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.

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.

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

BACKGROUND: In 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. METHODS: A 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. RESULTS: Thirteen 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. CONCLUSIONS: While 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.

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.

Efficacy of photobiomodulation therapy in the management of oral mucositis in patients with head and neck cancer: A systematic review and meta-analysis of randomized controlled trials.

Numerous studies have examined the effectiveness of photobiomodulation therapy (PBMT) in reducing chemoradiotherapy (CRT)-induced oral mucositis (OM) in patients with head and neck cancer (HNC). Despite this, there is an urgent need to update the meta-analyses on this topic. This meta-analysis aims to explore the impact of PBMT on CRT-induced OM in these patients. We conducted a systematic search in PubMed, Embase, Cochrane, LILACS, and Web of Science from January 2000 to October 2023. This search focused on randomized controlled trials (RCTs) that assessed the effects of PBMT on CRT-induced OM. The study included a total of 14 RCTs encompassing 869 patients with HNC. The incidence of OM in the PBMT group was significantly lower from the second week onwards compared to the control group (RR = 0.49, CI = 0.25-0.97, I2 = 71%, p = 0.04), and this was present until the seventh week (RR = 0.77, CI = 0.61-0.99, I2 = 89%, p = 0.04). Furthermore, the occurrence of severe mucositis in the PBMT group decreased from the third week (RR = 0.51, CI = 0.29-0.90, I2 = 12%, p = 0.02) until the conclusion of the intervention (RR = 0.45, CI = 0.24-0.85, I2 = 80%, p = 0.01). Additionally, PBMT showed beneficial effects in alleviating OM-related pain (WMD = -1.09, 95% CI = -1.38 to -0.880, I2 = 13%, p < 0.00001). The use of He-Ne or InGaAlP lasers with a power range of 10-25 mW demonstrated the most favorable outcomes in preventing and treating OM. PBMT has shown considerable efficacy in reducing the incidence, severity, and pain associated with OM in patients with HNC. Future studies are encouraged to further investigate the most effective parameters for PBMT in the management of OM.

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.

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.

Influence of anxiety/depression on chemotherapy-induced oral mucositis and related quality of life: A prospective cohort study.

OBJECTIVE: The impact of anxiety and depression on chemotherapy-induced oral mucositis has not been extensively explored in the literature. The aim of the present study was to evaluate anxiety/depressive symptoms, health-related quality of life, and oral health-related quality of life and their association with oral mucositis among individuals receiving chemotherapy. METHODS: This is a prospective longitudinal study carried out at a Brazilian referral service. The Hospital Anxiety and Depression Scale (HADS), World Health Organization Quality of Life-BREF (WHOQOL-BREF), and Oral Health Impact Profile questionnaire (OHIP-14) were applied at D0 (before chemotherapy) and D15 of chemotherapy. Clinicodemographic data and oral mucositis severity scores were evaluated. RESULTS: A total of 37 individuals (median age: 49 years) were included in the study. Nearly 38% of patients developed chemotherapy-induced oral mucositis and had higher anxiety/depression scores at baseline. Oral mucositis had a negative impact on oral health-related quality of life regarding functional limitation, physical pain, physical disability, and handicap. CONCLUSION: Anxiety/depressive symptoms are associated with oral mucositis that affects overall health and oral health-related quality of life.

A randomized phase II study of acyclovir for the prevention of chemotherapy-induced oral mucositis in patients undergoing autologous hematopoietic stem cell transplantation.

