Immediate pain alleviation in oral mucositis and other oral ulcerative diseases through photobiomodulation therapy: the preemptive treatment concept.

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

Immunotherapy-Related Oral Adverse Effects: Immediate Sequelae, Chronicity and Secondary Cancer.

(1) Background: Immunotherapy-related adverse effects (irAEs) have been reported to manifest in oral tissues, mainly as lichenoid and non-lichenoid lesions and salivary gland dysfunction; however, the characterization of oral irAEs and their clinical impact is limited. (2) Methods: This is a retrospective clinical chart review of 14 patients with oral irAEs, describing the impact of the oral irAEs in terms of the immediate effect, treatment, chronicity of the irAEs and the development of oral cancer. (3) Results: Common symptoms were pain and dry mouth, causing no-to-severe pain and/or dry mouth sensation. The immediate sequala ranged from sensitivity to certain foods up to elimination of oral intake. Treatment included conventional palliation techniques with or without systemic steroids. Discontinuation of the immunotherapy agents was required in 6 patients. Innovative treatment modalities included photobiomodulation for oral mucosal pain relief, and salivary gland intraductal irrigations for relief of salivary gland hypofunction. Late sequala included the development of proliferative leukoplakia and oral cancer. (4) Conclusions: Patients treated with immunotherapy may develop debilitating oral irAEs. They should be followed for oral involvement so treatment may be initiated when the symptoms are mild to avoid discontinuation of the immunotherapy. Patients that develop oral lichenoid lesions should receive long-term follow-up, as they may have higher risk for oral cancer.

World Workshop on Oral Medicine VIII: Barriers to research in oral medicine: results from a global survey.

OBJECTIVES: To explore factors influencing research interest and productivity and perceived barriers to conducting research in Oral Medicine (OM). METHODS: Invitations to participate in an online survey were e-mailed to a network of international OM practitioners and related professional organizations. Questions captured respondents' demographic/professional variables and gauged research interest, productivity, and perceived barriers to conducting research specifically in OM. Statistical analysis was conducted via descriptive, logistic regression, and multivariate modeling. RESULTS: Five hundred and ninety-three OM practitioners from 55 countries completed the survey, with 54%, 25%, and 21% practicing in high, upper-middle, and lower-middle-income countries, respectively. Eighty-six percent of respondents were interested in conducting research. Age (less interest with an increase in age), working in academia, and practicing in a lower-middle vs high-income country were significant predictors of research interest. Self-reported research productivity was significantly greater among males, those working in academia, and those who graduated from programs that mandated research presentation/publication. Obtaining research funding was a significant barrier among respondents from lower and upper-middle-income countries, whereas finding time for research was a reported barrier by respondents from high-income countries. CONCLUSION: The results of this survey identified perceived barriers to conducting research in OM and highlighted solutions to address such barriers.

Clinical use of photobiomodulation for the prevention and treatment of oral mucositis: the real-life experience of MASCC/ISOO members.

AIM: To assess clinical use and patient outcome of photobiomodulation (PBM) for oral mucositis (OM) prevention and treatment among specialized practitioners. METHODS: A poll was emailed to the members of the Mucositis Study Group of MASCC/ISOO. The PBM parameters used by the respondents were analyzed using exploratory statistical methods to identify combinations of PBM parameters (patterns) that characterize the variance in the protocols (principal component analysis). RESULTS: Responses were received from 101 MSG members, with 78 providing analyzable data. Most of the responders were dental practitioners or oral medicine specialists. PBM was used by 59% of the responders for OM or targeted therapy stomatitis. Technical parameters varied widely. Most responders used wavelengths ∼650 nm intra-orally. The spot-size and distance from the tissue were the main factors driving the variation. All PBM users noted that PBM relieved pain, either immediately or a delayed effect. High likelihood of pain relief (measured as responder's report of pain relief in 67-100% of patients) was reported by 22% and 19% of PBM users for immediate pain relief and delayed pain relief, respectively. The most common reported barriers to using PBM were financial considerations, time constraints, lack of training or experience and concern about the potential for malignant transformation or increased risk of cancer recurrence. CONCLUSIONS: The use of PBM for OM prevention or treatment is in early phases of adoption in practices, facing some obstacles to implement it. A wide variation in technical parameters was found. Nonetheless, responses indicate that PBM provided pain relief.

