Publications

Abstract Purpose: Cryotherapy is an effective mucositis intervention for selected chemotherapy regimens, but reliance on ice chips has limited its applicability. Our objective was to assess the efficacy and tolerability of a reusable, self-contained, device as an alternative delivery mode. Methods: A total of 164 patients randomized 2:1 received the device (Chemo Mouthpiece; CMP]) + best supportive…

Abstract Background: Oral mucositis (OM) remains a significant toxicity of concomitant chemoradiation (CRT) for head and neck cancer (HNC). This trial assessed the safety and efficacy of EC-18, an innate immune response mitigator, in attenuating severe OM (SOM) in HNC patients being treated with CRT. Methods: This was a two-stage, Phase 2, randomized, double-blind, placebo-controlled, multi-institutional trial.…

Abstract An association between periodontitis and oral cancer risk and progression has been suggested. It seems most likely that periodontitis plays an indirect role in oral cancer risk and progression in which its contribution to a chronic inflammatory state characterized by the persistent release of pro-inflammatory cytokines contributes to oxidative stress and DNA damage, potentially…

Abstract Purpose: Oral mucositis (OM) is a significant complication of cytotoxic cancer therapy and has no effective therapies. Unfortunately, the termination rate of clinical trials (CTs) testing potential OM interventions remains high. Here, we compared the characteristics of failed trials and matched completed trials to identify common features, which might inform better study design. Methods: CTs for…

Abstract Background: Barrier films or dressings were reported to be effective in preventing radiation dermatitis (RD) in breast cancer patients, but their comparative efficacy is unknown. Methods: A systematic literature search was performed on Embase, MEDLINE and Cochrane CENTRAL Registry of Clinical Trials from inception to October 20, 2023. Randomised controlled trials (RCTs) comparing barrier films or…

Abstract Oral mucositis (OM) remains a significant toxicity among patients being treated with radiotherapy (RT) alone or with concomitant chemotherapy (CRT) for cancers of the head and neck (HNC). Given its clinical significance as an unmet need and its potential commercial viability, the pharmaceutical industry has been actively pursuing an effective intervention. Despite this interest…

Abstract Objectives: Immune-related adverse events (irAEs) are common. Oral irAEs tend to cluster in patients who experience concurrent toxicities. We aimed to characterize the frequency and trajectory of non-oral irAEs in patients who developed oral irAEs, assess their relationship with non-oral irAEs, and compare those characteristics with patients without oral irAEs. Methods: A retrospective chart review was…

Abstract It has been 24 years since rapamycin (sirolimus) was approved to mitigate solid organ transplant rejection and 16 years since mTOR (mammalian/mechanistic target of rapamycin) inhibitors reached patients as a cancer therapy. While the clinical benefits of mTOR inhibitors (mTORi) are robust, so too are their toxicities. Among the most common issues is the…

Abstract Photobiomodulation therapy (PBMT) is recommended for prevention and treatment of oral mucositis, a painful condition that occurs in cancer patients. Intraoral PBMT is limited to treating distal oral mucosa and oropharynx. Extraoral PBMT may provide a more efficient intervention. The goal of this study was to develop a clinically viable protocol for extraoral PBMT.…

Abstract The causes of variation in toxicity to the same treatment regimen among seemingly similar patients remain largely unknown. There was tremendous optimism that the patient’s germline genome would be strongly predictive of treatment-related toxicity and could be used to personalize treatment and improve therapeutic outcomes. However, there has been limited success in discovering robust…

Abstract Introduction: Oral mucositis (OM) remains a significant, highly symptomatic, disruptive side effect of radiation and concomitant chemoradiation therapy used for the treatment of squamous cell cancers of the head and neck. Despite its clinical and economic burden, implementation of an effective intervention has been elusive. Areas covered: Increased understanding of the complexity of the biological basis…

Abstract Purpose: No Food and Drug Administration-approved intervention exists for oral mucositis (OM) from chemoradiotherapy (CRT) used to treat head and neck cancers. RRx-001 is a hypoxia-activated, cysteine-directed molecule that affects key pathways involved in OM pathogenesis. This phase 2a, multi-institutional trial was designed to assess the safety and feasibility of 3 schedules of a fixed…

Abstract Introduction: Oral mucositis (OM) is among the most common, damaging side effects of head and neck radiation therapy and may interfere with patients’ ability to comply with optimal treatment. Areas covered: The increasing unmet clinical need, recent clinical trial successes, and the commercial potential have catalyzed interest in the development of effective intervention for OM. A…

