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Mucositis research and treatment are a rapidly evolving field providing constant new avenues of research and potential therapies. The MASCC/ISOO Mucositis Study Group regularly assesses available literature relating to pathogenesis, mechanisms, and novel therapeutic approaches and distils this to summary perspectives and recommendations. Reviewers assessed 164 articles published between January 2011 and June 2016 to identify progress made since the last review and highlight new targets for further investigation. Findings were organized into sections including established and emerging mediators of toxicity, potential insights from technological advances in mucositis research, and perspective. Research momentum is accelerating for mucositis pathogenesis, and with this has come utilization of new models and interventions that target specific mechanisms of injury. Technological advances have the potential to revolutionize the field of mucositis research, although focused effort is needed to move rationally targeted interventions to the clinical setting. [ABSTRACT FROM AUTHOR]

Aim: Dental treatment is necessary in oncology patients since pre-existing oro-dental disease may influence cancer treatment and prognosis. This study investigated the applicability of two indices in reflecting the actual oral health status of 100 non-cancer patients who were admitted for dental complaints/routine controls.

Objective To assess the severity of xerostomia (subjective dry mouth) in haematopoietic stem cell transplantation (HSCT) patients and to investigate the association of xerostomia with other chronic oral complications.Design Cross-sectional study.Study participants and methods Participants were 48 patients with a history of HSCT recruited among members of the Dutch Stem Cell Transplantation Contact Group, and a comparison group of 41 age- and sex-matched individuals. Data were collected using the Xerostomia Inventory (XI score) and a seven-item oral health questionnaire.Results HSCT patients had a higher XI score than the comparison group, and a greater severity of several oral complaints: painful oral mucosa, altered taste, limited opening of the mouth and problems with tooth brushing. HSCT patients did not report greater pain during cold stimulation of teeth, chipped and cracked teeth or bleeding gums. In HSCT patients, the XI score correlated significantly with the severity of oral mucosal pain, altered taste, limited opening of the mouth, painful teeth following cold stimuli, chipped or cracked teeth, problems with tooth brushing and bleeding gums. In the comparison group, no correlations were observed between XI score and these oral problems.Conclusion HSCT patients have more severe xerostomia, which is associated with other oral complaints. Dental professionals should monitor these patients post-transplant for oral complications. Symptoms of dry mouth should be relieved and secondary complications should be prevented. [ABSTRACT FROM AUTHOR]

Introduction: Minimal important change estimates (MIC) are useful for interpreting results of clinical research with quality of life (QoL) as an endpoint. For the European Organisation for Research and Treatment of Cancer head and neck cancer module, the EORTC QLQ-HN43, no such thresholds are established., Methods: Head and neck cancer patients under active treatment (n = 503) from 15 countries completed the EORTC QLQ-HN43 three times (t1: before treatment, t2: three months after t1, t3: six months after t1). A subgroup completed a Subjective Significance Questionnaire (SSQ), indicating experienced change from the previous time point in four QoL domains. QoL was assumed to deteriorate after t1 and improve again until t3. The MIC was established using the average of mean differences in SSQ groups (MIC mean ) and estimates based on logistic regressions (MIC predict ). Additionally, minimal detectable changes (MDC) were computed using 0.5 standard deviation and standard error of the mean., Results: For swallowing, speech, dry mouth, and global QoL, the MIC for deterioration were 13, 14, 26, and 10 respectively. The MIC for improvement were 8 (swallowing), 6 (dry mouth), and 5 (global QoL); no MIC for speech improvement can be presented because of insufficient correlation between change score and anchor. The MDC estimates for deterioration were 15, 14, 15, and 11. For improvement, the MDC estimates were 13, 14, 14, and 11., Conclusions: Our results underline that no single MIC or MDC can be applied to all EORTC QLQ-HN43 scales, and that the MIC for deterioration seems larger than those for improvement., Competing Interests: Declaration of Competing Interest Authors declare they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: The authors report no potential conflicts of interests to declare., (© 2024 Published by Elsevier Ltd.)

