Occurrence Of Oral Mucositis Research Articles

Analysis of the association between salivary proteins and oral mucositis in patients with head and neck cancer undergoing IMRT: a longitudinal study

IntroductionThis longitudinal study assessed the association between salivary protein composition and the clinical onset/severity of oral mucositis (OM) in patients with head and neck tumours treated with intensity-modulated-radiotherapy (IMRT).MethodsSaliva samples/clinical data were obtained from 40 head and neck cancer patients treated at Guy’s Hospital before -IMRT(T0) and after-IMRT (T1 = 6 m, T2 = 12 m) (ethics approval/consent).Salivary flow rate, total protein concentration, and secretion rate were determined from saliva samples and compared with pre-treatment values. OM was assessed, total/specific salivary proteins, including mucin 5B and 7, IgA, cystatin-S, albumin, and α-amylase, were quantified.Results95% patients experienced OM during IMRT, with 33 subjects reaching grade 2&3. At T1, there was a significant reduction in salivary flow rate, total protein secretion rate, α-amylase and cystatin-S compared to baseline. Remarkably IMRT did not significantly alter mucin 5B and 7, or the IgA secretion rate at any time point. At T1, all the analyzed proteins were associated with the OM outcomes. In addition, there was a significant inverse correlation between IgA concentration at T0 and the severity of OM during IMRT.ConclusionThis study revealed significant associations between several salivary proteins and OM in patients with head and neck cancer undergoing IMRT. Further longitudinal studies are needed to confirm these results.Clinical significanceThe study contributes to the understanding of certain salivary proteins association with OM. This could be the first step towards identifying potential salivary markers that could offer perspectives for personalized medicine approaches to improve their quality of life (QoL).Research questionWhat is the association between salivary proteins and the occurrence and severity of OM in head and neck cancer patients?AimTo assess the association between salivary protein composition with the clinical onset/severity of oral mucositis (OM) in head and neck cancer patients treated with intensity modulated radiotherapy.Null hypothesisThere is no association between salivary proteins and onset/severity of OM in HNC patients.

Dentist Involvement in the Treatment of Radiation-Induced Oral Mucositis-A Pilot Cross-Sectional Study.

Objectives: Oral mucositis (OM) occurs in more than 95% of patients irradiated in the head and neck area. This paper aims to determine the occurrence and characteristics of OM in patients with head and neck cancer (HNC), as well as the involvement of dentists/oral medicine specialists in treating such patients. Methods: This study was conducted at the Department of Otorhinolaryngology and Department of Oral Medicine, University Hospital Center Zagreb, from April to August 2022, on patients irradiated in the head and neck area. A unique OM questionnaire was created on the incidence, characteristics, oral care, and involvement of dentists in the overall care. Results: Thirty patients filled out the questionnaire. Of the 22 patients who had developed OM, 14 had grade-three OM. Ten patients were treated for OM in line with the instructions of an oral medicine specialist, eight based on the instructions of a specialist responsible for monitoring of the underlying disease, and four were not treated at all. Sixteen patients had not been referred to a dentist before the start of RT. Conclusions: These results showed insufficient care and treatment of OM, as well as insufficient involvement of dentists in the oncology team.

Effectiveness of intraoral stentsin reducing oral adverse events during radiotherapy for maxillary or nasal cavity malignant tumors.

Many patients experience oral adverse events during head and neck cancer radiotherapy (RT). The methods of management of such events are under debate. One such technique is the intraoral stent (IOS) technique, which removes normal tissue from the irradiation field. This retrospective study examined the factors associated with the occurrence of oral mucositis (OM) and dysgeusia and the efficacy of IOSs in preventing them. Twenty-nine patients who underwent RT in the maxilla or nasal cavity between 2016 and 2022 were included. They were investigated for background characteristics, treatment factors (IOS and dose-volume histogram), and oral adverse events (OM and dysgeusia). Significant risk factors for the incidence of grade ≥ 2 (Common Terminology Criteria for Adverse Events v5.0) OM were the non-use of IOSs (p = 0.004) and diabetes (p = 0.025). A significant risk factor for the incidence of grade ≥ 1 dysgeusia was concomitant chemotherapy (p = 0.019). The radiation dose to the tongue was significantly lower in the IOS group than in the non-IOS group. Our findings suggest that the use of an IOS during RT reduces the severity of OM by reducing irradiation to the tongue. Therefore, the use of an IOS is recommended during RT performed in the maxilla or nasal cavity.

