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United Kingdom Oral Mucositis in Cancer Care Guidance: Second Edition Barry Quinn, Maureen Thomson, Jeff Horn, Jenny Treleaven, David Houghton, Lorraine Fulman, Sonja Hoy, Frances Campbell Expert Reviews on the Second Edition: ‘I think it’s an excellent resource - I think the appendices would be particularly useful in the clinical setting’ (R. Logan, President ISOO) ‘I absolutely love the stratification of people at risk. We tried to get it, but somehow couldn’t find a clear position. So I will use yours as an inspiration for our second edition’ (D. Riesenbeck, Oncologist, Germany) ‘I think this is an excellent, user- friendly document, your group has done outstanding work’ (A. Hovan, Dentist, Canada) ‘I think the material is very informative & useful in clinical settings’ (M. Tanay, Nurse Tutor, UK) Background: Changes to the oral cavity can be caused by numerous factors including the disease, the direct and indirect impact of cancer treatments and supportive care, existing co-morbidities and underlying oral health problems. The United Kingdom Oral Mucositis in Cancer Care (UK OMiC), a multi- professional expert group was founded in 2011 to address the challenges of oral complications secondary to disease and treatment in the cancer and supportive care setting. Methods: The first edition of the oral care clinical guidance produced in 2012 has been widely used within the United Kingdom and many other countries to help support and improve practice. The group has continued to disseminate the guidance, through the delivery of several national study days, numerous educational workshops and lectures, while continuing to collaborate with international organisations. Results: This presentation focuses on the second edition of the oral care guidance (2015) which is based on the most recent evidence, including MASCC guidance, clinician and patient feedback and expert opinion. Incidence: The incidence of OM in the cancer setting is much higher than previously thought and can be expected to occur in at least 50% of patients undergoing chemotherapy to treat a solid tumour, although some studies and reports (Sonis et al 2004, Elad et al 2014) indicate that the incidence is likely to be much higher. As many as 98% of patients undergoing haematopoietic stem cell transplantation (HSCT) are thought to be affected by OM and oral damage (Wardley et al 2000). Kostler et al. (2001) estimate that as many as 97% of all patients receiving radiotherapy (with/without chemotherapy) for head and neck cancers will suffer from some degree of OM. With the increasing use of targeted drug therapies, problems in the oral cavity may increase(Quinn et al 2015). Key achievements of UKOMiC include: Multi-Professional Study Days 4 national study days with over 200 attendees Training Multiple clinical based interactive training sessions Website 8,800 visits from 6,400 unique visitors Guidance First & Second Edition of Guidance 4600 downloads of the guidance 5000 hard copies distributed The guidance continues to focus on the key principles of: Accurate Assessment • Use a recognised grading system • Assess high-risk patients on a daily basis Regular Care • Encourage good oral hygiene (toothbrush and toothpaste) • Well-balanced diet, avoidance of alcohol & tobacco • Use a saline mouthwash to gargle and rinse • Treat dry lips using appropriate products Prevent/reduce oral damage Moderate Risk: Increase frequency of saline mouthwashes Ice cubes to reduce oral damage and dry mouth • Anti-infective prophylaxis • Caphosol ® Mucosal protectants MuGard ® Gelclair ® OraLife ® High risk: In addition to the interventions for moderate-risk patients, consider the following; Daily vitamin B supplements (if patient has known alcohol issues) Prophylactic insertion of enteral feeding tube before commencement of treatment Palifermin HSCT +/-TBI Treatment interventions Grade 1 or 2 OM: • Ensure good oral hygiene and increase the frequency of saline rinses • Monitor nutritional status • Monitor for oral infection, swab and treat as required • Consider: Paracetamol