Predictors for Emergency Admission Among Homeless Metastatic Cancer Patients and Association of Social Determinants of Health with Negative Health Outcomes.

Background/objectives: Social determinants of health (SDOHs) are especially impactful with respect to emergency reliance among patients with cancer.

Methods: To better predict the extent to which SDOHs affect emergency admissions in homeless patients with metastatic disease, we employed machine learning models, Lasso, ridge, random forest (RF), and elastic net (EN) regression. We also examined prostate cancer (PC), breast cancer (BC), lung (LC) cancer, and cancers of the lip, oral cavity, and pharynx (CLOP) for association between key SDOH variables-homelessness and living alone-and clinical outcomes.

Genetic Variants Influence the Severity of Oral Mucositis in Pediatric Osteosarcoma Patients.

Background: The variability in patients' risk of oral mucositis (OM) has been, in part, attributed to differences in host genomics. The aim better define the role of genomics as an OM risk by investigating the association between genetic variants and the presence and severity of OM in pediatric patients with osteosarcoma (OS) undergoing chemotherapy (CT).

Methods: A longitudinal observational retrospective study was conducted.

Financial Burden of Dental Care Among Patients With Head and Neck Cancer.

Importance: Patients undergoing treatment for head and neck cancer (HNC) experience oral complications requiring substantial dental treatment. This treatment is commonly not reimbursed by medical insurers, presenting a potential financial burden for patients.

Objective: To characterize the dental care needs and associated cost burden for patients with HNC.

A New Hypothesis Describing the Pathogenesis of Oral Mucosal Injury Associated with the Mammalian Target of Rapamycin (mTOR) Inhibitors.

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 development of ulcers of the oral mucosa (mTOR-inhibitor associated stomatitis; mIAS).

Monte Carlo based dosimetry of extraoral photobiomodulation for prevention of oral mucositis.

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.

Comparisons of Non-Oral Immune-Related Adverse Events Among Patients With Cancer With Different Oral Toxicity Profiles.

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.

Avasopasem for the treatment of radiotherapy-induced severe oral mucositis.

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 for its pathogenesis has yielded potential druggable targets such as the mitigation of superoxide formation and oxidative stress.

Radiotherapy-induced severe oral mucositis: pharmacotherapies in recent and current clinical trials.

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 range of small molecules are under development - some still in the preclinical stage, but others close to NDA submission.

Application of big data analyses to compare the impact of oral and gastrointestinal mucositis on risks and outcomes of febrile neutropenia and septicemia among patients hospitalized for the treatment of leukemia or multiple myeloma.

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 multiple myeloma (MM) or leukemia.

Methods: We utilized generalized linear models to assess the association between adverse events-UM and GIM-among hospitalized MM or leukemia patients and the outcome of febrile neutropenia (FN), septicemia, burden of illness, and mortality.

Precision medicine for risk prediction of oral complications of cancer therapy-The example of oral mucositis in patients receiving radiation therapy for cancers of the head and neck.

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 customize cancer treatment plans to optimize tumor kill and minimize regimen-related toxicities.

Two-Year Tumor Outcomes of a Phase 2B, Randomized, Double-Blind Trial of Avasopasem Manganese (GC4419) Versus Placebo to Reduce Severe Oral Mucositis Owing to Concurrent Radiation Therapy and Cisplatin for Head and Neck Cancer.

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 2-year tumor outcomes and exploratory data on trismus and xerostomia.

Methods And Materials: Patients with locally advanced oral cavity or oropharynx cancer to be treated with definitive or postop cis and RT were randomized to 1 of 3 arms: 30 mg avasopasem, 90 mg avasopasem, or placebo.

The Path to an Evidence-Based Treatment Protocol for Extraoral Photobiomodulation Therapy for the Prevention of Oral Mucositis.

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. Additionally, to date there has been no dose modeling study, a task essential to developing a justified treatment protocol.

Validation of a Monte Carlo Modelling Based Dosimetry of Extraoral Photobiomodulation.

An in vivo validation study was performed to confirm the accuracy of extraoral photobiomodulation therapy (PBMT) dosimetry determined by modelling. The Monte Carlo technique was utilized to calculate the fluence rate and absorbed power of light delivered through multi-layered tissue. Optical properties used during Monte Carlo simulations were taken from the literature.

The broadening scope of oral mucositis and oral ulcerative mucosal toxicities of anticancer therapies.

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.

GM-1111 reduces radiation-induced oral mucositis in mice by targeting pattern recognition receptor-mediated inflammatory signaling.

Purpose: Oral mucositis (OM) is a common, painful side effect of radiation therapy used for the treatment of head and neck cancer (HNC). Activation of the innate immune system upon irradiation has been identified as a key precipitating event of OM. To better understand OM's pathogenesis, we studied pattern recognition receptors (PRRs) and their downstream pro-inflammatory cytokines in a mouse model of radiation-induced OM.

Superoxide Dismutase as an Intervention for Radiation Therapy-Associated Toxicities: Review and Profile of Avasopasem Manganese as a Treatment Option for Radiation-Induced Mucositis.

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 of radiation-associated normal tissue injury as physiologic antioxidant mechanisms are overwhelmed by the accumulation of effects produced by fractionated treatment regimens.

A hypothesis for the pathogenesis of radiation-induced oral mucositis: when biological challenges exceed physiologic protective mechanisms. Implications for pharmacological prevention and treatment.

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 on OM's pathobiology.

Oral side effects of immune checkpoint inhibitor therapy (ICIT): An analysis of 4683 patients receiving ICIT for malignancies at Massachusetts General Hospital, Brigham & Women's Hospital, and the Dana-Farber Cancer Institute, 2011 to 2019.

Background: Immune checkpoint inhibitors (ICIs) are increasingly accepted as a treatment option for several cancers. Although various systemic immune-related adverse events (irAEs) have been characterized, the effect of ICIs on the oral cavity and contiguous structures is still poorly understood.

Methods: Electronic medical records of 4683 patients in the Mass General Brigham Registered Patient Data Registry who received ICI therapy (ICIT) between December 2011 and September 2019 were reviewed.

Treatment for Oral Mucositis-Current Options and an Update of Small Molecules Under Development.

Despite its history as one of the most impactful toxicities associated with cytotoxic cancer therapy, oral mucositis (OM) remains an unmet clinical need which affects hundreds of thousands of patients. Descriptions of its complex pathogenesis have provided mechanistic targets which are being exploited to develop an effective therapeutic intervention. Favorable results of recently completed clinical trials in which agents focused on interrupting the early stages of the mucositis biological cascade were assessed provide reason for optimism, not only for oral mucositis but also for halo indications which share its pathobiogenesis.

Robust pathway sampling in phenotype prediction. Application to triple negative breast cancer.

Background: Phenotype prediction problems are usually considered ill-posed, as the amount of samples is very limited with respect to the scrutinized genetic probes. This fact complicates the sampling of the defective genetic pathways due to the high number of possible discriminatory genetic networks involved. In this research, we outline three novel sampling algorithms utilized to identify, classify and characterize the defective pathways in phenotype prediction problems, such as the Fisher's ratio sampler, the Holdout sampler and the Random sampler, and apply each one to the analysis of genetic pathways involved in tumor behavior and outcomes of triple negative breast cancers (TNBC).