Depressive symptoms and oral mucositis in children with oncological diseases: a cross-sectional study.

The aim of this study was to investigate the correlation between depressive symptoms and the occurrence of oral mucositis in children with oncological diseases treated at a reference hospital. This was a cross-sectional study conducted with individuals aged 4 to 18 years, diagnosed with primary neoplasms. Data was collected by using a questionnaire that assessed the degree of oral mucositis according to the World Health Organization index, the risk of oral mucositis according to the Child's International Mucositis Evaluation Scale, and depressive symptoms using the Children's Depression Inventory. The data were analyzed and subjected to Spearman's correlation, chi-square test, and Fisher's exact test, considering p<0.05. A statistically significant correlation was observed between depressive symptoms and the degree of oral mucositis (p = 0.044), and also between the "pain" variable within the risk of oral mucositis and depressive symptoms (p = 0.021). Based on the findings, it can be inferred that oral mucositis may be associated with the development of depressive symptoms and may be influenced by the individual's hospitalization, thereby affecting the quality of life of pediatric patients.

The Role of Biotics as a Therapeutic Strategy for Oral Mucositis - A Systematic Review

ObjectivesOral mucositis (OM) is an acute and highly prevalent side effect of cancer treatments. Currently, there is no effective strategy for its prevention or treatment. This systematic review aimed to assess the effectiveness of biotics used as a therapeutic strategy for the management of OM.Materials and MethodsThe PRISMA checklist was followed and PubMed, Web of Science, and Scopus were screened for clinical and pre-clinical studies assessing the potential effects of biotics in OM. Inclusion criteria included in vivo studies related to oral mucositis evaluating the effect of biotics, and written in Portuguese, English, French, Spanish, or Dutch. The following exclusion criteria were used: systematic reviews and meta-analyses, reviews, case reports, opinion papers or comments, conference papers, letters without results, articles not related to oral therapy-induced mucositis or biotics, or in vitro articles that do not simulate oral mucositis.ResultsFrom a total of 1250 articles retrieved, 9 were included in this systematic review. Four clinical studies reported a reduction in oral mucositis occurrence with Lactobacillus species (Lactobacillus casei and Lactobacillus brevis CD2) and Bacillus clausii UBBC07. In pre-clinical studies, Lactococcus lactis genetically modified and Lactobacillus reuteri reduced the severity of OM and Streptococcus salivarius K12 also decreased the size of the ulcers.ConclusionThe findings of this systematic review suggest that probiotic supplementation may potentially reduce the incidence of therapy-induced OM and decrease its severity in patients undergoing cancer treatment. However, the available evidence is marred by significant heterogeneity across studies.

The Implementation of an Integrated Oral Care Protocol for Pediatric Cancer Patients: a Qualitative Study.

In this study, we evaluated the impact of an integrated oral care protocol for pediatric patients undergoing antineoplastic treatment from the perspective of the multidisciplinary team, oral healthcare team, and caregivers. This was a qualitative study carried out in the pediatric sector of a reference cancer hospital in Brazil. Focus group and individual semi-structured interview techniques were used, and the data were analyzed by the Discourse of the Collective Subject (DCS) method. A total of 44 professionals involved in providing care to children and adolescents with cancer and 38 caregivers were interviewed. All interviewees perceived an improvement in the patients' oral health condition. Health professionals reported a reduction in the occurrence and severity of oral mucositis (OM). Communicating with the medical team and understanding the importance of oral care to the patient's systemic condition were the greatest difficulties reported by the oral healthcare team. This implementation project contributed to establishing a complete multidisciplinary team to assist pediatric patients in all their needs during antineoplastic treatment. The integrated oral care protocol further contributed to reducing the occurrence and severity of OM by increasing its surveillance and diagnostic efficiency, which, altogether, improved the patients' quality of life.

