Clinical and biochemical assessment of the effect of glutamine in management of radiation induced oral mucositis in patients with head and neck cancer: Randomized controlled clinical trial.

BACKGROUND: This study aimed to evaluate the effect of oral glutamine suspension on salivary levels of transforming growth factor beta 1 (TGF-ß1), a cytokine involved in inflammation and Tumor progression, and the severity of radiation-induced oral mucositis (RIOM) in head and neck cancer patients. This is the first study to investigate the impact of glutamine on TGF-ß1 levels in head and neck cancer patients with radiation induced oral mucositis (RIOM). METHODS: In this randomized controlled clinical trial, 50 HNC patients were enrolled and received either glutamine oral suspension or maltodextrin as a placebo from the baseline of RIOM to the end of radiotherapy. Salivary TGF-ß1 levels were measured at baseline and after treatment. Also, RIOM was assessed using the World Health Organization (WHO) Oral Toxicity Scale, the Oral Mucositis Assessment Scale (OMAS), the Pain Visual Analog Scale (Pain-VAS), the incidence of opioid use, and body mass index (BMI). RESULTS: Glutamine significantly reduced salivary TGF-ß1 levels and improved RIOM symptoms, such as pain, opioid use, and weight loss. The reduction of TGF-ß1 levels was associated with the improvement of RIOM severity. CONCLUSION: Glutamine may modulate the inflammatory response and enhance wound healing in RIOM by decreasing salivary TGF-ß1 levels. These findings support the use of glutamine as a potential intervention for RIOM and nutritional support for improving radiation sensitivity. TRIAL REGISTRATION: This study was registered on clinicalTrials.gov with identifier no. NCT05856188.

Nurses' knowledge on assessment and management of cancer therapy-associated oral mucositis.

AIM: This study aimed to explore baseline nursing knowledge on assessment and management of patients at risk for developing cancer therapy-associated oral mucositis (OM) at a tertiary hospital in Ghana. DESIGN: A descriptive generic qualitative study design was conducted. The study population were nurses who cared for patients diagnosed with cancer. METHODS: Participants were recruited using a purposive non-probability sampling technique. Data were obtained through face-to-face interviews using semi-structured interview guide. Data collection and analysis were done concurrently. RESULTS: The study found that nurses had knowledge on the pre-treatment assessment of clients undergoing cancer treatment; however, they had insufficient knowledge on the standardized tool for the assessment of OM. They also lack a definitive approach to prevent and treat OM. Nurses provided general education on cancer treatment but paid little attention to the education on the possible side effect that includes OM. Additionally, insufficient knowledge level of nurses on cancer treatment-associated mucositis and lack of structured protocol for OM coupled with unavailable tools for assessing the oral mucosa were also identified as militating against the management of OM. Findings from this study will guide policy that will improve the care that clients who are at risk of oral mucositis receive.

Assessment of salivary alpha amylase and mucin-4 before and after non-surgical treatment of peri-implant mucositis.

BACKGROUND: The present study was based on the null hypothesis that there is no difference in clinicoradiographic parameters and whole salivary alpha amylase (AA) and mucin-4 levels before and after non-surgical mechanical debridement (NSMD) of patients with peri-implant mucositis (PM). The aim was to assess whole salivary AA and mucin-4 levels before and after treatment of PM. METHODS: Patients with PM (Group-1) and individuals without peri-implant diseases (Group-2) were included. Demographic data was collected and peri-implant modified plaque and bleeding indices (mPI and mBI, respectively), probing depth (PD) and crestal bone loss were measured at baseline. Levels of AA and mucin-4 were assessed in unstimulated whole saliva samples. All patients underwent full-mouth non-surgical periodontal therapy (NSPT) and NSMD; and clinical parameters and salivary biomarkers were re-assessed after 3 months. Level of significance was set at P < 0.01. RESULTS: Twenty-six and 32 individuals were included in groups 1 and 2, respectively. None of the participants had periodontitis. At baseline clinical periodontal parameters (PI [P < 0.001], GI [P < 0.001], clinical AL [P < 0.001] and PD [P < 0.001]) were significantly high in Group-1 than Group-2. At 3-month follow-up, there was a statistically significant reduction in clinical periodontal and peri-implant parameters (PI [P < 0.01], GI [P < 0.01], and PD [P < 0.01]) in Group-1 compared with their baseline values. At baseline, salivary AA levels were significantly high in Group-1 than Group-2 (P < 0.01). At 3-month follow-up, there was no significant difference in whole salivary AA levels among patients in groups 1 and 2. CONCLUSIONS: The AA and mucin-4 levels are potential biomarkers for evaluation of peri-implant diseases including PM. Mechanical instrumentation continues to be the most predictable treatment option for the management of peri-implant diseases.