Clinicians' experience with topical benzydamine and morphine for the management of oral mucositis: adverse effects and barriers.

INTRODUCTION: Among the evidence-based agents outlined in the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) mucositis guidelines, benzydamine and morphine are advised for the management of oral mucositis (OM) in certain cancer patients. This study is aimed to collect information from a group of highly experienced healthcare professionals in the field of oral mucositis about their clinical experience with these agents. METHODS: A survey questionnaire about the clinical experience with topical benzydamine and morphine to manage oral mucositis and their related adverse effects (AEs) was electronically distributed to the members of the Mucositis Study Group of MASCC/ISOO. RESULTS: Eighty-eight entries were recorded (response rate 25%), and 54 entries submitted complete questionnaires about the drug-related AE (completion rate 65%) and were used for the data analysis. Of the respondents, 44% and 27.7% prescribed benzydamine and morphine to manage their patients' oral mucositis, respectively. Lack of availability in the respondent's country was the common reason for not prescribing benzydamine and morphine (18.9% and 5.4%, respectively); however, a large portion of the respondents indicated that 'another reason' stopped them from prescribing these agents (51.3% and 73%, respectively). AEs to benzydamine or morphine were observed by 25.9% and 12.9% of respondents, respectively, with mild numbness and tingling as the most common drug-related AE for both agents. CONCLUSION: The use of topical benzydamine and morphine for the management of OM varies between countries. While relatively common, the AEs related to these agents are mild. Mitigating the barriers for prescribing them may increase their use.

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

Disclaimer: This article is based on recommendations from the 12th WALT Congress, Nice, October 3-6, 2018, and a follow-up review of the existing data and the clinical observations of an international multidisciplinary panel of clinicians and researchers with expertise in the area of supportive care in cancer and/or PBM clinical application and dosimetry. This article is informational in nature. As with all clinical materials, this paper should be used with a clear understanding that continued research and practice could result in new insights and recommendations. The review reflects the collective opinion and, as such, does not necessarily represent the opinion of any individual author. In no event shall the authors be liable for any decision made or action taken in reliance on the proposed protocols. Objective: This position paper reviews the potential prophylactic and therapeutic effects of photobiomodulation (PBM) on side effects of cancer therapy, including chemotherapy (CT), radiation therapy (RT), and hematopoietic stem cell transplantation (HSCT). Background: There is a considerable body of evidence supporting the efficacy of PBM for preventing oral mucositis (OM) in patients undergoing RT for head and neck cancer (HNC), CT, or HSCT. This could enhance patients' quality of life, adherence to the prescribed cancer therapy, and treatment outcomes while reducing the cost of cancer care. Methods: A literature review on PBM effectiveness and dosimetry considerations for managing certain complications of cancer therapy were conducted. A systematic review was conducted when numerous randomized controlled trials were available. Results were presented and discussed at an international consensus meeting at the World Association of photobiomoduLation Therapy (WALT) meeting in 2018 that included world expert oncologists, radiation oncologists, oral oncologists, and oral medicine professionals, physicists, engineers, and oncology researchers. The potential mechanism of action of PBM and evidence of PBM efficacy through reported outcomes for individual indications were assessed. Results: There is a large body of evidence demonstrating the efficacy of PBM for preventing OM in certain cancer patient populations, as recently outlined by the Multinational Association for Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). Building on these, the WALT group outlines evidence and prescribed PBM treatment parameters for prophylactic and therapeutic use in supportive care for radiodermatitis, dysphagia, xerostomia, dysgeusia, trismus, mucosal and bone necrosis, lymphedema, hand-foot syndrome, alopecia, oral and dermatologic chronic graft-versus-host disease, voice/speech alterations, peripheral neuropathy, and late fibrosis amongst cancer survivors. Conclusions: There is robust evidence for using PBM to prevent and treat a broad range of complications in cancer care. Specific clinical practice guidelines or evidence-based expert consensus recommendations are provided. These recommendations are aimed at improving the clinical utilization of PBM therapy in supportive cancer care and promoting research in this field. It is anticipated these guidelines will be revised periodically.

Confounding factors in the assessment of oral mucositis in head and neck cancer.