A prospective interventional study of recombinant human interleukin-11 mouthwash in chemotherapy-induced oral mucositis

BackgroundThis prospective interventional study aimed to evaluate and analyse the efficacy of rhIL-11 mouthwash compared to Kangfuxin fluid in treatment and blank control in prevention of oral mucositis (OM) in patients receiving chemotherapy.Materials and MethodsIn total, 50 patients in the treatment group and 62 patients in the prevention group were included. Subsequently, each group was divided into an experimental group and a control group. In the treatment group, the experimental patients received recombinant human interleukin-11 (rhIL-11) mouthwash, whereas the control group received Kangfuxin fluid. In the prevention group, experimental patients still received rhIL-11 mouthwash based on routine oral care, whereas the control group only received routine oral care. Meanwhile, we observed and recorded the efficacy in the treatment group, and the occurrence and grades of OM in the prevention group.ResultsThrough statistical analysis, the results showed that on the seventh day of treatment, the experimental group showed more improvement compared to the control group, and it was statistically significant (p = 0.032). The average healing time in the experimental group (3.59 ± 1.927 days) was shorter than that in the control group (4.96 ± 2.421 days; p = 0.031). In the prevention group, we observed the incidence of oral mucositis. No significant differences were found in the occurrence and grades of OM in the experimental and control groups (p = 0.175).ConclusionOur preliminary results indicate that rhIL-11 mouthwash may be a superior option to treat OM, especially in severe cases, compared to Kangfuxin fluid. However, there is no advantage in prevention.

Impact of periodontal status on the oral mucositis in patients receiving high-dose chemotherapy.

Oral mucositis (OM) is a frequent complication of cancer treatments. Oral mucositis and periodontal disease have a common inflammatory pattern. The purpose of this study was to evaluate the OM and its association with periodontal status in patients with hematologic malignancies who undergo high-dose chemotherapy. Fifty-five patients who received high-dose chemotherapy were included in the study. Full-mouth periodontal clinical measurements including plaque index (PI), gingival index (GI), clinical attachment level (CAL), and probing depth (PD) values were recorded before the condition chemotherapy regime. OM monitoring was initiated 1day after the chemotherapy and maintained for 20days. Twenty-two of patients (40%) were observed oral mucositis after high-dose chemotherapy. Patients with mucositis had significantly higher GI scores than those who did not have mucositis (p < 0.05). There was a significantly moderate positive correlation between the grade of mucositis and GI scores (p < 0.05). In patients with periodontitis, the incidence of grade 1-2 mucositis was significantly higher than in the healthy group (p < 0.05). In individuals with periodontitis and gingivitis, the healing duration of mucositis was significantly longer than the healthy group (p < 0.05). The results of this study showed that the severity grades of oral mucositis may increase in patients with gingival inflammation. The results also suggest that periodontal diseases may have a significant impact on the duration of oral mucositis. The current study contributes to our understanding of the importance of oral health status in reducing the occurrence, severity, and duration of OM in hematological cancer patients treated with high-dose chemotherapy.

Relationship of Oropharyngeal Colonization Microorganisms to Clinical Outcomes within 100 Days after Allogeneic Hematopoietic Stem Cell Transplantation

Little is known about oropharyngeal colonization microorganisms in patients during allogeneic hematopoietic stem cell transplantation (allo-HSCT), and updated epidemiologic investigations are advisable. This study aimed to characterize oropharyngeal colonization microorganisms in patients during allo-HSCT and confirm whether they were related to clinical outcomes. This retrospective, matched case-control study included 1267 consecutive patients undergoing allo-HSCT between January 2018 and December 2020 at our institution. Patients with oropharyngeal colonization microorganisms were those with a positive throat swab before or on the day of transplantation without the occurrence of any symptoms of infection. Propensity score matching was used. Characteristics of oropharyngeal colonization microorganisms were evaluated among patients in the transplant medicine wards and compared with clinical outcomes within 100 days in positive and negative colonization groups. A total of 127 patients had oropharyngeal colonization microorganisms before or on the day of transplantation. Using propensity score matching, we matched the 127 patients in the positive colonization group with 508 patients in the negative colonization group at a 1:4 ratio (total of 635 cases). None of the differences in clinical traits between the 2 groups remained significant. Among the 127 patients with oropharyngeal colonization microorganisms, 90 patients suffered from the documented infection subsequently, and the others were asymptomatic. A total of 82 single gram-negative bacteria were identified in 127 isolates. There were no differences between the positive and negative colonization groups in the occurrence of oral mucositis, Epstein-Barr virus, or acute graft-versus-host disease and relapse within 100 days. However, the rate of neutrophil or platelet recovery was significantly lower in the positive colonization group compared with the negative colonization group (hazard ratio [HR], .71; 95% confidence interval [CI], .59 to .84; P < .001; HR .69; 95% CI, .58 to .83; P = .003; separately). The risk of bloodstream infection was higher in the positive colonization group compared with the negative colonization group (HR, 6.09; 95% CI, 3.16 to 11.75; P < .001). The continency rate between the bacteria isolated from the blood samples and oropharyngeal colonization microorganisms among the patients with positive results was 73.3%. Patients in the positive colonization group were more vulnerable to cytomegalovirus infection compared with the negative colonization group (HR, 1.41; 95% CI, 1.00 to 1.99; P = .049). The nonrelapse mortality at day +100 was higher in the positive colonization group (HR, 3.46; 95% CI, 1.69 to 7.08; P < .001). The survival probability within 100 days was significantly lower in the positive colonization group (HR, 3.38; 95% CI, 1.78 to 6.41; P < .001). Our data show that the presence of oropharyngeal colonization microorganisms is related to clinical outcomes, and that oropharyngeal microorganism monitoring may be useful during allo-HSCT.