Assessment and prevalence of concomitant chemo-radiotherapy-induced oral mucositis in patients with oral squamous cell carcinoma

Background/aim: Quantification of oral mucositis that progresses during concomitant chemo-radiotherapy (CCRT) is essential for its management. It is important to determine the methods that are simple, reliable and beneficial in foreseeing mucositis at earlier stages of treatment. Materials and methods: A prospective study was conducted on 100 oral cancer patients receiving CCRT following the inclusion criteria. Patients were evaluated for mucositis i.e. erythema and ulcers by using the World Health Organization (WHO) scale and the oral mucositis assessment scale (OMAS), whereas mature and immature cells were identified by exfoliative cytology. Clinical examination and procedure of oral cavity were performed before, on days 5, 17, and at the end of treatment. Results: Oral mucositis was observed in all oral squamous cell carcinoma (OSCC) patients receiving CCRT on different days with noteworthy increase from day 5 of CCRT to the end of treatment. For OMAS grading related to ulceration and erythema, Grade 1 (7.2%; 34%) was most commonly seen on the 5th day of CCRT, Grade 2 (29%; 19%) and Grade 3 (19%) were most frequently seen at the 17th day and end of CCRT, accordingly. With respect to WHO scale grades 1 and 2 (18.3%; 21.5%) was most frequently observed at the 17th day of CCRT, whereas grades 3 and 4 (12.5%; 2%) was noted at the end of CCRT. There was statistically significant increase in the percentage of immature cells at the end of CCRT (99%). A significant association (P < 0.0000) was observed among the days of smear and maturation stages of epithelial cells as well as among WHO mucositis grading, OMAS and types of epithelial cells, respectively. Conclusion: According to the findings of the study, oral mucositis grade is directly proportional to the progressing days of CCRT. Oral mucositis is frequently related to adverse clinical outcomes, affecting the patient's quality of life. It is essential to develop methods that can be employed for the assessment of CCRT associated oral mucositis.

Photobiomodulation in oral mucositis in patients with head and neck cancer: a systematic review and meta-analysis followed by a cost-effectiveness analysis.

BACKGROUND: Oral mucositis (OM) is an oral toxicity caused by cancer treatment, found often in patients with head and neck cancer. Low-intensity laser therapy for OM has anti-inflammatory, analgesic, and tissue reparative properties. OBJECTIVE: The objective of this work is to perform a systematic review and meta-analysis of the randomized clinical trials of OM laser therapy in patients undergoing treatment for head and neck cancers, followed by a cost-effectiveness analysis of the therapy. METHOD: The search terms, mucositis and phototherapy, laser therapy and mucositis, photobiomodulation and mucositis, and low-level laser therapy and mucositis, were used to search the databases of PubMed, Web of Science, and MEDLINE. Randomized clinical trials were divided into two groups: one treated with laser therapy and the other given a placebo. Only 13 studies were included in the systematic review, and 6 studies in the meta-analysis. RESULTS: The results of the systematic review and meta-analysis show that the laser therapy presented good results in clinical improvement and pain reduction, decreasing the patients' likelihood of developing OM, with degrees of debilitating lesions, to 64% (RR = 0.36 [95% CI = 0.29-0.44]). The cost-effectiveness analysis revealed an incremental cost of R$ 3687.53 for the laser group, with an incremental effectiveness of 132.2. The incremental cost-effectiveness ratio (ICER) was 27.89, for the severe OM cases that were avoided. CONCLUSION: It was concluded, therefore, that photobiomodulation for OM in patients receiving head and neck cancer treatment was clinically effective and cost-effective.

Burden of Oral Mucositis: A Systematic Review and Implications for Future Research.

