)0.28-12-2020.

Guidance on mucositis assessment from the MASCC Mucositis Study Group and ISOO: an international Delphi study.

Background: Mucositis is a common and highly impactful side effect of conventional and emerging cancer therapy and thus the subject of intense investigation. Although common practice, mucositis assessment is heterogeneously adopted and poorly guided, impacting evidence synthesis and translation. The Multinational Association of Supportive Care in Cancer (MASCC) Mucositis Study Group (MSG) therefore aimed to establish expert recommendations for how existing mucositis assessment tools should be used, in clinical care and trials contexts, to improve the consistency of mucositis assessment. Methods: This study was conducted over two stages (January 2022-July 2023). The first phase involved a survey to MASCC-MSG members (January 2022-May 2022), capturing current practices, challenges and preferences. These then informed the second phase, in which a set of initial recommendations were prepared and refined using the Delphi method (February 2023-May 2023). Consensus was defined as agreement on a parameter by >80% of respondents. Findings: Seventy-two MASCC-MSG members completed the first phase of the study (37 females, 34 males, mainly oral care specialists). High variability was noted in the use of mucositis assessment tools, with a high reliance on clinician assessment compared to patient reported outcome measures (PROMs, 47% vs 3%, 37% used a combination). The World Health Organization (WHO) and Common Terminology Criteria for Adverse Events (CTCAE) scales were most commonly used to assess mucositis across multiple settings. Initial recommendations were reviewed by experienced MSG members and following two rounds of Delphi survey consensus was achieved in 91 of 100 recommendations. For example, in patients receiving chemotherapy, the recommended tool for clinician assessment in clinical practice is WHO for oral mucositis (89.5% consensus), and WHO or CTCAE for gastrointestinal mucositis (85.7% consensus). The recommended PROM in clinical trials is OMD/WQ for oral mucositis (93.3% consensus), and PRO-CTCAE for gastrointestinal mucositis (83.3% consensus). Interpretation: These new recommendations provide much needed guidance on mucositis assessment and may be applied in both clinical practice and research to streamline comparison and synthesis of global data sets, thus accelerating translation of new knowledge into clinical practice. Funding: No funding was received.

Efficacy of topical agents in oral mucositis prevention: Systematic review and network meta-analysis.

BACKGROUND: Oral mucositis (OM) is considered one of the most common side effects of patients undergoing cancer therapy. OM prevention plays a crucial role in the effectiveness of cancer treatment and the patient's quality of life. Different preventive treatments have been proposed in clinical trials, however with inconclusive results. MATERIALS AND METHODS: A systematic review search was conducted in PubMed, Scopus, Web of Science, and Cochrane Database to answer the PICO question: in cancer patients, do specific topical agents compared to standard treatments or placebo reduce the onset and severity of oral mucositis? The risk of bias was assessed, and a network meta-analysis was conducted. RESULTS: Of 2913 results, 30 randomized clinical trials were considered suitable for inclusion. A total of 2564 patients were analyzed, of which 1284 belonged to the test group and 1280 belonged to the control group. Natural products were the most used, followed mainly by antimicrobial agents, coating agents, and basic oral care measures. Topical sucralfate resulted in the most powerful intervention for the OM prevention (OR = 0.04, 95%C.I. = 0.01-0.25, p-value = 0.001). CONCLUSION: Due to its cytoprotective action, low cost, ease of administration, and safety, sucralfate could become a potential ally to prevent the onset of OM during cancer therapy.

Impact of dose volume parameters and clinical characteristics on radiation-induced acute oral mucositis for head and neck cancer patients treated with carbon-ion radiotherapy dose volume outcome analysis.

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.

Long-term survival of cancer patients after photobiomodulation therapy for prevention and treatment of oral mucositis.

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.

The predictive value of hematological inflammatory markers for severe oral mucositis in patients with nasopharyngeal carcinoma during intensity-modulated radiation therapy: A retrospective cohort study.

BACKGROUND: This study aims to investigate the predictive value of the circulating blood cell count, including neutro-philto-lymphocyte ratio (NLR), platelet-to-lymphocyte (PLR), and thesystemic inflammation index (SII) for the development of severe oral mucositis (SOM) induced by radiation in patients undergoing radiotherapy for nasopharyngeal carcinoma (NPC). METHODS: In this retrospective study, 142 NPC patients were screened, and based on mucositis toxicity grade, they were categorized into two groups: SOM and nonSOM. Peripheral blood cell counts were conducted prior to Intensity-Modulated Radiation Therapy (IMRT). Associations between blood cell count, NLR, PLR, SII, and SOM occurrence were examined. RESULTS: Revealed elevated NLR and SII levels, along with reduced lymphocyte (LYM), eosinophil (EOS), and basophil (BAS) in patients with SOM. LYM, EOS, BAS, NLR, and SII were effective predictors of the severity of radiation-induced oral mucositis (RIOM) in NPC patients. CONCLUSIONS: The occurrence of SOM was strongly linked to the hematological status at the start of Radiation Therapy (RT). Integrating BAS count and NLR into comprehensive risk prediction models could prove valuable for predicting SOM in NPC patients.