Abstract Purpose: Oral ulcerative mucositis (UM) and gastrointestinal mucositis (GIM) have been associated with increased likelihood of systemic infection (bacteremia and sepsis) in patients being treated for hematological malignancies. To better define and contrast differences between UM and GIM, we utilized the United States 2017 National Inpatient Sample and analyzed patients hospitalized for the treatment of…

Abstract Aim: To study the association between periodontitis, tooth loss, and rheumatoid arthritis (RA) by using a large national dataset. Materials and methods: An observational cross-sectional study was performed using the National Health and Nutrition Examination Survey cycles (2009-2014). RA status was detected using a questionnaire. Periodontal status was assigned on the basis of the clinical attachment…

Abstract Oral complications of cancer therapy are common, markedly symptomatic, negatively impact patients’ quality of life, and add significantly to the cost of care. Patients’ risk of treatment-related toxicities is not uniform; most patients suffer at least one side effect, while others tolerate treatment without any. Understanding those factors which impact risk provides opportunities to…

Abstract Immune checkpoint inhibitors (ICIs) are a revolutionary class of antineoplastic therapy that restore anti-tumor immunity. Consequences of this enhanced immune response include a multitude of immune related adverse events (irAEs) that can affect any body system, including the mouth. Orofacial irAEs reproduce features of numerous immune-mediated conditions, including oral lichen planus, mucous membrane pemphigoid,…

Abstract Disclaimer: This article is based on recommendations from the 12th WALT Congress, Nice, October 3-6, 2018, and a follow-up review of the existing data and the clinical observations of an international multidisciplinary panel of clinicians and researchers with expertise in the area of supportive care in cancer and/or PBM clinical application and dosimetry. This article is…

Abstract Purpose: Avasopasem manganese (GC4419), an investigational selective dismutase mimetic radioprotector, reduced duration, incidence, and severity of severe oral mucositis (World Health Organization grade 3-4) in a phase 2b, randomized, double-blind trial of patients receiving concurrent cisplatin (cis) and radiation therapy (RT) for head and neck cancer. We report the secondary endpoints of final 1- and…

Abstract Objective: To compare the reported efficacy and costs of available interventions used for the management of oral lichen planus (OLP). Materials and methods: A systematic literature search was performed from database inception until March 2021 in MEDLINE via PubMed and the Cochrane library following PRISMA guidelines. Only randomized controlled trials (RCT) comparing an active intervention with…

Abstract Cancer therapeutics are dynamically evolving, and include traditional chemotherapy and hormone therapy, as well as more recently developed treatment modalities, such as tyrosine kinase inhibitors, monoclonal antibodies and the revolutionary approach based on immune checkpoint inhibition. These regimens are unfortunately not free of adverse events, and patients with cancer are a susceptible population experiencing…

Abstract Oral mucositis (OM) is a common, highly symptomatic complication of cancer therapy that affects patients’ function, quality of life, and ability to tolerate treatment. In certain patients with cancer, OM is associated with increased mortality. Research on the management of OM is ongoing. Oral mucosal toxicities are also reported in targeted and immune checkpoint…

Abstract Background: The ability to consistently and accurately assess oral mucositis (OM) is critical to descriptions of its incidence and severity and in evaluating the effectiveness of potential interventions. The lack of a single grading scale compounds outcome interpretation. Consequently, we assessed the concordance of three of the most commonly used OM grading criteria (World Health…

Abstract Oral mucositis (OM) remains a significant unmet need for patients being treated with standard concomitant chemoradiation (CRT) regimens for head and neck cancers (HNC). OM’s pathogenesis is complex and includes both direct and indirect damage pathways. In this paper, the field is reviewed with emphasis on the initiating and sustaining role of oxidative stress…

Abstract Oral mucositis is a painful complication of hematopoietic stem cell transplantation for which photobiomodulation therapy (PBMT) is a safe and effective intervention. Extraoral delivery of PBMT has clinical advantages over intraoral delivery but requires additional dosimetric considerations due to the external tissue layers through which the light must propagate before reaching the oral mucosa.…

Abstract Objective: In this research, we assessed the usefulness of network meta-analysis (NMA), in creating a hierarchy to define the most effective oral care intervention for the prevention and management of ventilation-associated pneumonia (VAP). Materials and methods: We applied NMA to a previously published robust pairwise meta-analysis. Statistical analyses were based on comparing rates of total VAP…