In recent years, the five-year survival rate for childhood cancer has increased to about 80%. However, childhood cancer therapy can have serious long-term adverse effects on general health later in life. Of survivors, 75% experience 1 or more late effects. This PhD research aimed to gain more insight into the long-term effects on oral health of childhood cancer therapy, 15 years or more after diagnosis. This study, which is part of the Dutch Childhood Cancer Survivor Study Late Effects 2 (DCCSS LATER 2 Study), showed that oral complications such as dental developmental disorders and hyposalivation occur frequently. Most important risk factors were head and neck radiotherapy of the salivary glands, (alkylating) cytostatic agents, and age at the time of the cancer diagnosis. Dentists should be aware of childhood cancer in the medical history of their patient and of the type of therapy received. Regular dental visits are an essential part of long-term follow-up care of childhood cancer survivors.

Objective: Oral cryotherapy is used to prevent the onset of oral mucositis, a common and debilitating adverse effect following cancer chemotherapy. A protective mechanism associated with oral cooling is thought to be mediated through reduced tissue microcirculation. The aim of the present study was to examine the underlying mechanism associated with oral mucosal cooling by measuring oral microcirculation and tissue oxygen saturation after cooling with ice chips (IC) and an intraoral cooling device (ICD)., Study Design: In a single-center randomized crossover study, 10 healthy volunteers were assigned (1:1) randomly to the order in which the two intraoral cooling procedures (IC/ICD) were to be commenced. On day 1, half of the study participants started with IC and then crossed over to intraoral cooling with the ICD on day 2, while the other half of the participants undertook the same two procedures in the reverse order. Total and functional capillary density (T/FCD) and tissue oxygen saturation (StO 2 ) measurements were obtained at baseline and 30 min following oral cooling., Results: Following 30 min of oral cooling, a statistically significant difference was found for FCD between IC and ICD (percentage points; +2 vs. -13; p  < 0.05). A statistically significant decrease in StO 2 was observed with both IC and ICD (%; 13 vs. 10) after 30 min of cooling as compared to baseline ( p  < 0.05). As for the participants' preference the ICD was preferred over IC by 9 out of 10 participants ( p  = 0.021)., Conclusions: Both microcirculation parameters and tissue oxygen saturation are altered in conjunction with oral cooling, indicating their potential mechanistic contribution towards cryoprevention of oral mucositis., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. J. Walladbegi reports personal fees from BrainCool AB. Dr. M. Jontell reports consultation fee from Braincool AB and grants from Braincool AB. Drs. J.E. Raber-Durlacher and D.M.J. Milstein have no conflicts of interest to disclose., (© 2023 The Authors.)

Background: Chemotherapy treatment of cancer in children can influence formation of normal tissues, leading to irreversible changes in their structure and function. Tooth formation is susceptible to several types of chemotherapy that induce irreversible changes in the structure of enamel, dentin and dental root morphology. These changes can make the teeth more prone to fracture or to caries when they have erupted. Recent studies report successful treatment of brain tumors with the alkylating drug temozolomide (TMZ) in combination with veliparib (VLP) in a glioblastoma in vivo mouse model. Whether these drugs also affect tooth formation is unknown., Aim: In this study the effect of TMZ/VLP on incisor formation was investigated in tissue sections of jaws from mice and compared with mice not treated with these drugs., Materials and Method: The following aspects were studied using immunohistochemistry of specific protein markers including: (1) proliferation (by protein expression of proliferation marker Ki67) (2) a protein involved in paracellular ion transport (expression of tight junction (TJ) protein claudin-1) and (3) in transcellular passage of ions across the dental epithelium (expression of Na+, K+ 2Cl- cotransporter/NKCC1)., Results: Chemotherapy with TMZ/VLP strongly reduced immunostaining for claudin-1 in distal parts of maturation ameloblasts. No gross changes were found in the treated mice, either in cell proliferation in the dental epithelium at the cervical loop or in the immunostaining pattern for NKCC1 in (non-ameloblastic) dental epithelium. The salivary glands in the treated mice contained strongly reduced immunostaining for NKCC1 in the basolateral membranes of acinar cells., Discussion/conclusions: Based on the reduction of claudin-1 immunostaining in ameloblasts, TMZ/VLP may potentially influence forming enamel by changes in the structure of TJs structures in maturation ameloblasts, structures that are crucial for the selective passage of ions through the intercellular space between neighboring ameloblasts. The strongly reduced basolateral NKCC1 staining seen in fully-grown salivary glands of TMZ/VLP-treated mice suggests that TMZ/VLF could also influence ion transport in adult saliva by the salivary gland epithelium. This may cause treated children to be more susceptible to caries.