Salivary inflammatory mediators as biomarkers for oral mucositis and oral mucosal dryness in cancer patients: A pilot study.

Oral mucositis (OM) is a common side effect in patients with cancer receiving chemotherapy and radiotherapy; however, no salivary mediator is known to be associated with OM. We aimed to determine candidate salivary inflammatory mediators potentially associated with OM in patients with cancer. To this end, we compared the relationships between OM grade, oral mucosal dryness, and inflammatory mediators (Interleukin (IL)-1β, IL-6, IL-10, IL-12p70, tumor necrosis factor (TNF), prostaglandin E2, and vascular endothelial growth factor) in patients with cancer and in healthy volunteers (HV). We collected saliva samples from 18 patients with cancer according to the following schedule: 1) within 14 days of treatment initiation, 2) within 3 days of OM occurrence, 3) when OM was improved or got worsened, and 4) within 7 days after chemotherapy completion. The oral care support team determined the OM grade at each sample collection point based on CTCAE version 5.0. Salivary inflammatory mediator concentrations were detected using cytometric bead array or enzyme-linked immunoassay. We compared oral mucosal dryness in pre- and post-index patients with cancer to that in HV (n = 33) using an oral moisture-checking device. Fourteen of eighteen patients experienced OM (four, grade 3 OM; four, grade 2 OM; six, grade 1 OM). IL-6, IL-10, and TNF salivary concentrations were significantly increased in the post-index group compared to those in the pre-index group (p = 0.0002, p = 0.0364, and p = 0.0160, respectively). Additionally, salivary IL-6, IL-10, and TNF levels were significantly higher in the post-index group than in the HV group (p < 0.0001, p < 0.05, and p < 0.05, respectively). Significant positive correlations were observed between OM grade and salivary IL-6, IL-10, and TNF levels (p = 0.0004, r = 0.4939; p = 0.0171, r = 0.3394; and p = 0007, r = 0.4662, respectively). Oral mucosal dryness was significantly higher in the HV than in the pre- and post-index groups (p < 0.001). Our findings suggest that salivary IL-6, IL-10, and TNF levels may be used as biomarkers for OM occurrence and grade in patients with cancer. Furthermore, monitoring oral mucosal dryness and managing oral hygiene before cancer treatment is essential.

Management of oral mucositis in children.

Children undergoing chemotherapy or hematopoietic stem cell transplantation may suffer from Oral mucositis. Therefore, the aim of this systematic review was to find the protocols which are used in the management of oral mucositis (OM) in children. A search was performed to find the related studies. After reading the searched articles, 15 studies were selected for this review. Good oral care, glutamine, some biological agents, and laser therapy, had a significant effect to reduce the pain sensation and occurrence of oral mucositis in children. It has been concluded that there are many types of management, such as oral care and laser therapy, which can be used to reduce the severity of oral mucositis.

Incidence, severity, and onset of oral mucositis in 5-FU based chemotherapy for gastrointestinal cancer.