OBJECTIVES: To prove our hypothesis that acyclovir prophylaxis in autologous hematopoietic stem cell transplantation (AHSCT) recipients with hematologic malignancies (HM) reduces the incidence of chemotherapy-induced oral mucositis (CIOM) by inhibiting the intraoral HSV reactivation during the neutropenic period, we conducted a randomized phase II study of acyclovir for the prevention of CIOM in adult HSV sero-positive AHSCT recipients. METHODS: Patients were randomized to either the study group (acyclovir 400 mg PO bid until neutrophil engraftment) or the control group (no prophylaxis) and received AHSCT. Oral examination and sampling for HSV were performed at three timepoints of AHSCT. RESULTS: In 54 patients who were randomized (for intention-to-analysis), the incidence of CIOM was 16.0% (4/25 patients) and 58.6% (17/29 patients) in the study group and the control group, respectively (P = 0.001). In 49 patients who completed the study (for per-protocol analysis), the incidence of CIOM was 13.0% (3/23 patients) and 61.5% (16/26 patients) in the study group and the control group, respectively (P = 0.001). In addition, HSV-1 PCR positivity in the study group was significantly lower than that the control group (4.3% vs. 46.2%, P = 0.001). A strong association between the HSV-1 reactivation status and CIOM was reconfirmed. CONCLUSIONS: Prophylactic use of oral acyclovir effectively reduced the incidence of CIOM in patients with HM who were undergoing AHSCT. TRIAL REGISTRATIONS: This trial was registered at the Clinical Research Information Service in the Republic of Korea under the number KCT0003885 (registration date 03/05/2019).

Hangeshashinto for prevention of oral mucositis in patients undergoing hematopoietic stem cell transplantation: a randomized phase II study.

PURPOSE: Oral mucositis (OM) is a side effect associated with cancer treatment. Hangeshashinto (HST), a Kampo medicine, was originally prescribed to treat diarrhea, gastritis, and stomatitis. Several reports have described the effects of HST for OM induced by chemotherapy in patients with gastric or colorectal cancer. In this study, the effects of HST for prevention of OM were investigated in patients undergoing hematopoietic stem cell transplantation (HSCT). METHODS: Thirty patients scheduled to receive allogeneic grafts were enrolled from July 2020 to December 2021. They were randomly assigned to two groups and instructed to wash their mouth using HST dissolved in saline solution or using only saline solution three times a day. The observation period was from the initiation date of the conditioning regimen to the date of engraftment, and the end point was the incidence of OM. RESULTS: Eighteen patients developed OM, the most severe of which was Grade (G)3. There was no significant difference in the incidence of OM between the HST group and the control group. However, a negative correlation tended to be observed between the duration using HST use and the duration of OM (G2-3: P = 0.027, G3: P = 0.047). CONCLUSIONS: The present study demonstrated that HST use did not clearly inhibit onset of OM but showed a tendency to inhibit OM exacerbation. However, further studies are necessary to fully understand the effects of HST on OM in patients undergoing HSCT. TRIAL REGISTRATION: This study was registered in the Japan Registry of Clinical Trials on 7 May 2020 (jRCTs071200012).

Therapeutic Effects of Hydrogel Formulations Incorporating Troxipide Nanoparticles on Oral Mucositis in Hamsters.

Purpose: Medical therapies, such as the use of anti-inflammatory agents, are commonly used for the treatment of oral mucositis (OM). However, these treatments have limited efficacy in treating severe cases of OM. In this study, we aimed to develop a carbopol gel incorporating troxipide (TRO) nanoparticles and methylcellulose (TRO-NP gel) and demonstrate its efficacy in accelerating wound healing in a hamster model of OM (OM model) induced by acetic acid injection. Methods: TRO nanoparticles were prepared using bead milling. The crystalline form was determined by powder X-ray diffraction, and the particle size was measured using a NanoSight LM10 instrument. The drug release was determined using a Franz diffusion cell, and the hamsters injected with acetic acid were selected to evaluate the therapeutic effect of OM. Results: After preparing TRO nanoparticles, we observed a mixture of crystals and amorphous TRO, and the particle size of TRO in the TRO-NP gel ranged from 50 to 280 nm. The TRO-NP gel exhibited a more uniform TRO distribution and viscosity compared to the Carbopol gel containing TRO microparticles (TRO-MP gel). However, the solubility of TRO was comparable in both TRO-MP and TRO-NP gels. The TRO-NP gel released a higher amount of TRO than that from the TRO-MP gel, with detectable release of TRO nanoparticles. TRO levels in the cheek pouches of hamsters treated with TRO-NP gel were higher than those treated with TRO-MP gel. The increased TRO levels in the cheek pouches of hamsters treated with TRO-NP gel were attenuated by treatment with 40 µM dynasore, an inhibitor of clathrin-dependent endocytosis (CME). Moreover, the therapeutic effect of the TRO-NP gel was superior to that of the TRO-MP gel in the hamster model of OM. Conclusion: We have designed a TRO-NP gel, and this gel showed excellent TRO delivery into the cheek pouch tissue through the CME pathway. Moreover, the TRO-NP gel treatment enhanced wound healing after acetic acid injection.

