Mucositis and Mouth Care

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1 Mucositis and Mouth Care Page 1 of 8 Table of Contents Introduction for the Learner (Resident/Oncology Fellow) Introduction for Clinical Faculty Evaluator... 2 Part 1: Learning Objectives Part 2: Teaching Outline Part 3: Evaluation Checklist... 7

2 Mucositis and Mouth Care Page 2 of 8 Introduction for the Learner (Resident/Fellow) Prior to your evaluation of competency: Complete the web-based palliative care training program Medical Resident Training in End-of-Life and Palliative Care before you undergo this competency assessment. The training program is available on the UMMS Intranet, click on Physicians. The course is listed under Helpful Links. It is also available via the internet at -- Review Part 1 (Learning Objectives), Part 2 (Teaching Outline) and Part 3 (Evaluation Checklist) THOROUGHLY so that you are aware of what is required of you. When you think you are suitably prepared for testing your competency in this area, ask the attending physician on your inpatient clinical rotation to evaluate the selected competency when the appropriate clinical situation arises. Ascertain that the attending/faculty member is certified to conduct the Palliative Care Competency Evaluation. Field evaluation of competency: During the course of a clinical rotation, it is anticipated that you will have opportunities to demonstrate your competency in Mucositis and Mouth Care with regard to palliative and end-of-life care during morning work rounds with your attending, and also throughout the day or during times of night call or cross-coverage. Identify a faculty member to evaluate your competency current service attending recommended, if s/he is certified to conduct evaluation. ASK FACULTY MEMBER TO REVIEW THIS COMPETENCY ASSESSMENT TOOL PRIOR TO YOUR PERFORMING THIS TASK SO THAT THEIR MEMORY WILL BE REFRESHED AS TO THE DESIRED CHARACTERISTICS OF PERFORMANCE THEY WILL BE EVALUATING during the course of the rotation. At the end of the rotation, the Clinical Faculty Evaluator completes the Evaluation Checklist (Part 3) of this document, and shares it with you. You will also complete the self-evaluation portion of the checklist as a measure of competency in practice based learning. Evaluation Checklist must be signed by faculty and Resident. Return Evaluation Checklist to Dr. Susan Wolfsthal, Internal Medicine Residency Director or Dr. Heather Mannuel, Hematology/Oncology Fellowship Director. Introduction for the Clinical Faculty Evaluator How to perform this competency assessment: A Medical Resident or Oncology Fellow has requested that you assess their competency in a selected palliative care domain during the time you are the attending physician on this service. To assist you with this evaluation, please do the following. Preparing for field evaluation of competency: Review this Competency Assessment Tool thoroughly including the Learning Objectives (Part 1), Teaching Outline (Part 2) and Evaluation Checklist (Part 3) prior to pre-discussion counseling with Resident (required). Format of competency evaluation: During the clinical rotation Based on the Learning Objectives (Part 1), Teaching Outline (Part 2), and Evaluation Checklist (Part 3) of this document and the content in Unit II, Module 5 of the palliative care training website, assess whether the Resident or Fellow meets the Learning Objectives during the course of this clinical rotation. End-of-rotation feedback Review strengths and weaknesses of competency evaluation with Resident/Fellow. Provide constructive feedback to improve Residents/Fellows performance and patient outcomes. Complete Evaluation Checklist (Part 3 of this document) Share with learner; allow learner to make his/her own selfassessment of performance. Faculty and Resident/Fellow must sign this Evaluation Checklist (Part 3). Learner is responsible for returning Evaluation Checklist to Dr. Wolfsthal (Residents) or Dr. Mannuel (Fellows).

3 Mucositis and Mouth Care Page 3 of 8 Part 1: Learning Objectives Note to learner and Clinical Faculty Evaluator: The Learning Objectives are listed in terms of fulfilling the six ACGME core competencies, listed below; these are reflected in Evaluation Checklist in Part 3 of this document. LEGEND to ACGME core competencies: OBJECTIVES A competent Medical Resident or Oncology Fellow will be able to: Recognize mucositis as a common and debilitating toxicity of cancer treatment. ACGME Competencies PC MK PBL&I IPCS P SBP Describe the pathophysiology of oral discomfort in patients with chronic and terminal diseases. Assess causes of oral discomfort in a given patient based on pathophysiologic mechanisms. Develop an effective cause-directed plan of care to relieve oral discomfort. Prescribe an appropriate and effective regimen to relieve this pain while cause-directed treatments are taking effect. Formulate a plan of treatment for symptomatic relief of oral mucosal lesions that is adjunctive to pain medications. Formulate a plan of mouth care for patients with dry mouth from a variety of cause. Discuss the contraindications of chlorhexidine mouthwash in patients with active mucositis/mouth ulcers. Foster a partnership with the patient / family caregivers and medical care team to foster their active participation in the care plan. LEGEND: PC Patient Care MK Medical Knowledge PBL&I Practice-Based Learning and Improvement IPCS Interpersonal and Communication Skills P Professionalism SBP Systems-Based Practice (Adapted from Weissman, DE, Ambuel, B, Hallenbeck, JL. Improving end-of-life care: A resource guide for physician education. 4th ed. Milwaukee: Medical College of Wisconsin, 2007 and Emanuel LL, von Gunten CF, Ferris FD. The Education in Palliative and End-of-life Care [EPEC] Curriculum. Chicago: American Medical Association; 1999).

