Development Of Oral Mucositis Research Articles

Association analysis of genetic polymorphisms of METTL3 with clinical outcomes in a Chinese pediatric population with primary brain tumors.

Methyltransferase-like 3 (METTL3) regulates numerous biological processes and diverse cancers. To explore the frequency distribution of METTL3 rs1061026, rs1139130, and rs1263801 polymorphisms, and their potential impacts on clinical outcomes and chemotherapy-induced toxicities in a cohort of Chinese pediatric patients diagnosed with primary brain tumors (PBTs). Genotyping for three investigated SNPs was performed in 107 pediatric patients with PBTs using the Sequenom MassARRAY iPLEX platform. Serum METTL3 levels were determined by Enzyme-Linked Immunosorbent Assay. Serum methotrexate (MTX) concentrations were quantified utilizing fluorescence polarization immunoassay. The three investigated SNPs were not significantly associated with the risks of relapse and metastasis after adjusting all confounders. Compared to individuals with the rs1139130 GG genotype, GA genotype carriers exhibited a significantly higher risk of oral mucositis (adjusted OR: 7.504; 95 % CI, 1.931-29.436; P = 0.004). The rs1139130 GA (adjusted OR: 5.091; 95 % CI, 1.351-19.176; P = 0.016) and AA (adjusted OR: 9.588; 95 % CI, 1.769-51.949; P = 0.009) genotype carriers exhibited a significantly lower risk of fever than GG genotype carriers. The median dose-normalized MTX concentrations at 42 h were lower with borderline significance in children with rs1061026 GT and GG genotypes (0.004 μmol/L per g/m2) than the TT genotype carriers (0.006 μmol/L per g/m2, P = 0.048). Patients with the rs1139130 GA genotype had significantly higher median serum METTL3 protein levels (59.91 ng/mL) than GG genotype carriers (44.57 ng/mL, P = 0.015). This study demonstrated the association of the rs1139130 polymorphism with the development of oral mucositis and fever and the rs1061026 polymorphism with MTX exposure.

The Effect of Gastrointestinal Mucositis Care Training Given to Pediatric Leukemic Patients and Caregivers on Mucosal Barrier Injury

Background Management of chemotherapy-induced mucosal barrier damage and oral/anal mucositis in leukemia is challenging. Objective The aim of this study was to investigate the effect of mucositis care training given to children receiving leukemia treatment and their caregivers on caregiver knowledge and skills, the development of gastrointestinal mucositis in children, the mean oral mucositis area in children, and the mucosal barrier injury laboratory-confirmed bloodstream infection in the clinic. Methods A stepped-wedge, quasi-experimental, unpaired control group design was used. The participants in the control group were given routine training, and the intervention group members were given mucositis care training in accordance with the guideline recommendations. Results No significant difference was found between groups in developing anal mucositis, but a significant difference in developing oral mucositis was documented, with the mean mucositis area of children being 8.36 ± 3.97 cm2 in the control group and 4.66 ± 2.90 cm2 in the intervention group. The mucosal barrier injury laboratory-confirmed bloodstream infection ratio was 4 per 1000 catheter days in the control group and 3 per 1000 catheter days in the intervention group. Conclusion Mucositis care training had a significant positive effect on caregivers’ knowledge and skills, the development of oral mucositis, and the mean oral mucositis area in children. However, the training had no effect on the development of anal mucositis or the infection rate in the clinic. Implications for Practice Nurses might increase the knowledge and skill levels of caregivers with training on mucositis care, prevent the development of mucositis, and reduce the mean mucositis area. Training might also contribute to the reduction in the infection rate of the clinic.