Treatment of locally advanced head and neck carcinoma not amenable for surgical resection or resected with high-risk features is usually based on (chemo-)radiation treatment. Oral mucositis represents one of the main side effects of (chemo-)radiation, with an important impact on quality of life and causing approximately 20% of early interruption of treatment, leading to a suboptimal dose administered. Treatment and prevention of oral mucositis have a central role in the therapeutic pathways of head and neck cancer patients but remains quite challenging. Although extensive research is conducted to identify interventions for the management of mucositis, very few interventions had sufficient evidence to generate an international expert consensus. This may be partially explained by confounding factors that could influence the development and assessment of oral mucositis. Little is known about the confounding factors of oral mucositis, which, if not well balanced in an experimental study, could lead to non-solid results. The current paper aims to review the main oral mucositis confounding factors related to head and neck cancer patients.

The broadening scope of oral mucositis and oral ulcerative mucosal toxicities of anticancer therapies.

Oral mucositis (OM) is a common, highly symptomatic complication of cancer therapy that affects patients' function, quality of life, and ability to tolerate treatment. In certain patients with cancer, OM is associated with increased mortality. Research on the management of OM is ongoing. Oral mucosal toxicities are also reported in targeted and immune checkpoint inhibitor therapies. The objective of this article is to present current knowledge about the epidemiology, pathogenesis, assessment, risk prediction, and current and developing intervention strategies for OM and other ulcerative mucosal toxicities caused by both conventional and evolving forms of cancer therapy.

Commonly used systemic drugs interfering with bone remodeling: a case report and literature review.

Bone regeneration and remodeling are crucial to healing after surgical interventions. Local and systemic factors impact healing. Some well-known medications actively alter bone remodeling. The objective of this report was to increase awareness of less commonly recognized medications that may delay the integration of bone grafts. This case report presents the delayed integration of a bone graft after tooth removal, socket preservation, and ridge augmentation procedures in a patient taking various medications that may have affected bone remodeling. The literature review enables the discussion of evidence regarding delayed bone remodeling associated with selective serotonin reuptake inhibitors (SSRIs), sodium-glucose cotransporter 2 (SGLT2) inhibitors, metformin, and nonsteroidal anti-inflammatory drugs (NSAIDs), and the clinical implications for patients taking these medications.

Oral white lesion in patients post-hematopoietic stem cell transplantation: a case series demonstrating the diagnostic dilemma.

The current National Institutes of Health (NIH) consensus paper excluded "white hyperkeratotic plaque" from the diagnostic criteria for oral chronic graft-versus-host disease (cGVHD) in order to ensure malignant transformation is not overlooked. Therefore, an isolated oral white plaque is recommended to be subjected to biopsy and pathologic examination. The cases described in this paper shed a new light on the clinical approach to oral white plaque post-hematopoietic stem cell transplantation. The objectives of this article are to demonstrate that a white plaque does not contradict a diagnosis of oral cGVHD, and to highlight the clinical considerations for taking a biopsy.

Oral Graft-Versus-Host Disease: A Pictorial Review and a Guide for Dental Practitioners.

INTRODUCTION: Graft-versus-host disease (GVHD) is a complication of haematopoietic stem cell transplantation (HSCT). GVHD may also develop following solid transplants or blood transfusions if white blood cells are transferred. GVHD affects multiple organs, including the oral tissues. OBJECTIVE: This pictorial review provides a background of GVHD to dental practitioners, describes the most common oral manifestations of GVHD and highlights the main treatment modifications needed to deliver dental care to patients with GVHD. METHODS: A narrative review enhanced with clinical photographs. RESULTS: Acute GVHD may manifest in the oral mucosa; however, it often develops immediately following HSCT when routine dental treatment is postponed. Chronic GVHD may manifest in the oral mucosa, the salivary glands and the musculoskeletal compartment. It may indirectly affect the teeth and the oral flora, putting the patient at risk for infections. Importantly, GVHD poses an increased risk for oral cancer. CONCLUSION: GVHD has a wide range of oral manifestations, some of which may affect dental treatment.

The impact of the COVID-19 outbreak on supportive care for oral mucositis: current concepts and practice.

