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.

MASCC/ISOO clinical practice statement: Current understanding on controversies in basic oral care in hemato-oncology and hematopoietic cell transplantation.

PURPOSE: A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise tool for clinicians, which concentrates on practical information needed for the management of oral complications of cancer patients. This CPS is focused on the current understanding of controversies that may arise while providing basic oral care in hemato-oncology patients and hematopoietic cell transplantation recipients (HCT). The CPS will summarize and elucidate controversies that have appeared in the literature and professional discussions. METHODS: This CPS was developed based on a critical evaluation of the literature followed by a structured discussion of a group of leading experts, members of the Oral Care Study Group of MASCC/ISOO. The information is presented in the form of succinct bullets to generate a short manual about the best standard of care. RESULTS: Controversies about the use of chlorhexidine (CHX) oral rinse, mechanical dental plaque removal procedures, the need for toothbrush replacement during phases of low blood cell counts, and the use of lidocaine mouthwash for oral pain were identified and discussed. Consensus about the best standard of care was outlined. CONCLUSION: The following ratifications are applicable for oral care in hemato-oncology patients and patients undergoing HCT: (1) CHX may reduce the risk of oral infections, although it was not found to reduce the risk of oral mucositis. (2) Toothbrushing and proficient interproximal cleaning should not be discouraged during HCT. (3) Toothbrushes do not need to be replaced daily and are preferred over cleansing swabs. (4) Lidocaine rinse, swish and spit, may be considered to palliate oral mucosal pain if applied in a certain manner.

MASCC/ISOO Clinical Practice Statement: The risk of secondary oral cancer following hematopoietic cell transplantation.

PURPOSE: A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise tool for clinicians that concentrates practical information needed for the management of oral complications of cancer patients. This CPS is focused on the risk of secondary oral cancer following hematopoietic cell transplantation (HCT). METHODS: This CPS was developed based on critical evaluation of the literature followed by a structured discussion of a group of leading experts, members of the Oral Care Study Group of MASCC/ISOO. The information is presented in the form of succinct bullets to generate a short manual about the best standard of care. RESULTS: Studies described a 7-16-fold higher risk of secondary oral cancer (mainly squamous cell carcinoma) in allogeneic HCT (alloHCT) recipients, particularly in those who developed chronic graft versus host disease (cGVHD). Risk increases over time and is influenced by several risk factors. In autologous HCT, oral cancer risk seemed only slightly elevated. CONCLUSION: Clinicians should be aware of the higher oral cancer risk in alloHCT survivors, and emphasize the importance of lifelong oral cancer surveillance (at least every 6-12 months) and avoiding cancer promoting lifestyle factors in an empathic way, particularly of those with (a history of) cGVHD. Post-HCT for Fanconi anemia or dyskeratosis congenita, education and rigorous follow-up is even more crucial. In case of suspected oral lesions in the presence of oral mucosal cGVHD, a GVHD intervention may facilitate diagnosis. Suspected lesions should be biopsied. More research is needed on the role of HPV in oral cancer post-HCT.

MASCC/ISOO Clinical Practice Statement: Management of oral manifestations of chronic graft-versus-host-disease.

PURPOSE: A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise tool for clinicians, which concentrates practical information needed for the management of oral complications of cancer patients. This CPS is focused on the management of oral manifestations of chronic graft-versus-host-disease (cGVHD). METHODS: This CPS was developed based on critical evaluation of the literature followed by a structured discussion of a group of leading experts, members of the Oral Care Study Group of MASCC/ISOO. The information is presented in the form of succinct bullets and table to generate a short manual about the best standard of care. RESULTS: The treatment goals in oral cGVHD are to relieve pain and xerostomia, improve oral function, prevent secondary infection, prevent deterioration of the dentition, and detect malignant transformation as early as possible. The prevention and treatment measures for oral mucosal lesions, hypofunction of the salivary glands, and sclerodermatous changes in the oral and perioral tissues are detailed, as well as the possible complications and side effects of these interventions. CONCLUSIONS: Patients post allogeneic hematopoietic cell transplantations, with cGVHD manifest in the oral and perioral tissues, should be regularly monitored and treated as needed by an oral care practitioner. This CPS provides the clinician with practical tools for examining, preventing, and treating the various sequalae that may affect the oral cavity in these patients.