BACKGROUND: Surprisingly little is known about the burden of oral mucositis (OM). We provide a systematic review of studies on the burden of OM (incidence, economic impact, health-related quality of life (HRQoL)). METHODS: Systematic literature searches were made in BIOSIS, EMBASE, and MEDLINE. Inclusion criteria were studies on OM in hematology/oncology patients of ≥ 18 years, journal articles, English language, and published between 2000 and 2016; OM treatment studies were excluded. Quality assessment was performed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: We screened 4,996 hits, and identified 68 studies of which 13 were without transparency on OM grading. The evidence level of 65 studies was rated 'low' or 'very low' in 58.5%, 'moderate' in 20% and 'high' in 21.5%. Mean value of incidence (7 studies) was 83.5% for all grades of OM with hematopoietic stem cell transplantation. OM incidence for all grades in head and neck cancer patients was 59.4-100%. Considering the economic impact, 16 studies showed highly variable numbers. HRQoL was measured in 16 studies using 13 different instruments. Statistically significant changes in HRQoL scores were demonstrated. CONCLUSION: OM is common, burdensome, costly and imposes major reductions in HRQoL. However, from a quality standpoint, the level of current evidence in OM is disappointing. The field needs continued attention to address methodological challenges.

Preventing and Treating Peri-Implantitis: A Cost-Effectiveness Analysis.

BACKGROUND: A large number of treatments for peri-implantitis are available, but their cost-effectiveness remains uncertain. This study evaluates the cost-effectiveness of preventing and treating peri-implantitis. METHODS: A Markov model was constructed that followed each implant over 20 years. Supportive implant therapy (SIT) for managing peri-implant mucositis and preventing development of peri-implantitis was either provided or not. Risk of peri-implantitis was assumed to be affected by SIT and the patient's risk profile. If peri-implantitis occurred, 11 treatment strategies (non-surgical or surgical debridement alone or combined with adjunct therapies) were compared. Treatments and risk profiles determined disease progression. Modeling was performed based on systematically collected data. Primary outcomes were costs and proportion of lost implants, as assessed via Monte Carlo microsimulations. RESULTS: Not providing SIT and performing only non-surgical debridement was both least costly and least effective. The next best (more costly and effective) option was to provide SIT and perform surgical debridement (additional 0.89 euros per 1% fewer implants lost). The most effective option included bone grafts, membranes, and laser treatment (56 euros per 1%). For patients at high risk, the cost-effectiveness of SIT increased, whereas in low-risk groups, a cost-optimized strategy was cost-effective. CONCLUSIONS: Although clinical decision-making will be guided mainly by clinical condition, cost-effectiveness analyses might add another perspective. Based on these findings, an unambiguous comparative effectiveness ranking was not established. However, cost-effectiveness was predominantly determined by provision of SIT and initial treatment costs. Transferability of these findings to other healthcare systems needs further confirmation.

Chemotherapy or radiation-induced oral mucositis.

Oral mucositis is a significant toxicity of systemic chemotherapy and of radiation therapy to the head and neck region. The morbidity of oral mucositis can include pain, nutritional compromise, impact on quality of life, alteration in cancer therapy, risk for infection, and economic costs. Management includes general symptomatic support and targeted therapeutic interventions for the prevention or treatment of oral mucositis. Evidence-based clinical practice guidelines are available to guide clinicians in the selection of effective management strategies.

Cost-effectiveness of the introduction of specialized oral care with laser therapy in hematopoietic stem cell transplantation.

Oral mucositis (OM) is one of the side effects of hematopoietic stem cell transplantation (HSCT), resulting in major morbidity. The aim of this study was to determine the cost-effectiveness of the introduction of a specialized oral care program including laser therapy in the care of patients receiving HSCT with regard to morbidity associated with OM. Clinical information was gathered on 167 patients undergoing HSCT and divided according to the presence (n = 91) or absence (n = 76) of laser therapy and oral care. Cost analysis included daily hospital fees, parenteral nutrition (PN) and prescription of opioids. It was observed that the group without laser therapy (group II) showed a higher frequency of severe degrees of OM (relative risk = 16.8, 95% confidence interval -5.8 to 48.9, p < 0.001), with a significant association between this severity and the use of PN (p = 0.001), prescription of opioids (p < 0.001), pain in the oral cavity (p = 0.003) and fever > 37.8°C (p = 0.005). Hospitalization costs in this group were up to 30% higher. The introduction of oral care by a multidisciplinary staff including laser therapy helps reduce morbidity resulting from OM and, consequently, helps minimize hospitalization costs associated with HSCT, even considering therapy costs.

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.

[Radio-induced oral and pharyngeal mucositis: management updates]. / Mucites radio-induites buccopharyngées : actualités sur la prise en charge.

Mucositis is a major side effect induced by radiotherapy and/or chemotherapy of head and neck cancer. This toxicity impacts patient's quality of life and may compromise optimal treatments. Pathophysiology, risk factors, incidence and consequences of mucositis will be discussed in this review. Its management remains principally supportive (pain medication and nutritional support); however, in recent years several studies have revealed that the use of low level energy laser is particularly useful in the prevention and treatment of chemo- and radio-induced mucositis.

