Management of oral and gastrointestinal mucosal injury: ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up

Oral and gastrointestinal mucositis caused by high-dose chemotherapy and/or radiation continues to be an important clinical problem. Fortunately, there have been strategic advances over the past decade in understanding the molecular basis of the injury, providing opportunities for the development of drugs and devices to manage toxicity. The guidelines detailed below represent updates from the version published in the 2011 Annals of Oncology 1.Peterson D.E. Bensadoun R.J. Roila F. Management of oral and gastrointestinal mucositis: ESMO Clinical Practice Guidelines.Ann Oncol. 2011; 22: vi78-vi84Abstract Full Text Full Text PDF PubMed Scopus (183) Google Scholar, which were primarily based on the previous version of the guidelines produced by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO) 2.Keefe D.M. Schubert M.M. Elting L.S. et al.Updated clinical practice guidelines for the prevention and treatment of mucositis.Cancer. 2007; 109: 820-831Crossref PubMed Scopus (606) Google Scholar. Three key advances have occurred in the four years following publication of the previous ESMO mucositis guidelines. Each of these advances (listed below) have been completed at the international, inter-professional level:•A comprehensive update of oral and gastrointestinal tract mucositis guidelines previously produced by the Mucositis Study Group of MASCC in 2007 2.Keefe D.M. Schubert M.M. Elting L.S. et al.Updated clinical practice guidelines for the prevention and treatment of mucositis.Cancer. 2007; 109: 820-831Crossref PubMed Scopus (606) Google Scholar. The most recent updated evidence-based guidelines, published in 2014 3.Lalla R.V. Bowen J. Barasch A. et al.MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy.Cancer. 2014; 120: 1453-1461Crossref PubMed Scopus (714) Google Scholar, represent the state-of-the-science for mucositis management in patients receiving conventional chemotherapy and/or head and neck radiation.•Expert opinion on the management of mucosal injury caused by targeted cancer therapies such as vascular endothelial growth factor receptor (VEGFR) inhibitor, epidermal growth factor receptor (EGFR) inhibitors, (multi-targeted) tyrosine kinase inhibitors (TKIs), and mammalian target of rapamycin (mTOR) inhibitors 4.Boers-Doets C.B. Raber-Durlacher J.E. Treister N.S. et al.Mammalian target of rapamycin inhibitor-associated stomatitis.Future Oncol. 2013; 9: 1883-1892Crossref PubMed Scopus (59) Google Scholar. Since oral complaints associated with mTOR inhibitors have been studied in detail, we are able to provide more in depth information about this specific side-effect. From other targeted treatments such as BRAF-, PARP-, CTLA4-, and MEK inhibitors there is no expert consensus available upon which to base recommendations or suggestions for treatment.•Novel approaches to enteral nutrition in patients receiving head and neck radiation 5.Nugent B. Lewis S. O'Sullivan J.M. Enteral feeding methods for nutritional management in patients with head and neck cancers being treated with radiotherapy and/or chemotherapy.Cochrane Database Syst Rev. 2013; 1: CD007904Crossref PubMed Scopus (64) Google Scholar, 6.Koyfman S.A. Adelstein D.J. Enteral feeding tubes in patients undergoing definitive chemoradiation therapy for head-and-neck cancer: a critical review.Intl J Radiat Oncol Biol Phys. 2012; 84: 581-589Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar, 7.Williams G.F. Teo M.T. Sen M. et al.Enteral feeding outcomes after chemoradiotherapy for oropharynx cancer: a role for a prophylactic gastrostomy?.Oral Oncol. 2012; 48: 434-440Crossref PubMed Scopus (45) Google Scholar, 8.Rutter C.E. Yovino S. Taylor R. et al.Impact of early percutaneous endoscopic gastrostomy tube placement on nutritional status and hospitalization in patients with head and neck cancer receiving definitive chemoradiation therapy.Head Neck. 2011; 33: 1441-1447Crossref PubMed Scopus (62) Google Scholar, 9.Silander E. Nyman J. Bove M. et al.Impact of prophylactic percutaneous endoscopic gastrostomy on malnutrition and quality of life in patients with head and neck cancer: a randomized study.Head Neck. 2012; 34: 1-9Crossref PubMed Scopus (160) Google Scholar. In France and French-speaking countries, the Société Francophone de Nutrition et Métabolisme (SFNEP) and the Association Francophone pour les Soins Oncologiques de Support (AFSOS) published comprehensive recommendations for cancer patients 10.SFNEP (Societe Francophone de Nutrition Enterale et Parenterale) SFNEP Oncology Nutrition Guidelines.Nutrition Clinique et Métabolisme. 