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.

Facial and trigeminal nerves neuropathy induced by atmospheric pressure changes: A meta-analysis.

BACKGROUND: Barometric pressure changes during flight or diving may cause facial barotrauma. Neuropathy of the fifth (CN5) or the seventh (CN7) cranial nerves is a rare manifestation of this condition. The aim of this study was to analyze risk factors for baroneuropathies of CN5 and CN7. METHODS: A search of PubMed and Cochrane Library databases was conducted to identify all published cases of CN5 and CN7 neuropathies. Only original case reports and series that documented events of neuropathies associated with the trigeminal nerve or facial nerve while flying, diving, or mountain climbing were included. Assessed variables included sex, medical history, age, setting (flight or diving), atmospheric pressure changes, number of episodes, symptoms, treatment, and recovery. RESULTS: We identified a total of 48 articles described >125 episodes in 67 patients. Mean age was 33.5 ± 12.1 years with a male predominance (76.1 %). Cases were equally distributed between flight and diving (50.7 %, 46.3 %, respectively). CN5 involvement was observed in 77.6 % of patients, with ear pain and facial numbness as the most common symptoms. The latter was correlated with positive otolaryngology medical history. CN7 was involved in 88.1 % of patients. Flying, as opposed to diving was correlated with spontaneous resolution of symptoms (86.7 % vs. 42.3 % of cases resolved spontaneously, respectively, p = 0.001). CONCLUSIONS: Flight is an equal risk factor to diving with respect to CN5 and CN7 barotrauma. Involvement of CN7 was observed in most cases, but possibly due to report-bias. Positive medical history is a risk factor for facial numbness.

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

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

Perforating dental implants and maxillary sinus pathology.

OBJECTIVES: To study the association between perforation dental implants into the maxillary sinus cavity and the development of sinus pathology. METHODS: We retrospectively examined 3732 computerized tomography (CT) scans to detect maxillary implants. The detected scans were grouped based on apparent or lack of perforated dental implants in the maxillary sinus (study and control group, respectively). Clinical data was gathered including the CT indication, patients' demographics, comorbidities and medications, implant features, and the radiographic appearance of the maxillary sinuses. We conducted a logistic regression to identify risk factors to develop radiopaque thickening in the sinuses. RESULTS: Included in the study were 198 patients with 719 maxillary implants; of these, 236 and 483 implants were in the study and control groups, respectively. Sinus opacification was associated with implants' perforations (p < 0.001), diameter, and side and place (p < 0.05). Implants' perforation (OR = 3.679; 95% CI = 1.891-7.157) and diameter (OR = 1.608; 95% CI = 1.067-2.424), sinus floor augmentation (OR = 2.341; 95% CI = 1.087-5.042), male gender (OR = 2.703; 95% CI = 1.407-5.192), and smoking (OR = 6.073; 95% CI = 2.911-12.667) were associated with ipsilateral sinus fullness. CONCLUSIONS: A first large study on the association between maxillary dental implant and sinus pathology. Dental implant perforation is associated with sinus opacification. Considering dental implant diameter, rather than vertical depth of penetration into the sinus, as an important criterion when examining perforated dental implants necessitates a new approach to clinical decision-making.

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.

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.

High-power laser photobiomodulation therapy for immediate pain relief of refractory oral mucositis.

PURPOSE: We aimed to evaluate the efficacy of high-power (class IV) laser photobiomodulation (PBM) therapy for immediate pain relief due to oral mucositis (OM) refractory to recommended first-line therapy. METHODS: This retrospective study included 25 cancer patients with refractory chemotherapy- or radiotherapy-induced OM (16 and 9 patients, respectively) that were treated for pain relief with an intraoral InGaAsP diode laser (power density = 1.4 W/cm2 ). Pain was self-assessed immediately before and after laser treatment using a 0-to-10 numeric rating scale ([NRS], "0" = no pain, "10" = intolerable pain). RESULTS: Patients reported an immediate decrease in pain following 94% (74 of 79) of the PBM sessions, in 61% (48 sessions) the pain reduction was over 50%, and in 35% (28 sessions) the initial pain was completely eliminated. There were no reports of increased pain post-PBM. For chemotherapy and radiotherapy-treated patients, mean reduction in pain NRS post-PBM was 4.8 ± 2.5 (p < 0.001) and 4.5 ± 2.8 (p = 0.001), indicating a post-PBM reduction of 72% and 60% of the initial pain level, respectively. The analgesic benefit of PBM remained for a mean of 6.0 ± 5.1 days. One patient reported a transient burning sensation after one PBM session. CONCLUSIONS: High-power laser PBM may provide nonpharmacologic, patient-friendly, long-lasting, rapid pain relief for refractory OM.

