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. The goal of this study was to develop a clinically viable protocol for extraoral PBMT. Monte Carlo modeling was used to predict the distribution of 850 nm light for four treatment sites, using anatomical data obtained from MRI and optical properties from the literature. Simulated incident light power density was limited to 399 mW/cm2 to ensure treatment safety and to prevent tissue temperature increase. The results reveal that total tissue thickness determines fluence rate at the oral mucosa, whereas the thickness of individual tissue layers and melanin content are of minor importance. Due to anatomical differences, the fluence rate varied greatly among patients. Despite these variations, a universal protocol was established using a median treatment time methodology. The determined median treatment times required to deliver efficacious dose between 1 and 6 J/cm2 were within 15 min. The developed PBMT protocol can be further refined using the combination of pretreatment imaging and the Monte Carlo simulation approach implemented in this study.

Oral lichen planus: comparative efficacy and treatment costs-a systematic review.

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 placebo or different active interventions for OLP management were considered. RESULTS: Seventy (70) RCTs were included. The majority of evidence suggested efficacy of topical steroids (dexamethasone, clobetasol, fluocinonide, triamcinolone), topical calcineurin inhibitors (tacrolimus, pimecrolimus, cyclosporine), topical retinoids, intra-lesional triamcinolone, aloe-vera gel, photodynamic therapy, and low-level laser therapies for OLP management. Based on the estimated cost per month and evidence for efficacy and side-effects, topical steroids (fluocinonide > dexamethasone > clobetasol > triamcinolone) appear to be more cost-effective than topical calcineurin inhibitors (tacrolimus > pimecrolimus > cyclosporine) followed by intra-lesional triamcinolone. CONCLUSION: Of common treatment regimens for OLP, topical steroids appear to be the most economical and efficacious option followed by topical calcineurin inhibitors. Large-scale multi-modality, prospective trials in which head-to-head comparisons interventions are compared are required to definitely assess the cost-effectiveness of OLP treatments.

Increasing HPV vaccination coverage to prevent oropharyngeal cancer: A cost-effectiveness analysis.

The incidence of oropharyngeal cancer (OPC) has been rising, especially among middle-aged men. While Human Papillomavirus (HPV) has been irrevocably implicated in the pathogenesis of oropharyngeal cancer (OPC), the current HPV vaccination uptake rate remains low in the US. The aim of our study was to evaluate the impact of increased HPV vaccination coverage on HPV-associated OPC incidence and costs. A decision analytic model was constructed for hypothetical cohorts of 9-year-old boys and girls. Two strategies were compared: 1) Maintaining the current vaccination uptake rates; 2) Increasing HPV vaccination uptake rates to the Healthy People 2030 target (80%) for both sexes. Increasing HPV vaccination coverage rates to 80% would be expected to prevent 5,339 OPC cases at a cost of $0.57 billion USD. Increased HPV vaccination coverage would result in 7,430 quality-adjusted life year (QALY) gains in the overall population, and it is estimated to be cost-effective for males with an incremental cost-effectiveness ratio of $86,940 per QALY gained under certain conditions. Expanding HPV vaccination rates would likely provide a cost-effective way to reduce the OPC incidence, particularly among males.

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. Morphological data of four study volunteers were acquired using magnetic resonance imaging (MRI) scans. Light emitting diode (LED) coupled to a power meter were utilized to measure transmitted power through each volunteer's cheek, in vivo. The transmitted power determined by Monte Carlo modelling was compared to the in vivo measurements to determine the accuracy of the simulations. Experimental and simulation results were in good agreement for all four subjects. The difference between the mean values of the measured transmission was within 12% from the respective transmission obtained using Monte Carlo simulations. The results of the study indicate that Monte Carlo modelling is a robust and reliable method for light dosimetry.

Disparities in Oral Cancer Screening Among Dental Professionals: NHANES 2011-2016.

