Association between salivary inflammatory mediators and oral mucositis in patients with cancer undergoing chemotherapy.

PURPOSE: Oral mucositis is a severe adverse event in patients undergoing chemotherapy and radiotherapy that may lead to the termination of cancer treatment. This study aimed to elucidate the relationship between salivary inflammatory mediators and oral mucositis in patients undergoing chemotherapy. METHODS: This prospective cohort study included 167 patients who underwent chemotherapy at our institution between June 2020 and November 2023. We evaluated the association between chemotherapy-induced oral mucositis and salivary inflammatory mediators using multiple comparison tests and logistic regression analyses. RESULTS: Of the 167 patients, 67 (40.1%) had oral mucositis. Dunn's multiple comparison test revealed that interleukin-6 was significantly higher in oral mucositis of grades 2 and ≥ 3 (P < 0.01) and tumor necrosis factor (TNF)-α was significantly higher in oral mucositis of grades 3-4 (P < 0.01). Logistic regression analysis showed that the risk of oral mucositis was significantly higher for tumor necrosis factor (TNF)-α > 4.4 pg/mL than for TNF-α ≤ 4.4 pg/mL (adjusted odds ratio, 2.4; 95% confidence interval, 1.1-5.3; P = 0.03). CONCLUSION: Saliva is useful in evaluating inflammation in patients with chemotherapy-induced oral mucositis. Furthermore, TNF-α may be a predictive marker for the severity of oral mucositis in patients undergoing chemotherapy.

In situ gel-forming oil solubilizing α-lipoic acid as a physical shielding alleviated chemotherapy-induced oral mucositis via inhibiting oxidative stress.

Oral mucositis (OM) is a common and serious complication of cancer chemoradiotherapy. OM managements mainly focused on topical healthcare or analgesia, which offers limited wound healing. Herein, in situ gel-forming oil (LGF) have been developed as a physical shielding for OM treatment. LGF oil, composed of soybean phosphatidyl choline (40 %, w/w), glycerol dioleate (54 %, w/w), and alcohols (6 %, w/w), is a viscous oil-like liquid. The contact angle of LGF oil on porcine buccal mucosa were 30°, significantly smaller than that of water (60°), indicating its good wetting and spreading properties. Besides, the adhesion force and adhesion energy of LGF oil toward porcine buccal mucosa was as high as 3.9 ± 0.2 N and 60 ± 2 J/m2, respectively, indicating its good adhesive property. Moreover, the hydrophobic α-lipoic acid (LA) as a native antioxidative agent was highly solubilized in LGF oil, its solubility in which was above 100 mg/mL. Upon contacting with saliva, LA-loaded LGF oil (LA-LGF) could rapidly transform from oil into gel that adheres on oral mucosa. Moreover, LA was slowly released from the formed LA-LGF gel, which benefited alleviating oxidative stress caused by chemoradiotherapy. In vivo animal experiments showed that LA-LGF could effectively promote the repairing of oral mucosa wound of 5-fluorouracil induced OM rats. Besides, the mucosa edema was greatly improved and new granulation around wound was produced after LA-LGF treatment. Meanwhile, the production of proinflammatory cytokines such as IL-1ß, TNF-α, 1L-6 was substantially inhibited by LA-LGF. Collectively, LGF oil as carrier of hydrophobic drug might be a promising strategy for oral mucositis.

Evaluation of oral complications in children undergoing chemotherapy: An observational study.

BACKGROUND: Chemotherapy, a cornerstone treatment for childhood cancers, can negatively impact oral health. This study aimed to evaluate the prevalence and evolution of oral complications in these patients. MATERIALS AND METHODS: A prospective observational study enrolled 44 children diagnosed with malignancy undergoing chemotherapy at a tertiary care institute in central India. Oral examinations were performed at baseline, with follow-ups at 3-6 and 9-12 months. Data collected included demographics, medical history, oral hygiene practices, and oral lesions. Blood counts and World Health Organization grading for mucositis were used. Descriptive statistics and appropriate statistical tests analyzed the data (P ≤ 0.05). RESULTS: Acute lymphoblastic leukemia (ALL) was the most prevalent malignancy. Children reported various oral complaints such as ulcers, bleeding gums, and difficulty eating. Mucositis prevalence significantly decreased over follow-up visits (baseline: 56.8% and second follow-up: 13.3%). Gingival inflammation was present, though mean scores decreased over time. Oral hygiene scores varied without significant changes. Caries experience scores increased from baseline to follow-up. CONCLUSION: This study identified a high prevalence of ALL and diverse oral complications in children undergoing chemotherapy. While mucositis severity lessened over time, other issues such as caries persisted. These findings highlight the critical need for preventive oral care strategies to safeguard this vulnerable population's oral health.

