Severity Of Oral Mucositis In Patients Research Articles

The predictive value of hematological inflammatory markers for severe oral mucositis in patients with nasopharyngeal carcinoma during intensity-modulated radiation therapy: A retrospective cohort study

BackgroundThis study aims to investigate the predictive value of the circulating blood cell count, including neutro-philto-lymphocyte ratio (NLR), platelet-to-lymphocyte (PLR), and thesystemic inflammation index (SII) for the development of severe oral mucositis (SOM) induced by radiation in patients undergoing radiotherapy for nasopharyngeal carcinoma (NPC). MethodsIn this retrospective study, 142 NPC patients were screened, and based on mucositis toxicity grade, they were categorized into two groups: SOM and nonSOM. Peripheral blood cell counts were conducted prior to Intensity-Modulated Radiation Therapy (IMRT). Associations between blood cell count, NLR, PLR, SII, and SOM occurrence were examined. ResultsRevealed elevated NLR and SII levels, along with reduced lymphocyte (LYM), eosinophil (EOS), and basophil (BAS) in patients with SOM. LYM, EOS, BAS, NLR, and SII were effective predictors of the severity of radiation-induced oral mucositis (RIOM) in NPC patients. ConclusionsThe occurrence of SOM was strongly linked to the hematological status at the start of Radiation Therapy (RT). Integrating BAS count and NLR into comprehensive risk prediction models could prove valuable for predicting SOM in NPC patients.

Oral glutamine: Is there a role in the amelioration of radiation-induced mucositis? A prospective case-control study at a tertiary care centre in North India.

The most frequently occurring painful and dose-limiting side effect of radiation therapy (RT) to the head and neck region is oral mucositis (OM). Several studies demonstrated that glutamine may reduce the severity and the duration of OM significantly during RT and chemo-radiotherapy in patients with head and neck cancer (HNC). Between January 2021 and August 2022, a prospective single institutional case-control study compared the efficacy and safety of oral glutamine on radiation-induced mucositis in patients with HNC. Of 60 biopsy-proven patients with HNC, 30 patients in the study arm received oral glutamine suspension (10 g in 500 mL of water) orally once daily, 2 hours before RT, receiving definitive or adjuvant RT and chemo-radiotherapy, while as 30 patients in the control arm received placebo with the same dose and schedule (n = 30 in the study arm and n = 30 in the control arm). A total of 27 (90%) in the glutamine arm and 28 (93.33%) patients in the control arm developed mucositis. Grade 3 mucositis (13.33%) and Grade 4 mucositis (6.66%), respectively, were significantly less ( P = .040 and P = .004) in the glutamine arm. The mean duration of grade 3 and grade 4 mucositis was significantly less in the glutamine arm (8.94 days in the study arm vs. 14.54 in the control arm; P = .0001). The mean time of onset of OM was significantly delayed in the glutamine arm in comparison to the control arm with P < .001. Glutamine delays the onset of OM and decreases the severity of OM in patients of HNC receiving RT with or without chemotherapy.

43021 Topical Epidermal Growth Factor Spray in Severe Oral Mucositis in Patients with Stevens- Johnson Syndrome and Toxic Epidermal Necrolysis

43021 Topical Epidermal Growth Factor Spray in Severe Oral Mucositis in Patients with Stevens- Johnson Syndrome and Toxic Epidermal Necrolysis