Allogeneic stem cell transplantation can cause chronic graft versus host disease (cGVHD). A number of patients manifest cGVHD in and around the mouth. It can present itself as clinically as mucosal lesions and/or salivary gland dysfunction and/or sclerotic changes. Cheeks and tongue are most commonly affected, but the palate, gingiva and lips can also be impacted. Oral cGVHD is associated with mucosal sensitivity, pain, (severe) oral dryness, altered taste, restricted mouth opening and difficulty swallowing, all of which may contribute to a significant decrease of the patient's quality of life. Patients also run an increased risk of developing squamous cell carcinoma of the oral mucosa. The diagnosis of cGVHD is almost always based on the patient's medical history and clinical picture. Treatment of symptoms is based on the patient's problem(s). Dental professionals can provide patients with supportive preventive care aimed at reducing symptoms and preventing further deterioration of oral health.

Purpose: The aim of this study was to explore what methods should be used to determine the minimal important difference (MID) and minimal important change (MIC) in scores for the European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module, the EORTC QLQ-HN43., Methods: In an international multi-centre study, patients with head and neck cancer completed the EORTC QLQ-HN43 before the onset of treatment (t1), three months after baseline (t2), and six months after baseline (t3). The methods explored for determining the MID were: (1) group comparisons based on performance status; (2) 0.5 and 0.3 standard deviation and standard error of the mean. The methods examined for the MIC were patients' subjective change ratings and receiver-operating characteristics (ROC) curves, predictive modelling, standard deviation, and standard error of the mean. The EORTC QLQ-HN43 Swallowing scale was used to investigate these methods., Results: From 28 hospitals in 18 countries, 503 patients participated. Correlations with the performance status were |r|< 0.4 in 17 out of 19 scales; hence, performance status was regarded as an unsuitable anchor. The ROC approach yielded an implausible MIC and was also discarded. The remaining approaches worked well and delivered MID values ranging from 10 to 14; the MIC for deterioration ranged from 8 to 16 and the MIC for improvement from - 3 to - 14., Conclusions: For determining MIDs of the remaining scales of the EORTC QLQ-HN43, we will omit comparisons of groups based on the Karnofsky Performance Score. Other external anchors are needed instead. Distribution-based methods worked well and will be applied as a starting strategy for analyses. For the calculation of MICs, subjective change ratings, predictive modelling, and standard-deviation based approaches are suitable methods whereas ROC analyses seem to be inappropriate., (© 2021. The Author(s).)

Many medications prescribed in the Netherlands have adverse effects on the oral mucosa. Adverse events often described are stomatitis, white lesions, abnormal pigmentation and sensibility disorders. Stomatitis is frequently observed in patients using medications for the treatment of malignancies or auto-immune diseases. Important causative classes of medicines are alkylating agents, anthracyclines, monoclonal antibodies, protein kinase inhibitors, purine derivatives, pyrimidine antagonists, taxanes and vinca alkaloids. White oral lesions often concern candidiasis and are frequently seen in patients using certain immunosuppressants and antibiotics. Abnormal pigmentation is frequently seen in patients using hydroxycarbamide, an antineoplastic agent. Sensibility disorders of the oral mucosa are described in several classes of medications, including protein kinase inhibitors. It is very important oral healthcare professionals can recognise possible adverse effects of medications on the oral mucosa. When it is probable an anomaly of the oral mucosa is caused by medication, the oral healthcare professional should contact the prescribing physician to discuss the possibility of adjusting or discontinuing the medication.