Dental tourism and the risk of barotrauma and barodontalgia.

Background and aim Dental tourism, which reflects the provision of health care services abroad, also includes a travelling component. Air travel after dental intervention may cause barotrauma and barodontalgia. This paper aimed to provide guiding principles regarding the minimal time interval between dental procedures and air travel to prevent these adverse effects.Methods A literature search was performed to reveal information with regards to complications related to flights following dental treatments. There is little research in this area and most of it has been conducted on the military aircrew population, which has different characteristics of flight and personnel than civilian commercial flights.Results The recommended time of flying is one week after most dental intervention and six weeks after a sinus lift procedure. The minimal time required between a procedure and flight is 24 hours after restorative treatment, 24-48 hours after simple extraction, 72 hours after nonsurgical endodontic procedure, surgical extraction, and implant placement, and at least two weeks after sinus lift procedure.Conclusions The provided guidelines may serve as a starting point for the clinician's decision-making. The tailoring of an individual treatment plan to the patient should take into consideration the patient's condition, dental procedure, complications and flight characteristics. Further research based on commercial flights is needed to formulate more accurate guidelines for the civilian population.

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.

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.

The Impact of Expectation for Pain Relief on Orofacial Pain Treatment Outcomes.

Aims: To examine the effects of expectations for pain relief on the objective and subjective outcome of chronic orofacial pain (OFP) treatment. Materials and Methods: Sixty individuals referred to the Orofacial Pain Clinic at the Hebrew University-Hadassah School of Dental Medicine between 2015 and 2017 with OFP reported their expectation for pain relief upon initial consultation. They were also interviewed by telephone after treatment and asked to recall their expectations, referred to as "recalled expectations" (RE). Correlations between RE and treatment success were calculated from pain diaries, and from subjective pain improvement rates (PIR) reported by the patients. Results: 21 males (35.0%) and 39 females (65%), mean age of 46.90 ± 15.77 years and mean pain duration of 49.07 ± 51.95 months participated in the study. All participants rated their expectations as "10" on a 0 to 10 scale during their first visit. RE did not correlate with diary ratings, (P = 0.773) but inversely correlated (-0.3) with PIR (P = 0.020) treatment outcomes. Conclusions: Expectations for pain relief, reported as 10 on a 0-10 scale during the first appointment, may reflect the patient's desire for complete relief of their pain rather than their expectations. Clinicians should therefore be aware of the need for clear communication and wording when examining for expectations. Inverse correlation between recalled expectations and subjective outcome may be due to the nature of recalled expectations when patients already knew their treatment outcomes, and may be explained by the concept of cognitive dissonance.

Long-term dental implications of infant oral mutilation: a case series.

Infant oral mutilation (IOM) is a ritual ceremony practised mostly in African cultures, in which the primary tooth bud of the deciduous canine is extracted. Complications and risks of IOM include pain, heavy bleeding and infection that may deteriorate to life-threating conditions. The main long-term consequence of IOM is future dental abnormalities. The scientific literature lacks in-depth analyses of the dental sequelae of this practice among adults who underwent it, and particularly of the aspect of dental treatment. Eight new cases of IOM are presented in this case series, with emphasis on dental diagnosis and treatment modalities. We describe different outcomes of this practice, such as enamel hypoplasia and crown deformations with later necrosis and infection of the root canal system, severe discolouration, immature root apex, impaction of a canine, failure of development and missing lower permanent incisors and canines, an odontoma-like structure, severe periodontal defect and root dilaceration. Familiarity with the practice of IOM is vital in order to identify its manifestations and arrive at the correct diagnosis and optimal course of treatment.