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Purpose: To update the clinical practice guidelines for the use of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the prevention and/or treatment of oral mucositis (OM).Methods: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment 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, the following guidelines were determined: Recommendation, Suggestion, and No Guideline Possible.Results: A total of 9 new papers were identified within the scope of this section, adding to the 62 papers reviewed in this section previously. A new Suggestion was made for topical 0.2% morphine for the treatment of OM-associated pain in head and neck (H&N) cancer patients treated with RT-CT (modification of previous guideline). A previous Recommendation against the use of sucralfate-combined systemic and topical formulation in the prevention of OM in solid cancer treatment with CT was changed from Recommendation Against to No Guideline Possible. Suggestion for doxepin and fentanyl for the treatment of mucositis-associated pain in H&N cancer patients was changed to No Guideline Possible.Conclusions: Of the agents studied for the management of OM in this paper, the evidence supports a Suggestion in favor of topical morphine 0.2% in H&N cancer patients treated with RT-CT for the treatment of OM-associated pain. [ABSTRACT FROM AUTHOR]

Purpose: This systematic review aimed to assess the updated literature for the prevention of salivary gland hypofunction and xerostomia induced by non-surgical cancer therapies. Methods: Electronic databases of MEDLINE/PubMed, EMBASE, and Cochrane Library were searched for randomized controlled trials (RCT) that investigated interventions to prevent salivary gland hypofunction and/or xerostomia. Literature search began from the 2010 systematic review publications from the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) up to February 2024. Two independent reviewers extracted information regarding study design, study population, cancer treatment modality, interventions, outcome measures, methods, results, risk of bias (RoB version 2), and conclusions for each article. Results: A total of 51 publications addressing preventive interventions were included. Eight RCTs on tissue-sparing radiation modalities were included showing significant lower prevalence of xerostomia, with unclear effect on salivary gland hypofunction. Three RCTs on preventive acupuncture showed reduced prevalence of xerostomia but not of salivary gland hypofunction. Two RCTs on muscarinic agonist stimulation with bethanechol suggested a preventive effect on saliva flow rate and xerostomia in patients undergoing head and neck radiation or radioactive iodine therapy. Two studies on submandibular gland transfer showed higher salivary flow rates compared to pilocarpine and lower prevalence of xerostomia compared to no active intervention. There is insufficient evidence on the effectiveness of vitamin E, amifostine, photobiomodulation, and miscellaneous preventive interventions. Conclusion: This systematic review continues to support the potential of tissue-sparing tecniques and intensity-modulated radiation therapy (IMRT) to preserve salivary gland function in patients with head and neck cancer, with limited evidence on other preventive strategies, including acupuncture and bethanecol. Preventive focus should be on optimized and new approaches developed to further reduce radiation dose to the parotid, the submandibular, and minor salivary glands. As these glands are major contributors to moistening of the oral cavity, limiting the radiation dose to the salivary glands through various modalities has demonstrated reduction in prevalence and severity of salivary gland hypofunction and xerostomia. There remains no evidence on preventive approaches for checkpoint inhibitors and other biologicals due to the lack of RCTs. [ABSTRACT FROM AUTHOR]

Background: Oral lichen planus (OLP) is a chronic inflammatory disorder of the oral mucosa. Currently there is no approved treatment for OLP. We report on the efficacy and safety of a novel mucoadhesive clobetasol patch (Rivelin®‐CLO) for the treatment of OLP. Methods: Patients with confirmed OLP and measurable symptomatic ulcer(s) participated in a randomized, double‐blind, placebo‐controlled, multicenter clinical trial testing a novel mucoadhesive clobetasol patch (Rivelin®‐CLO) in OLP across Europe, Canada, and the United States. Patients were randomized to placebo (nonmedicated), 1, 5, 20 µg Clobetasol/patch, twice daily, for 4 weeks. The primary endpoint was change in total ulcer area compared to baseline. Secondary endpoints included improvement from baseline in pain, disease activity, and quality of life. Results: Data were analyzed and expressed as mean [SD]. One hundred thirty‐eight patients were included in the study; 99 females and 39 males, mean age was 61.1 [11.6] years. Statistical analyses revealed that treatment with 20‐μg Rivelin®‐CLO patches demonstrated significant improvement with ulcer area (p = 0.047), symptom severity (p = 0.001), disease activity (p = 0.022), pain (p = 0.012), and quality of life (p = 0.003) as compared with placebo. Improvement in OLP symptoms from beginning to the end of the study was reported as very much better (best rating) in the 20‐µg group (25/32) patients compared to the placebo group (11/30), (p = 0.012). Adverse events were mild/moderate. Candidiasis incidence was low (2%). Conclusions: Rivelin®‐CLO patches were superior to placebo demonstrating statistically significant, clinically relevant efficacy in objective and subjective improvement and, with a favorable safety profile. [ABSTRACT FROM AUTHOR]