mouthwash 4 x per day • Benzydamine 0.15% mouthwash (Difflam ® ), Caphosol ® , Saliva replacement, Mucosal protectants, e.g. Episil ® , Gelclair ® or MuGard ® OraLife ® Grade 3 or 4 OM: Opioid analgesics (severe OM may require a syringe driver) • Intravenous and/or enteral hydration and feeding • Increase frequency of Caphosol ® & Mucosal protectants, e.g. Episil ® , Gelclair ® or MuGard ® OraLife ® • Tranexamic acid to treat localised bleeding Take swabs to identify the nature of bacterial, fungal and/or viral infections Conclusion: It is anticipated that this second edition of the guidance will further assist health care professionals in planning and implementing oral care into everyday practice, thus reducing a significant health burden for the patient and reduce demands on limited health care resources. The challenge remains as new and developing targeted agents including TKI’s and immunotherapy continue to be used in clinical practice. Elad, S.et al (2014) Basic Oral Care for hematology-oncology patients: A Position paper from the joint taskforce of MASCC/ISOO and EBMT. Journal of Supportive Care Kostler, W. J, et al (2001) Oral mucositis complicating chemotherapy and/or radiotherapy: options for prevention and treatment Cancer Journal for Clinicians (51):290–315. Quinn, B. et al (2015) Mouth Care Guidance and Support in Cancer and Palliative Care: Second Edition. www. ulkomic.co.uk Wardley AM. Et al (2000) Prospective evaluation of oral mucositis in patients receiving myeloablative conditioning regimens and haemopoietic progenitor rescue. BrJHaematol. 110:292–299 Contents 1.0 Executive Summary 2.0 Assessment of the Oral Cavity 3.0 Care of the Oral Cavity 4.0 Prevention of Oral Mucositis and Oral Complications 5.0 Treatment of Oral Mucositis and Oral Complications 6.0 Appendices 7.0 References Second Edition Mouth care guidance and support in cancer and palliative care Contributors Maureen Thomson Consultant Radiographer (Chair) Dr Barry Quinn Lead Nurse Cancer & Palliative Care/ Honorary Senior Lecturer (Guidance Lead) Jeff Horn Clinical Nurse Specialist (CNS) Haematology Dr Jenny Treleaven Consultant Haematologist David Houghton Senior Pharmacist Lorraine Fulman Information & Support Radiographer Sonja Hoy CNS Head, Neck and Thyroid Cancer Frances K Campbell CNS Head and Neck Cancer Expert reviewers M. Tanay (UK) Professor R. Logan (Australia) Dr D. Riesenbeck (Germany) Dr A. Hovan (Canada) 2nd Edition May 2015 OM Grade Clinical Presentation 1 Soreness +/- erythema, no ulceration. 2 Erythema, ulcers. Patients can swallow solid diet. 3 Ulcers, extensive erythema. Patients cannot swallow solid diet. 4 OM to the extent that alimentation is not possible. WHO Oral Toxicity Scale Left inside cheek Soft palate Left lateral and ventral tongue Floor of mouth Upper inside lip Right inside cheek Right lateral and ventral tongue Lower inside lip Oral Sites to be Evaluated Mouth Care Quick Guide Patient Risk Factors 1,2,3 Dehydration Poor nutritional intake Type and extent of malignancy, other co-morbidity factors Type and dose of anti-cancer therapy Inability or lack of motivation towards undertaking oral hygiene Other drugs and therapies causing dryness or changing the normal mucosal environment e.g. opiates, diuretics, sedatives, oxygen therapy Age (older adults and children are more susceptible to oral problems) Rapid breathing Pre-existing dental problems Alcohol/tobacco use 1. Barasch & Peterson (2003). 2. Beck (2004). 3. Quinn (2008). UK Oral Mucositis in Cancer Group | Mouth care guidance and support in cancer and palliative care Appendix 1.0: 9 Mouth care guidance and support in cancer and palliative care | Treatment of Oral Mucositis and Oral Complications 5.0 Treatment of Oral Mucositis and Oral Complications All treatment plans should be based upon the grading of oral damage. 