2012; 26 (20 April 2015, date last accessed)http://www.em-consulte.com/revue/NUTCLI/26/4/table-des-matieres/Google Scholar, 11.Bachmann P. Romero G. Deneuve S. et al.Référentiel de pratiques professionnelles: prise en charge nutritionnelle des cancers des voies aérodigestives supérieures.Nutr Clin Métab. 2014; 28: 207-215Crossref Scopus (4) Google Scholar, 12.French Speaking Society of Clinical Nutrition and Metabolism Clinical nutrition guidelines of the French Speaking Society of Clinical Nutrition and Metabolism (SFNEP): summary of recommendations for adults undergoing non-surgical anticancer treatment.Dig Liver Dis. 2014; 46: 667-674Abstract Full Text Full Text PDF Scopus (50) Google Scholar. Mucositis is defined as inflammatory and/or ulcerative lesions of the oral and/or gastrointestinal tract. Infectious disease, immune deficiency and medications can be causative. High-dose cancer chemotherapy and radiotherapy in head and neck cancer are two of the major causes of mucositis. The terms oral mucositis and stomatitis are often used interchangeably, but they do not reflect identical processes 4.Boers-Doets C.B. Raber-Durlacher J.E. Treister N.S. et al.Mammalian target of rapamycin inhibitor-associated stomatitis.Future Oncol. 2013; 9: 1883-1892Crossref PubMed Scopus (59) Google Scholar, 13.National Cancer Institute PDQ®. Oral mucositis. In Oral Complications of Chemotherapy/Head http://www.cancer.gov/cancertopics/pdq/supportivecare/oralcomplications/HealthProfessional/page5 (9 April 2015, date last accessed).Google Scholar. 'Mucositis' is a Medical Subject Heading term that describes inflammation of mucosa resulting from chemotherapeutic agents or ionising radiation. It typically manifests as erythema or ulcerations and may be exacerbated by local factors, such as secondary infections and trauma. Examples of chemotherapeutic agents which may cause oral mucositis are cyclophosphamide, doxorubicin, vincristine, etoposide, ifosfamide, methotrexate, docetaxel, paclitaxel, cisplatin, carboplatin, oxaliplatin, irinotecan, 5-fluorouracil (5-FU), leucovorin, and vinorelbine.'Stomatitis' refers more generally to any inflammatory condition of oral tissues 13.National Cancer Institute PDQ®. Oral mucositis. In Oral Complications of Chemotherapy/Head http://www.cancer.gov/cancertopics/pdq/supportivecare/oralcomplications/HealthProfessional/page5 (9 April 2015, date last accessed).Google Scholar. This term should be used for oral complaints not related to chemotherapeutic agents or ionising radiation, such as targeted therapies. Clinically important adverse events (AEs) that disrupt the normal oral function have been described related to use of targeted therapies. These include altered taste and taste loss, oral sensitivity and pain without the presence of clinical oral lesions, and xerostomia 4.Boers-Doets C.B. Raber-Durlacher J.E. Treister N.S. et al.Mammalian target of rapamycin inhibitor-associated stomatitis.Future Oncol. 2013; 9: 1883-1892Crossref PubMed Scopus (59) Google Scholar. Compared with mTOR inhibitor-associated stomatitis, less attention has been paid to these AEs and they have not been accurately described. Examples of targeted agents which may cause stomatitis are bevacizumab, erlotinib, sorafenib, sunitinib, gefitinib, and lapatinib. Regarding stomatitis induced by mTOR inhibitors, Sonis et al. proposed the term 'mTOR inhibitor-associated stomatitis' (mIAS) in order to provide clarity and delineation from oral mucositis due to conventional cytotoxic chemotherapy and radiation 14.Sonis S. Treister N. Chawla S. et al.Preliminary characterization of oral lesions associated with inhibitors of mammalian target of rapamycin in cancer patients.Cancer. 2010; 116: 210-215PubMed Google Scholar. There is consensus among oral medicine specialists managing patients with oral mucosal lesions associated with mTOR inhibitors that the term mIAS is preferable to the term oral mucositis 4.Boers-Doets C.B. Raber-Durlacher J.E. Treister N.S. et al.Mammalian target of rapamycin inhibitor-associated stomatitis.Future Oncol. 2013; 9: 1883-1892Crossref PubMed Scopus (59) Google Scholar, 15.Watters A.L. Epstein J.B. Agulnik M. Oral complications of targeted cancer therapies: a narrative literature review.Oral Oncol. 