Candidiasis is a highly pervasive infection posing major health risks, especially for immunocompromised populations. Pathogenic Candida species have evolved intrinsic and acquired resistance to a variety of antifungal medications. The primary goal of this literature review is to summarize the molecular mechanisms associated with antifungal resistance in Candida species. Resistance can be conferred via gain-of-function mutations in target pathway genes or their transcriptional regulators. Therefore, an overview of the known gene mutations is presented for the following antifungals: azoles (fluconazole, voriconazole, posaconazole and itraconazole), echinocandins (caspofungin, anidulafungin and micafungin), polyenes (amphotericin B and nystatin) and 5-fluorocytosine (5-FC). The following mutation hot spots were identified: (1) ergosterol biosynthesis pathway mutations (ERG11 and UPC2), resulting in azole resistance; (2) overexpression of the efflux pumps, promoting azole resistance (transcription factor genes: tac1 and mrr1; transporter genes: CDR1, CDR2, MDR1, PDR16 and SNQ2); (3) cell wall biosynthesis mutations (FKS1, FKS2 and PDR1), conferring resistance to echinocandins; (4) mutations of nucleic acid synthesis/repair genes (FCY1, FCY2 and FUR1), resulting in 5-FC resistance; and (5) biofilm production, promoting general antifungal resistance. This review also provides a summary of standardized inhibitory breakpoints obtained from international guidelines for prominent Candida species. Notably, N. glabrata, P. kudriavzevii and C. auris demonstrate fluconazole resistance. [ABSTRACT FROM AUTHOR]

Oral mucositis is a painful and debilitating condition that occurs in the majority of head and neck cancer patients receiving radiation and/or chemotherapy. While some patient and treatment related factors are known to contribute to the incidence and severity of disease, reliable biomarkers remain elusive. In the following study, we investigated the association of salivary DNA methylation derived biological aging, cellular frequency and protein concentration measures with the severity of oral mucositis and overall survival in a cohort of head and neck cancer (HNC) patients (n = 103). DNA methylation profiling was performed on saliva samples obtained prior to treatment. Biological aging measures included Horvath2, PhenoAge, FitAge and GrimAge, and cellular frequency included epithelial and specific immune cell populations. Severe mucositis (i.e. grade 3 or 4) occurred in nearly half of patients. For malignant HNC patients (n = 84), every 1-SD increase in GrimAge was associated with 2.62-times risk of severe mucositis (95 % CI: 1.38, 5.57), while a 1-SD increase in monocyte frequency was associated with a decreased risk (OR [95 %CI]: 0.40 [0.18, 0.80]). Over a median follow-up of 53 months, 39 of 103 participants died. Six protein scores (TNFSF14, GCSF, MATN3, GDF8, nCDase, TNF-β) were associated with survival at q < 0.15. We provide evidence that the risk-related biological aging measure GrimAge may be a useful predictor of mucositis severity in HNC patients. Salivary monocyte frequency may be protective against mucositis, and this measure could be used as a predictive biomarker while also providing clues into the pathobiology of the disease. [ABSTRACT FROM AUTHOR]

Smoking during cancer treatment is associated with reduced treatment response and cancer recurrence in patients with tobacco-related cancers. The purpose of this study was to examine smoking characteristics in head and neck cancer patients (n = 503) with a history of smoking and examine the impact of an intensive clinical tobacco intervention to patients who were currently smoking. All participants completed an interviewer-administered questionnaire at study enrollment which examined smoking behaviours, motivations to quit, and strategies used to cessate smoking. Follow-up assessments were completed at 6- and 12-months which monitored whether patients had quit smoking, remained cessated, or continued to smoke since study recruitment. For those who were currently smoking (n = 186, 37.0%), an intensive clinical tobacco intervention that utilized the 3A's—Ask, Advise, Arrange—and the Opt-Out approach was offered to assist with smoking cessation at their new patient visit and followed-up weekly during their head and neck radiation therapy for 7 weeks. At 6 months, 23.7% (n = 41) of those who were smoking successfully quit; 51.2% quit 'cold turkey' (defined as using no smoking cessation assistance, aids or pharmacotherapy to quit), while 34.9% used pharmacotherapy (varenicline (Champix)) to quit. On average, it took those who were smoking 1–5 attempts to quit, but once they quit they remained cessated for the duration of the study. Although the head and neck cancer patients in this study reported high levels of nicotine dependence, many were able to successfully cessate. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article presents the clinical practice guideline update on medication-related osteonecrosis of the jaw (MRONJ). Topics mentioned include bone-modifying agents (BMAs) that have been linked with MRONJ, prevention and management of MRONJ in patients with cancer who receive BMAs for oncologic indications, and the importance of collaboration among the cancer care team, dentists, and dental specialists.