Oral Risk Factors in Patients with Cancer Undergoing Chemotherapy - A Pilot Study.

BACKGROUND: Treatment modalities for cancer including surgery, radiotherapy and chemotherapy, have some complications even in the oral cavity. The literature describes oral lesions that may arise as a result of chemotherapy. However, information regarding oral symptoms in advanced cancer patients is poor. OBJECTIVE: To identify the oral manifestations like oral mucositis, dry mouth and loss of taste in patients undergoing chemotherapy treatment. METHODS: We evaluated 60 patients affected by malignancy undergoing chemotherapy treatment. The clinical and pathological data such as age, gender, diagnosis of malignancy and types of treatments with anticancer chemotherapeutic drug treatment, were obtained. Patients were routinely evaluated for the presence of oral mucositis based on the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 scale for adverse effects and graded. Other findings like dry mouth and loss of taste were recorded. RESULTS: Of the 60 patients, 40 (66.6%) were male, and 20 (33.3%) females with a mean age of 53.7 years. Most patients about 63% and 83% were diagnosed with dry mouth and loss of taste, respectively and 71% of patients had mucositis. Chemotherapy drugs like Cyclophosphamide, carboplatin, nanoxel, paclitaxel, oxaliplatin, docetaxel and doxorubicin, were directly associated with oral mucositis. CONCLUSION: Patients treated with chemotherapy for cancer most often suffer from a multitude of intense and debilitating oral dysfunctions. Oral lesions found in patients undergoing chemotherapy were mucositis, dry mouth and loss of taste. These adverse effects and an appropriate symptomatic therapy need to be discussed with the patients. Chemotherapy has a significant but transient effect on the oral symptoms.

Evaluation of oral mucositis level and affecting factors in cancer patients receiving chemotherapy.

OBJECTIVES: This study aimed to evaluate the severity of oral mucositis and the contributing factors among cancer patients undergoing chemotherapy. METHODS: This study was planned cross-sectional. The study was conducted at a medical oncology clinic between January and July 2022. The sample consisted of 245 patients with cancer receiving chemotherapy. Data were collected using a personal, oral health and disease-related characteristics questionnaire and the World Health Organization Oral Mucositis Assessment Scale by researchers. Intraoral examination of the patients was carried out by researchers. The data were analyzed by independent-sample t-tests, Chi-square tests, paired-sample t-tests, and multivariate logistic regression (p < 0,05). RESULTS: The patients had mean age 62.31 ± 10.70. Patients of 32.7% were with lung cancer. 52%of the patients (n = 128) receiving chemotherapy developed oral mucositis. The independent variables the presence chronic disease(OR:1.85), chemotherapy protocol (OR:3.52) and the dependent variables ECOG performance score (OR:2.25) were variable that affected the development of oral mucositis (p < 0.05). Patients of 35.5% were oral mucositis score of 1. Patients those who had breast cancer, who received doxorubicin or cyclophosphamide chemotherapy protocols, and who had previously developed oral mucositis were found to have a higher rate of oral mucositis (p < 0.05). In addition, oral mucositis was more prevalent in patients with chronic diseases other than cancer (57%), those who used medication continuously (57.2%), those with oral and dental diseases (56.9%), those who had dental check-ups before cancer treatment (79.2%), and those who had information about oral mucositis(70.2%) (p < 0.05). CONCLUSION: In conclusion, nearly half of the patients (52%, n = 128) receiving chemotherapy developed oral mucositis and of all patients of 35.5% had an oral mucositis score of 1 in the second round of chemotherapy. Patients those who had breast cancer, who received doxorubicin or cyclophosphamide chemotherapy protocols, and who had previously developed oral mucositis were found to have a higher rate of oral mucositis.