Abstract Toxicities associated with radiation therapy are common, symptomatically devastating, and costly. The best chance to effectively mitigate radiation-associated normal tissue side effects are interventions aimed at disrupting the biological cascade, which is the basis for toxicity development, while simultaneously not reducing the beneficial impact of radiation on tumor. Oxidative stress is a key initiator…

Abstract Introduction: Oral mucositis (OM) is a common toxicity of cytotoxic cancer regimens and remains one of the most painful, injurious, and treatment-disrupting side effects of radiation and ablative therapy. Despite its frequency and impact, approved definitive preventive or therapeutic options remain limited. Areas covered: This review focuses on mechanistically active small molecules and biologicals…

Abstract Low level laser therapy (LLLT) has been noted to be effective in mitigating the development of oral mucositis among patients being treated with chemoradiation for cancers of the head and neck. To explain the biological basis for this observation we performed a comprehensive literature search. Our investigation identified a substantial number of LLLT-activated pathways…

Abstract Context: Despite numerous proposed mechanisms, no definitive pathophysiology underlying radiotherapy-induced fatigue (RIF) has been established. However, the dysregulation of a set of 35 genes was recently validated to predict development of fatigue in prostate cancer patients receiving radiotherapy. Objectives: To hypothesize novel pathways, and provide genetic targets for currently proposed pathways implicated in RIF development through…

Abstract The association between chronic inflammatory disorders and oral carcinogenesis has been both a source of interest and contention. Based upon its central importance in oral carcinogenesis, the finding that the PI3k/Akt/mTOR pathway is activated in oral lichen planus, chronic graft-versus-host disease, and chronic oral candidiasis suggests that it may provide a link between benign…

ABSTRACT Introduction: Oral mucositis is a frequent and devastating toxicity secondary to cancer treatment, which may affect 20–40% of patients receiving conventional chemotherapy and 60–85% of patients undergoing hematopoietic stem cell transplantation. The pathobiology of mucositis includes a complex cascade of biologic events in which pro-inflammatory cytokines, ROS, second messengers, and the oral microbiome contribute…

Mucositis is a common complication of chemotherapy, radiotherapy and targeted agents. It often affects compliance to anticancer therapies as it frequently causes schedule delays, interruptions or discontinuations of treatment. Moreover, the economic impact related to the management of mucositis is topical and several estimations of additional hospital costs due to this clinical condition have been…

Alessandro Villa, Stephen Sonis,Toxicities associated with head and neck cancer treatment and oncology-related clinical trials,Current Problems in Cancer,Volume 40, Issues 5–6,2016,Pages 244-257,ISSN 0147-0272,https://doi.org/10.1016/j.currproblcancer.2016.06.001.(http://www.sciencedirect.com/science/article/pii/S0147027216300368)

Abstract Purpose of review: The goals of this review are to describe the complexity of factors influencing the risk of cancer regimen-related mucosal injury (CRRMI), to evaluate the contribution of the innate immune response to CRRMI risk, to compare the concordance of genome analytics in describing mechanism and risk, and to determine if common biological pathways…

Abstract Purpose: To assess the safety of the superoxide dismutase mimetic GC4419 in combination with radiation and concurrent cisplatin for patients with oral cavity or oropharyngeal cancer (OCC) and to assess the potential of GC4419 to reduce severe oral mucositis (OM). Patients and methods: Patients with locally advanced OCC treated with definitive or postoperative intensity modulated radiation…

Abstract Oral mucositis (OM) is among the most common, painful, and debilitating toxicities of cancer regimen–related treatment, resulting in the formation of ulcers, which are susceptible to increased colonization of microorganisms. Novel discoveries in OM have focused on understanding the host-microbial interactions, because current pathways have shown that major virulence factors from microorganisms have the…

Abstract Purpose: Oral mucositis (OM) is a frequent and painful sequela of concomitant chemoradiation (CRT) used for the treatment of head and neck cancer (HNC) for which there is no effective intervention. This randomized, placebo-controlled study evaluated the efficacy of a novel, mucoadhesive topical tablet formulation of clonidine in mitigating CRT-induced OM in patients with HNC.…

Abstract Introduction: Oral mucositis is a significant unmet clinical need for many cancer patients. The biological complexity of mucositis’ pathogenesis provides a number of mechanistic targets suitable as pharmacologic targets. The diversity of targets has stimulated drug development in search of an effective intervention. In this paper, we review a range of agents that are currently…