4 Mucositis and Mouth Care Page 4 of 8 Part 2: Teaching Outline for Learner and Clinical Faculty Evaluator (From Weissman, et al. 1 ) Portions of this outline were adapted from Emanuel LL, Ferris FD, von Gunten CF, Von Roenn J, EPEC-O: Education in Palliative and End-of-Life Care for Oncology, The EPEC Project, Chicago, IL, 2005 Introduction Oral mucositis is a common complication of both chemotherapy and radiation therapy for cancer. It is the dose-limiting toxicity of concurrent chemotherapy and radiotherapy and of accelerated and hyperfractionated radiotherapy. From the patient s perspective, mucositis is a debilitating toxicity of therapy. Prevalence The overall incidence of oral mucositis is approximately 40% in patients who receive standard-dose chemotherapy. However, the incidence varies with the type of medication and the doses and schedules used, and mucositis occurs in up to 100% of patients undergoing high-dose chemotherapy with hematopoietic stem cell transplantation. Prognosis Mucositis is generally self-limiting. The prognosis is generally good if the co-morbidities such as pain, decreased oral intake, fluid deficits, and dental caries are also managed. However, mucositis has an impact on overall treatment outcomes. In patients receiving hematopoietic stem cell transplantation, mucositis is associated with an increased risk of infection and additional hospital days, days of parenteral nutrition, intravenous opioid use, and greater 100-day mortality. In general, the combination of neutropenia and mucositis increases the risk of infection. Pathophysiology Increasing understanding of the pathophysiology of mucositis reveals it to be a complex problem that is not simply a result of injury to the basal epithelial stem cells. Oral mucositis is caused by direct injury from radiation or chemotherapy, secondary infection, or graft versus host disease. The pathobiology of mucositis is a multistage process including initiation, message generation, amplification of signaling, ulceration, and healing. The initiation phase is characterized by both DNA and non-dna damage in the epithelial submucosa. The initial insult with radiation or chemotherapy triggers a cascade of biological events, many of which are mediated by the generation of reactive oxygen species. During the message generation phase, a number of transcription factors are upregulated (e.g., Nuclear factor kappa beta proteins, or NF-KB) leading to the production of pro-inflammatory cytokines and enzymes. The tissue injury caused by these factors is accelerated and amplified through feedback loops during the third phase, signaling/ amplification. These events lead to the clinical phase of concern, ulceration. The oral bacteria which colonize the ulcer s surface potentiate the injury through the shedding of cell wall products. These products activate macrophages, stimulate cytokines, and increase the injury. The final phase, healing, occurs spontaneously and is dependent on extracellular matrix signals, which are not well understood, and epithelial cell migration, proliferation, and differentiation. Assessment Mucositis is a mucosal barrier injury, characterized clinically by oral erythema, ulceration, and pain following the use of known stomatotoxic therapy. The timing and location of the oral lesions help differentiate mucositis from oral infections and graft versus host disease. Oral viral infections frequently coincide with fever and are typically localized and involve keratinized mucosa of the hard palate, gingiva, and dorsal tongue. Oral ulcers secondary to graft versus host disease are seen in patients who have undergone allogeneic stem cell transplantation, and may develop after hematologic recovery. These ulcers are often lichenoid in character and may be associated with xerostomia. Chemotherapy-induced mucositis most commonly involves the soft palate, antrum of the tongue/floor of the mouth, and buccal mucosa. Chemotherapy-induced mucositis generally presents 5-7 days after treatment and resolves within 2 days to a few weeks. While chemotherapy-induced mucositis tends to be acute, radiation-induced mucosal injury has a more chronic course. Radiation therapy-related mucositis is a function of the cumulative dose delivered. Mucositis is generally first seen after Gy have been delivered to the mucosa. At about 30 Gy, ulcerative mucositis develops. Mucositis due to radiation typically lasts 6 weeks. Management Prevention The prevention of oral mucositis has been an important goal. Four theoretical approaches have been articulated. 1. Reduce mucous membrane exposure to the cytotoxic agent. Oral cryotherapy is recommended for patients receiving bolus 5-FU. Theoretically, placing ice in the mouth 5 minutes before bolus treatment with 5-FU and for 30 minutes after chemotherapy cools the oral cavity, leading to vasoconstriction and decreased oral cavity medication exposure. Randomized trials have demonstrated a 50% reduction in 5-FU-induced oral mucositis with cryotherapy. Additional studies are under way. 2. Reduce infectious and inflammatory complications. Another mechanistically based therapy is glutamine supplementation. L-glutamine may decrease treatment-induced metabolic deficiencies and promote healing. Studies of L-glutamine oral rinses for mucositis have not shown efficacy, likely due to poor absorption when administered topically. AES-14, a proprietary vehicle which enhances mucosal uptake of L-glutamine, reduced the incidence of mucositis when used as a two-to-three-times-daily oral rinse in a placebo-controlled Phase III trial in patients at risk for mucositis secondary to anthracycline-based chemotherapy. Additional studies are under way. Antimicrobials are largely used for the treatment of associated or secondary infections. Iseganan, an analog of protegrin-l, has broad-spectrum antimicrobial activity. Early studies suggest its use reduces mucositis, though more data are needed.