ORAL MUCOSITIS IN PATIENTS TREATED WITH METHOTREXATE SUBMITTED TO PROPHYLACTIC PHOTOBIOMODULATION IN AN ONCOLOGY SERVICE

Objective To evaluate the incidence of oral mucositis (OM) in patients treated with methotrexate (MTX), undergoing prophylactic photobiomodulation in the oral cavity in a pediatric oncology service. Study Design A cross-sectional study was performed with 14 patients who underwent 52 chemotherapy sessions in total. Photobiomodulation and clinical examination of the oral cavity were performed daily from the first day of chemotherapy until hospital discharge. When present, OM was classified according to the National Cancer Institute table. Results During hospitalizations for MTX, OM was present in 23% of cases, with Grade 1 responsible for 10% and Grade 2 for 13%. By contrast, OM after hospital discharge, was present in 11% of the cases, appearing only in Grade 2. Among the other signs and symptoms found were odynophagia, dysphagia, and pseudomembranous candidiasis. The average dose of MTX performed during hospitalization was 18,750mg. Each patient performed an average of 3 photobiomodulation sessions per hospitalization. The median time to develop mucositis after hospital discharge was 3 days. Conclusion Prophylactic photobiomodulation was associated with a low incidence of OM and no cases of severe OM in patients undergoing high-dose MTX. To evaluate the incidence of oral mucositis (OM) in patients treated with methotrexate (MTX), undergoing prophylactic photobiomodulation in the oral cavity in a pediatric oncology service. A cross-sectional study was performed with 14 patients who underwent 52 chemotherapy sessions in total. Photobiomodulation and clinical examination of the oral cavity were performed daily from the first day of chemotherapy until hospital discharge. When present, OM was classified according to the National Cancer Institute table. During hospitalizations for MTX, OM was present in 23% of cases, with Grade 1 responsible for 10% and Grade 2 for 13%. By contrast, OM after hospital discharge, was present in 11% of the cases, appearing only in Grade 2. Among the other signs and symptoms found were odynophagia, dysphagia, and pseudomembranous candidiasis. The average dose of MTX performed during hospitalization was 18,750mg. Each patient performed an average of 3 photobiomodulation sessions per hospitalization. The median time to develop mucositis after hospital discharge was 3 days. Prophylactic photobiomodulation was associated with a low incidence of OM and no cases of severe OM in patients undergoing high-dose MTX.

Study for the prevention of oral mucositis.

TPS12149 Background: Oral mucositis (OM) is a serious complication of cancer treatments characterized by erythema and ulcerations of the mouth. Consequences of OM include pain, diminished functionality, and infections leading to decreased quality of life and discontinuity in therapy. About 20-40% of patients receiving chemotherapy develop OM within 7 days of treatment initiation. Current clinical guidelines recommend prophylactic oral care, cryotherapy, KGF-1, palifermin, and photobiomodulation to prevent OM in specific patient groups. Benzydamine is approved for the prevention of OM in head and neck cancer patients receiving radiotherapy or radio-chemotherapy but has not been well studied for chemotherapy alone. The effectiveness of oral topical treatments is limited by dilution in the saliva and swallowing shortening the duration of their action. Bocaliner is a novel medical device that is hypothesized to enhance the effects of treatments by prolonging the oral retention of topical therapies within the oral cavity. Methods: The Study for the Prevention of Oral Mucositis (SPOM) is a randomized controlled Phase I/II trial that aims to evaluate the efficacy of two different tools (benzydamine mouthwash and Bocaliner) in reducing the incidence and severity of OM in patients undergoing systemic chemotherapy (NCT05338398). A total of 100 adult patients with hematologic malignancies undergoing chemotherapy in a centralized hematology center in Armenia will be randomized into two different treatment groups: saline mouthwash and benzydamine mouthwash (0.15%, 120mL) 3-5 times a day for a total of two weeks. Half of the patients within each group will also randomly receive Bocaliner, which will be placed inside of their mouth immediately after the application of the mouthwash for 20 minutes. Block randomization will be applied with 4 patients per block with 1:1 randomization based on gender, Bocaliner use, and mouthwash type. The primary endpoint is the difference in OM incidence measured by the WHO Oral Toxicity Scale. The secondary endpoints are differences in OM symptoms evaluated using a modified version of the PROMS questionnaire. Safety and tolerability of the medical device will be determined for the Phase I component of the study based on responses to standardized tryout (Day 0) and follow-up questionnaires (Day 14). Other outcomes include the duration and severity of OM. Statistical analysis will explore further clinically meaningful associations between patient data, received therapies, and outcomes. Forty-two patients have already completed the study, while the enrollment of other participants continues and is planned to be completed by the end of 2023. Clinical trial information: NCT05338398 .

BPI23-009: Oncologists’ Perceptions of a Novel Superoxide Dismutase Mimetic (Avasopasem Manganese) for Treating Severe Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer

"BPI23-009: Oncologists’ Perceptions of a Novel Superoxide Dismutase Mimetic (Avasopasem Manganese) for Treating Severe Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer" published on 31 Mar 2023 by National Comprehensive Cancer Network.

Predicting Nomogram for Severe Oral Mucositis in Patients with Nasopharyngeal Carcinoma during Intensity-Modulated Radiation Therapy: A Retrospective Cohort Study.