77 Background: 5-fluorouracil has been used in treatment of gastrointestinal cancers for more than 40 years. Numerous toxicities of 5-FU are known. Little is known about the occurrence, natural course and causes of oral mucositis (OM) of 5-FU in GI tumors. There is little data on the additional toxicity of VEGF and EGFR antibodies together with 5-FU. We followed the occurrence, severity and localization of OM of 5-FU in consecutive patients as part of their cancer treatment. The primary aim of the study was to determine the severity, course and risk factors of OM up to the first six cycles of ctx. OM was evaluated by repeated inspections of the oral cavity and patient questionnaires. Methods: Pts who received 5-FU for the first time or who had not received ctx for at least 12 months. 64 consecutive pts were included in the observational study from March 2018 to March 2019. Out of 64 pts a total of 41 (28 m/13f) had complete documentations (inspections of the oral cavity and questionnaires) and were available for the evaluation. Results: Mean age 65 ys (range 42-83), 60% were treated for CRC, 22% esophageal/gastric cancer, and 18% other GI-cancers. 13 were non-smokers, 25 former smokers; 7 pts had daily alcohol consumption while 7 pts never consumed alcohol. 10/41 pts wore a dental prosthesis. The mean BMI was 26.5 (range 18.8-41.5). Initial very good/ good oral hygiene was given in 3/20 patients. 80% of the pts developed xerostomia after the first cycle, almost every patient needed support for symptoms due to oral problems during ctx. Of 41 pts, an OM could be documented in 38 pts. A total of 93% of the patients developed a mild course of the mucositis with grade 1-2. OM developed between the 2nd and 3rd cyle in the majority of pts. At the third cyle, only 8 pts had OM of grade 0, while 23 pts had grade 1 and 9 pts were grade 2. It was of note here that of these 9 pts with grade 2, 6 had grade 0 in the 2nd cycle. During cycle 5 and 6 only seven pts had a CTC score of 0, but no pat developed a CTC 3 or 4 OM. We could not document a connection between the occurrence of oral mucositis and the oral hygiene measures used, as no severe course of OM CTC Grad 3 or 4 could be detected. We could not find any relation to the type of 5-FU therapy (doublet, triplet +/- monoclonal antibodies). Conclusions: The incidence of oral mucositis with CTC score of 1 and 2 was 93%, but serious grade 3 and 4 mucositis rates were not observed. Xerostomia was observed in 80% after the first course of treatment. Symptomatic mucositis occurs early within 4 weeks after starting chemotherapy. Local measures appear suitable for symptom control of OM.

A randomized clinical trial of granulocyte macrophage colony stimulating factor mouthwash for oral mucositis in head and neck cancer.

Oral mucositis (OM) is a significant problem for patients with head and neck cancer (HNC). The purpose of this double-blind, randomized clinical trial (RCT) was to evaluate the effectiveness of the granulocyte macrophage colony stimulating factor (GM-CSF) mouthwash compared to Salt and Soda mouthwash for both the prevention (prior to onset of OM) and treatment (beginning at the onset of OM to its healing) of radiation therapy (RT)-induced OM. A total of 91 patients with HNC were randomized to receive: GM-CSF throughout both the prevention and treatment phases (GG group); Salt and Soda throughout both phases (SS group) or Salt and Soda during the prevention phase followed by GM-CSF at the onset of OM (SG group). Three groups were compared on the occurrence and grades of OM, functional status, pain, chewing, and swallowing during and after RT. No significant differences were found in the occurrence and grades of OM in the patients who used GM-CSF vs. Salt and Soda in the prevention phase. In addition, no differences were seen among the three groups in functional status, pain, chewing, and swallowing during and after RT. Given that GM-CSF was no more effective than Salt and Soda mouthwash for the prevention or treatment of OM, the readily available and cheaper mouthwash can be used at considerable cost savings.

Genetic polymorphisms of genes involved in oxidative stress and inflammatory management in oncopediatric patients with chemo-induced oral mucositis.