Quality assessment of reporting of animal studies on pathogenesis and treatment of peri-implant mucositis and peri-implantitis. A systematic review using the ARRIVE guidelines.

OBJECTIVES: To address the following focused question: What is the quality of reporting of pre-clinical research for the study and treatment of mucositis/peri-implantitis? MATERIALS AND METHODS: Electronic databases of the PubMed and the Cochrane Library were searched for animal studies reporting on pathogenesis or therapy of either peri-implant mucositits or peri-implantitis and completed by dual manual searches in duplicate between 1992 and May 2011. Quality assessment (i.e. grading of a checklist of 20 items in different categories) of selected full-text articles was performed according to the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. RESULTS: Following screening, 75 publications were eligible for the review. For publications reporting on pathogenesis (n = 7) and therapy (n = 1) of peri-implant mucositis, minimum gradings were assigned to items 5 (Methods/Ethical Statement), 9 (Methods/Housing and husbandry), 11 (Methods/Allocation animals to experimental groups), 14 (Results/Baseline data), and 17 (Results/Adverse events). For publications reporting on pathogenesis (n = 34) and therapy (n = 33) of peri-implantitis, minimum grades were mainly assigned to items 9, 11, 14, and 17. CONCLUSIONS: This systematic review has identified missing information in the publications on pre-clinical research for the study and treatment of mucositis/peri-implantitis.

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.

Chemotherapy- and radiotherapy-induced oral mucositis: pathobiology, epidemiology and management.

Oral mucositis is a debilitating complication of anticancer treatment, characterised by erythematous, atrophic, erosive or ulcerative lesions. Oral mucositis is almost always painful, affects eating, sleeping, and speech and affects the physiological and social well-being of the patient. The pathophysiology of the condition is not well understood. Guidelines to the treatment of oral mucositis are often contradictory so that there is no evidence based standard treatment protocol. Therefore the treatment is empiric. This paper offers a brief review of current knowledge of the pathophysiology and treatment of oral mucositis.

Incidence of oral mucositis, its treatment and pain management in patients receiving cancer treatment at Radiation Oncology Departments in Spanish hospitals (MUCODOL Study).

OBJECTIVE: To estimate the incidence of oral mucositis (OM) in patients receiving radiotherapy, describe the treatments used to manage pain in OM grades 3 and 4 and assess relief of pain and patient satisfaction. PATIENTS AND METHODS: All patients older than 18 years consecutively attending a Radiation Oncology Department over 5 working days were included in a cross-sectional study. The data recorded were RTOG scale of OM (1, 2, 3 or 4), age and sex. In a second stage, a clinical cohort was followed for 2 months. Pain management was assessed in patients with grades 3 and 4. RESULTS: Two thousand and forty-seven patients (98.5%) from 55 participating centres were eligible for the fi rst stage. The overall risk of OM was 16.4% (95% CI 14.8- 18.1); prevalence was 26.4%. In the second stage, 282 (91.6%) of the patients recruited were eligible. At the baseline visit, 95.7% of the population had OM grade 3 and 4.3% grade 4. At two months, OM was resolved in 62.3%, grade 1 in 20%, grade 2 in 10.3% and grade 3 in only 7.4% (p<0.05). 98.9% of the patients had head and neck cancer. From baseline to the two-months session, reported pain fell from 96.1% of affected patients to 39.8%(p<0.01), while chronic pain increased (19.5% vs. 38.2%, p<0.05). Verbal scale OM pain intensity indicated intense pain at baseline in 42.2% and a mean visual analogue scale (VAS) score of 5.6 (2.3). Mean VAS scores fell significantly according to pain intensity due to the OM and cancer (p<0.01). CONCLUSIONS: Pain due to OM, a common complication of chemotherapy and radiation, limits nutritional intake and oral function. Analgesia protocols need to be assessed to improve the quality of life of these patients.

A review of quality assessment of the methodology used in guidelines and systematic reviews on oral mucositis.