Oral mucositis is an acute adverse reaction with high incidence during radiotherapy. Severe oral mucositis can seriously affect patients' quality of life and compliance with radiotherapy. The aim of this study was to identify the risk factors for severe oral mucositis and to develop a nomogram for predicting severe oral mucositis in patients with nasopharyngeal carcinoma. One hundred and ninety patients with nasopharyngeal carcinoma were retrospectively screened in this study. Least absolute shrinkage and selection operator regression and multivariate logistic regression analyses were performed to identify the best predictors of severe oral mucositis. A nomogram was constructed based on the factors. Finally, the discriminative ability of the nomogram was evaluated. Four independent factors predicting severe oral mucositis were identified: age, N stage, the cycle of induction chemotherapy, and dose-volumetric parameter V40 (%) of oral cavity. The area under the receiver of operating characteristic curve of the nomogram was 0.759 (95% confidence interval: 0.691-0.827). A predictive nomogram for severe oral mucositis was established and validated in this study. The nomogram provides a reliable and practical model for clinically predicting the probability of severe oral mucositis in patients with nasopharyngeal carcinoma before intensity-modulated radiation therapy.

Oral Candida spp. Colonisation Is a Risk Factor for Severe Oral Mucositis in Patients Undergoing Radiotherapy for Head & Neck Cancer: Results from a Multidisciplinary Mono-Institutional Prospective Observational Study.

Simple SummaryThis study aims to find a correlation between Candida spp. oral colonisation prior to radiotherapy and (i) the development of severe oral mucositis (OM) (grade 3/4) and (ii) early development of severe OM (EOM). Candida spp. in the oral cavity appears to be a predictive factor of EOM. Preventive treatment could aid in reducing incidence of EOM. Further clinical trials are required to confirm our findings.Background: This study aims to find a correlation between Candida spp. oral colonisation prior to radiotherapy (RT) and (i) the development of severe oral mucositis (OM) (grade 3/4) and (ii) early development of severe OM (EOM). Methods: The protocol was registered on ClinicalTrials.gov (ID: NCT04009161) and approved by the ethical committee of the ‘Fondazione Policlinico Universitario Gemelli IRCCS’ (22858/18). An oral swab was obtained before RT to assess the presence of Candida spp. Severe OM occurring before a dose of 40 Gy was defined as EOM. Results: No patient developed G4 OM, and only 36/152 patients (23.7%) developed G3 OM. Tumour site and lymphocytopenia were risk factors for severe OM (OR for tumour site: 1.29, 95% CI: 1–1.67, p = 0.05; OR for lymphocytopenia: 8.2, 95% CI: 1.2–55.8, p = 0.03). We found a correlation between Candida spp. and EOM (OR: 5.13; 95% CI: 1.23–21.4 p = 0.04). Patients with oral colonisation of Candida spp. developed severe OM at a mean dose of 38.3 Gy (range: 28–58; SD: 7.6), while negative patients did so at a mean dose of 45.6 Gy (range: 30–66; SD: 11.1). Conclusions: Candida spp. in the oral cavity appears to be a predictive factor of EOM.

The incidence of severe oral mucositis in patients undergoing different conditioning regimens in haematopoietic stem cell transplantation

PurposeOral mucositis is a common complication during haematopoietic stem cell transplantation (HSCT). This study aimed to assess the incidence of severe mucositis in patients undergoing different HSCT regimens.MethodsThis single-centre retrospective study reviewed daily oral assessment for 467 consecutive patients who underwent different transplant regimens for matched unrelated or related allogeneic HSCT with post-transplant methotrexate, haploidentical or mismatched HSCT with post-transplant cyclophosphamide (PTCy), or autologous HSCT. Oral care and cryotherapy with melphalan were used. Patient demographic data, oral mucositis WHO grade, use of total parenteral nutrition (TPN) and patient-controlled analgesia (PCA) were collected.ResultsGrade 3–4 oral mucositis was common in myeloablative total body irradiation (TBI)-based regimens cyclophosphamide/ TBI (CyTBI) (71%) and fludarabine/ TBI (FluTBI) with PTCy (46%), as well as reduced-intensity fludarabine/melphalan (FluMel) (43%) and carmustine/etoposide/cytarabine/melphalan (BEAM) autologous HSCT (41%). In contrast, grade 3–4 oral mucositis was less common in reduced-intensity haploidentical regimen melphalan/fludarabine/TBI with PTCy (19%), all non-myeloablative regimens (0–9%) and high-dose melphalan autologous HSCT (26%). TPN and PCA use were correlated to oral mucositis severity.ConclusionsSevere oral mucositis was associated with myeloablative TBI, methotrexate and melphalan in combination with methotrexate and in BEAM. Use of PTCy was preferable over methotrexate to prevent oral mucositis.