Oral mucositis (OM) is a painful inflammatory oral condition that affects children who undergo chemotherapy. Oxidative stress is a known OM mediator and pro-inflammatory cytokines contribute to the amplification of the immune response.Objective:To investigate the possible associations of rs4880 (superoxide dismutase 2, SOD2 47 C/T), rs7943316 (catalase, CAT −21 A/T), rs1800629 (tumor necrosis factor α, TNF- α −308 G/A), and rs1800795 (interleukin 6, IL-6 −174 G/C) polymorphisms with chemo-induced OM occurrence and severity in oncopediatric patients.Methodology:We conducted a single-center, observational cross-sectional study with sample collection of oral epithelial cells from 95 children and adolescents with hematological cancers who underwent chemotherapy, followed by genomic DNA extraction. Single-nucleotide polymorphisms (SNPs) were assessed with PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism). Demographic data and information concerning OM occurrence were obtained from dental charts of the multidisciplinary oral care team. Information on OM severity was obtained from appropriately-filled Oral Assessment Guide records. Descriptive and inferential statistics were conducted with Student's T test, chi-squared test, and Fisher's exact test, with p≤0.05.Results:The mean age was 10 years-old and most patients were male individuals (57.89%). Female sex was considered a protective factor for OM occurrence (OR=4.83; CI=[1.14; 16.57]). The AA genotype for CAT was the most frequent amongst individuals with severe OM (p=0.04). The GA genotype for TNF- α was the most frequent amongst individuals without severe OM (p=0.03). For SOD2 and IL-6 , the most frequent genotypes were CT and GG respectively for all groups (p>0.05).Conclusion:The AA genotype for CAT −21 A/T was a tendency among the group with severe OM. Data on TNF- α −308 G/A were inconclusive. No associations were detected for SOD2 47 C/T and IL-6 −174 G/C polymorphisms in oncopediatric patients with chemo-induced oral mucositis.

How can the dental surgeon promote oral health in patients submitted to chemotherapy?

Lesions that affect the oral cavity resulting from chemotherapy can lead to systemic impairment, increasing thelength of hospital stay, impairing the patient’s quality of life. Through a integrative review, this work aims toshow the conduct and importance of dentists in promoting oral health and preventing an oral infectious focus.The search was performed in the Pubmed, Cochrone, SciElo and Virtual Health Library (VHL) databases, usingthe descriptors in English, oral care and Chemotherapy and Cancer treatment and dentistry, filtering only articlesin English and published between 2006 and 2021. The search located six hundred and twenty articles, but onlyseven met the search criteria. One author used a mouthwash containing propolis where 65% of patients werecured on the seventh day after the onset of oral mucositis (OM) lesions. One author used cryotherapy withchamomile infusion, patients who underwent this approach did not pass grade I, being effective in reducingthe occurrence of OM, and the other two authors proposed a protocol for oral cavity care. All authors obtainedsatisfactory results.KEYWORDSDentistry; Antineoplastics; Oncology.

A Dose-Escalation Phase Ib International Study to Evaluate the Safety, Pharmacokinetics and Efficacy of ST-617 for the Attenuation of Oral Mucositis in Patients Receiving Chemoradiation for H&N Cancer

Oral Mucositis (OM) is a common, painful, and costly toxicity associated with cytotoxic chemoradiation regimens used to treat H&N cancer, which may interfere with planned treatment and negatively impact tumor control. There are currently no approved interventions to mitigate the incidence, severity or duration of OM. Oxidative stress is a critical event in OM's pathogenesis. Through its effect on Nrf2, ST-617 has marked anti-oxidative activity/properties. Supportive Therapeutics is developing ST-617, a dithioethione, for the attenuation of OM. The objective of this trial was to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of ST-617 in patients at high risk of severe OM (SOM).A dose escalation trial was performed in which ST-617, administered as an oral suspension, 1-2 hours before the administration of daily RT fractions at 9 study sites in South Africa and Australia. Eighteen patients with diagnoses of oral or oropharyngeal CA were enrolled (up to 6 pts/dose). Patients received concomitant cisplatin either weekly or tri-weekly. ST-617 was administered 3 days prior to CRT, and then continuing daily concomitant with BSC (Best Supportive Care) until the end of treatment. Safety outcomes, using CTCAE criteria (v 4.03) were used. Dose escalation occurred in the absence of toxicity. OM occurrence and severity were assessed by trained and validated evaluators using WHO, NCI-CTC and RTOG criteria; scores were centrally assigned. The primary efficacy endpoints included the incidence and duration of SOM (WHO grades 3 or 4) vs historical controls. PD tracking measured total ROS/RNS, GSH/GSSG, regulation in plasma and buccal epithelial cells.17 pts completed the 50, 100 and 150mg/day with no safety issues. No early dose limiting toxicity (DLT) or serious Adverse Event linked to ST-617 were observed. AEs observed were mainly nausea which is usually associated with CRT as expected. As overall SOM incidence (baseline to the last day of radiation) of 50% was less than expected and was related to ST-617 dose: 50 mg/day 83% (n = 6); 100 mg/day 33% (n = 9); 200 mg/day 33% (n = 3). The 100 mg/day dose was well tolerated with no grade 4 OM. No CRT dose interruptions or delays due to OM were noted Total ROS/RNS levels in plasma and buccal samples show significant decrease with increased ST-617 dosing from 50 to 100 mg/day. ST-617 did not alter tumor response at 1 year post-CRT (n = 17).ST-617 administration was safe at all doses tested. The course and severity of patients treated with ST-617 compared favorably with historical controls. A dose-response effect on SOM incidence was noted. Mechanistic correlation between ROS/RNS levels was seen. A randomized, controlled, double blind trial is planned with the recommended dose of 100mg/day.