Purpose: This observational case registry study was designed to describe the natural history of cancer patients with medication-related osteonecrosis of the jaw (ONJ) and evaluate the ONJ resolution rate.Methods: Adults with a diagnosis of cancer and with a new diagnosis of ONJ were enrolled and evaluated by a dental specialist at baseline and every 3 months for 2 years and then every 6 months for 3 years until death, consent withdrawal, or loss to follow-up. The primary endpoint was the rate and time course of ONJ resolution. Secondary endpoints included frequency of incident ONJ risk factors, ONJ treatment patterns, and treatment patterns of antiresorptive agents for subsequent ONJ.Results: Overall, 327 patients were enrolled; 207 (63%) were continuing on study at data cutoff. Up to 69% of evaluable patients with ONJ had resolution or improvement during the study. ONJ resolution (AAOMS ONJ staging criteria) was observed in 114 patients (35%); median (interquartile range) time from ONJ onset to resolution was 7.3 (4.5-11.4) months. Most patients (97%) had received antiresorptive medication before ONJ development, 9 patients (3%) had not; 68% had received zoledronic acid, 38% had received denosumab, and 10% had received pamidronate (56% had received bisphosphonates only, 18% had received denosumab only, and 21% had exposure to both).Conclusions: These results are consistent with those observed in clinical trials evaluating skeletal-related events in patients with advanced malignancy involving bone. Longer follow-up will provide further information on ONJ recurrence and resolution rates between medically and surgically managed patients. [ABSTRACT FROM AUTHOR]

Introduction: This systematic review aims to update on the prevalence of odontogenic-related infections and the efficacy of dental strategies in preventing dental-related complications in cancer patients since the 2010 systematic review.Review Method: A literature search was conducted in the databases MEDLINE/PubMed and EMBASE for articles published between 1 January 2009 and 30 June 2016. Each study was assessed by 2 reviewers and the body of evidence for each intervention was assigned an evidence level.Results: After examination of the abstracts and full-text articles, 59 articles satisfied the inclusion criteria. The weighted prevalence of dental infections and pericoronitis during cancer therapy was 5.4 and 5.3%, respectively. The frequency of dental-related infections during intensive chemotherapy after complete, partial, and minimal pre-cancer dental evaluation/treatment protocols ranged from 0 to 4%. Protocols involving third molars extractions had the highest complications (40%).Conclusions: In view of the low prevalence of infections and the potential for complications after third molar extractions, it is suggested that partial dental evaluation/treatment protocols prior to intensive chemotherapy; whereby minor caries (within dentin), asymptomatic third molars or asymptomatic teeth without excessive probing depth (<8 mm), mobility (mobility I or II) or with periapical lesions of <5 mm were observed; is a viable option when there is insufficient time for complete dental evaluation/treatment protocols. The use of chlorhexidine, fluoride mouth rinses as well as composite resin, resin-modified glass ionomer cement (GIC), and amalgam restorations over conventional GIC in post head and neck radiation patients who are compliant fluoride users is recommended. [ABSTRACT FROM AUTHOR]

Patients undergoing radiation therapy for the head and neck are susceptible to a significant and often abrupt deterioration in their oral health. The oral morbidities of radiation therapy include but are not limited to an increased susceptibility to dental caries and periodontal disease. They also include profound and often permanent functional and sensory changes involving the oral soft tissue. These changes range from oral mucositis experienced during and soon after treatment, mucosal opportunistic infections, neurosensory disorders, and tissue fibrosis. Many of the oral soft tissue changes following radiation therapy are difficult challenges to the patients and their caregivers and require life-long strategies to alleviate their deleterious effect on basic life functions and on the quality of life. We discuss the presentation, prognosis, and management strategies of the dental structure and oral soft tissue morbidities resulting from the administration of therapeutic radiation in head and neck patient. A case for a collaborative and integrated multidisciplinary approach to the management of these patients is made, with specific recommendation to include knowledgeable and experienced oral health care professionals in the treatment team. [ABSTRACT FROM AUTHOR]