AIMS AND OBJECTIVES: The objective of this study was to identify and to assess the quality of evidence-based guidelines and systematic reviews we used in the case of oral mucositis, to apply general quality criteria for the prevention and treatment of oral mucositis in patients receiving chemotherapy, radiotherapy or both. DESIGN: Systematic review. METHODS: Literature searches were carried out in several electronic databases and websites. Publications were included if they concerned oral mucositis involving adults treated for cancer and had been published after 1 January 2000. As far as systematic reviews were concerned, the article had to report a search strategy, if the search was minimally conducted in the database PubMed or Medline and the articles included in the review were subjected to some kind of methodological assessment. The Appraisal of Guidelines for Research and Education (AGREE) instrument was used to assess the quality of the guidelines and the Overview Quality Assessment Questionnaire (OQAQ) was used for the quality of systematic reviews. RESULTS: Thirty-one articles met the inclusion criteria of which 11 were guidelines and 20 were systematic reviews. Nine of the 11 guidelines did not explicitly describe how they identified, selected and summarised the available evidence. Reviews suffered from lack of clarity, for instance, in performing a thorough literature search. The quality varied among the different guidelines and reviews. CONCLUSION: Most guidelines and systematic reviews had serious methodological flaws. RELEVANCE TO CLINICAL PRACTICE: There is a need to improve the methodological quality of guidelines and systematic reviews for the prevention and treatment of oral mucositis if they are to be used in clinical practice.

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.

Risk, outcomes, and costs of radiation-induced oral mucositis among patients with head-and-neck malignancies.

PURPOSE: To study the risk, outcomes, and costs of radiation-induced oral mucositis (OM) among patients receiving radiotherapy (RT) to head and neck primary cancers. METHODS AND MATERIALS: A retrospective cohort consisting of 204 consecutive head-and-neck cancer patients who received RT with or without chemotherapy during 2002 was formed; their records were reviewed for clinical and resource use information. Patients who had received prior therapy, had second primary cancers, or received palliative radiation therapy were excluded. The risk of OM was analyzed by multiple variable logistic regression. The cost of care was computed from the provider's perspective in 2006 U.S. dollars and compared among patients with and without OM. RESULTS: Oral mucositis occurred in 91% of patients; in 66% it was severe (Grade 3-4). Oral mucositis was more common among patients with oral cavity or oropharynx primaries (odds ratio [OR], 44.5; 95% confidence interval [CI], 5.2 to >100; p < 0.001), those who received chemotherapy (OR = 7.8; 95% CI, 1.5-41.6; p = 0.02), and those who were treated with altered fractionation schedules (OR = 6.3; 95% CI, 1.1-35.1; p = 0.03). Patients with OM were significantly more likely to have severe pain (54% vs. 6%; p < 0.001) and a weight loss of > or =5% (60% vs. 17%; p < 0.001). Oral mucositis was associated with an incremental cost of $1700-$6000, depending on the grade. CONCLUSIONS: Head-and-neck RT causes OM in virtually all patients. Oral mucositis is associated with severe pain, significant weight loss, increased resource use, and excess cost. Preventive strategies are needed.

Alimentary tract mucositis in cancer patients: impact of terminology and assessment on research and clinical practice.

BACKGROUND AND SIGNIFICANCE: The field of terminology and assessment of oral and gastrointestinal mucosal injury caused by high-dose cancer therapies in cancer patients has undergone important evolution in recent years. The advances are important for several clinical and research reasons. These reasons include improved patient management and design and conduct of clinical trials based on molecularly targeted therapies. For several decades leading up to the 1980s, terminology was characterized by varying use of "mucositis" and "stomatitis" to describe oral mucosal inflammatory changes and ulceration caused by cancer treatments. In addition, oral mucositis was viewed principally as an epithelial event and one that likely did not intersect with causative mechanisms associated with gastrointestinal mucositis. The term "stomatitis" was directed to oral toxicities and seemed to isolate these conditions from parallel events occurring throughout the alimentary tract and potentially other tissues as well. These perspectives and varying use of these terms resulted in several dilemmas, including (1) difficulty in accurately reporting incidence and severity of oral mucositis and, (2) an under-appreciation of potential significance of alimentary tract mucosal toxicity relative to overall course of therapy, patient quality of life, and in some cases, survivorship. These and related components of the model relative to mucositis have undergone strategic shifts over the past 15 years. A 1989 National Institutes of Health Consensus Development Conference targeted oral mucositis research as one of the key areas for investigation relative to causation, clinical impact, and potential links with other complications in cancer patients. Research in this area over the past 15 years has evolved such that oral and gastrointestinal mucositis are now appropriately framed as a continuum of pathobiologic changes over time, with clinical impact that may well contribute to overall symptom clustering in selected patient cohorts. OBJECTIVES: This paper will review history, current status, and new research directions associated with terminology and assessment of mucosal injury in cancer patients in the context described above.