Effects of a semi-interpenetrating network hydrogel loaded with oridonin and DNase-I on the healing of chemoradiotherapy-induced oral mucositis.

The aim of this study was to develop a semi-interpenetrating network (IPN) hydrogel system suitable for the oral environment, capable of controlled release of DNase-I and oridonin (ORI), to exert antimicrobial, anti-inflammatory, and reparative effects on chemoradiotherapy-induced oral mucositis (OM). This IPN was based on the combination of ε-polylysine (PLL) and hetastarch (HES), loaded with DNase-I and ORI (ORI/DNase-I/IPN) for OM treatment. In vitro studies were conducted to evaluate degradation, adhesion, release analysis, and bioactivity including cell proliferation and wound healing assays using epidermal keratinocyte and fibroblast cell lines. Furthermore, the therapeutic effects of ORI/DNase-I/IPN were investigated in vivo using Sprague-Dawley (SD) rats with chemoradiotherapy-induced OM. The results demonstrated that the IPN exhibited excellent adhesion to wet mucous membranes, and the two drugs co-encapsulated in the hydrogel were released in a controlled manner, exerting inhibitory effects on bacteria and degrading NETs in wound tissues. The in vivo wound repair effect, microbiological assays, H&E and Masson staining supported the non-toxicity of ORI/DNase-I/IPN, as well as its ability to accelerate the healing of oral ulcers and reduce inflammation. Overall, ORI/DNase-I/IPN demonstrated a therapeutic effect on OM in rats by significantly accelerating the healing process. These findings provide new insights into possible therapies for OM.

Chemotherapy-induced oral mucositis: hierarchical analysis of recurrence factors.

PURPOSE: This study aimed to analyze, through a hierarchical model, the risk factors associated with the recurrence of chemo-induced oral mucositis (OM) in children and adolescents. METHODS: A retrospective cohort with 31 individuals of both sexes, aged 1-18 years, who were undergoing chemotherapy, and presented OM lesions was conducted. Data collection included analysis of medical records, interviews, and intraoral examination. Information regarding patients' socioeconomic and demographic profile, underlying disease, antineoplastic regimen, hematological condition, and oral health status were collected. To assess the association of independent variables with the outcome, the Chi-square, Fisher's Exact, and Mann-Whitney tests were used, in addition to a binary logistic regression model, with a maximum error of 5% and a 95% confidence interval. RESULTS: Significant associations were observed between the history of OM and the diagnosis of the child/adolescent, neutrophil count, previous cancer treatments and the chemotherapy scheme in use (p < 0.05). Binary logistic regression revealed a 13.69 higher risk of developing OM recurrence in individuals who received high-dose methotrexate (MTX) therapy. CONCLUSION: Socioeconomic and demographic factors did not influence OM recurrence. However, clinical variables, such as neutropenia, diagnosis of leukemia, and high-dose MTX protocols increase the chance of OM new cases.

Impact of Educational Guidelines on Oral Mucositis Severity and Quality of Life in Oncology Patients Receiving Chemotherapy: A Quasi-Experimental Study.

BACKGROUND: Oral mucositis (OM) is a prevalent side effect of chemotherapy that negatively impacts patient quality of life (QoL). Educational guidelines may provide strategies to mitigate these effects. OBJECTIVE: To evaluate the effectiveness of educational guidelines on the severity of OM and QoL in oncology patients undergoing chemotherapy. METHODS: A quasi-experimental study was conducted. Patients (n = 108) were randomly assigned to an intervention group receiving educational guidelines or a control group receiving routine care. Outcomes were assessed at baseline and at one and three months post-intervention. Data were collected using a structured interview including assessments of personal characteristics, clinical data, chemotherapy side effects, OM severity, and QoL. RESULTS: Baseline QoL scores were comparable between groups. Post-intervention, the intervention group experienced significant improvements in QoL (p ≤ 0.05), while the control group showed a decline. OM severity was significantly reduced in the intervention group compared to the control group at both time points (p ≤ 0.05). CONCLUSION: Educational guidelines are an effective intervention for reducing OM severity and improving QoL in oncology patients receiving chemotherapy. Implementation of these guidelines can enhance patient well-being and support optimal treatment outcomes.