The outbreak of coronavirus disease 2019 (COVID-19) markedly affected the way healthcare professionals approach patients with cancer worldwide, not only in terms of therapeutic decision-making but also in terms of supportive care. With the rapid appearance of signs and symptoms and the need of close re-assessment, standard management of oral mucositis has been challenged by physical distancing and limited resources due to the global crisis. Building on the clinical experience developed during the acute phase by members of the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO), the implications of COVID-19 on the prevention, assessment, and treatment of mucositis are critically reported. Inspired by the restructuring of supportive care measures in response to the pandemic, suggestions for new models of approaching acute side effects are also discussed.

MASCC/ISOO clinical practice guidelines for the management of mucositis: sub-analysis of current interventions for the management of oral mucositis in pediatric cancer patients.

OBJECTIVE: The aim of this sub-analysis was to highlight the MASCC/ISOO clinical practice guidelines for the management of oral mucositis (OM) in pediatric patients and to present unique considerations in this patient population. METHODS: This sub-analysis of the pediatric patient population is based on the systematic review conducted by the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISSO) published in 2019/2020. Studies were scored and assigned a level of evidence based on previously published criteria. Data regarding adverse effects and compliance was collected from the original publications. RESULTS: A total of 45 papers were included and assessed in this sub-analysis, including 21 randomized controlled trials (RCTs). Chewing gum was demonstrated to be not effective in preventing OM in pediatric cancer patients in 2 RCTs. The efficacy of all other interventions could not be determined based on the available literature. CONCLUSION: There is limited or conflicting evidence about interventions for the management of OM in pediatric cancer patients, except for chewing gum which was ineffective for prevention. Therefore, currently, data from adult studies may need to be extrapolated for the management of pediatric patients. Honey and photobiomodulation therapy in this patient population had encouraging potential. Implementation of a basic oral care protocol is advised amid lack of high level of evidence studies.

Oral verruciform xanthoma in chronic graft-versus-host disease patients.

BACKGROUND: Verruciform xanthoma (VX) is an uncommon benign epithelial lesion which mainly appears in inflamed oral epithelium. In this study, our aim was to present new cases of oral VX (OVX) in chronic graft-versus-host disease (cGVHD) and review the literature. METHODS: We conducted a retrospective chart review of cGVHD patients (2012-2019) to reveal cases of OVX. The demographics, medical background, clinical presentation, treatment provided, and follow-up were obtained. Additionally, Medline was searched using the terms "graft-versus-host disease," "verruciform xanthoma," and "oral." Of the articles, the above-mentioned demographic and clinical features were retrieved. RESULTS: The patient pool included 133 oral cGVHD patients. Three cGVHD patients (males, aged 15-49 years, post-hematologic malignancy) were diagnosed with OVX. All patients had oral mucosal lichenoid lesions, but not in close proximity to the VX lesion. Medline searches revealed 9 cases of OVX in cGVHD patients reported in the literature. Eleven of the 12 patients had oral mucosal lichenoid lesions. Four patients had multiple OVX lesions. All lesions were asymptomatic. Six patients had lesions in the masticatory mucosa (hard palate and gingiva) and 4 patients had lesions in the buccal mucosa. CONCLUSIONS: To the best of our knowledge, this is the largest published OVX in cGVHD series, including 12 patients. It appears that despite the higher prevalence in cGVHD patients relative to the general population, OVXs do not necessarily develop in sites with lichenoid lesions. It is advised that clinicians be familiar with the clinical and histological features in order to consider OVX in the differential diagnosis of oral lesions in cGVHD patients.

Oral Manifestations of Systemic Diseases.

Signs and symptoms representative of a systemic condition can manifest in the oral cavity and orofacial region. Such conditions may be previously diagnosed, or the orofacial manifestation may be the presenting sign of an acute or chronic systemic condition not previously diagnosed. Pathologic processes in the mouth, jaws, and contiguous structures could have a direct and indirect impact on the patient's overall systemic condition. Moreover, systemic conditions may result in compromised function of the orofacial region or impact patients' oral health profile. This article reviews selected systemic conditions that present or impact on the oral cavity and orofacial region.

MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy.