2011; 47: 441-448Crossref PubMed Scopus (95) Google Scholar, 16.Li E. Trovato J.A. New developments in management of oral mucositis in patients with head and neck cancer or receiving targeted anticancer therapies.Am J Health Syst Pharm. 2012; 69: 1031-1037Crossref PubMed Scopus (19) Google Scholar, 17.Pilotte A.P. Hohos M.B. Polson K.M. et al.Managing stomatitis in patients treated with mammalian target of rapamycin inhibitors.Clin J Oncol Nurs. 2011; 15: E83-E89Crossref PubMed Scopus (54) Google Scholar, 18.de Oliveira M.A. Martins E Martins F. Wang Q. et al.Clinical presentation and management of mTOR inhibitor-associated stomatitis.Oral Oncol. 2011; 47: 998-1003Crossref PubMed Scopus (89) Google Scholar. Examples of mTOR inhibitors are temsirolimus and everolimus. 'Alimentary tract mucositis' refers to the expression of mucosal injury across the continuum of oral and gastrointestinal mucosa, from the mouth to the anus. Incidence of World Health Organization (WHO) grade 3 or 4 oral mucositis in patients receiving head and neck radiation (e.g. 60–70 Gy) to the oral cavity approaches 85%, but all treated patients have some degree of oral mucositis. Mucositis is one of the prime limiting factors of chemoradiation for advanced head and neck carcinoma. The oral pain associated with the lesions frequently leads to the need for enteral nutritional support with or without use of a feeding tube or gastrostomy, as well as use of opioids, with the objective of maintaining dose intensity throughout the entire radiation regimen. Incidence of WHO grade 3 or 4 oral mucositis can be as high as 75% in patients undergoing haematopoietic stem cell transplantation (HSCT), depending on the intensity of the conditioning regimen used and the use of methotrexate prophylactically to prevent graft-versus-host disease. Management of oral and gastrointestinal mucositis is one of the main challenges during the period of aplasia, with risk of sepsis related to degree of mucosal barrier breakdown and depth of marrow suppression. A wide range of standard or high-dose chemotherapeutic regimens continues to be causative of clinically significant oral and gastrointestinal mucositis 1.Peterson D.E. Bensadoun R.J. Roila F. Management of oral and gastrointestinal mucositis: ESMO Clinical Practice Guidelines.Ann Oncol. 2011; 22: vi78-vi84Abstract Full Text Full Text PDF PubMed Scopus (183) Google Scholar. Chemotherapy with 5-FU, capecitabine, irinotecan, or tegafur can lead to a clinically significant incidence of alimentary tract mucositis (e.g. ∼25% of advanced colorectal cancer patients experiencing grade 3–4 diarrhoea secondary to irinotecan and oxaliplatin 2.Keefe D.M. Schubert M.M. Elting L.S. et al.Updated clinical practice guidelines for the prevention and treatment of mucositis.Cancer. 2007; 109: 820-831Crossref PubMed Scopus (606) Google Scholar). Eighteen percent of patients receiving carboplatin and paclitaxel plus radiotherapy develop severe oesophagitis. Phase I modelling of drug dose and sequence may be of benefit to future patients relative to these treatment paradigms. In recent years, unique oral mucosal lesions have been reported in association with administration of targeted cancer therapeutics (e.g. TKIs and mTOR inhibitors). Elting et al. determined via meta-analysis that mucosal toxicities associated with selected targeted agents were most frequent among patients treated with bevacizumab, erlotinib, sorafenib, or sunitinib, although this difference was confined to low-grade stomatitis 19.Elting L.S. Chang Y.C. Parelkar P. et al.Risk of oral and gastrointestinal mucosal injury among patients receiving selected targeted agents: a meta-analysis.Support Care Cancer. 2013; 21: 3243-3254Crossref PubMed Scopus (39) Google Scholar. The clinical significance of these findings is unclear given its low incidence and mild severity. This analysis by Elting et al. shows that stomatitis, gastritis, oesophagitis, and xerostomia are occasional complications of therapy with the targeted agents that they studied, but these problems are not significantly more common or more serious than those observed with standard of care regimens. In a systematic review evaluating 44 studies of mTOR inhibitors, mIAS has been identified as the most frequent AE overall (73.4%) 20.Kwitkowski V.E. Prowell T.M. Ibrahim A. et al.FDA approval summary: temsirolimus as treatment for advanced renal cell carcinoma.Oncologist. 