Association of oral mucositis induced by anthracycline-cyclophosphamide and subsequent docetaxel treatment for perioperative breast cancer.

PURPOSE: Anthracycline-cyclophosphamide followed by docetaxel-containing chemotherapy is effective for perioperative breast cancer treatment. However, these treatments frequently induce oral mucositis (OM), with an incidence ranging from 20 to 50%. The association of OM development between different chemotherapeutic treatments remains unclear. Consequently, this study aimed to compare OM development during docetaxel-containing chemotherapy between patients with and without OM experience during previous anthracycline-cyclophosphamide treatments to assess the association between OM development and treatment regimens. METHODS: Seventy-two patients with breast cancer receiving anthracycline-cyclophosphamide followed by docetaxel-containing chemotherapy as a perioperative treatment were categorized into the control (no prior OM experience with anthracycline-cyclophosphamide) and OM-experience (OM development during previous treatment) groups and retrospectively evaluated. The primary endpoint was the incidence of all-grade OM in the first docetaxel-containing chemotherapy cycle. Additionally, the incidences of OM and dysgeusia during all treatment cycles and factors associated with the incidence of OM were evaluated. RESULTS: The incidence of all-grade OM in the first cycle was significantly higher in the OM-experience group (54.2%) than in the control group (10.4%; P < 0.0001). Furthermore, its incidence in all treatment cycles was higher in the OM-experience group (66.7%) than in the control group (12.5%, P < 0.0001). However, the incidence of dysgeusia did not differ between the groups. Multivariate logistic regression analysis revealed OM experience during previous anthracycline-cyclophosphamide treatment and concomitant pertuzumab use as independent risk factors for OM development in subsequent docetaxel-containing chemotherapy. CONCLUSION: Our study suggests that patients experiencing OM with anthracycline-cyclophosphamide during perioperative breast cancer treatment exhibit symptoms following subsequent docetaxel-containing chemotherapy.

Application of In Situ Mucoadhesive Hydrogel with Anti-Inflammatory and Pro-Repairing Dual Properties for the Treatment of Chemotherapy-Induced Oral Mucositis.

Chemotherapy-induced oral mucositis (CIOM) is a prevalent complication of chemotherapy and significantly affects the treatment process. However, effective treatment for CIOM is lacking due to the unique environment of the oral cavity and the single effect of current drug delivery systems. In this present study, we propose an innovative approach by combining a methacrylate-modified human recombinant collagen III (rhCol3MA) hydrogel system with hyaluronic acid-epigallocatechin gallate (HA-E) and dopamine-modified methacrylate-alginate (AlgDA-MA). HA-E is used as an antioxidant and anti-inflammatory agent and synergizes with AlgDA-MA to improve the wet adhesion of hydrogel. The results of rhCol3MA/HA-E/AlgDA-MA (Col/HA-E/Alg) hydrogel demonstrate suitable physicochemical properties, excellent wet adhesive capacity, and biocompatibility. Notably, the hydrogel could promote macrophage polarization from M1 to M2 and redress human oral keratinocyte (HOK) inflammation by inhibiting NF-κB activation. Wound healing evaluations in vivo demonstrate that the Col/HA-E/Alg hydrogel exhibits a pro-repair effect by mitigating inflammatory imbalances, fostering early angiogenesis, and facilitating collagen repair. In summary, the Col/HA-E/Alg hydrogel could serve as a promising multifunctional dressing for the treatment of CIOM.

In vitro cytoprotective and in vivo anti-oral mucositis effects of melatonin and its derivatives.