Background: Photobiomodulation (PBM) has shown efficacy in preventing and treating cancer therapy-induced mucositis and dermatitis. However, there is contradictory information regarding the effect of PBM on (pre)malignant cells, which has led to questions regarding the safety of this technique. We address this issue using an orthotopic mouse model (Cal-33) with human squamous cell carcinoma of the oral cavity., Methods: Mice with actively growing orthotopic Cal-33 head and neck carcinoma tumors were divided into 4 groups: control, PBM only, radiation therapy (RT) only, and PBM + RT. We performed three experiments: (1) PBM at 660 nm, 18.4 J/cm 2 , and 5 RT × 4 Gy doses delivered daily; (2) PBM at 660 nm, 18.4 J/cm 2 , and 1 × 15 Gy RT; and (3) PBM at 660 nm + 850 nm, 45 mW/cm 2 , 3.4 J/cm 2 , and 1 × 15 Gy RT. Mice were weighed daily and tumor volumes were evaluated by IVIS. Survival time was also evaluated., Results: Animals treated with RT survived significantly longer and had significantly smaller tumor volume when compared with the control and PBM-only treatment groups. No significant differences were noted between the RT alone and PBM + RT groups in any of the experiments., Conclusion: Our results suggest that PBM at the utilized parameters does not provide protection to the tumor from the killing effects of RT.

Graft-versus-host disease (GVHD) is a serious complication after allogeneic hematopoietic stem cell transpl antation, which frequently affects the mouth. GVHD is the result of an immunological attack of donor-derived cells against the tissue of patients. Chronic oral GVHD can affect the mucosa and/or damage salivary glands and can cause sclerotic changes to the head and neck area. Patients can experience painful oral and gingival mucosa, dry mouth, taste changes and limited mouth opening. Due to painful mucosa and salivary glands, and limited mouth opening, performing oral hygiene and dental interventions can be difficult. Immunosuppression in combination with altered salivary production increases the risk of secondary infectious complications, such as dental caries and candida infections. Dental professionals can play an important role in the prevention of oral complications.

Background: We validated the new European Organisation for Research and Treatment of Cancer Quality of Life Head and Neck Module (EORTC QLQ-HN43)., Methods: We enrolled 812 patients with head and neck cancer from 18 countries. Group 1 completed the questionnaire before therapy, and 3 and 6 months later. In group 2 (survivors), we determined test-retest reliability using intraclass correlation coefficients (ICC). Internal consistency was assessed using Cronbach's Alpha, the scale structure with confirmatory factor analysis, and discriminant validity with known-group comparisons., Results: Cronbach's alpha was >0.70 in 10 of the 12 multi-item scales. All standardized factor loadings exceeded 0.40. The ICC was >0.70 in all but two scales. Differences in scale scores between known-groups were >10 points in 17 of the 19 scales. Sensitivity to change was found to be sufficient in 18 scales., Conclusions: Evidence supports the reliability and validity of the EORTC QLQ-HN43 as a measure of quality of life., (© 2019 Wiley Periodicals, Inc.)

This commentary attempts to clarify the setting of photobiomodulation (BPM) therapy in the management of oral mucositis. The suggested dose range balances efficacy data with our current understanding about PBM safety. The literature about the molecular basis of photobiomodulation and its controversial relationship to malignant transformation is briefly presented.

Cancer is the second most frequent cause of death in children. Because the prognosis for childhood malignancies has improved, attention has now focused on long-term consequences of cancer treatment. The immediate effects of chemotherapy on soft tissues have been well described; however, there is less information about long-term effects of chemotherapy on the development of dental tissues. To test the association between the effect of chemotherapy on enamel development, we examined two groups of rats: one that had received an intraperitoneal dose of 200 mg/kg of irinotecan, whereas the other (control) group had received vehicle only. Rats were killed at 6, 48 and 96 hr post-injection; the mandibles dissected out, fixed for histological evaluation and scanned for mineralization defects by Micro-CT. Our results showed structural changes in the ameloblast layer along with a significant reduction in mineralization and thickness of enamel at 96 hr after chemotherapy. These data demonstrate that irinotecan induces structural changes in forming enamel that become apparent after anticancer chemotherapy treatment., (© 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)