Therapeutic effectiveness of anlotinib combined with etoposide in extensive-stage small-cell lung cancer: a single-arm, phase II trial.

BACKGROUND: Anlotinib plus chemotherapy as first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC) achieves good efficacy, but there is still room for improvement. This clinical study examined the effectiveness of anlotinib plus etoposide for maintenance therapy in ES-SCLC. METHODS: The current single-arm, prospective phase II study was performed at Jiangsu Cancer Hospital (March 2019 to March 2022). After successful primary etoposide-based therapy, anlotinib was administered at 12 mg/day on days 1 to 14 of 21-day cycles until disease progression or consent withdrawal. All patients also received etoposide at 50 mg/day on days 1 to 14 of 21-day cycles for a maximum of six cycles. Progression-free survival (PFS) constituted the primary study endpoint. Secondary endpoints were overall survival (OS), objective remission rate (ORR), disease control rate (DCR), and safety. In addition, adverse events (AEs) were assessed. RESULTS: Twenty-eight patients were treated. Median PFS and OS were 8.02 (95%CI 5.36-10.67) and 11.04 (95%CI 10.37-11.68) months, respectively. Totally 9 and 18 participants showed a partial response and stable disease, respectively; ORR and DCR were 32.14% and 96.43%, respectively. The commonest all-grade AEs were fatigue (n = 11, 39.28%), hypertension (n = 11, 39.28%), loss of appetite (n = 9, 32.14%), oral mucositis (n = 7, 25.00%) and proteinuria (n = 6, 21.40%). Grade 3-4 AEs included fatigue (n = 4, 14.28%), hypertension (n = 2, 7.14%), hand and foot syndrome (n = 2, 7.14%), oral mucositis (n = 1, 3.57%), hemoptysis (n = 1, 3.57%), proteinuria (n = 1, 3.57%), gingival bleeding (n = 1, 3.57%), and serum creatinine elevation (n = 1, 3.57%). CONCLUSION: Maintenance anlotinib plus etoposide achieves promising PFS and OS in clinical ES-SCLC. REGISTRATION NUMBER: ChiCTR1800019421.

The role of Hippophae rhamnoides L. on 5-fluorouracil-induced oral mucositis in rats.

Current study aimed to research the effect of Hippophae rhamnoides (HRE) on potantial oral oxidative and inflammatory damage of 5-FU in rats. The rats were assigned to three groups; healthy (HG), 5-FU 100mg/kg (FUG) and HRE 50mg/kg +5-FU 100mg/kg (HRFU). The 5-FU was injected in the FUG group intraperitoneally. The HRFU was injected 5-FU at 100mg/kg IP one hour after the 50mg/kg HRE was given orally. Olive oil was used as a solvent for the HG. HRE was given to the rats three times a day for ten days. 5-FU was given one dose on the 1st, 3rd and 5th days. On the 10th day, the tissues removed from the animals were euthanized with high-dose anaesthesia and were macroscopically examined. The levels of the oxidant, antioxidant and proinflammatory cytokines were investigated.It was seen that HRE alleviated the symptoms of severe mucositis by antagonizing the effects of 5-FU on oxidant, antioxidant and proinflammatory cytokines such as malondialdehyde, total glutathione, superoxide dismutase, catalase, nuclear factor kappa-B and interleukin-6 in inner cheek and tongue tissue. These results recommend that HRE may be benefical in the cure of 5-FU-associated oral mucositis.

Proposal of a prophylactic photobiomodulation protocol for chemotherapy-induced oral and oropharyngeal mucositis: a randomized clinical trial.