2010; 15: 428-435Crossref PubMed Scopus (172) Google Scholar. The lesion was the third most frequent severe AE (20.7%), accounting for 27.3% of dose reductions, and 13.1% of discontinuations, and was the most frequent dose-limiting toxicity (52.5%). The majority of mIAS occurs soon after initiation of the agent 21.Rugo H.S. Pritchard K.I. Gnant M. et al.Incidence and time course of everolimus-related adverse events in postmenopausal women with hormone receptor-positive advanced breast cancer: insights from BOLERO-2.Ann Oncol. 2014; 25: 808-815Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar. The study by Elting et al. further showed most of the targeted agents studied were associated with significantly higher risks (2- to 8-fold) of developing either all-grade or high-grade diarrhoea than the conventional regimens 19.Elting L.S. Chang Y.C. Parelkar P. et al.Risk of oral and gastrointestinal mucosal injury among patients receiving selected targeted agents: a meta-analysis.Support Care Cancer. 2013; 21: 3243-3254Crossref PubMed Scopus (39) Google Scholar. Their analysis showed that patients treated with erlotinib, gefitinib, lapatinib, sorafenib, and sunitinib have a significantly higher risk of having both all-grade and high-grade diarrhoea than those receiving conventional regimens. The risk can be as high as 8-fold for patients treated with lapatinib. These results are consistent with prior reviews and case series on this topic. Keefe et al. indicated that diarrhoea is a common side-effect of targeted therapy and, when used in combination with chemotherapy, these targeted drugs can cause severe diarrhoea 22.Keefe D. Stringer A. The potential successes and challenges of targeted anticancer therapies.Curr Opin Support Palliat Care. 2010; 4: 16-18Crossref Scopus (4) Google Scholar. Harandi et al. also reported that diarrhoea is strongly associated with the use of anti-EGFR TKIs 23.Harandi A. Zaidi A.S. Stocker A.M. Laber D.A. Clinical efficacy and toxicity of anti-EGFR therapy in common cancers.J Oncol. 2009; 2009 (9 April 2015, date last accessed): 567486Crossref PubMed Scopus (101) Google Scholar. Other studies cited diarrhoea as a common side-effect as well 24.Elez E. Macarulla T. Tabernero J. Handling side-effects of targeted therapies: safety of targeted therapies in solid tumours.Ann Oncol. 2008; 19: vii146-vii152Abstract Full Text PDF PubMed Scopus (7) Google Scholar, 25.Pessi M.A. Zilembo N. Haspinger E.R. et al.Targeted therapy-induced diarrhea: a review of the literature.Crit Rev Oncol Hematol. 2014; 90: 165-179Crossref PubMed Scopus (35) Google Scholar. Mechanisms underlying diarrhoea caused by targeted therapies have been less extensively studied than diarrhoea occurring secondary to chemotherapy. Additional research is thus needed relative to pathobiology of targeted therapy-associated diarrhoea, as well as optimal strategies for its prevention and treatment. Diagnosis of oral and gastrointestinal mucositis caused by cancer therapy is typically based upon history and clinical examination. The temporal relationship between timing of administration of chemotherapy or radiation in relation to the symptoms and signs is often sufficient to clinically document the condition. Diagnosis of oral mucosal lesions caused by targeted cancer therapies can typically be clinically confirmed by history and clinical examination. However, unlike oral mucositis caused by conventional cancer therapy, oral mucosal lesions may first occur several weeks or months after the initial dose exposure 14.Sonis S. Treister N. Chawla S. et al.Preliminary characterization of oral lesions associated with inhibitors of mammalian target of rapamycin in cancer patients.Cancer. 2010; 116: 210-215PubMed Google Scholar. A variety of assessment scales exist for staging of oral and/or gastrointestinal injury. The WHO scale is frequently utilised in the context of grading mucosal injury as a primary outcome. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 26.National Cancer Institute CTCAE; http://evs.nci.nih.gov/ftp1/CTCAE/About.html (9 April 2015, date last accessed).Google Scholar instrument is also commonly utilised in oncological clinical trials. Scales developed for oral mucositis secondary to conventional chemotherapy and radiation therapy have several limitations when applied to targeted agents. Two assessment tools, the Vanderbilt Head and Neck Symptom Survey version 2.0 (VHNSS2.0) 27.Cooperstein E. Gilbert J. Epstein J.B. et al.Vanderbilt Head and Neck Symptom Survey version 2.0: report of the development and initial testing of a subscale for assessment of oral health.Head Neck. 2012; 34: 797-804Crossref PubMed Scopus (71) Google Scholar and the mIAS scale 28.Boers-Doets C.B. Lalla R.V. The mIAS scale: a scale to measure mTOR inhibitor-associated stomatitis.Support Care Cancer. 