5 Mucositis and Mouth Care Page 5 of 8 3. Modify epithelial proliferative capabilities. Keratinocyte growth factor, a member of the fibroblast growth factor family, is an epithelial mitogen which acts through a subset of fibroblast growth factor receptors expressed predominantly on epithelial cells. Keratinocyte growth factor is upregulated after epithelial injury and plays a role in tissue repair. A double-blind, randomized, placebo-controlled study of the intravenous administration of recombinant human keratinocyte growth factor (rhukgf-l, palifermin) in patients undergoing high-dose chemotherapy and hematopoietic stem cell transplantation demonstrated a reduction in the severity and duration of oral mucositis, improvement in quality of life, and decrease in opioid usage and days of total parenteral nutrition in patients who received rhukgf-l. Additional studies are under way. 4. Reduce and inhibit proinflammatory cytokines. A topical, nonsteroidal anti-inflammatory agent, benzydamine, has recently been shown to reduce the frequency and severity of oral ulcerations and the associated oral pain in patients with radiationinduced oral ulcers. Benzydamine, in addition to its analgesic and antimicrobial activities, inhibits the production and effects of proinflammatory cytokines. Treatment Once mucositis begins, treatment is supportive. Little has been shown to change the overall course of mucositis. General measures such as oral hygiene and dietary modification, topical local anesthetics, and systemic analgesics have been recommended. Other options are currently being studied. Oral hygiene: Good oral hygiene appears to reduce the severity of oral mucositis. Patients should: Brush gently with a soft-bristled toothbrush using fluoridecontaining toothpaste two or three times daily. Floss gently, daily, to remove food build-up. Rinse the mouth every 4 hours with a dilute saline and baking soda solution (½ teaspoon salt plus ½ teaspoon baking soda in a cup of warm water). While this may be soothing, it has not been formally evaluated. Chlorhexidine use is no longer recommended, as it appears no better than sterile saline. In patients with radiotherapy- related mucositis, data suggest that chlorhexidine may worsen symptoms. Remove dentures at night. Limit food contact: Limit the amount of time food is allowed to come into contact with the oral mucosa. Recommend foods that require little or no chewing. Advise against foods that are irritating (e.g., acidic, spicy, salty, coarse, or dry). Pain relief is challenging. Local anesthetics provide some pain relief. These include topical lidocaine, benzocaine, tetracaine, chirocaine, and cocaine, as well as EMLA and magic mouthwash rinse (a mixture of lidocaine, diphenhydramine, and magnesium/aluminum antacids). Topical analgesics that may be useful include doxepin and topical opiates such as fentanyl. In addition, mucoadherent film-forming agents such as hydroxypropylene cellulose gels, sucralfate solutions, and Gelclair may be soothing. Systemic analgesics are frequently used. Patient-controlled analgesia with an opioid is recommended.13 Follow standard opioid dosing guidelines Summary Mucositis is a mucosal barrier injury characterized by oral erythema, ulceration, and pain. Its pathobiology is a multiphase process that has only recently been described. Preventive approaches include diminishing mucosal delivery of anticancer agents, using antimicrobial/anti-inflammatory interventions, modifying the underlying pathobiology, and reducing/inhibiting pro-inflammatory cytokines. Once mucositis is present, treatment focuses on good oral hygiene and comfort measures. Key Take-Home Points Understanding the pathobiology of mucositis provides the opportunity to develop pathogenesis-based therapies. Mucositis is a debilitating toxicity of treatment. Chemotherapy produces an acute injury while the mucosal injury from radiation therapy tends to be chronic. Pearls New agents for prevention are under evaluation. Management focuses on symptomatic relief. 1. To differentiate viral ulcers from treatment-induced mucositis, note that viral ulcers typically are localized and involve keratinized mucosa Oral ulcers secondary to graft versus host disease may occur after hematologic recovery. Provide adequate analgesia! 4. Make a partnership with your patient and the family caregiver; draw them into the interdisciplinary team and foster their active participation in the care plan. Pitfall Using some of the old mouthwash mixes, which recent evidence suggests are actually harmful when compared in headto-head trials. Don t use them. References Clarkson JE, Worthington HV, Eden TOB. Interventions for treating oral mucositis for patients with cancer receiving treatment. Cochran Database of Systematic Reviews 2007, Issue1 Art No: CD Dahlin C. Oral complications at the end-of-life. American Journal of Nursing. July, 2004; 104(7): DeConno F, Martini C, Sbanotto A, Ripamonti C, Ventafridda V. In Hanks G, Cherny NI, Christakis NA, Fallon M, Kaasa S, Portenoy RK (Eds). Oxford Textbook of Palliative Medicine (4th Ed.). NewYork: Oxford University Press pp Henson DF, Zrnold R. Fast Facts and Concepts #121L Oral mucositis: Diagnosis and Assessment. September, End-of-life Physician Education Resource Center. Hoffman H. Mucositis: Diagnosis and management. Head Neck. 2004;26:77-84.