Efficacy and safety of a colostrum- and Aloe vera-based oral care protocol to prevent and treat severe oral mucositis in patients undergoing hematopoietic stem cell transplantation: a single-arm phase II study

Oral mucositis is one of the worst effects of the conditioning regimens given to patients undergoing hematopoietic stem cell transplantation. It is characterized by dry mouth, erythema, mucosal soreness, ulcers, and pain, and it may impact patient outcomes. Bovine colostrum and Aloe vera contain a wide variety of biologically active compounds that promote mucosal healing. A non-randomized phase II study was designed to assess the safety and efficacy of a combined bovine colostrum and Aloe vera oral care protocol to prevent and to treat severe oral mucositis in transplant patients. Two commercially available products were given to patients in addition to the standard protocol: Remargin Colostrum OS® mouthwash and Remargin Colostrum Gastro-Gel® taken orally. Forty-six (78.0%) patients experienced oral mucositis, 40 (67.8%) developed mild–moderate forms, and 6 (10.2%) severe ones. Comparing the study group’s outcomes with those of a homogeneous historical control group, severe oral mucositis decreased significantly (10.2% vs. 28.4%; P < 0.01), as did its duration (0.5 ± 1.9 vs. 1.5 ± 3.0 days; P < 0.01). Febrile neutropenia episodes (69.5% vs. 95.1%; P < 0.01) and duration (4.0 ± 4.7 vs. 6.2 ± 4.5 days; P < 0.01) also decreased. These findings show that the experimental protocol seems effective in preventing severe forms of oral mucositis. However, a randomized controlled trial is necessary to confirm this.

A phase Ⅱ prospective trial of photobiomodulation therapy in limiting oral mucositis in the treatment of locally advanced head and neck cancer patients.

This study aimed to compare the historical incidence rate of severe oral mucositis (OM) in head and neck cancer patients undergoing definitive concurrent chemoradiation therapy (CRT) versus a prospective cohort of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with prophylactic photobiomodulation therapy (PBMT). This US-based, institutional, single-arm, phase Ⅱ prospective clinical trial was initiated in 50 patients (age ≥ 18 years, Karnofsky Performance Scale Index > 60, with locally advanced HNSCC (excluding oral cavity) receiving definitive or adjuvant radiation therapy (RT) with concurrent platinum-based chemotherapy (CT). PBMT was delivered three times per week throughout RT utilizing both an intraoral as well extraoral delivery system. Primary outcome measure was incidence of severe OM utilizing both the National Cancer Institute Common Toxicity Criteria, version 4.0 (NCI-CTCAE) Grade ≥3 and the World Health Organization Mucositis Grading Scale (WHO) Grade ≥3 versus historical controls; secondary outcome measures included time to onset of severe OM following therapy initiation. At baseline, all patients included in final analysis (N = 47) had OM Grade 0. Average RT and CT dose was (66.3 ± 5.1) Gy and (486.1 ± 106.8) mg/m2, respectively. Severe OM was observed in 11 of 47 patients (23%, confidence interval: 12, 38). OM toxicity grade trended upward during treatment, reaching a maximum at 7 weeks (WHO: 1.8 vs. NCI-CTCAE: 1.7). Subsequently, OM grade returned to baseline 3 months following completion of RT.The mean time toonset of severe OM was (35 ± 12) days. The mean time to resolution of severe OM was (37 ± 37) days. Compared to historical outcomes, PBMT aides in decreasing severe OM in patients with locally advanced HNSCC. PBMT represents a minimally invasive, prophylactic intervention to decrease OM as a major treatment-related side effect.

Phase 2 pilot trial of RRx-001 as an anti-mucositis agent in patients with head and neck cancer treated with chemoradiation (PREVLAR).