INTRODUCTION: As early detection of oral cancers is associated with better survival, oral cancer screening should be included in dental visits for adults. This study examines the rate and predictors of oral cancer screening exams among U.S. adults with a recent dental visit. METHODS: Individuals aged ≥30 years who received a dental visit in the last 2 years, in the 2011-2016 National Health and Nutrition Examination Survey were analyzed in December 2018. Weighted multivariable logistic regression models examined the likelihood of intraoral and extraoral oral cancer screening exams, adjusting for age, sex, race/ethnicity, education, marital status, poverty income ratio, health insurance, tobacco smoking, and alcohol consumption. Subgroup analyses were conducted among races/ethnicities, smokers, and alcohol consumers. Statistical significance was set at p<0.01. RESULTS: A total of 37.6% and 31.3% reported receiving an intraoral and extraoral oral cancer screening exam, respectively. Minority racial/ethnic groups versus white, non-Hispanics, less-educated versus more-educated, uninsured and Medicaid-insured versus privately insured, and low-income versus high-income participants were less likely to have received intraoral or extraoral oral cancer screening exams. There was no difference in the likelihood of being screened based on smoking status. Alcohol consumers were more likely to be screened. Among subgroups, less-educated and low-income individuals were less likely to be screened. CONCLUSIONS: A significantly higher proportion of minority race/ethnicity and low SES individuals report not receiving an oral cancer screening exam, despite a recent dental visit. This selective screening by dental professionals is incompliant with guidelines and concerning because these groups are more likely to present with an advanced stage of oral cancer at diagnosis. An understanding of the reasons for discriminatory oral cancer screening practices could help develop effective interventions.

Impact of the insurance type of head and neck cancer patients on their hospitalization utilization patterns.

BACKGROUND: Head and neck cancer (HNC) patients with Medicaid, Medicare, or no insurance show poor outcomes in comparison with privately insured patients. It was hypothesized that nonprivate insurance coverage biases the selection of the treatment site to favor hospitals that are not associated with optimum treatment outcomes. This study assessed the relation between the insurance type of HNC patients and the hospital type for inpatient care. METHODS: Adult HNC patients were identified from the Nationwide Inpatient Sample (2012 and 2013). The primary exposure was the insurance provider type. The outcome was the hospital type, which was classified by the hospital's ownership and its location and teaching status. Multivariate multinomial logistic regression models were constructed to control for the patient's age, sex, race, income, mortality risk, and geographic location. The analysis was weighted and was adjusted for multiple comparisons. RESULTS: In all, 37,466 HNC patients representing 187,330 patients nationally were identified. After adjustments for age, sex, race, income, and mortality risk, in comparison with privately insured patients, Medicaid, Medicare, and uninsured patients demonstrated 1.14 to 2.29 increased odds of undergoing treatment at rural, urban nonteaching, private investor-owned, or government (nonfederal) hospitals (P < .05). This trend remained apparent even after adjustments for the geographic location. CONCLUSIONS: Uninsured patients or patients insured by government programs predominantly underwent care for HNC at hospital types most often associated with inferior survival outcomes. This finding could explain some proportion of insurance-related disparities in HNC outcomes. Further studies are warranted to determine whether interventions to promote equitable access to optimal hospital settings for patients, regardless of their insurance type, might improve outcomes among nonprivate insurance holders. Cancer 2018;124:760-8. © 2017 American Cancer Society.

The economic burden of toxicities associated with cancer treatment: review of the literature and analysis of nausea and vomiting, diarrhoea, oral mucositis and fatigue.

Side effects or toxicities are frequent, undesirable companions of almost all forms of non-surgical cancer therapy. It is unusual for patients to complete treatment with radiation or chemotherapy without experiencing at least one form of therapy-associated tissue injury or systemic side effect. Often, toxicities do not occur as solitary events; rather, they result in clusters of symptoms that share a common biological aetiology. Like any disease, cancer treatment-related toxicities (CTRTs) vary in their severity. But, in contrast to most diseases in which incidence is described as being present or absent, the current approach to CTRT typically limits reporting to severe cases only. Not only does this dilute the frequency with which CTRTs occur, but it also undermines our ability to determine the full burden of their impact and to accurately assess the cost effectiveness of potential toxicity interventions. In this article, we report the results of a directed literature review for the years 2000-2012, in which we studied and compared three tissue-based toxicities (nausea and vomiting, diarrhoea, and oral mucositis) and one systemic toxicity (fatigue). Our results confirm the heavy burden of resource use and cost associated with CTRTs. The inclusion of fatigue in our analysis provided an opportunity to compare and contrast a toxicity in which there are both acute and chronic consequences. Our findings also demonstrate a number of challenges to, and opportunities for, future study. Among the most obvious are the lack of provider consistency in diagnosis and grading, especially when there is no global agreement on severity scales. Compounding this inconsistency is the disconnect between healthcare providers and patients that exists when describing toxicity severity and impact. In many cases, cancer can be thought of as a chronic disease that requires prolonged but episodic treatment once the acute disease is eradicated. This change reflects increasing treatment successes, but it also implies that the burden of CTRTs will be expanded and prolonged. Creation of hierarchical attribution of costs in the presence of simultaneous CTRTs, accurate coding, and consistent tracking tools for toxicities will be imperative for effective appraisal of the costs associated with cancer treatment regimen toxicities.