The role of oral microbiota in the development of oral mucositis in pediatric oncology patients treated with antineoplastic drugs: a systematic review

BackgroundIn the pediatric oncology population, oral mucositis as a consequence of chemotherapy is a highly prevalent complication which strongly affects both the quality of life and treatment possibilities of the patients. Still, the etiopathological mechanisms carrying to its development are not fully understood, although a possible role of oral dysbiosis has been previously investigated with unclear conclusions. The aim of this systematic review was to assess the available evidence on the role of microbiota in the development of oral mucositis.MethodsA systematic literature search was performed following PRISMA guidelines. Three electronic databases were searched up until April 2023 and a following manual search included the reference lists of the included studies and reviews. Studies reporting microbiological and clinical data of pediatric patients treated by antineoplastic drugs were included.ResultsThirteen studies met the inclusion criteria, reporting an average mucositis prevalence of 57,6%. Candida albicans infections were frequently observed in studies performing microbiological analysis on oral lesions, in contrast with the low rate detection of the Herpes simplex viruses. Bacterial species such as coagulase-negative Staphylococci and Streptococcus viridans were detected more frequently on lesion sites. Studies reporting a quantitative analysis of the general flora did not show comparable results. Risk of bias assessment among studies was generally considered high or very high.ConclusionsWhile the specific role of certain microbiological agents, such as Candida albicans, was frequently reported among studies, data regarding the general dynamics of oral microbiota in the development of oral mucositis are lacking in the current literature. Thus, more studies are needed to provide the knowledge required in order to improve protocols for the prevention and treatment of this threatening complication.

ПРИМЕНЕНИЕ ГИГИЕНИЧЕСКОГО ПРОТОКОЛА ДЛЯ ПРЕДУПРЕЖДЕНИЯ РАЗВИТИЯ ОСЛОЖНЕНИЙ СО СТОРОНЫ ОРГАНОВ И ТКАНЕЙ ПОЛОСТИ РТА У ОНКОЛОГИЧЕСКИХ ПАЦИЕНТОВ В ПЕРИОД ХИМИОТЕРАПИИ

An increase in diagnostic capabilities contributes to the early detection of oncological diseases, which is statistically reflected in the number of detected pathologies. The prevalence of cancer is increasing every year. Chemotherapy is one of the leading methods of treatment in oncology. According to the literature, from 20 to 80% of cancer patients experience complications of chemotherapy treatment from the organs and tissues of the oral cavity. The most common complication is oral mucositis. Such damage to the oral mucosa causes discomfort, pain, difficulty in eating, swallowing, and interferes with speech function. In advanced cases, oral mucositis leads to extreme weight loss, sepsis, and premature death. The development of oral mucositis is a complex multi-step process. Despite the fact that it is based on damage to the DNA structure of the cells of the oral mucosa, the microflora of the oral cavity plays an important role in the further development of the process. The influence of representatives of the microflora on the development of inflammatory processes is enormous. In the oral cavity, microorganisms are presented in the form of microbial communities - biofilms. Biofilm management is the basis for preventing inflammation of the oral mucosa and destruction of hard dental tissues. Due to the negative effect of chemotherapeutic drugs on the local immunity of the oral cavity, on salivation, there is a deterioration in the hygienic status of cancer patients. Taking into account the available data, we decided to conduct a study on the effect of mechanical action on oral biofilms in order to prevent complications from the organs and tissues of the oral cavity during chemotherapy treatment. The obtained results demonstrate the influence of the hygienic protocol on the state of the oral cavity of cancer patients during chemotherapy.

Investigation of the Prevalence of Oral Mucositis and Associated Risk Factors in Chronic Obstructive Pulmonary Disease Patients: A Prospective Cross-Sectional Study.

This study was conducted to determine the prevalence of oral mucositis in chronic obstructive pulmonary disease patients and the risk factors likely to be effective in the development of oral mucositis. This prospective cross-sectional study was carried out with 147 patients with chronic obstructive pulmonary disease who were monitored for 7 days from their admittance to the chest diseases clinic of a university hospital between January 2021 and January 2022. Patient Information Form, Oral Assessment Guide, and World Health Organization Mucositis Grading Scale were used to obtain the study data. While 81% of the patients in the study were male, the mean age was 64.6 ± 10.0 years, and the duration of chronic obstructive pulmonary disease diagnosis was 8.58 ± 6.52 years. In the study, while 61.9% of the total 147 patients monitored for 7 days had findings in favor of oral mucositis, the severity of oral mucositis and the mean total oral mucosa score of the patients were found to increase significantly in these 7 days of the monitoring period (P <.001). As per the logistic regression findings, the duration of chronic obstructive pulmonary disease diagnosis (95% CI 1.05-1.49; P =.010), the presence of medication use containing corticosteroids (95% CI 6.05-72.17; P <.001), and the amount of oxygen administered to the patient (95% CI 1.07-3.44; P =.029) were found to be significant risk factors associated with the development of oral mucositis. The results indicate that the severity of oral mucositis has a tendency to increase in chronic obstructive pulmonary disease patients from the third day of treatment, and oral care is critically important in patients, who are with a longer diagnosis of chronic obstructive pulmonary disease, who are treated with medications containing corticosteroids and who need high-intensity oxygen therapy.