PATTERNS OF ORAL MUCOSITIS IN ADVANCED OSCC PATIENTS MANAGED WITH PROPHYLACTIC PHOTOBIOMODULATION THERAPY – INSIGHTS FOR FUTURE PROTOCOL DEVELOPMENT

<h3>Background</h3> Photobiomodulation therapy (PBMT) is recommended for the prevention of radiation-induced oral mucositis (OM) in head and neck patients. It is unclear to what extent the delivered PBMT therapy effectively provides an adequate uniform dose to the at-risk tissues. <h3>Objective</h3> To characterize oral sites affected by radiation-induced OM and its clinicopathologic outcomes in oral squamous cell carcinoma (OSCC) patients subjected to prophylactic PBMT. <h3>Methods</h3> The site distribution of OM, OM grading (NCI, Version 4.0), OM-related pain (visual analog scale), analgesic protocol (WHO), and use of enteral nutrition were evaluated weekly during treatment for OSCC patients with prophylactic PBMT. Data analysis was performed using descriptive statistics. <h3>Results</h3> One hundred forty-five OSCC patients were included. The most frequently affected sites by OM included lateral tongue (44.1%) and buccal mucosa (37.2%). Keratinized oral mucosae sites, including the tongue dorsum (6.21%) and retromolar trigone (8.3%), were also affected. Peak OM scores were observed at weeks 5, 6 and 7, with severe OM (NCI grades 3 and 4) rates of 11%, 20%, and 25%, respectively. The cumulative occurrence of severe OM was 23%, which developed as early as week 3 and as late as week 7. The highest mean value of OM-related pain (2.7) was observed in the sixth week, and 13.8% of the patients required feeding support. <h3>Conclusions</h3> Compared to previously published studies that did not provide PBMT, OM, pain and analgesia and tube feeding use reduction was seen. Keratinized surfaces should also be included in the prophylactic PBMT for OM aiming to reduce severe OM.

Phase Ib, international, dose-escalation study to evaluate the safety, pharmacokinetics (PK) and efficacy of ST-617 for the attenuation of oral mucositis (OM) in patients receiving chemoradiation (CRT) for head and neck (H&amp;N) cancer.

6075 Background: OM is a common, painful, and costly toxicity associated with cytotoxic regimens used to treat H&amp;N cancers, which may result in radiotherapy treatment interruptions to negatively impact tumor control. There are currently no approved interventions to successfully prevent or delay OM onset among patients being treated with radiation therapy, with or without concomitant chemotherapy (CRT). Oxidative stress is a critical event in OM’s pathogenesis. Through its effect on Nrf2, ST-617 has marked anti-oxidative activity/properties. Supportive Therapeutics is developing ST-617, a dithioethione, for the attenuation of OM onset, duration and severity. The objective of this trial was to assess the safety, tolerability, PK, PD and efficacy of ST-617 in patients at high risk of severe OM (SOM). Methods: A dose escalation trial in which ST-617 administered as an oral suspension, 1-2 hours before the administration of daily RT fractions was performed at 9 study sites in South Africa and Australia. Eighteen patients with diagnoses of oral or oropharyngeal CA were enrolled (up to 6 pts/dose). Patients received concomitant cisplatin either weekly or tri-weekly. ST-617 was administered 3 days prior to CRT, and then continuing daily until the end of treatment. Safety outcomes, using CTCAE criteria (v 4.03) were used. Dose escalation occurred in the absence of toxicity. OM occurrence and severity were assessed by trained and validated evaluators using WHO, NCI-CTC and RTOG criteria; scores were centrally assigned. The primary efficacy endpoints included the incidence and duration of SOM (WHO grades 3 or 4) vs historical controls. PD tracking measured total ROS/RNS, GSH/GSSG, regulation in plasma and buccal epithelial cells. Results: 17 pts completed the 50, 100 and 150mg/day with no safety issues. No early dose limiting toxicity (DLT) or serious Adverse Event linked to ST-617 were observed. AEs observed were mainly nausea which is usually associated with CRT as expected. The 100 mg/day dose has been well tolerated with no grade 4 OM. No CRT dose interruptions or delays due to OM has been observed. Total ROS/RNS levels in plasma and buccal samples show significant decrease with increased ST-617 dosing from 50 to 100 mg/day. Conclusions: ST-617 administration was safe at all doses tested. The course and severity of patients treated with ST-617 compared favorably with historical controls. Mechanistic correlation between ROS/RNS levels was seen. A randomized, controlled, double blind trial is planned with the recommended dose of 100mg/day. Clinical trial information: 20180138.