Photobiomodulation therapy (PBMT) is widely used in oncology settings, but lack of assessment standardization is the main barrier to optimization of clinical protocols. This study analyzed three PBMT protocols for preventing oral and oropharyngeal mucositis (OM) in patients undergoing chemotherapy (CT) and/or hematopoietic stem cell transplantation (HSCT). This is a preliminary randomized blind clinical trial. Group 1 received intraoral prophylactic PBMT, Group 2 received intraoral and oropharyngeal PBMT, and Group 3 received intraoral, oropharyngeal, and extraoral PBMT. The applications were from the first day of CT to day + 10. Clinicodemographic data, CT regimens, types of HSCT, hematological exams, occurrence/severity of OM, odynophagia, and OM-related opportunistic infections were assessed. Sixty participants (age range: 18-74 years) were included; 70% of them underwent CT and 30% HSCT. About 43.3% of patients had OM, while odynophagia was reported by 23.3%. Both Groups 1 and 2 revealed better results. Multivariate analysis showed that HSCT directly influenced the occurrence of OM. Individuals who had undergone allogeneic HSCT were 1.93 times more likely to develop OM (p < 0.001). Group 3 exhibited a higher frequency of OM, albeit of lower grades. This group consisted of half the population who had undergone HSCT, had the highest percentage of melphalan use, and had the lowest mean leukocyte count. The three proposed protocols were effective in preventing and reducing OM, with good tolerance and no reported adverse effects. PBMT is a safe and effective approach to OM prophylaxis in adults undergoing CT/HSCT.

A novel chitosan-based doxepin nano-formulation for chemotherapy-induced oral mucositis: a randomized, double-blinded, placebo-controlled clinical trial.

OBJECTIVES: Considering the prevalence of oral mucositis, we aimed to use the analgesic effects of doxepin with chitosan's antimicrobial and bio-adhesive nature to fabricate a nano-formulation for treating chemotherapy-induced oral mucositis. MATERIALS AND METHODS: Nanogel was fabricated via ionic gelation and characterized. Sixty patients were randomly divided and received four different treatments for 14 days: diphenhydramine + aluminum-magnesium mouthwash (control), doxepin mouthwash (DOX MW), chitosan nanogel (CN), and doxepin/chitosan nanogel (CN + DOX). Lesions were assessed with four indices, National Cancer Institute (NCI), World Health Organization (WHO), World Conference on Clinical and Research in Nursing (WCCNR) and visual analog scale (VAS) before and 3, 7, and 14 days after interventions. Kruskal-Wallis test was used for pairwise comparison. RESULTS: CN had semisolid consistency, uniform spherical shape, an average size of 47.93 ± 21.69 nm, and a zeta potential of + 1.02 ± 0.16 mV. CN + DOX reduced WHO, WCCNR, and VAS scores significantly more than the control three days after the intervention. Seven days after the intervention, CN + DOX reduced NCI and WCCNR considerably more than the control; it reduced WCCNR significantly more than CN. Fourteen days after the intervention, CN + DOX decreased NCI markedly more than the control. CONCLUSION: Chitosan-based doxepin nano-formulation might be a promising alternative for routine treatments of oral mucositis.

EFFICACY AND SAFETY OF A DEXAMETHASONE-BASED MOUTHWASH TO PREVENT CHEMOTHERAPY-INDUCED STOMATITIS IN WOMEN WITH BREAST CANCER: A MULTICENTRE, OPEN-LABEL, RANDOMISED PHASE 2 STUDY.

PURPOSE: No standard approach other than oral care is available for preventing chemotherapy-induced stomatitis in patients with breast cancer. In this randomized, controlled phase 2 trial, we aimed to assess the efficacy and safety of a dexamethasone-based mouthwash in preventing chemotherapy-induced stomatitis in patients with early breast cancer. BASIC PROCEDURES: Patients with breast cancer scheduled for epirubicin and cyclophosphamide (EC) or docetaxel and cyclophosphamide (TC) therapy were selected and allocated in a 1:1 ratio to the intervention and control groups. The intervention group received chemotherapy, oral care, and a dexamethasone-based mouthwash, whereas the control group received chemotherapy and oral care. The primary endpoint was the incidence of stomatitis. This was a phase 2 study, and the significance level for the analysis of the primary endpoint was set a priori at 0.2. MAIN FINDINGS: Data pertaining to 58 patients in the control group and 59 patients in the intervention group were analyzed. Stomatitis incidence was 55% and 38% in the control and intervention groups, respectively (risk ratio, 0.68; 80% confidence interval, 0.52-0.88; P = .052). Stomatitis severity was lower in the intervention group than in the control group (P = .03). The proportion of patients who adhered to the mouthwash regimen was 87% (interquartile range, 67.8%-95.3%). No severe oral infections were observed. PRINCIPAL CONCLUSIONS: The dexamethasone-based mouthwash safely reduced stomatitis incidence and severity in patients receiving chemotherapy for early breast cancer. Phase 3 clinical trials are warranted for validating our results.