Oxidative Stress and Chemoradiation-Induced Oral Mucositis: A Scoping Review of In Vitro, In Vivo and Clinical Studies.

Chemoradiation-induced mucositis is a debilitating condition of the gastrointestinal tract eventuating from antineoplastic treatment. It is believed to occur primarily due to oxidative stress mechanisms, which generate Reactive Oxygen Species (ROS). The aim of this scoping review was to assess the role of oxidative stress in the development of Oral Mucositis (OM). Studies from the literature, published in MEDLINE and SCOPUS, that evaluated the oxidative stress pathways or antioxidant interventions for OM, were retrieved to elucidate the current understanding of their relationship. Studies failing inclusion criteria were excluded, and those suitable underwent data extraction, using a predefined data extraction table. Eighty-nine articles fulfilled criteria, and these were sub-stratified into models of study (in vitro, in vivo, or clinical) for evaluation. Thirty-five clinical studies evaluated antioxidant interventions on OM’s severity, duration, and pain, amongst other attributes. A number of clinical studies sought to elucidate the protective or therapeutic effects of compounds that had been pre-determined to have antioxidant properties, without directly assessing oxidative stress parameters (these were deemed “indirect evidence”). Forty-seven in vivo studies assessed the capacity of various compounds to prevent OM. Findings were mostly consistent, reporting reduced OM severity associated with a reduction in ROS, malondialdehyde (MDA), myeloperoxidase (MPO), but higher glutathione (GSH) and superoxide dismutase (SOD) activity or expression. Twenty-one in vitro studies assessed potential OM therapeutic interventions. The majority demonstrated successful a reduction in ROS, and in select studies, secondary molecules were assessed to identify the mechanism. In summary, this review highlighted numerous oxidative stress pathways involved in OM pathogenesis, which may inform the development of novel therapeutic targets.

Comparison of the use of Solidago chilensis (Arnica) and low-level laser therapy for the prevention of oral mucositis in patients submitted of head and neck radiotherapy and/or high toxicity chemotherapy

The oral mucositis is an adverse event of radiotherapy and/or high toxicity chemotherapy. The Solidago chilensis (Arnica) has been used for its antiseptic, analgesic, healing and anti-inflammatory properties. Objective: The purpose of this study was to evaluate the uses of Arnica for oral mucositis prevention in patients submitted to radiotherapy for head and neck tumors treatment and/or high toxicity chemotherapy. Methodology: The determination of the cytotoxicity index of the aqueous extract was determined in vitro. The oral mucosa was evaluated in days 0, 10 and 14 of patients in the groups: treated with lasertherapy (L, n=18), treated with Arnica (A, n=24) and, treated with lasertherapy associated with Arnica (LA, n=4). It was considered significant p&lt;0.05. Results: It was determined IC50=90,74 μg/mL of Arnica’s aqueous extract in SCC-4 cells. The development of oral mucositis was associated with the type of treatment for oral mucositis prevention: L, A, and LA (χ2 = 24,72, p&lt;0.0001). The level of oral mucositis had significant interaction with the type of prevention treatment [F(2) = 9.545, p&lt;0.0001] and, within 14 days [F(2) = 11.995, p&lt;0.0001]. Conclusions: The results obtained suggest which the use of Solidago chilensis (Arnica) can be an important therapeutic option for treatment with low-level laser therapy for oral mucositis prevention in patients submitted of head and neck radiotherapy and/or high toxicity chemotherapy.