Early versus Late Fluconazole Prophylaxis in Autologous Hematopoietic Cell Transplantation

Candidemia is a major complication in hematopoietic cell transplantation (HCT), and antifungal prophylaxis with fluconazole decreases the incidence of this complication. We compared 2 strategies for fluconazole prophylaxis in patients with hematologic malignancy undergoing autologous HCT between 1997 and 2017. From 1997 to 2003, fluconazole prophylaxis (400 mg/d) was given to all HCTs, started with the conditioning regimen (early prophylaxis), and given until neutrophil engraftment or the need of non-prophylactic antifungal therapy. From 2004 on, fluconazole (400mg daily) was started only if (and when) the patient developed oral mucositis (late prophylaxis). Among 571 HCT, 270 received early prophylaxis, 112 received late prophylaxis, and 189 did not receive fluconazole because they did not develop oral mucositis. The incidence of candidemia was 1.8% in the early prophylaxis group, 0% in the late prophylaxis group, and 1.1% in the no prophylaxis group (P=.31). Among patients receiving fluconazole, the median duration of prophylaxis was 17 days (range, 6-36 days) in the early prophylaxis group and 6 days (range, 2-16 days) in the late prophylaxis group (P < .001). The initiation of fluconazole prophylaxis guided by the occurrence of oral mucositis (late prophylaxis) was as good as early fluconazole prophylaxis.

Effect of Honey-Lemon Spray Versus Benzydamine Hydrochloride Spray on Radiation-Induced Acute Oral Mucositis in Head and Neck Cancer Patients: A Pilot, Randomized, Double-Blind, Active-Controlled Clinical Trial.

Introduction: Oral mucositis (OM) is the most prevalent side effect in patients with head and neck cancer (HNC). It causes an obvious decrease in quality of life (QoL) in these patients, so different medications have been recommended for OM, however, without optimal response. This randomized trial aimed to assess the effects of a honey-lemon spray compared with benzydamine hydrochloride in prevention of radiation-induced OM in patients with HNC. Materials and Methods: Forty-six patients with HNC received external beam radiotherapy for 5 days per week. Patients were randomized to treatment with either benzydamine hydrochloride spray or honey-lemon spray for 5 weeks and continued for 1 week after the end of treatment. The oral cavity was examined weekly, with a score given to each site based on the degree of mucositis using a 4-point scale, and a mean mucositis score was calculated as the primary outcome. Occurrence of OM, pain, QoL, and adverse effects were defined as secondary outcomes. Patients, therapists, and outcome assessors were blinded to group allocation. Results: No significant group differences occurred in the mucositis score, pain, or QoL. Mucositis occurrence rates were higher in the benzydamine hydrochloride group compared with the honey-lemon group (hazard ratio = 2.1, 95% confidence interval: 1.1 to 4.2). Two patients in the honey-lemon group had mild nausea and burning throat; no adverse effects occurred in the benzydamine hydrochloride group. Conclusions: There were no significant group differences in mucositis severity between patients treated with honey-lemon spray and benzydamine hydrochloride. The potential preventive effects of honey-lemon spray need to be confirmed in further trials. The trial registration number is IRCT20161024030467N1.