Assessment of Oxidative Stress-Induced Oral Epithelial Toxicity.

Reactive oxygen species (ROS) are highly reactive molecules generated in living organisms and an excessive production of ROS culminates in oxidative stress and cellular damage. Notably, oxidative stress plays a critical role in the pathogenesis of a number of oral mucosal diseases, including oral mucositis, which remains one of cancer treatments' most common side effects. We have shown previously that oral keratinocytes are remarkably sensitive to oxidative stress, and this may hinder the development and reproducibility of epithelial cell-based models of oral disease. Here, we examined the oxidative stress signatures that parallel oral toxicity by reproducing the initial events taking place during cancer treatment-induced oral mucositis. We used three oral epithelial cell lines (an immortalized normal human oral keratinocyte cell line, OKF6, and malignant oral keratinocytes, H357 and H400), as well as a mouse model of mucositis. The cells were subjected to increasing oxidative stress by incubation with hydrogen peroxide (H2O2) at concentrations of 100 µM up to 1200 µM, for up to 24 h, and ROS production and real-time kinetics of oxidative stress were investigated using fluorescent dye-based probes. Cell viability was assessed using a trypan blue exclusion assay, a fluorescence-based live-dead assay, and a fluorometric cytotoxicity assay (FCA), while morphological changes were analyzed by means of a phase-contrast inverted microscope. Static and dynamic real-time detection of the redox changes in keratinocytes showed a time-dependent increase of ROS production during oxidative stress-induced epithelial injury. The survival rates of oral epithelial cells were significantly affected after exposure to oxidative stress in a dose- and cell line-dependent manner. Values of TC50 of 800 µM, 800 µM, and 400 µM were reported for H400 cells (54.21 ± 9.04, p < 0.01), H357 cells (53.48 ± 4.01, p < 0.01), and OKF6 cells (48.64 ± 3.09, p < 0.01), respectively. Oxidative stress markers (MPO and MDA) were also significantly increased in oral tissues in our dual mouse model of chemotherapy-induced mucositis. In summary, we characterized and validated an oxidative stress model in human oral keratinocytes and identified optimal experimental conditions for the study of oxidative stress-induced oral epithelial toxicity.

Effectiveness of Cryotherapy on Cancer Therapy-Induced Oral Mucositis: An Umbrella Review.

BACKGROUND: Oral mucositis (OM) considerably affects the experience of patients with cancer during treatment. This study investigated the effects of cryotherapy on cancer therapy-induced OM. OBJECTIVE: This study aimed to systematically appraise evidence on whether cryotherapy can reduce the incidence and severity of OM. METHODS: We conducted an umbrella review to examine the effect of cryotherapy on cancer-related OM. The primary outcome was the incidence and severity of OM. We performed a subgroup analysis including solid cancers and hematological malignancies. RESULTS: Five meta-analyses were included. Cryotherapy could more effectively reduce the incidence of severe OM (risk ratio [RR], 0.37; 95% prediction interval [PI], 0.22-0.64). In the subgroup analyses of solid cancers or hematological malignancies, cryotherapy significantly reduced the incidence of grades 2 to 4 OM in patients with solid cancers (RR, 0.51; 95% PI, 0.34-0.78 and RR, 0.52; 95% PI, 0.36-0.74). However, no significant difference was observed in the incidence of OM in patients with hematological malignancies regarding any grade or grade 3 or 4 OM. Moreover, cryotherapy did not significantly reduce the OM duration (mean difference, -0.13; 95% PI, -20.89 to 20.63; mean difference, -2.99, 95% PI, -8.10 to 2.12). CONCLUSION: Cryotherapy can reduce the incidence of severe OM induced by chemotherapy or radiotherapy. IMPLICATION FOR PRACTICE: We recommend the inclusion of this safe, simple, and convenient intervention in chemotherapy or radiotherapy plans. Additional clinical trials are warranted to extend the limited evidence on the effectiveness of cryotherapy in reducing the severity and duration of OM.