A Decrease in Vitamin D Levels Is Associated with Methotrexate-Induced Oral Mucositis in Children with Acute Lymphoblastic Leukemia

INTRODUCTIONChildren with acute lymphoblastic leukemia (ALL) are at increased risk of vitamin D deficiency, which might make them more susceptible to developing adverse events. Previous studies showed that the vitamin D receptor is expressed in the mucosa and that a relation exists between low vitamin D levels and an increased inflammatory mucosal state and impaired mucosal tissue barriers. We examined the prevalence of vitamin D deficiency and the change in vitamin D levels in children with ALL during high-dose methotrexate (HD-MTX) treatment and studied the association between vitamin D levels and MTX-induced oral mucositis.PATIENTS AND METHODSWe assessed 25(OH)D2, 25(OH)D3 and 24,25(OH)2D3 levels in 99 children with ALL before start of 4x 5g/m2 HD-MTX (T0) and in 81/99 children after discontinuation of HD-MTX (T1). Two cut-off values for Vitamin D deficiency exist: 25(OH)D3 levels <30 nmol/L and <50 nmol/L. Oral mucositis was defined as grade ≥ 3 according to the National Cancer Institute Criteria.RESULTSVitamin D deficiency occurred in respectively 8% (<30 nmol/L) and 33% (<50 nmol/L) of patients at T0, and more frequently in children >4 years of age as compared to children between 1-4 years of age. A decrease in 25(OH)D3 levels during HD-MTX therapy was associated with the development of oral mucositis (OR 1.6; 95% CI [1.1 - 2.4]). 25(OH)D3 and 24,25(OH)2D3 levels at T0 and the change in 24,25(OH)2D3 levels during therapy were not associated with the development of oral mucositis.CONCLUSIONThis study showed that vitamin D deficiency occurs frequently in pediatric ALL patients above the age of 4 years. A decrease in 25(OH)D3 levels during MTX therapy was associated with a higher chance of developing oral mucositis in children with ALL. DisclosuresNo relevant conflicts of interest to declare.

Risk factors associated with the development of oral mucositis in pediatric oncology patients: Systematic review and meta-analysis.

Oral mucositis (OM) is an acute toxicity related to cancer treatment. This systematic review aimed to identify potential risk factors associated with the development of OM in pediatric cancer patients. A search was performed in four electronic databases to identify studies that analyzed risk factors for OM in pediatric cancer patients. Nineteen articles were included. The incidence of OM ranged from 20% to 80.4%. Chemotherapeutic agents were potential risk factors for OM in eight (42%) studies. Hematological, hepatic, and renal parameters were also considered in eight (42%) studies, while specific individual factors were reported in five (26.3%) studies. Baseline disease, oral microbiota, genetic profile, and biomarkers were reported in four (21.5%) studies each. Meta-analysis showed that groups submitted to high-risk chemotherapy for OM had a 2.79-fold increased risk of OM. Identifying risk factors for OM is essential in order to allow individualized and early prevention treatment.

ABCG2 polymorphism, age and leukocyte count may contribute to oral mucositis in oncopediatric patients.

The study investigated the relationship between genetic polymorphisms and the development of oral mucositis in pediatric patients undergoing chemotherapy involving methotrexate. A longitudinal study was conducted with 64 patients, and oral mucositis was evaluated by the modified Oral Assessment Guide, which aims to diagnose and classify oral mucositis. Epithelial cells were obtained by mouthwash and DNA was extracted. The polymorphisms MTHFR (rs1801133), DNMT3B (rs2424913), ABCC2 (rs717620), ABCG2 (rs2231137) and ABCG2 (rs2231142) were analyzed by PCR-RFLP method. Demographic, hematological and biochemical data were collected from medical records. Statistical analysis was performed using the SPSS software adopting a p-value of 0.05. Male sex predominated (56.2%), and the mean age was 10.8 years (± 4.9). Oral mucositis affected 65.6% of the patients, of which 61.9% developed the severe form of the disease. For the ABCG2 gene (rs2231142), the rare A allele and CA genotype were more frequent in individuals with mucositis (p= 0.02; RR = 0.60; CI = 0.387 - 0.813). The severity of the disease was mainly observed in younger patients (median = 9 years; p=0.02). Patients with severe oral mucositis presented lower leukocytes count (median = 2.150 mm3) compared to patients with the mild/moderate form (median = 4.200 mm3; p=0.03). Female patients and each 10,000-platelet increase were protective factors against the onset of oral mucositis (p=0.02). It is concluded that rs2231142 polymorphism increases the likelihood of oral mucositis and younger patients and patients with low leukocytes counts are more likely to develop severe form.