Oral mucositis in head and neck cancer: risk, biology, and management.

Of the toxicities associated with conventional forms of treatment for head and neck cancers, probably none has such a consistent legacy as oral mucositis.1 Despite the fact that mucosal injury was noted as far back as Marie Curie's first forays into therapeutic radiation, an effective intervention has yet to be developed. In addition to its historic link to radiation, new therapeutic strategies including induction chemotherapy often produce mucositis, and targeted therapies appear to alter mucositis risk and its severity and course.2 The symptomatic effect of oral mucositis is profound. Disabling oral and oropharyngeal pain prevents patients from eating normally, requires opiate analgesics, and in some cases results in alteration or discontinuation of anticancer therapy.3 Furthermore, the health and economic consequences of oral mucositis are far from trivial. The incremental cost of oral mucositis in patients with head and neck cancer exceeds $17,000 (USD).4.

Oral mucositis.

Oral mucositis remains one of the most common and troubling side effects of standard chemoradiation regimens used for the treatment of head and neck cancer. Virtually all patients who receive cumulative radiation doses of more than 30 Gy that includes oral mucosal fields will develop the condition. Not only does mucositis cause extreme discomfort, often necessitating opioid analgesia, but it is also associated with increased use of health resources and cost of treatment. The incremental cost of mucositis in patients with head and neck cancer is more than $17 000 (US). Much has been learned about the pathobiology that underlies the condition. The departure from the historical paradigm of direct cell death as being the primary cause for mucosal injury in favor of a more comprehensive view of the impact of chemoradiation on all the cells of the mucosa, has resulted in a picture of mucositis pathogenesis, which is biologically broad based. Although there are currently few treatment options for oral mucositis at the moment, the recognition that its underlying biology is complex has provided a range of treatment options that are currently being developed.

Links between regimen-related toxicities in patients being treated for colorectal cancer.

PURPOSE OF REVIEW: To summarize the available evidence on cooccurring gastrointestinal toxicities and their potential link with other symptoms in cancer patients. The information obtained from colorectal cancer patient cohorts will be used as an example. RECENT FINDINGS: In recent years, it has become clear that gastrointestinal toxicities do not occur in isolation in cancer patients. Rather, they may link or associate with many other disturbances. Data have emerged that suggest that many of the complications of cancer chemotherapy occur in clusters and seem to support the sharing of common pathogenesis for clustering toxicities. SUMMARY: During the last few years, research in symptom clusters and cooccurring linked toxicities has markedly changed, progressively shifting from a simplistic descriptive picture to more comprehensive and pathogenetically driven analyses. Still, many questions remain to be answered, and whether and how toxicity aggregations vary during the treatment course remains to be elucidated.

Patient-reported measurements of oral mucositis in head and neck cancer patients treated with radiotherapy with or without chemotherapy: demonstration of increased frequency, severity, resistance to palliation, and impact on quality of life.

BACKGROUND: The risk, severity, and patient-reported outcomes of radiation-induced mucositis among head and neck cancer patients were prospectively estimated. METHODS: A validated, patient-reported questionnaire (OMDQ), the FACT quality of life (QOL), and the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scales were used to measure mucositis (reported as mouth and throat soreness), daily functioning, and use of analgesics. Patients were studied before radiotherapy (RT), daily during RT, and for 4 weeks after RT. RESULTS: Contrary to previous reports, the risk of mucositis was virtually identical in the 126 patients with oral cavity or oropharynx tumors (99% overall; 85% grade 3-4) compared with 65 patients with tumors of the larynx or hypopharynx (98% overall; 77% grade 3-4). The mean QOL score decreased significantly during RT, from 85.1 at baseline to 69.0 at Week 6, corresponding with the peak of mucositis severity. The mean functional status score decreased by 33% from 18.3 at baseline to 12.3 at Week 6. The impact of mucositis on QOL was proportional to its severity, although even a score of 1 or 2 (mild or moderate) was associated with a significant reduction in QOL (from 93.6 at baseline to 74.7 at Week 6). Despite increases in analgesic use from 34% at baseline to 80% at Week 6, mean mucositis scores exceeded 2.5 at Week 6. CONCLUSIONS: Mucositis occurs among virtually all patients who are undergoing radiation treatment of head and neck cancers. The detrimental effects on QOL and functional status are significant, and opioid analgesia provides inadequate relief. Preventive rather than symptom palliation measures are needed.