Effects of early nutritional intervention on oral mucositis and basic conditions in patients receiving radiotherapy for head and neck cancer: Randomized controlled trial (ChiCTR2000031418).

BACKGROUND & AIMS: This study aims to observe the effects of early nutritional intervention on radiation-induced oral mucositis (OM) and the nutritional status of patients with head and neck cancer (HNC) receiving radiotherapy. METHODS: Eligible patients receiving radiotherapy for HNC were randomly divided into an early nutritional intervention group (enteral nutritional intervention was administered at the beginning of radiotherapy) and a late nutritional intervention group (enteral nutritional intervention was administered at the beginning of eating restriction) in a 1:1 ratio. The primary endpoint was radiation-induced OM. Secondary endpoints included nutrition-related indicators, immune function, overall survival (OS), progression-free survival (PFS), quality of life, and other radiotherapy-induced adverse effects. RESULTS: A total of 100 patients were enrolled between 2020 and 2021, including 50 each in the early nutritional intervention group and in the late group. The incidence of Grade-III/IV OM was lower in the early treatment group than in the late treatment group (2% vs 14%, P = 0.059). By week 7 weight loss was significantly lower in the early group than in the late group (1.08 kg, 95% CI: 0.08-2.09, P = 0.035). Regarding the PG-SGA scores after receiving radiotherapy, the early group comprised more well-nourished and fewer malnourished patients than those in the late group (P = 0.002). The scores of the immune function indices of T cell CD3+, CD4+/CD8+, and B cell CD19+ were slightly higher in the early group than in the late group; however, the difference was not statistically significant (all P > 0.05). PFS and OS were better in the early group than in the late group; however, the differences were not statistically significant (P > 0.05). CONCLUSIONS: Early nutritional intervention can effectively improve the nutritional status and reduce the incidence of high-grade OM in patients with HNC receiving radiotherapy. TRIAL REGISTRATION: Chinese Clinical Trials Registry (http://www.chictr.org.cn). CHICTR-ID: ChiCTR2000031418.

Prospective study on health-related quality of life, oral mucositis and oral health on during treatment of head and neck cancer.

BACKGROUND: Few studies have examined health related Quality of Life (HR-QoL) during the treatment of head and neck cancer (HNC) with even fewer focusing on the impact of oral mucositis (OM) on HR-QoL. Studies performed during treatment of HNC makes it possible to follow fluctuations in HR-QoL, OM and other treatment related side effects. The aim was to prospectively analyze HR-QoL, changes in clinical variables and the impact of OM on HR-QoL during HNC treatment. MATERIALS AND METHODS: Patients were recruited before commencing curative cancer treatment and were given professional oral care weekly during oncologic treatment. HR-QoL was reported before, during (week 2, 4 and 6) and three months after treatment using the EORTC Quality of Life questionnaires C30 and H&N35 and the stimulated whole salivary secretion rate was determined at the same time-points. OM (erythema and ulceration) was registered using the Oral Mucositis Assessment Scale (OMAS), at baseline, weekly during treatment and post treatment. Differences in HR-QoL between different timepoints were analyzed. To analyze the impact of OM on HR-QoL the patients were categorized into two groups: no/mild OM (OMAS ulceration score 0-1) or severe OM (OMAS ulceration score ≥ 2) and HR-QoL was compared between the two OM groups at three timepoints during treatment. RESULTS: Fifty-seven patients (43 men, 14 women), with a mean age of 58 years were included. Patients reported progressively impaired HR-QoL, with peak issues noted at weeks 4 and 6, particularly in social eating, senses, appetite loss, sticky saliva, and decreasing salivary secretion rates were determined. Patients with severe OM reported worse HR-QoL compared to those with no/mild OM. Persistent problems 3 months post treatment were appetite loss, dry mouth, senses (smell and taste) and problems with social eating. CONCLUSION: Patients experienced exacerbated symptoms and problems weeks 4 and 6 of oncological treatment, especially among those with severe OM, stressing the importance of clinically monitoring the patients to reduce and alleviate their symptoms. Persistent problems three months post treatment are likely associated with the reduced salivary secretion rate indicating that patients should be monitored also after completed oncological treatment.

Efficacy of natural products in preventing oral mucositis resulting from cancer therapies: A network meta-analysis of randomized controlled trials.