Oral mucositis in patients with oncological pathology of the oropharyngeal region: review

Oral mucositis is one of the most common effects of chemoradiotherapy in patients with oropharyngeal cancer. The development of oral mucositis is the main cause of interruption of antitumor therapy, which significantly affects the results of treatment of the main disease. Despite the fact that the disease is well studied in the literature, today there is no universal treatment and prevention protocol. The aim of this review is to analyze scientific publications devoted to the problems of etiology, pathogenesis, clinic, diagnosis, treatment and prevention of oral mucositis.

Female sex as an independent prognostic factor in the development of oral mucositis during autologous peripheral stem cell transplantation

Oral mucositis (OM) is a frequent complication of stem cell transplantation-associated toxicity in haematological malignancies, contributing to mortality. Therapy still remains mainly supportive. We assessed risk factors in retrospective analysis of 192 autologous peripheral stem cell transplantation patients with lymphoma and multiple myeloma (MM), respectively. Futhermore, we examined the hormone levels both in serum and saliva during transplantation in 7 postmenopausal female patients with lymphoma compared to healthy controls using electrochemiluminescence immunoassay (ECLIA). Multivariable analysis revealed neutrophil engraftment (p < 0.001; p = 0.021) and female sex (p = 0.023; p = 0.038) as independent predictive factors in the combined patient group and in the lymphoma group, and neutrophil engraftment (p = 0.008) in the MM group. Of the 85 female participants 19 were pre- and 66 postmenopausal. Fifteen of the pre-, and 49 of the postmenopausal women developed ulcerative mucositis (p = 0.769), more often with lymphoma than MM (p = 0.009). Serum estrogen decreased significantly both in postmenopausal controls and transplantated patients compared to premenopausals, with no difference in saliva. Serum progesterone level was significantly (p = 0.026) elevated at day + 7 of transplantation, while salivary progesterone increased at day + 7 and + 14. Our results indicate a predominantly negative effect of female sex hormones on oral immunity with role in the aetiopathogenesis of OM.

Oncological-Therapy Related Oral Mucositis as an Interdisciplinary Problem-Literature Review.

Oral mucositis is a toxic side effect of non-surgical cancer treatments: chemotherapy and radiotherapy, which strongly impair quality of life and can not only cause strong pain, but also lead to problems with basic physiological needs as eating and swallowing. Development of oral mucositis is associated with type, dosage, and schedule of radiation or chemotherapy and other factors related to patients. Management of oral mucositis is a valid problem, requiring topical application of anesthetics, coating agents, cryotherapy, low level laser therapy, pharmacological methods as usage of keratinocyte growth factors, supplementation of vitamins, and a proper diet. Another approach to oral mucositis measurement includesphotobiomodulation, which brings analgesic and anti-inflammatory effects.Although oral mucositis is a general health issues, the role of proper dental care is essential. It should include elimination of all potential sources of mucosal injury and microorganisms inhabiting theoral cavity through oral hygiene education, professional management ofdental plaque, and treatment of the caries and periodontium, which are necessary to reduce the risk of inflammation in the oral cavity. This paper describes the possibilities of monitoring oral mucositis, taking into account the latest therapeutic achievements.

Features of basic indicators of oral fluid in children after hematopoietic cell transplantation (pilot study)

Relevance. Treatment of patients with refractory forms of acute lymphoblastic leukemia causes a number of complications from the organs and tissues of the oral cavity. It can be both early complications – cytotoxic reactions with the development of oral mucositis, and late, leading to a violation of the mineralization of hard tooth tissues, and to underdevelopment of the teeth. Oral fluid plays an important role in maintaining oral homeostasis. One of the most important functions that it performs is maintaining the physiological balance of the processes of re- and demineralization of tooth enamel. Since demineralization processes begin in childhood at higher pH values than in adults, when the hydrogen index decreases below 6.4, demineralization processes begin to prevail over remineralization, and the solubility of hydroxylapatite crystals which enamel consists of increases.The objective was to assess the basic indicators of oral fluid and oral hygiene indices in this group of patients.Methods and materials. During the examination of the oral cavity, the intensity of caries and hygiene indices were determined. For the study, oral fluid was collected, followed by determination of its viscosity and hydrogen index.Results. These patients showed a lower level of oral fluid hydrogen index and a lower level of oral hygiene compared to healthy children. In addition, during the study, it was found that there is a direct relationship between the pH of the oral fluid and the time elapsed since the hematopoietic cell transplantation.Conclusion. The detected changes are factors that predispose to an increase in the intensity of caries, and require early preventive measures.Authors declare no conflict of interest.The authors confirm that they respect the rights of the people participated in the study, including obtaining informed consent when it is necessary, and the rules of treatment of animals when they are used in the study. Author Guidelines contains the detailed information.