6078 Background: Severe oral mucositis (SOM) is a dose limiting toxicity during radiotherapy and cisplatin for head and neck cancers. The aim of this 4-arm randomized controlled pilot trial was to evaluate the efficacy of different schedules of a novel radioprotectant, RRx-001 versus standard-of-care (SOC), to reduce duration, time to onset and incidence of SOM in patients received cisplatin-based chemoradiotherapy (CRT) for oral cavity or oropharyngeal cancer (OCC). Methods: Patients with locally advanced OCC treated with definitive or postoperative CRT were randomized to receive RRx-001 by 15-minute intravenous infusion in one of three different schedules versus none. The days and severity of mucositis were prospectively evaluated. Oral mucositis was assessed weekly during and after CRT as well as 28 days after completion. The pre-specified efficacy endpoints were duration of grade 3-4 SOM, resolution of SOM, time to onset of SOM and incidence of SOM. Results: A total of 53 patients were enrolled between June 2018 and July 2019 across 11 institutions. Forty-five (out of 53) patients received study drug and were efficacy evaluable. RRx-001 were well tolerated with no associated serious adverse events. All RRx-001 arms numerically outperformed SOC on the pre-specified efficacy measures, and the greatest effect estimate was observed on Arm 1 (RRx-001 pretreatment only + CRT). The following endpoints favored treatment with RRx-001. Median SOM duration by treatment was 22 and 40 days for Arm 1 and SOC respectively. Time to onset of SOM was by 38 days (Arm 1) vs. 26 days (SOC). On Arm 1, 83% of patients had SOM resolution vs 60% on SOC). Gastrostomy requirement was reduced by 45%. No patients on Arm 1 developed grade 4 mucositis vs 30% developed grade 4 mucositis on the SOC arm. Furthermore, the incidence of oropharyngeal dysphagia, which can substantially impair nutrition, was reduced by treatment with RRx-001, occurring at 50% vs 70% for Arm 1 vs SOC respectively. Treatment with RRx-001 resulted in highly significant decrease in the duration of SOM through 60 Gy with a median SOM of 1 day vs 17 days for Arm 1 vs SOC respectively (Wilcoxon rank-sum test p &lt; 0.001). Median cumulative cisplatin dose was significantly greater for RRx-001 Arm 1 than SOC (557.4 mg vs. 438 mg, Wilcoxon p = 0.025). Conclusions: Compared with SOC, SOM among RRx-001-treated patients given 3 different treatment schedules was less severe, of shorter duration, demonstrated delayed time to onset and resolved earlier. Overall, the incidence, duration and severity of SOM and dysphagia was reduced. The safety profile of RRx-001 was similar to SOC. These results will inform the design of a Phase 3 pivotal study of RRx-001 in the prevention of SOM in at-risk cancer patients. Clinical trial information: NCT03515538.

Low-Level Laser Therapy: A Literature Review of the Prevention and Reduction of Oral Mucositis in Patients Undergoing Stem Cell Transplantation.

Oral mucositis (OM) is a highly debilitating complication of high-dose chemotherapy and total body irradiation used in conditioning regimens for hematopoietic stem cell transplantation (HSCT). Research has studied low-level laser therapy (LLLT) as an alternative treatment for OM because of its anti-inflammatory activity, biomodulation, and analgesic effects. This study reviews evidence on the effectiveness of LLLT using diode lasers on the prevention and reduction in severity of OM in patients with cancer undergoing HSCT. A literature search was performed in PubMed®, CINAHL®, Scopus®, and MEDLINE® databases. Six randomized controlled trials and one cohort study met the inclusion criteria. The data demonstrate promising outcomes for reducing the incidence and severity of OM using LLLT. Larger, tightly controlled clinical trials are needed in the future.

Preventive effects of betamethasone valerate ointment for radiation-induced severe oral mucositis in patients with oral or oropharyngeal cancer: protocol for a multicentre, phase II, randomised controlled trial (Bet-ROM study)

IntroductionThis is a randomised, multi-centre, open-label, phase II study to evaluate the efficacy of betamethasone valerate ointment on radiation-induced oral mucositis in patients with head and neck cancer undergoing concomitant...