Oral mucositis and outcomes of autologous hematopoietic stem-cell transplantation following high-dose melphalan conditioning for multiple myeloma.

The purpose of this study was to assess the relationship between oral mucositis (OM) and adverse clinical and economic outcomes of autologous hematopoietic stem-cell transplantation (HSCT) following high-dose melphalan (Alkeran) conditioning in patients with multiple myeloma. A retrospective study of 115 consecutive autologous HSCT recipients with multiple myeloma who received high-dose melphalan conditioning before transplantation was undertaken at a single academic center. OM severity was assessed twice weekly using a validated scale beginning 3-4 days following conditioning and continuing until hospital discharge or day 28, whichever occurred first. OM was graded, based on presence/extent of erythema/ulceration across eight oropharyngeal sites, as follows: 0 = no erythema or ulceration; I = erythema but no ulceration; II = ulceration, 1 site; III = ulceration, 2 sites; IV = ulceration, 3 sites; and V = ulceration, > or = 4 sites. Analyses examined the relationship between worst OM grade and selected clinical and economic outcomes, including days with fever, days of total parenteral nutrition (TPN),days of parenteral narcotic therapy, incidence of significant infection, and inpatient days and charges. The mean age of study subjects was 54 years; 19 patients (17%) received total-body irradiation, and 55 patients (48%) experienced OM grade > or = II (ie, ulceration). The worst OM grade was significantly (P < 0.05) associated with numbers of days of TPN and parenteral narcotic therapy, length of hospitalization, and total inpatient charges. Worst OM grade was not associated with the number of febrile days or the risk of significant infection. OM is associated with worse clinical and economic outcomes in multiple myeloma patients undergoing autologous HSCT following high-dose melphalan conditioning.

Oral mucositis and outcomes of allogeneic hematopoietic stem-cell transplantation in patients with hematologic malignancies.

GOALS OF THE WORK: To assess the relationship between oral mucositis (OM) and adverse clinical and economic outcomes in patients with hematologic malignancies receiving allogeneic hematopoietic stem-cell transplantation (HSCT). MATERIALS AND METHODS: A retrospective chart review study of 281 allogeneic HSCT recipients with hematologic malignancies was undertaken at a single academic center. OM extent and severity were assessed across eight oropharyngeal sites using a validated scale, which was scored as follows: no erythema/ulceration=0; erythema only=I; ulceration, one site=II; ulceration, two sites=III; ulceration, three sites=IV and ulceration, four or more sites=V. OM assessments began on the day of conditioning and continued twice weekly within 28 days or hospital discharge. Analyses examined the relationship between the worst OM grade and selected adverse outcomes, including days with fever, days of total parenteral nutrition (TPN), days of parenteral narcotic therapy, incidence of significant (common terminology criteria (CTC) grade 3 or 4) infection, mortality and inpatient days and charges. MAIN RESULTS: The mean age of the study subjects was 41 years. Of the patients, 96% (n = 269) received total body irradiation and 76% (n = 214) experienced an OM grade of > or =II (i.e., ulceration). The worst OM grade was significantly (p < 0.05) associated with the number of days of TPN and parenteral narcotic therapy, number of days with fever, incidence of significant infection, time in hospital and total inpatient charges. CONCLUSIONS: OM is associated with worse clinical and economic outcomes in patients with hematologic malignancies undergoing allogeneic HSCT.

A biological approach to mucositis.

Oral mucositis is a common toxicity associated with both antineoplastic head and neck radiation and chemotherapy. In addition to exacting a terrible symptomatic toll, mucositis is associated with a number of adverse health and economic outcomes. Furthermore, its presence may compromise the use of optimum agents, doses, or dosing schedules. The current lack of an approved, effective mucositis treatment has sparked interest in the development of interventions that are based on the biological mechanisms that lead to mucosal injury. While our understanding of the molecular and cellular pathways leading to mucositis is still evolving, it is now clear that the condition represents the culmination of a dynamic sequence of events that involve all cells and tissues in the mucosa. Five phases characterize the pathophysiologic progression that results in mucositis: initiation, upregulation and message generation, signaling and amplification, ulceration, and healing. Each phase offers a potential target for therapeutic intervention.