Effect of cryotherapy in preventing mucositis associated with the use of 5-fluorouracil.

Objective:to evaluate the effect of oral cryotherapy compared to physiological serum on the development of oral mucositis in outpatient cancer patients using the 5-fluorouracil antineoplastic agent.Method:this is a controlled, randomized, double-blind, and multi-center clinical trial, conducted with 60 patients undergoing chemotherapy. The experimental group (n=30) used oral cryotherapy during the infusion of the 5-FU antineoplastic agent, while the control group (n=30) performed mouthwash with physiological serum at their homes. The oral cavity of the participants was assessed at three times: before randomization, and on the 7th and 14th days after using 5-FU. For data analysis, descriptive analyses and the ANOVA, paired t, and McNemar tests were used.Results:there was no statistically significant difference between the experimental and control groups in the assessments regarding the grade of mucositis. However, cryotherapy presented the chance to reduce the presence of intragroup mucositis, between the first and second assessments (p=0.000126).Conclusion:cryotherapy did not obtain statistical significance in relation to oral hygiene with serum, but it proved to be effective intragroup. Record number: RBR-4k7zh3

Abstract 4860: Association between timing of radiotherapy and severity of oral mucositis in head-neck cancer patients

Abstract Background: Oral mucositis is a very painful and debilitating complication of radiotherapy, occurring in nearly all head and neck cancer patients. It can severely affect quality of life and lead to treatment interruptions that subsequently impact clinical outcomes. With limited treatment options, there is an urgent need to develop new strategies for mucositis prevention. Animal studies have shown that sensitivity to genotoxic stress strongly depends on the time of a day therapy is administered. Therefore, radiotherapy could be conducted at optimal times of a day associated with best tolerability, to reduce mucosal damage. This hypothesis is partially supported by two clinical trials that reported less severe oral mucositis in head and neck cancer patients treated in the morning vs. late afternoon; but results were not significant and times of a day not fully covered. Methods: This study examined the associations between timing of radiotherapy and development of oral mucositis in 219 head neck cancer patients treated at Roswell Park Comprehensive Cancer Center, using data from Electronic Medical Records. Patients’ treatment time was consistent throughout a 6/7-week course, and mucositis survey was self-reported weekly during treatment, providing a unique resource for this study. The primary endpoint is “soreness quality score” (SQS), a five-level score “0-no, 1-a little, 2-moderate, 3-quite a lot, and 4-extreme” in assessing patients’ soreness severity for mouth and throat in the past 24 hours. We used a generalized linear model approach to assess the association between radiotherapy time and the maximum SQS (MSQS) reported during treatment, adjusting for age, smoking, treatment type, survey week and cancer site. Results: Multivariate analyses revealed treatment time to be significantly associated with MSQS (p-value=0.025), with lowest MSQS (lsmean=2.26, ste=0.18) seen for patients treated in the early morning (8:30-&amp;lt;9:30am). MSQS increased in patients treated at later times, peaking in the early afternoon (lsmean=2.92 (ste 0.21) and 2.84 (ste 0.18) for patients treated at 12:00-&amp;lt;13:30pm and 13:30-&amp;lt;15:00pm, respectively), then decreased for patients treated in late afternoon (lsmean=2.37, ste=0.25). Among patients treated between 8:30-&amp;lt;9:30am, 43.2% developed severe oral mucositis (SQS grade 3 or 4), compared to 69.2% among those treated between 13:30-&amp;lt;15:00pm. Conclusion: To our knowledge, this is the first study to find a significant variation of oral mucositis severity by treatment hour of radiotherapy; the variation shows an arc shape with the peak in the early afternoon. Our results suggest that identifying an optimal time of a day for radiotherapy may substantially prevent severe oral mucositis in head and neck cancer patients. Further studies are worthwhile to confirm our findings, and to find optimal treatment times for individual patients. Citation Format: Fangyi Gu, William D. Duncan, YingDong Feng, Austin Miller, Nicolas Schlecht, Alan Hutson, Anurag K. Singh. Association between timing of radiotherapy and severity of oral mucositis in head-neck cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4860.