5.1 Mild/Moderate Mucositis/ Oral Complications (Grade 1-2) Ensure oral hygiene is adequate including plaque removal. Consider increasing the frequency of saline rinses. Consider the need to remove dentures if they are irritating. Offer support with smoking cessation. Closely monitor nutritional status and refer to dietician if eating and drinking are affected. Provide simple analgesia, which may include soluble paracetamol 1 g four times daily (tablets should be dissolved in water and used as a mouthwash before swallowing). It should be remembered that paracetamol may mask fever. Escalate to soluble co- codamol 30/500 if required. The use of non steroidal anti-inflammatory drugs may be contraindicated due to the risk of bleeding and renal impairment (Keefe et al., 2007). Consider Benzydamine 0.15% oral solution (Difflam®), 10ml rinsed around the mouth and spat out. Repeat as required. If the patient complains of stinging, dilute 10 ml of Difflam® with 10 ml of water prior to administration and use 10 ml. However, this may be poorly tolerated in patients receiving head and neck radiotherapy and any patient with severe mucositis. Consider the use of low level laser therapy (Lalla et al, 2014). Consider increasing folinic acid rescue for methotrexate-induced mucositis. Check to see if the patient has evidence of oral infection and if so ensure an anti-infective agent is prescribed (see Section 5.4) (Quinn 2008). Consider Caphosol® (4–10 times a day) to prevent grade 1 and 2 OM becoming more severe (Quinn 2013). Consider applying a coating protectant. Consider a saliva replacement/ substitute. 5.2 Severe Mucositis/Oral Complications (Grade 3-4) In addition to the recommendations for mild/moderate the following should be considered: Use of stronger analgesia, including Oxynorm®, Sevredol® and Oramorph® to alleviate pain (some liquid based analgesia may have an alcohol base which should be used with caution as it may cause irritation to the mucosa). If patients continue to suffer with pain from mucositis, consider using further opioid analgesia and review administration route, such as fentanyl patches, patient-controlled analgesia or a syringe driver (seek advice from the acute pain team or the palliative care service). Laxative medications should be prescribed as standard to prevent constipation and associated nausea (Watson et al, 2011). Ensure intravenous and/or enteral hydration and feeding is prescribed, as oral intake may be reduced (following consultation with the dietician). Consider Caphosol® (4–10 times a day). Consider applying a coating protectant, e.g. Gelclair®, Oralife gel®, MuGard® Episil®. The product should be rinsed around the mouth to form a protective layer over the sore areas, and generally applied 1 hour before eating. These products are not to be swallowed. Risk Classification: Risk Factors Intervention Patients with a previous history of grade 2 OM. Patients receiving agents known to cause OM such as Capecitabine, 5-Fluorouracil, Docetaxel, Cyclophosphamide, anthracycline containing regimens, and targeted treatments including Epidermal Growth Factor Receptor (EGFR) inhibitors. Palliative radiotherapy to the head and neck region. Pharmacological agents and/ or co-morbidities predisposing the patient to xerostomia. The very young and the elderly. Increasing the frequency of saline mouthwashes (National Cancer Institute (US) 2013). Ice chips are recommended for 5 -fluorouracil bolus treatment and for high dose Melphalan (Keefe et al., 2007; Worthington et al., 2011; Lalla et al., 2014). Swish ice chips in the mouth for 30 minutes, beginning 5 minutes before treatment is administered. Benzydamine 0.15% oral solution (Difflam ® ) use 10 ml rinsed around the mouth and spat out 4 times a day. In the head and neck setting, Difflam is recommended for patients receving radiation only (up to 50Gy) (Peterson et al 2011, Lalla et al, 2014). Caphosol ® (4–10 times a day), recommended to start on the first day of chemotherapy or the first day of radiotherapy to head and neck region (Papas et al., 2003, Quinn 2013). Consider mucosal protectants, including Gelclair ®, Oralife gel ® MuGard ® (available in USA). MODERATE RISK of Oral Damage and/or OM e.g. WHO grade 2 In addition to the preventative interventions for low risk patients, consider: Acknowledgement EUSA Pharma Scan here to be taken directly to the Second Edition UKOMiC Guidance