According to our preliminary study, melatonin and its N-amide derivatives (N-(2-(1-4-bromobenzoyl-5-methoxy-1H-indol-3-yl)ethyl)acetamide (BBM) and 4-bromo-N-(2-(5-methoxy-1H-indol-3-yl)ethyl)benzamide (EBM)) inhibited the marker of acute inflammation in tests in vitro and in vivo. The anti-inflammatory agent is intended for the prevention and treatment of chemotherapy-induced toxicity. In this study aimed to evaluate the effect of melatonin and its derivatives on mechanisms related to chemotherapy-induced oral mucositis by in vitro ROS and 5-FU-induced human keratinocyte cells as well as in vivo oral mucositis model. In in vitro H2O2-induced HaCaT cells, BBM had the highest level of protection (34.57%) at a concentration 50 µM, followed by EBM (26.41%), and melatonin (7.9%). BBM also protected cells against 5-FU-induced to 37.69-27.25% at 12.5-100 µM while EBM was 36.93-29.33% and melatonin was 22.5-11.39%. In in vivo 5-FU-induced oral mucositis in mice, melatonin, BBM, and EBM gel formulations protected tissue damage from 5-FU similar to the standard compound, benzydamine. Moreover, the weight of mice and food consumption recovered more quickly in the BBM group. These findings suggested that it was possible to develop BBM and EBM as new therapeutic agents for the treatment of oral mucositis.

TNF-α promoter hypomethylation is frequent in oncopediatric patients who recovered from mucositis.

The aim of this study was to investigate the DNA methylation profile in genes encoding catalase (CAT) and superoxide dismutase (SOD3) enzymes, which are involved in oxidative stress mechanisms, and in genes encoding pro-inflammatory cytokines interleukin-6 (IL6) and tumor necrosis factor-alpha (TNF-α) in the oral mucosa of oncopediatric patients treated with methotrexate (MTX®). This was a cross-sectional observational study and the population comprised healthy dental patients (n = 21) and those with hematological malignancies (n = 64) aged between 5 and 19 years. Oral conditions were evaluated using the Oral Assessment Guide and participants were divided into 4 groups: 1- healthy individuals; 2- oncopediatric patients without mucositis; 3- oncopediatric patients with mucositis; 4- oncopediatric patients who had recovered from mucositis. Methylation of DNA from oral mucosal cells was evaluated using the Methylation-Specific PCR technique (MSP). For CAT, the partially methylated profile was the most frequent and for SOD3 and IL6, the hypermethylated profile was the most frequent, with no differences between groups. For TNF-α, the hypomethylated profile was more frequent in the group of patients who had recovered from mucositis. It was concluded that the methylation profiles of CAT, SOD3, and IL6 are common profiles for oral cells of children and adolescents and have no association with oral mucositis or exposure to chemotherapy with MTX®. Hypomethylation of TNF-α is associated with oral mucosal recovery in oncopediatric patients who developed oral mucositis during chemotherapy.

The Efficacy of Three Different Oral Hygiene Regimens in Preventing Chemotherapy-Induced Oral Mucositis in Pediatric Patients Receiving Hematopoietic Stem Cell Transplantation.

BACKGROUND: Oral mucositis is one of the side effects developed post-hematopoietic stem cell transplant. This retrospective study aimed to assess the efficacy of a mouthwash mixture (lidocaine, sodium alginate, sucralfate, pheniramine) versus hyaluronic acid and a solution of sodium bicarbonate in terms of healing time and weight gain in the treatment of oral mucositis in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation with hemato-oncological malignancies. METHODS: A total of 171 patients that received chemotherapy for the hematopoietic stem cell transplant were divided into three groups; group 1, treated with a mixed mouthwash of lidocaine, sodium alginate, sucralfate, and pheniramine; group 2, treated with hyaluronic acid; and group 3, treated with an aqueous solution of 5% sodium bicarbonate. Weight and mucositis scale scores derived from medical records of patients. RESULTS: There was a statistically significant difference in the mucositis scale scores between the groups on the transplant day and days 5, 10, 15 and 20 after the transplantation. At these measurement points, Group 2 (receiving hyaluronic acid) had a lower score, and Group 3 (who received sodium bicarbonate) had a higher score, especially on days 5 and 10 after the transplantation. CONCLUSION: The results suggest that hyaluronic acid is a more effective treatment option than the other oral care solutions that are frequently used for prophylaxis and treatment of oral mucositis.

Oral mucositis & oral health related quality of life in women undergoing chemotherapy for breast cancer in Karachi, Pakistan: A multicenter hospital based cross-sectional study.