Oral Mucositis Association with Periodontal Status: A Retrospective Analysis of 496 Patients Undergoing Hematopoietic Stem Cell Transplantation

Background: Hematopoietic stem cell transplantation (HSCT) can induce serious oral complications, including oral mucositis (OM). The presence of periodontal inflammation before HSCT is believed to be associated with OM. The aim of our study was to determine the prevalence and severity of OM in patients undergoing HSCT and its relation to periodontal status. Patients and methods: This is a retrospective study of patients who underwent HSCT and a detailed dental examination between 2007 and 2015. The dental and periodontal status of all patients was evaluated by clinical and radiographic examination prior to HSCT. Oral health was assessed with the gingival index, the the community periodontal index, presence of plaque-related gingivitis, and marginal periodontitis. During the HSCT period, patients were examined daily for the presence of OM, which was graded according to World Health Organization (WHO) classification if present. The patients were assigned to the groups according to type of transplantation: autologous HSCT, myeloablative allogeneic HSCT, and non-myeloablative allogeneic HSCT. Results: A total of 496 patients were included in the study. OM was present in 314 of 496 patients (63.3%): 184/251 (73.3%) in the autologous group, 100/151 (66.2%) in the myeloablative allogeneic group, and 30/94 (31.9%) in the nonmyeloablative allogeneic group. Significantly more patients suffered from OM in the autologous and myeloablative groups versus the nonmyeloablative conditioning group (p < 0.001). The presence of periodontal inflammation did not significantly differ among the groups. There was only a borderline trend for the higher prevalence of OM in the non-myeloablative allogeneic nonmyeloablative group when periodontal inflammation was present (0.073939). Conclusions: Oral mucositis prevalence and severity after stem cell transplantation is not widely affected by the oral hygiene and periodontal disease presence before HSCT. We confirmed the wide-known connection of the conditioning regimen intensity to the prevalence of OM.

1729TiP Rationale and design of the phase IIb/III VOICE trial of clonidine MBT for the prevention of severe oral mucositis in patients with OPC receiving chemoradiotherapy

Clonidine MBT (Validive®) is an orally delivered prophylactic treatment for chemoradiotherapy (CRT)-induced severe oral mucositis (SOM) in patients with oropharyngeal cancer (OPC). Clonidine MBT is a novel, extended release formulation designed to adhere to the gums and dissolve slowly, releasing clonidine in the oral cavity over many hours. OPC occurs in the macrophages-rich regions at the back of the tongue and throat. CRT is used 1st line in OPC but tumor radiation also irradiates neighboring macrophages, inducing local expression of pro-inflammatory cytokines.

Risk factors for severe radiation-induced oral mucositis in patients with oral cancer

Background/purposeRadiotherapy for head and neck cancer often causes severe oral mucositis. The purpose of this retrospective study was to further examine the risk factors for developing severe oral mucositis in patients with oral cancer undergoing radiotherapy as a compliment to a previous study performed by our group. Materials and methodsA total of 181 patients with oral cancer undergoing radiotherapy were enrolled in the study. The association between a number of potential risk factors and grade 3 oral mucositis were analyzed using the cox proportional hazard model and a logistic regression analysis. ResultsGrade 3 oral mucositis occurred in 56 patients. The cox proportional hazard model analysis revealed that those with lower hemoglobin levels, concurrent cisplatin and cetuximab administration, and a larger number of teeth showed a significantly higher incidence of severe oral mucositis. Logistic regression analysis revealed that patients who had lower hemoglobin levels, received concurrent cisplatin or cetuximab treatment, and were not administered pilocarpine showed a significantly higher incidence of severe oral mucositis. The presence of teeth may stimulate the oral mucosa and become a risk factor for mucositis, and the administration of pilocarpine might reduce the risk. ConclusionThis study describes the risk factors of severe radiation-induced oral mucositis in oral cancer patients and shows the possibility of risk reduction by pilocarpine. This information could help patients avoid painful mucositis.

Impact of muscle volume loss on acute oral mucositis in patients undergoing concurrent chemoradiotherapy after oral cancer resection

This study evaluated the association between skeletal muscle mass depletion and severe oral mucositis in patients undergoing concurrent chemoradiotherapy after oral cancer resection. Skeletal muscle mass was evaluated in 60 patients using the skeletal muscle index, which was based on skeletal muscle cross-sectional area (on computed tomography) at the level of the third lumbar vertebra. In accordance with the grading criteria of the Radiation Therapy Oncology Group, patients with a grade ≥3 were defined as having severe oral mucositis. Multivariate logistic regression analysis was used to evaluate independent risk factors for severe oral mucositis. Eleven patients (18.3%) were diagnosed with low skeletal muscle mass. Severe oral mucositis occurred in 17 (28.3%) patients, and the mean skeletal muscle index was 42.8 cm2/m2. A low skeletal muscle mass (hazard ratio 18.1; P=0.001) and a chemotherapy regimen consisting of 5-fluorouracil and cisplatin (versus cisplatin only) (hazard ratio 5.5; P=0.015) were independent risk factors for severe oral mucositis. Future prospective studies are warranted to identify effective pre- and perioperative exercises and nutrition programmes to increase low skeletal muscle mass and reduce the incidence of severe oral mucositis in patients undergoing concurrent chemoradiotherapy after oral cancer resection.