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United Kingdom Oral Mucositis in Cancer Care Guidance: Second EditionBarry Quinn, Maureen Thomson, Jeff Horn, Jenny Treleaven, David Houghton, Lorraine Fulman, Sonja Hoy, Frances Campbell

Expert Reviews on the Second Edition:

‘I think it’s an excellent resource - I think the appendices would be particularly useful in the clinical setting’(R. Logan, President ISOO)

‘I absolutely love the stratification of people at risk. We tried to get it, but somehow couldn’t find a clear position. So I will use yours as an inspiration for our second edition’ (D. Riesenbeck, Oncologist, Germany)

‘I think this is an excellent, user-friendly document, your group has done outstanding work’ (A. Hovan, Dentist, Canada)

‘I think the material is very informative & useful in clinical settings’(M. Tanay, Nurse Tutor, UK)

Background: Changes to the oral cavity can be caused by numerous factors including the disease, the direct and indirect impact of cancer treatments and supportive care, existing co-morbidities and underlying oral health problems.

The United Kingdom Oral Mucositis in Cancer Care (UKOMiC), a multi-professional expert group was founded in 2011 to address the challenges of oral complications secondary to disease and treatment in the cancer and supportive care setting.

Methods: The first edition of the oral care clinical guidance produced in 2012 has been widely used within the United Kingdom and many other countries to help support and improve practice. The group has continued to disseminate the guidance, through the delivery of several national study days, numerous educational workshops and lectures, while continuing to collaborate with international organisations.

Results: This presentation focuses on the second edition of the oral care guidance (2015) which is based on the most recent evidence, including MASCC guidance, clinician and patient feedback and expert opinion.

Incidence: The incidence of OM in the cancer setting is much higher than previously thought and can be expected to occur in at least 50% of patients undergoing chemotherapy to treat a solid tumour, although some studies and reports (Sonis et al 2004, Elad et al 2014) indicate that the incidence is likely to be much higher.

As many as 98% of patients undergoing haematopoietic stem cell transplantation (HSCT) are thought to be affected by OM and oral damage (Wardley et al 2000). Kostler et al. (2001) estimate that as many as 97% of all patients receiving radiotherapy (with/without chemotherapy) for head and neck cancers will suffer from some degree of OM. With the increasing use of targeted drug therapies, problems in the oral cavity may increase(Quinn et al 2015).

Key achievements of UKOMiC include:

Multi-Professional Study Days 4 national study days with over 200 attendees Training Multiple clinical based interactive training sessions Website 8,800 visits from 6,400 unique visitors Guidance First & Second Edition of Guidance 4600 downloads of the guidance 5000 hard copies distributed

The guidance continues to focus on the key principles of:

Accurate Assessment• Use a recognised grading system• Assess high-risk patients on a daily

basis

Regular Care• Encourage good oral

hygiene (toothbrush and toothpaste)

• Well-balanced diet, avoidance of alcohol & tobacco

• Use a saline mouthwash to gargle and rinse

• Treat dry lips using appropriate products

Prevent/reduce oral damage

Moderate Risk: • Increase frequency of saline mouthwashes • Ice cubes to reduce oral damage and dry mouth• Anti-infective prophylaxis• Caphosol® • Mucosal protectants MuGard® Gelclair® OraLife®

High risk: • In addition to the interventions for moderate-risk patients, consider the following; • Daily vitamin B supplements (if patient has known alcohol issues) • Prophylactic insertion of enteral feeding tube before commencement of treatment• Palifermin HSCT +/-TBI

Treatment interventions

Grade 1 or 2 OM: • Ensure good oral

hygiene and increase the frequency of saline rinses

• Monitor nutritional status • Monitor for oral infection, swab and

treat as required • Consider: Paracetamol mouthwash

4 x per day • Benzydamine 0.15%

mouthwash (Difflam®), Caphosol®, Saliva replacement, Mucosal protectants, e.g. Episil®, Gelclair® or MuGard® OraLife®

Grade 3 or 4 OM: • Opioid analgesics (severe OM may require a syringe driver) • Intravenous and/or enteral hydration and feeding • Increase frequency of Caphosol® & Mucosal protectants, e.g. Episil®,

Gelclair® or MuGard® OraLife® • Tranexamic acid to treat localised bleeding • Take swabs to identify the nature of bacterial, fungal and/or viral

infections

Conclusion: It is anticipated that this second edition of the guidance will further assist health care professionals in planning and implementing oral care into everyday practice, thus reducing a significant health burden for the patient and reduce demands on limited health care resources. The challenge remains as new and developing targeted agents including TKI’s and immunotherapy continue to be used in clinical practice.