6 Mucositis and Mouth Care Page 6 of 8 Keefe DM, Schubert MM, Elting LS, Sonis ST, Epstein JB, Raber-Durlacher JE, et al. Updated clinical practice guidelines for the prevention and treatment of mucositis. Cancer. Mar ;109(5): Available at journalclub/documents/oralmucositis1.pdf Treister NS, Woo SB. Chemotherapy induced oral mucositis Available at article/ overview Worthington HV, Clarkson JE, Eden OB. Interventions for preventing oral mucositis for patients with cancer receiving treatment (Review) The Cochrane Collaboration. John Wiley and Sons, Ltd Available at

7 Mucositis and Mouth Care Page 7 of 8 Part 3: Evaluation Checklist Date: Learner name: Evaluator/Attending: o Resident PGY Level: [ ] 1 [ ] 2 [ ] 3 [ ] 4 [ ] 5 o Fellowship Year: [ ] 1 [ ] 2 [ ] 3 [ ] 4 [ ] 5 Rotation Site: [ ] Inpatient Cancer Center [ ] Inpatient GIM [ ] Oncology Clinic [ ] Continuity GIM clinic [ ] Other Please rate the trainee s competency/skills/knowledge/attitude using the following scales: For competency/skills For knowledge and attitudes (e.g. Medical Knowledge) 4 = Competent to perform independently 4 = Superior 3 = Competent to perform with minimal supervision 3 = Satisfactory 2 = Competent to perform with close supervision / coaching 2 = Below average 1 = Needs further basic instruction 1 = Insufficient needs further learning n/o = not observed n/o = not observed OBJECTIVES Patient Care Developed an effective cause-directed plan of care to relieve oral discomfort. Prescribed an appropriate and effective regimen to relieve this pain while cause-directed treatments are taking effect. Formulated a plan of treatment for symptomatic relief of oral mucosal lesions that is adjunctive to pain medications. Formulated a plan of mouth care for patients with dry mouth from a variety of causes. Overall Performance: Medical Knowledge Recognized oral discomfort due to infection, dryness, or mucositis is an extremely common and debilitating condition in patients with terminal illnesses. Recognized mucositis as a common and debilitating toxicity of cancer treatment. Described the pathophysiology of oral discomfort in patients with chronic and terminal diseases. Discussed the contraindication of chlorhexidine mouthwash in patients with active mucositis/mouth ulcers. Overall Performance: Interpersonal and Communication Skills Assessed causes of oral discomfort in a given patient based on pathophysiologic mechanisms. Overall Performance:

8 Mucositis and Mouth Care Page 8 of 8 Part 3: Evaluation Checklist (Continued) Professionalism Fostered a partnership with the patient / family caregivers and medical care team to foster their active participation in the care plan. Overall Performance: Resident/Fellow strengths: Resident/Fellow areas for improvement: Overall impression: Did the Resident/Fellow demonstrate competency in a manner so as to do no harm? Resident/Fellow self-evaluation of performance: May comment on any of the above checklist items or other reflections on performance; perceived strengths, and need for improvement and learning. Clinical Faculty Evaluator/Attending Clinical Faculty Evaluator/Attending PRINTED NAME/DATE Resident/Fellow Resident/Fellow PRINTED NAME/DATE

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