BACKGROUND: Oral mucositis is an inflammatory condition of oral cavity which is a common and serious side effect of cancer treatment. Severe oral mucositis compromises basic functions like eating and swallowing causing malnutrition also affecting overall patient's oral health related quality of life. The aim of the study was to find the frequency of oral mucositis in patients with breast cancer during their chemotherapy, the factors associated with oral mucositis & the overall patient's oral health related quality of life. METHODS: A cross-sectional study was conducted and a total of 160 women diagnosed with breast cancer, receiving chemotherapy and who had undergone at least one cycle of chemotherapy were recruited from two hospital settings. In-person interviews were done, patients were asked questions about their sociodemographic history, personal habits, oral history and oral findings, breast cancer stage, chemotherapy history and Oral Health Related Quality of Life. Their oral examination was done at the end of the interview to assess presence or absence of oral mucositis, using World Health Organization oral mucositis tool. Oral Health Related Quality of Life was assessed using Oral Health Impact Profile-14 questionnaire. RESULTS: Our results showed that out of 160 patients 88 (55%) of the breast cancer cases developed oral mucositis during chemotherapy. The mean Oral Health Impact Profile -14 scores in patients with oral mucositis was high 18.36±0.96 showing poor Oral Health Related Quality of Life. Occasional frequency of brushing was significantly associated with oral mucositis (Prevalence ratio:2.26, 95%_CI 1.06-4.84) compared to those patients who brushed once and twice daily. Low level of education showed negative association with oral mucositis (Prevalence ratio:0.52, 95%_CI 0.31-0.88). CONCLUSION: Our study showed significant positive association of occasional brushing with OM and protective association of low level of education with the development of OM. Emphasis should be given to oral hygiene instructions and dental education to cancer patients in oncology clinics with the prescription of mouth washes, gels and toothpaste to patients to decrease OM during chemotherapy.

Two cases of severe oral mucositis caused by atezolizumab plus bevacizumab combination therapy for hepatocellular carcinoma.

Atezolizumab is an immune checkpoint inhibitor specific for the programmed death-1 (PD-1) receptor. In this case report, we describe two cases of oral mucositis that developed following the initiation of a systemic chemotherapy regimen comprising atezolizumab and bevacizumab for recurrent hepatocellular carcinoma. After 2 or 3 cycles of treatment, each patient presented with mucosal ulcers in the mouth, oral pain, difficulty in speech and oral intake, and both were admitted to our hospital for management. Following rule out of other conditions such as pharyngeal ulcers, herpetic mucositis, denture or oral trauma, or necrotizing mucositis, both patients were diagnosed with oral mucositis as a severe immune-related adverse event. Oral candidiasis was observed in both cases and should be considered a risk factor for the development of oral mucositis. Chemotherapy was discontinued and treatment with prednisolone was started, along with supportive care. The oral mucositis improved, and prednisolone was gradually reduced; however, in one patient, discontinuation of chemotherapy led to a recurrence of hepatocellular carcinoma. The other patient was lost to follow-up. In patients with risk factors, attention must be paid to the development of oral mucositis during immune checkpoint inhibitor treatment.

Single nucleotide polymorphisms conferring susceptibility to leukemia and oral mucositis: a multi-center pilot study of patients prior to conditioning therapy for hematopoietic cell transplant.

PURPOSE: Leukemias have been associated with oral manifestations, reflecting susceptibility to cancer therapy-induced oral mucositis. We sought to identify SNPs associated with both leukemia and oral mucositis (OM). METHODS: Whole exome sequencing was performed on leukemia and non-cancer blood disorder (ncBD) patients' saliva samples (N = 50) prior to conditioning therapy. WHO OM grading scores were determined: moderate to severe (OM2-4) vs. none to mild (OM0-1). Reads were processed using Trim Galorev0.6.7, Bowtie2v2.4.1, Samtoolsv1.10, Genome Analysis Toolkit (GATK)v4.2.6.1, and DeepVariantv1.4.0. We utilized the following pipelines: P1 analysis with PLINK2v3.7, SNP2GENEv1.4.1 and MAGMAv1.07b, and P2 [leukemia (N = 42) vs. ncBDs (N = 8)] and P3 [leukemia + OM2-4 (N = 18) vs. leukemia + OM0-1 (N = 24)] with Z-tests of genotypes and protein-protein interaction determination. GeneCardsSuitev5.14 was used to identify phenotypes (P1 and P2, leukemia; P3, oral mucositis) and average disease-causing likelihood and DGIdb for drug interactions. P1 and P2 genes were analyzed with CytoScape plugin BiNGOv3.0.3 to retrieve overrepresented Gene Ontology (GO) terms and Ensembl's VEP for SNP outcomes. RESULTS: In P1, 457 candidate SNPs (28 genes) were identified and 21,604 SNPs (1016 genes) by MAGMAv1.07b. Eighteen genes were associated with "leukemia" per VarElectv5.14 analysis and predicted to be deleterious. In P2 and P3, 353 and 174 SNPs were significant, respectively. STRINGv12.0 returned 77 and 32 genes (C.L. = 0.7) for P2 and P3, respectively. VarElectv5.14 determined 60 genes from P2 associated with "leukemia" and 11 with "oral mucositis" from P3. Overrepresented GO terms included "cellular process," "signaling," "hemopoiesis," and "regulation of immune response." CONCLUSIONS: We identified candidate SNPs possibly conferring susceptibility to develop leukemia and oral mucositis.