Elad, S.et al (2014) Basic Oral Care for hematology-oncology patients: A Position paper from the joint taskforce of MASCC/ISOO and EBMT. Journal of Supportive Care

Kostler, W. J, et al (2001) Oral mucositis complicating chemotherapy and/or radiotherapy: options for prevention and treatment Cancer Journal for Clinicians (51):290–315.

Quinn, B. et al (2015) Mouth Care Guidance and Support in Cancer and Palliative Care: Second Edition. www.ulkomic.co.uk

Wardley AM. Et al (2000) Prospective evaluation of oral mucositis in patients receiving myeloablative

conditioning regimens and haemopoietic progenitor rescue. BrJHaematol. 110:292–299

Contents1.0 • Executive Summary

2.0 • Assessment of the Oral Cavity

3.0 • Care of the Oral Cavity

4.0 • Prevention of Oral Mucositis and Oral Complications

5.0 • Treatment of Oral Mucositis and Oral Complications

6.0 • Appendices

7.0 • References

Second Edition

Mouth care guidance and support incancerandpalliativecare

ContributorsMaureen Thomson ConsultantRadiographer(Chair)

Dr Barry Quinn LeadNurseCancer&PalliativeCare/

HonorarySeniorLecturer(GuidanceLead)

Jeff Horn ClinicalNurseSpecialist(CNS)Haematology

Dr Jenny Treleaven ConsultantHaematologist

David Houghton SeniorPharmacist

Lorraine Fulman Information&SupportRadiographer

Sonja Hoy CNSHead,NeckandThyroidCancer

Frances K Campbell CNSHeadandNeckCancer

Expert reviewers M. Tanay (UK) Professor R. Logan (Australia) Dr D. Riesenbeck (Germany) Dr A. Hovan (Canada)

2ndEditionMay2015

OM Grade Clinical Presentation

1 Soreness +/- erythema, no ulceration.

2Erythema, ulcers. Patients can swallow solid diet.

3Ulcers, extensive erythema. Patients cannot swallow solid diet.

4OM to the extent that alimentation is not possible.

WHO Oral Toxicity Scale

Left inside cheek

Soft palate

Left lateral and ventral tongue

Floor of mouth

Upper inside lip

Right inside cheek

Right lateral and ventral tongue

Lower inside lip

Oral Sites to be Evaluated

Mouth Care Quick Guide

Patient Risk Factors1,2,3

• Dehydration

• Poor nutritional intake

• Type and extent of malignancy, other co-morbidity factors

• Type and dose of anti-cancer therapy

• Inability or lack of motivation towards undertaking oral hygiene

• Other drugs and therapies causing dryness or changing the normal mucosal environment e.g. opiates, diuretics, sedatives, oxygen therapy

• Age (older adults and children are more susceptible to oral problems)

• Rapid breathing

• Pre-existing dental problems

• Alcohol/tobacco use

1. Barasch & Peterson (2003). 2. Beck (2004). 3. Quinn (2008).

UK Oral Mucositis in Cancer Group | Mouth care guidance and support in cancer and palliative care

Appendix 1.0:

9

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5.0Treatment of Oral Mucositis and Oral Complications

All treatment plans should be based upon the grading of oral damage.

5.1 Mild/Moderate Mucositis/Oral Complications (Grade 1-2)

• Ensureoralhygieneisadequateincludingplaqueremoval.

• Considerincreasingthefrequencyofsalinerinses.

• Considertheneedtoremovedenturesiftheyareirritating.

• Offersupportwithsmokingcessation.

• Closelymonitornutritionalstatusandrefertodieticianifeatinganddrinkingareaffected.

• Providesimpleanalgesia,whichmayincludesolubleparacetamol1gfourtimesdaily(tabletsshouldbedissolvedinwaterandusedasamouthwashbeforeswallowing).Itshouldberememberedthatparacetamolmaymaskfever.Escalatetosolubleco-codamol30/500ifrequired.Theuseofnonsteroidalanti-inflammatorydrugsmaybecontraindicatedduetotheriskofbleedingandrenalimpairment(Keefeetal.,2007).