BACKGROUND: Oral mucositis significantly compromises the quality of life for patients undergoing cancer therapies. This study aimed to evaluate the effectiveness of natural products in either preventing or alleviating oral mucositis resulting from cancer treatments. METHODS: A systematic review and network meta-analysis were conducted, sourcing data from the Cochrane Library, PubMed, Embase, Airiti Library, and Wan Fang Data Knowledge Service Platform until August 2023. The study was registered in PROSPERO (CRD42021285433). Confidence in Network Meta-Analysis (CINeMA) and R software 4.1.3 were used for analysis. RESULTS: From 1556 identified articles, 36 randomized controlled trials (RCTs) were analyzed, involving 2083 patients. Honey, notably, was found to significantly reduce the overall incidence of oral mucositis compared to standard care, with a relative risk (RR) of 0.80 (95% CI: 0.67-0.96). It was particularly effective against moderate-to-severe oral mucositis (grade ≥ 2), reducing incidence with RR of 0.48 (95% CI: 0.30-0.75) versus placebo and 0.56 (95% CI: 0.34-0.93) against standard care. Other natural products, including propolis, chamomile, and P. major L., also demonstrated significant efficacy in reducing the incidence of oral mucositis. Regarding pain relief, honey, and P. major L. emerged as effective, significantly reducing pain severity with a mean difference (MD) of -2.96 (95% CI: -3.80 to -1.94) compared to placebo. CONCUSSION: This network meta-analysis supports the use of honey, propolis, chamomile, and P. major L. as effective natural products in the prevention and treatment of oral mucositis among cancer patients. Specifically, honey is highlighted for its significant impact on reducing both the overall incidence and the severity of moderate-to-severe oral mucositis. By leveraging their anti-inflammatory and antioxidant properties, integrating these natural products into the standard care regimen could markedly improve the well-being of individuals undergoing cancer therapy.

Emerging pharmacotherapy trends in preventing and managing oral mucositis induced by chemoradiotherapy and targeted agents.

INTRODUCTION: The introduction of targeted therapy and immunotherapy has tremendously changed the clinical outcomes and prognosis of cancer patients. Despite innovative pharmacological therapies and improved radiotherapy (RT) techniques, patients continue to suffer from side effects, of which oral mucositis (OM) is still the most impactful, especially for quality of life. AREAS COVERED: We provide an overview of current advances in cancer pharmacotherapy and RT, in relation to their potential to cause OM, and of the less explored and more recent literature reports related to the best management of OM. We have analyzed natural/antioxidant agents, probiotics, mucosal protectants and healing coadjuvants, pharmacotherapies, immunomodulatory and anticancer agents, photobiomodulation and the impact of technology. EXPERT OPINION: The discovery of more precise pathophysiologic mechanisms of CT and RT-induced OM has outlined that OM has a multifactorial origin, including direct effects, oxidative damage, upregulation of immunologic factors, and effects on oral flora. A persistent upregulated immune response, associated with factors related to patients' characteristics, may contribute to more severe and long-lasting OM. The goal is strategies to conjugate individual patient, disease, and therapy-related factors to guide OM prevention or treatment. Despite further high-quality research is warranted, the issue of prevention is paramount in future strategies.

Effect of Photobiomodulation on Salivary Cytokines in Head and Neck Cancer Patients with Oral Mucositis: A Systematic Review.

Background: Oral mucositis is a common and distressing side effect of head and neck oncology treatment. Photobiomodulation therapy can be utilized to prevent and treat oral mucositis. Its impact on salivary cytokines has yet to be thoroughly investigated. This is the first systematic review aiming to evaluate the effect of photobiomodulation on salivary cytokines in patients undergoing anticancer treatment. Methods: Numerous data resources, from the Web of Science, Embase, ScienceDirect, PubMed, Cochrane Library, and Scopus were sought. Articles published up until February 2024 were included if they met the following inclusion criteria: clinical trials reporting the effect on salivary cytokines in patients undergoing anticancer therapy. The methodological quality was assessed using several appraisal tools. Results: Four studies were deemed eligible for inclusion. All the studies were conducted in Brazil and used an InGaAlP diode laser with a wavelength of 660 nm. The included studies had a relatively low risk of bias. The head and neck cancer patients' salivary cytokines that were assessed by the studies, along with photobiomodulation therapy, included IL-12p70, TNF-α, IL-6, IL-8, IL-10, CXCL8, and IL-1ß. The results varied among the studies. Conclusions: Our results show that photobiomodulation demonstrated positive results for reducing the severity of OM in all the included studies. Among the examined salivary cytokines, IL-6 is the most relevant cytokine for oral mucositis development and severity. A variation in the cytokine levels between the studies was noted due to differences in the type of anticancer treatment and saliva sampling.

Dentist Involvement in the Treatment of Radiation-Induced Oral Mucositis-A Pilot Cross-Sectional Study.

Objectives: Oral mucositis (OM) occurs in more than 95% of patients irradiated in the head and neck area. This paper aims to determine the occurrence and characteristics of OM in patients with head and neck cancer (HNC), as well as the involvement of dentists/oral medicine specialists in treating such patients. Methods: This study was conducted at the Department of Otorhinolaryngology and Department of Oral Medicine, University Hospital Center Zagreb, from April to August 2022, on patients irradiated in the head and neck area. A unique OM questionnaire was created on the incidence, characteristics, oral care, and involvement of dentists in the overall care. Results: Thirty patients filled out the questionnaire. Of the 22 patients who had developed OM, 14 had grade-three OM. Ten patients were treated for OM in line with the instructions of an oral medicine specialist, eight based on the instructions of a specialist responsible for monitoring of the underlying disease, and four were not treated at all. Sixteen patients had not been referred to a dentist before the start of RT. Conclusions: These results showed insufficient care and treatment of OM, as well as insufficient involvement of dentists in the oncology team.