Comparison between hangeshashinto and dexamethasone for IL-1α and ß-defensin 1 production by human oral keratinocytes.

OBJECTIVE: Human ß-defensin 1 (hBD-1) is a antimicrobial peptide that is constantly secreted by oral tissues. Hangeshashinto (HST), a traditional Japanese medicine, has been reported to be effective against stomatitis. This study aimed to clarify the profile of HST by comparing the system of production of interleukin-1α (IL-1α) and hBD-1 in human oral mucosal epithelial cells with dexamethasone (DEX), a steroid used for the treatment of stomatitis. METHODS: Human oral keratinocytes (HOK) were treated with HST, DEX, or HST components (baicalein, baicalin, berberine, and glycyrrhizin) for 24 h, and subsequently cultured for 24 h with or without Pam3CSK4 or lipopolysaccharide (LPS). The cell supernatants, total RNA, and intracellular proteins were collected, and changes in IL-1α and hBD-1 protein production and gene expression were evaluated using ELISA and RT-PCR. The phosphorylation of NF-kB and the cell proliferative ability of HOK were evaluated by western blotting and XTT assay, respectively. RESULTS: DEX (0.01-10 µM) significantly suppressed IL-1α and hBD-1 production induced by either Pam3CSK4 or LPS, and also decreased cell growth. In contrast, HST inhibited Pam3CSK4- and LPS-induced IL-1α production at a concentration range of 12.5-100 µg/mL without affecting the cell proliferative capacity and hBD-1 production of HOK. Baicalein and baicalin, which are flavonoid ingredients of HST, showed anti-IL-1α production. CONCLUSION: HST may be useful as a therapeutic agent for stomatitis and other inflammatory diseases of the oral cavity.

Disproportionality Analysis of Stomatitis Associated with Anticancer Drugs Using the Japanese Adverse Drug Event Report Database.

INTRODUCTION: Anticancer drug-induced stomatitis can affect a patient's quality of life and the continuation of drug treatment. Although there have been reports of the occurrence of stomatitis associated with anticancer agents in clinical trials, few Japanese participants have been enrolled in clinical trials and have not been sufficiently investigated. In addition, there has been little attention on research on anticancer drugs associated with stomatitis by patient stratification with different carcinogenic sites. Therefore, the aim of this study was to determine the disproportionality associated with stomatitis for various types of anticancer drugs in different types of cancer patients using the Japanese Adverse Drug Event Report (JADER) database. METHODS: The aim of this study was to identify the disproportionality of stomatitis by analyzing the type of anticancer drug and cancer patients using the Japanese Pharmacovigilance Database. Data obtained from spontaneous reports of adverse events with more than 10 stomatitis outbreaks reported in the JADER database between April 2004 and March 2023 were analyzed. The safety signal for an adverse event was defined as the lower limit of the 95% confidence interval of the reported odds ratio of >1. RESULTS: There were 6,178 reports of drugs associated with stomatitis. Among these, 41 drugs were suggested to be associated with stomatitis, and 41 drugs were detected as signals. These drugs were classified based on their efficacy: antipyrimidines (six drugs), folate metabolism antagonists (three drugs), alkylating agents (four drugs), platinum (three drugs), topoisomerase inhibitors (three drugs), microtubule inhibitors (three drugs), mammalian target of rapamycin (mTOR) inhibitors (two drugs), kinase inhibitors (seven drugs), anti-growth factor antibodies (five drugs) immune checkpoint inhibitors (one drug), and others (four drugs). CONCLUSION: The drugs that may be associated with stomatitis were cell cycle-dependent drugs, epidermal growth factor receptor-tyrosine kinase inhibitors, and mTOR inhibitors. Moreover, this study suggested that anti-growth factor antibodies and immune checkpoint inhibitors may be associated with stomatitis development.