BACKGROUND: Mucositis is a significant toxicity of cancer therapy with numerous systemic sequelae. The goal of this systematic review was to update the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines for the management of mucositis. METHODS: The literature was reviewed systematically to identify interventions for mucositis. Studies were rated according to the presence of major and minor flaws according to previously published criteria. The body of evidence for each intervention and in each treatment setting was assigned a level of evidence based on previously published criteria. Guidelines were developed based on the level of evidence, with 3 possible guideline determinations: recommendation, suggestion, or no guideline possible. RESULTS: The guideline covers evidence from 1197 publications related to oral or gastrointestinal mucositis. Thirteen new guidelines were developed for or against the use of various interventions in specific treatment settings, and 11 previous guidelines were confirmed after aa review of new evidence. Thirteen previously established guidelines were carried over because there was no new evidence for these interventions. CONCLUSIONS: The updated MASCC/ISOO Clinical Practice Guidelines for mucositis provide professional health caregivers with a clinical setting-specific, evidence-based tool to help with the management of mucositis in patients who have cancer.

Repurposing Existing Medications for Coronavirus Disease 2019: Protocol for a Rapid and Living Systematic Review

BackgroundCoronavirus Disease 2019 (COVID-19) has no known specific treatments. However, there might be in vitro and early clinical data as well as evidence from Severe Acute Respiratory Syndrome and Middle Eastern Respiratory Syndrome that could inform clinicians and researchers. This systematic review aims to create priorities for future research of drugs repurposed for COVID-19. MethodsThis systematic review will include in vitro, animal, and clinical studies evaluating the efficacy of a list of 34 specific compounds and four groups of drugs identified in a previous scoping review. Studies will be identified both from traditional literature databases and pre-print servers. Outcomes assessed will include time to clinical improvement, time to viral clearance, mortality, length of hospital stay, and proportions transferred to the intensive care unit and intubated, respectively. We will use the GRADE methodology to assess the quality of the evidence. DiscussionThe challenge posed by COVID-19 requires not just a rapid review of drugs that can be repurposed but also a sustained effort to integrate new evidence into a living systematic review. Systematic review registrationPROSPERO 2020 CRD42020175648

Photobiomodulation Therapy for Cancer Treatment-Related Salivary Gland Dysfunction: A Systematic Review.

Objective: Symptoms and clinical signs of decreased saliva secretion are a common after cancer therapy. The goal of this research is to systematically review the evidence about the efficacy of photobiomodulation therapy (PBMT) for the management of cancer treatment-related xerostomia or salivary hypofunction. Methods: PubMed was searched for articles investigating the clinical effects of PBMT on cancer therapy-related xerostomia or hyposalivation. The publications that met the eligibility criteria were evaluated for the quality of the study design, physical parameter setting reproducibility, specifics of the treatment protocol, clinical outcomes, and adverse effects. The strongest evidence was given a heavier weight in the overall conclusions. Results: A total of 314 articles were identified, and 5 controlled trials were included in this systematic review. Most of the studies were in head and neck cancer patients treated with radiotherapy (RT) or radiochemotherapy (RT-CT), and one study was in dry mouth associated with hematopoietic stem cell transplantation (HSCT). Data showed conflicting results for either prevention or treatment of RT- or RT-CT-induced dry mouth or hyposalivation. The data for HSCT-related dry mouth were positive. Conclusions: Despite positive preliminary outcomes in most of the trials, it is too early to confidently determine the efficacy of PBM for cancer therapy-related hyposalivation or xerostomia.

Systematic review of natural and miscellaneous agents, for the management of oral mucositis in cancer patients and clinical practice guidelines - part 2: honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents.

OBJECTIVE: To update the clinical practice guidelines for the management of oral mucositis (OM) that were developed by the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). This part focuses on honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents. METHODS: A systematic review was conducted by the Mucositis Study Group of MASCC/ISOO. The body of evidence for each intervention, in each clinical setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, one of the following guidelines were determined: Recommendation, Suggestion, No Guideline Possible. RESULTS: A total of 78 papers were identified within the scope of this section, of which 49 were included in this review and merged with nine publications that were reported in the previous guidelines update. A new Suggestion was made for honey (combined topical and systemic delivery) for the prevention of OM in head and neck cancer patients receiving radiotherapy with or without chemotherapy. A new Suggestion clarified that chewing gum is not effective for the prevention of OM in pediatric patients with hematological or solid cancer treated with chemotherapy. No guideline was possible for other interventions. CONCLUSIONS: Numerous natural products and herbal remedies were studied for the management of OM. Of the agents reviewed in this systematic review, a guideline in favor was made for honey (combined topical and systemic), while a guideline against was made for chewing gum. Additional research is warranted to clarify the potential of other interventions.