Protective effect of cryotherapy against oral mucositis among allogeneic hematopoietic stem cell transplant recipients using melphalan-based conditioning.

PURPOSE: Oral cryotherapy is an effective method to prevent oral mucositis (OM) induced by chemotherapeutic agents, such as melphalan (Mel). However, there is limited data about cryotherapy in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients; thus, the current study aimed to examine the efficacy of cryotherapy among allo-HSCT recipients treated with Mel-containing regimens. METHODS: Medical records of 78 consecutive allo-HSCT recipients were retrospectively analyzed. Baseline characteristics and clinical courses between the patients who received cryotherapy (cryotherapy group, n = 42) and those who did not (control group, n = 36) were compared, especially focusing on methotrexate (MTX) use as a part of graft-versus-host disease (GVHD) prophylaxis. RESULTS: Binary logistic regression analysis revealed that a higher dose of Mel (OR, 3.82; 95%CI, 1.085-13.46; P = 0.037) or MTX use (OR, 7.61; 95% CI, 2.41-23.97; P < 0.001) was associated with the incidence of OM. MTX use was also significantly associated with the duration of OM (ß = 0.515; 95% CI, 9.712-21.636; P < 0.001). Among 31 patients without MTX use, cryotherapy was associated with a significant reduction of OM development (0% in the cryotherapy group vs 35% in the control group, P = 0.021). We did not find such an association in 47 patients with MTX use. CONCLUSION: Cryotherapy was useful to prevent the incidence of OM in allo-HSCT recipients in the cases without MTX for GVHD prophylaxis.

Oral hygiene protocols reduce the severity and incidence of oral mucositis during antineoplastic treatment: a systematic review and meta-analysis of randomized and non-randomized clinical trials.

OBJECTIVE: The objective of this systematic review was to determine whether oral and dental hygiene protocols (DHPs) reduce the incidence and severity of oral mucositis (OM) during antineoplastic treatment. MATERIALS AND METHODS: This PROSPERO-registered systematic review (CRD42021295322) was based on searches of publicly accessible databases, including PubMed, Scopus, Web of Science, LILACS, EBSCOhost, LIVIVO, Embase, and gray literature (Google Scholar, ProQuest, and Energy) until December 2021. Twenty-five articles from these searches and 14 articles retrieved from the references therein were evaluated in this systematic review and meta-analysis. The risk of bias (RoB) was assessed using RoB-2 and ROBINS-I for randomized (RCT) and non-randomized (n-RCT) clinical trials, respectively. A meta-analysis was performed on RCTs and n-RCTs in two subgroups to evaluate oral mouth rinses or DHP. GRADE-pro was used to assess the degree of certainty of the evidence. RESULTS: Of the 3367 articles retrieved, 25 RCTs and 14 n-RCTs involving 2109 and 754 patients, respectively, were included in the analyses. RoB was low for RCTs and moderate-to-very severe for n-RCTs. High heterogeneity and publication RoB were identified. In RCTs, mouth rinses (p = 0.830) and DHP (p = 0.100) did not reduce the incidence of OM. However, mouth rinses strongly reduced the severity of OM (p < 0.001; Cohen's d = - 1.87, 95% confidence interval [CI] = - 2.49 to - 1.24). In non-RCTs, mouth rinses (p < 0.001) and DHP (p < 0.001) reduced the relative risk of OM 0.38 (95% CI = 0.24 to 0.59) and 0.64 (95% CI = 0.53 to 0.70) times, respectively. In addition, DHP strongly reduced OM severity (Cohen's d = - 0.81, 95% CI = - 1.03 to - 0.59). GRADE-pro showed high certainty of OM severity and incidence in RCTs and non-RCTs, respectively, and low (OM incidence in RCTs) to very low (OM severity in non-RCTs) certainty in other outcomes. CONCLUSION: DHPs strongly reduce the severity and moderately reduce the incidence of OM. However, further studies with low heterogeneity are needed to validate these findings.