Management of Adverse Reactions Related to Lenvatinib Plus Pembrolizumab Treatment Among Patients With Renal Cell Carcinoma.

Renal cell carcinoma is the predominant histological type of kidney cancer with historically poor patient outcomes. Lenvatinib in combination with pembrolizumab is an approved first-line regimen for people with advanced renal cell carcinoma that showed clinically meaningful improvements in efficacy over sunitinib in the CLEAR trial; however, reduced patient exposure to treatment (often stemming from adverse reactions) is a potential therapeutic barrier that must be addressed. Here, we present management strategies for adverse reactions associated with this treatment combination: fatigue, diarrhea, musculoskeletal pain, hypertension, stomatitis, decreased appetite, rash, nausea, and proteinuria. Dosing modification of lenvatinib and pembrolizumab should be made according to the prescribing information for each medication. Clinicians should consider that some adverse reactions, such as diarrhea, may be attributable to lenvatinib, or may be a symptom of immune-related adverse reactions to pembrolizumab (such as colitis). Adverse reactions can generally be managed by: (1) advising the patient on precautionary measures (eg, for stomatitis, practice dental hygiene, avoid irritating foods, and maintain adequate hydration), (2) monitoring for changes in symptoms from baseline (eg, changes in bowel movements, blood pressure or level of fatigue), (3) interrupting/dose reducing lenvatinib or interrupting pembrolizumab, if warranted, and advising the patient to manage their current symptoms via self-care (managing diarrhea with antidiarrheal agents and hydration), and (4) implementing medical interventions (eg, thyroid replacement or antihypertensive therapy) when needed. Through successful management of adverse reactions, oncology clinicians can improve the well-being of their patients and likely enhance adherence rates to treatment with lenvatinib and pembrolizumab.

Risk factors for oral mucositis in patients with solid tumors under treatment with cetuximab: a retrospective cross-sectional study.

BACKGROUND: This study retrospectively analyzed the risk factors for oral mucositis (OM) during cetuximab treatment. MATERIAL AND METHODS: We screened patients using cetuximab and retrospectively evaluated the presence of OM based on medical records. We collected information from 2 years of evaluations. Patient medical records were reviewed to obtain data on chemotherapy cycle and dose, sex, age, primary tumor, TNM stage, and head and neck radiotherapy (HNR) history. The X2 test and multinomial logistic regression were used for statistical analysis (SPSS 20.0, p < 0.05). RESULTS: Among 1831 patients, OM was showed in 750 in any grade (41%), during cetuximab treatment. Most patients were female (n=944, 51.6%), <70years-old (n=1149, 62.8%), had larynx cancer (n=789, 43.1%) in T4 (n=579, 47.7%), N0 (n=509, 52.6%) stages. Primary tumor surgery was performed in 1476 (80.6%) patients, radiotherapy in 606 (33.1%) patients and cetuximab protocols most used involved up to four cycles (n=1072, 58.5%) of <400mg (n=996, 54.4%) cetuximab doses. Female (OR [odds ratio] = 2.17, CI95% = 1.26-3.75), >70 years-old patients (OR = 16.02, CI95% = 11.99-21.41), with HHNR (OR = 1.84, 1.41-2.40), treated with >4 cycles (OR = 1.52, CI95% = 1.16-2.01) and high doses of cetuximab (OR = 3.80, CI95% = 2.52-5.71) are the greatest risk factors for OM. CONCLUSIONS: Since the clinical benefit of cetuximab in the treatment of older patients is limited and there is a high OM, especially in women with head and neck treated with radiotherapy, high doses and a high number of cetuximab cycles must be administered with caution.