Methotrexate in saliva and risk in the development of chemotherapeutic mucositis in children

The aim of the study was to assess the possible direct effect of anticancer therapy with methotrexate (MTX) in bio liquids on the oral mucosa in the development of oral mucositis (OM). Twenty one children and adolescents participated in this study. Chemotherapy with MTX was administered in the following concentrations of 1; 2; 5 g/m2 of body surface area during 24 hours (including four episodes with OM). Twenty seven episodes of chemotherapy with high dose MTX were assessed in the samples of saliva on the 6th; 12; 24; 42; 48; 54 hour from the start of infusion and in the samples of blood on the 42; 48; 54 hour from the start of infusion. Сoncentration of methotrexate was measured by standard fluorescent polarization immunoassay using MTX reagent pac kit according to the manufacturer's instructions. Analysis of dynamics of methotrexate concentration in samples was performed using a linear model of mixed effects, on the basis of which the average values ​​(M) and confidence intervals for them were calculated (95 % CI). The analysis of the correlation of the levels of methotrexate in the blood and oral liquid was performed at individual time points (42; 48 and 54 hours) using the Spearman method (r). It was determined that excretion of MTX in the oral cavity repeated its clearance in blood. MTX concentration in saliva was less than 1/10 from its concentration in blood. During the first day, MTX concentration had decimicromol level and then until 54 hour it had santimicromol level. MTX concentration in saliva on the 6; 12; 24 hour in children with OM was lower by 2 times than in children without OM (P &lt; 0,001). There was no significant difference in those parameters between two groups (with or without OM) in the following observed hours. This data does not support hypothesis concerning involvement of salivary MTX in OM pathogenesis.

Relationship Between Renal Dysfunction and Oral Mucositis in Patients Undergoing Concurrent Chemoradiotherapy for Pharyngeal Cancer: A Retrospective Cohort Study.

The aim of this retrospective cohort study was to investigate the association between renal dysfunction (RD) and the development of oral mucositis (OM) in patients undergoing concurrent chemoradiotherapy (CCRT) for pharyngeal cancer including radiation to the oral cavity. Of 130 patients diagnosed as having pharyngeal cancer who received CCRT at the Okayama University Hospital Head and Neck Cancer Center, 44 were finally selected. During the observation period, 24 (54.5%) patients experienced severe OM (grade 3). The Cox proportional hazards regression model demonstrated that RD (hazard ratio(HR)=2.45, 95% confidence interval(CI)=1.067-6.116, p=0.035) and nasopharynx/oropharynx as center of the irradiated area (HR=2.56, 95% CI=1.072-5.604, p=0.034) were significantly associated with the incidence of severe OM (grade 3). In patients with pharyngeal cancer treated with CCRT including radiation to the oral cavity, RD at baseline can be a risk factor for developing severe OM.

Management of Mucositis with the Use of Leucovorin As Adjunct to Pralatrexate in Treatment of Peripheral T-Cell Lymphomas (PTCL) — Results from a Prospective Multicenter Phase 2 Clinical Trial