Avasopasem Manganese Protects Against Radiation Induced Oral Mucositis and Enhances the Response of Squamous Cell Carcinoma of the Head and Neck to Ionizing Radiation and Radioimmune Therapy

Locoregional recurrence (LRR) is the major cause of morbidity and mortality in patients with squamous cell carcinoma of the head and neck (HNSCC). For those patients that experience surgically unresectable LRR, median overall survival (OS) is less than one year. Approaches utilizing stereotactic ablative radiotherapy (SabR) and immuno-oncology agents such as Nivolumab (α-PD-1 inhibitor) in the salvage setting have become alternatives to conventional chemoradiation therapy. Despite improvements in OS, rates of acute oral mucositis (OM) and late toxicities (skin fibrosis) remain concerns with SabR in the context of re-irradiation. Here we present pre-clinical evidence that avasopasem manganese (GC4419), a highly selective superoxide dismutase mimetic that has received FDA Breakthrough Therapy Designation and is currently in a Phase III trial for reducing severe OM in patients undergoing chemoradiotherapy for locally advanced HNSCC (NCT03689712) also enhances the anti-tumor radiation response of HNSCC tumors. We demonstrate in pre-clinical animal models that avasopasem protects the normal mucosa of the mouse tongue from primary irradiation toxicity. We will also report the results of ongoing studies examining whether avasopasem protects murine mucosa from reirradiation as with SabR as a salvage therapy. Utilizing clonogenic survival assays, we demonstrate that avasopasem at physiologically achievable concentrations exhibits single agent anti-cancer activity and also enhances the response of HNSCC lines to irradiation. In tumor growth delay (TGD) experiments utilizing the syngeneic HNSCC tumor model, AT-84, when avasopasem is delivered in combination with biologically equivalent fractionation schedules of 17 Gy x 1 fxn, 10.24 Gy x 2 fxn, or 5 Gy x 5 fxn, an enhancement of the radiation response is achieved. This potentiation of the anti-tumor response with GC4419 is more pronounced at fraction doses exceeding the threshold considered for intensity modulated radiation therapy. In addition, when avasopasem is combined with radiation and an α-PD-1 inhibitor, a further enhancement of the radiation response is observed, indicating that it compliments radiotherapy combined with immunotherapy. The pre-clinical data strongly suggest that avasopasem should be combined with radio-immune therapy to not only enhance local tumor control, but also to provide normal tissue protection with SabR which may allow dose escalation and further improve treatment outcomes. Whether radiation combined with avasopasem and checkpoint inhibitor has an effect on metastasis is under examination.

Oral microbiome and onset of oral mucositis in patients with squamous cell carcinoma of the head and neck.

Oral mucositis (OM) is a debilitating sequela for patients treated for squamous cell carcinoma of the head and neck (HNSCC). This study investigated whether oral microbial features before treatment or during treatment are associated with the time to onset of severe OM in patients with HNSCC. This was a cohort study of newly diagnosed patients with locoregional HNSCC who received chemotherapy with or without radiotherapy from April 2016 to September 2017. OM was based on the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0. The oral microbiome was characterized on the basis of the 16S ribosomal RNA V4 region with the Illumina platform. A mixture cure model was used to generate hazard ratios for the onset of severe OM. Eighty-six percent of the patients developed OM (n=57 [33 nonsevere cases and 24 severe cases]) with a median time to onset of OM of 21 days. With adjustments for age, sex, and smoking status, genera abundance was associated with the hazard for the onset of severe OM as follows: 1) at the baseline (n=66), Cardiobacterium (P=.03) and Granulicatella (P=.04); 2) immediately before the development of OM (n=57), Prevotella (P=.03), Fusobacterium (P=.03), and Streptococcus (P=.01); and 3) immediately before the development of severe OM (n=24), Megasphaera (P=.0001) and Cardiobacterium (P=.03). There were no differences in α-diversity between the baseline samples and Human Microbiome Project data. Changes in the abundance of genera over the course of treatment were associated with the onset of severe OM. The mechanism and therapeutic implications of these findings need to be investigated in future studies.