• ConsiderBenzydamine0.15%oralsolution(Difflam®),10mlrinsedaroundthemouthandspatout.Repeatasrequired.Ifthepatientcomplainsofstinging,dilute10mlofDifflam®with10mlofwaterpriortoadministrationanduse10ml.However,thismaybepoorlytoleratedinpatientsreceivingheadandneckradiotherapyandanypatientwithseveremucositis.

• Considertheuseoflowlevellasertherapy(Lallaetal,2014).

• Considerincreasingfolinicacidrescueformethotrexate-inducedmucositis.

• Checktoseeifthepatienthasevidenceoforalinfectionandifsoensureananti-infectiveagentisprescribed(seeSection5.4)(Quinn2008).

• ConsiderCaphosol®(4–10timesaday)

topreventgrade1and2OMbecomingmoresevere(Quinn2013).

• Considerapplyingacoatingprotectant.

• Considerasalivareplacement/substitute.

5.2 Severe Mucositis/Oral Complications (Grade 3-4)In addition to the recommendations for mild/moderate the following should be considered:

• Useofstrongeranalgesia,includingOxynorm®,Sevredol®andOramorph®toalleviatepain(someliquidbasedanalgesiamayhaveanalcoholbasewhichshouldbeusedwithcautionasitmaycauseirritationtothemucosa).Ifpatientscontinuetosufferwithpainfrommucositis,considerusingfurtheropioidanalgesiaandreviewadministrationroute,suchasfentanylpatches,patient-controlledanalgesiaorasyringedriver(seekadvicefromtheacutepainteamorthepalliativecareservice).Laxativemedicationsshouldbeprescribedasstandardtopreventconstipationandassociatednausea(Watsonetal,2011).

• Ensureintravenousand/orenteralhydrationandfeedingisprescribed,asoralintakemaybereduced(followingconsultationwiththedietician).

• ConsiderCaphosol®(4–10timesaday).

• Considerapplyingacoatingprotectant,e.g.Gelclair®,Oralifegel®,MuGard®Episil®.Theproductshouldberinsedaroundthemouthtoformaprotectivelayeroverthesoreareas,andgenerallyapplied1hourbeforeeating.Theseproductsarenottobeswallowed.

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Risk Classification:

Risk Factors Intervention

Patientswithaprevioushistoryofgrade2OM.

PatientsreceivingagentsknowntocauseOMsuchasCapecitabine,5-Fluorouracil,Docetaxel,Cyclophosphamide,anthracyclinecontainingregimens,andtargetedtreatmentsincludingEpidermalGrowthFactorReceptor(EGFR)inhibitors.

Palliativeradiotherapytotheheadandneckregion.Pharmacologicalagentsand/orco-morbiditiespredisposingthepatienttoxerostomia.

Theveryyoungandtheelderly.

Increasing the frequency of saline mouthwashes (NationalCancerInstitute(US)2013).

Ice chips arerecommendedfor5-fluorouracilbolustreatmentandforhighdoseMelphalan(Keefeetal.,2007;Worthingtonetal.,2011;Lallaetal.,2014).

Swishicechipsinthemouthfor30minutes,beginning5minutesbeforetreatmentisadministered.

Benzydamine 0.15% oral solution (Difflam®)use10mlrinsedaroundthemouthandspatout4timesaday.

Intheheadandnecksetting,Difflamisrecommendedforpatientsrecevingradiationonly(upto50Gy)(Petersonetal2011,Lallaetal,2014).

Caphosol® (4–10 times a day), recommendedtostartonthefirstdayofchemotherapyorthefirstdayofradiotherapytoheadandneckregion(Papasetal.,2003,Quinn2013).

Consider mucosal protectants, including Gelclair®, Oralife gel® MuGard® (availableinUSA).

MODERATE RISK of Oral Damage and/or OM e.g. WHO grade 2

In addition to the preventative interventions for low risk patients, consider:

Acknowledgement EUSA Pharma Scan here to be taken directly to the Second Edition UKOMiC Guidance