Background: A frequent complication of Pralatrexate therapy is development of oral mucositis. In a recent pivotal trial of pralatrexate (PROPEL, O'Connor et al. J Clin Onc 2011) the incidence of ≥ Grade 2 mucositis was 52%, occurring primarily in the first treatment cycle. Mucositis often leads to dose reduction or omission and possibly, diminished efficacy of pralatrexate in relapsed/refractory (R/R) PTCL. Leucovorin (d,l-folinic acid) is an approved rescue therapy for high-dose methotrexate (MTX) therapy, mitigating gastrointestinal lining, and bone marrow cell toxicity and has been used adjunctively with pralatrexate to manage mucositis. The objective of this prospective Phase 2, single-arm study was to evaluate the effect of leucovorin on the incidence of pralatrexate-induced mucositis in patients with R/R PTCL, including primary cutaneous T-cell lymphomas.Methods: Eligible patients had diagnosis of PTCL, including CTCL, confirmed by local hematopathologist or dermatopathologist and were deemed appropriate for pralatrexate therapy by investigator. Study treatment consisted of two cycles of Pralatrexate, (6 weekly doses (30 mg/m2) followed by 1 week of rest per cycle, currently approved label). All patients received vitamin B12 and folic acid supplementation; oral leucovorin, 25 mg TID was self-administered for 2 consecutive days (a total of 6 doses) beginning 24 hours after each dose of Pralatrexate. Patients underwent in-clinic oral mucositis assessment at baseline and at each visit prior to pralatrexate administration by healthcare professional. Patients also completed a daily oral mucositis questionnaire (OMDQ) from Day 1 of Cycle 1 to the end of treatment visit. Mucositis was assessed by the investigator and recorded as an AE along with grade and causality. Toxicities were assessed using Common Terminology Criteria (CTCAE V4.03). Responses were assessed by the investigator per revised Response Criteria for Malignant Lymphoma (Cheson 2007) and Modified SWAT Criteria for CTCL.The primary endpoint was the incidence of Grade 2 or higher oral mucositis in Cycle 1. Secondary endpoints included the incidence of ≥ Grade 3 mucositis, and overall response rate.Results: A total of 30 patients have been enrolled as of time of data analysis. The majority of patients were male, white, with the median age of 63 yrs (range, 31-85). To date (5 July 2018) 11 patients have completed the study treatment, 12 patients discontinued (1 AE, 9 PD, 1 death, and 1 withdrawal) and 7 patients remain in the trial. All 30 subjects reached the assessment of the primary endpoint. The primary endpoint of the study has been met. Twenty (67%) patients have reported TEAEs, of which 11 (37%) have been ≥Grade 3 AEs. Overall toxicity profile was consistent with previously reported in the PROPEL trial. Most common Pralatrexate-related AEs were fatigue in 6 (20%) patients and diarrhea that occurred in 4 (13%) patients. SAEs occurred in 9 patients (only pyrexia in >1 pt; N=2), none were treatment-related. The rate of ≥2 mucositis was 4% (95% C.I. = 0, 20%). No Grade 3 or higher mucositis occurred; Grade 1 mucositis was observed in 4 patients. Assessment of treatment response rate (secondary endpoint) is ongoing and will be reported at the meeting.Conclusions: Overall safety profile of the study treatment was consistent with pivotal trial of Pralatrexate in R/R PTCL. Leucovorin as adjunctive treatment resulted in a significant reduction in rates of both ≥Grade 2, and ≥Grade 3 mucositis and should be considered in patients treated with Pralatrexate. DisclosuresShustov:SPECTRUM PHARMACEUTICALS: Consultancy, Research Funding. Bhat:SPECTRUM PHARMACEUTICALS: Employment.

The Prevalence and Investigation of Risk Factors of Oral Mucositis in a Pediatric Oncology Inpatient Population; a Prospective Study.

Oral mucositis can be a frequent and severe complication of chemotherapy in children. It can result in pain, infection, depression, prolonged admission, treatment delays, increase in patient morbidity, and increased costs. To record the prevalence and severity of oral mucositis among inpatients and explore the relationship of risks factors and the development of oral mucositis. During an 18-month period 643 clinical inpatient assessments were completed on 73 children who were admitted and had received chemotherapy in the last 14 days. There were 43 episodes of oral mucositis in 31 children; 42.5% of the inpatient population. World Health Organization assessment identified 32.6% of episodes were grade 1, 34.9% grade 2, 14.0% grade 3, and 18.6% grade 4. Analysis revealed significant associations between patient diagnosis (P<0.0001), chemotherapy cycles (P<0.0001), day 8 and 9 of the chemotherapy cycle (P<0.05), and neutropenia (P<0.0001) and oral mucositis. Children had increased length of admission with increasing severity of oral mucositis (P=0.0005). The prevalence of oral mucositis was 42.5% among inpatients and admission length was increased with increasing severity. Patient diagnosis, chemotherapy treatment block, day of chemotherapy cycle, and neutropenic status were shown to influence the risk of developing oral mucositis.