2013; 21: S140Google Scholar can be of use within this population. The VHNSS was designed to screen both for tumour and for treatment-specific symptoms in patients with head and neck cancer undergoing concurrent chemoradiation and following cancer therapy. The list of possible symptoms is quite detailed. Since the oral complaints associated with targeted therapies are not fully explored, the VHNSS2.0 can be used to assess signs and symptoms of oral complaints, also not developed for this population 27.Cooperstein E. Gilbert J. Epstein J.B. et al.Vanderbilt Head and Neck Symptom Survey version 2.0: report of the development and initial testing of a subscale for assessment of oral health.Head Neck. 2012; 34: 797-804Crossref PubMed Scopus (71) Google Scholar. In addition, the Bristol stool chart is available for the assessment of the consistency of the stool 29.Lewis S.J. Heaton K.W. Stool form scale as a useful guide to intestinal transit time.Scand J Gastroenterol. 1997; 32: 920-924Crossref PubMed Scopus (1896) Google Scholar. Two of the most commonly utilised scales for oral mucositis are the WHO and NCI-CTCAE scales 26.National Cancer Institute CTCAE; http://evs.nci.nih.gov/ftp1/CTCAE/About.html (9 April 2015, date last accessed).Google Scholar: WHO scale for oral mucositisGrade 0 = no oral mucositisGrade 1 = erythema and sorenessGrade 2 = ulcers, able to eat solidsGrade 3 = ulcers, requires liquid diet (due to mucositis)Grade 4 = ulcers, alimentation not possible (due to mucositis) National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 26.National Cancer Institute CTCAE; http://evs.nci.nih.gov/ftp1/CTCAE/About.html (9 April 2015, date last accessed).Google Scholar The definition used for this grading is 'A disorder characterised by inflammation of the oral mucosal sic: "mucosa"'.Grade 1 = asymptomatic or mild symptoms; intervention not indicatedGrade 2 = moderate pain; not interfering with oral intake; modified diet indicatedGrade 3 = severe pain; interfering with oral intakeGrade 4 = life-threatening consequences; urgent intervention indicatedGrade 5 = death Most of the scales that are utilised for clinical care incorporate the collective measurement of oral symptoms, signs, and functional disturbances. By comparison, some scales are primarily centred on clinician-based observation of mucosal tissue injury (e.g. erythema, ulceration). These latter scales have particular value in clinical trial-based assessment of oral mucositis. In contrast, there is a limited number of instruments available for assessment of gastrointestinal mucositis. These scales typically measure indirect outcomes of mucosal injury, including diarrhoea. However, interpretation of such data can be confounded by other clinical conditions and interventions that also contribute to the event being measured. New technologies may lead to enhanced assessment strategies for gastrointestinal mucositis. Tracheal mucositis, pharyngeal mucositis, laryngeal mucositis, small intestinal mucositis, rectal mucositis, and anal mucositis are terms that can be scored separately in the CTCAEv4.03 within the system organ class 'Gastrointestinal disorders–Other, specify'. Diarrhoea is a term that is scored frequently within gastrointestinal mucositis also, which should not be confused with loose stool. The Bristol stool chart 29.Lewis S.J. Heaton K.W. Stool form scale as a useful guide to intestinal transit time.Scand J Gastroenterol. 1997; 32: 920-924Crossref PubMed Scopus (1896) Google Scholar is a useful tool to help identify variation in consistency of stool. The stools are classified into seven types, with types 5 and 6 tending towards diarrhoea but still loose stool and type 7 actually as diarrhoea, since that is watery stool. Since according to the NCI-CTCAE definition only watery stool is diarrhoea, this delineation between the two types is important. Furthermore, it is important to delineate this range of stool consistency in order to optimise clinical for these one can with no chemotherapy dose for the with a loose or stool. either high-dose with risk for and/or chemotherapy dose may be in the with severe diarrhoea. A disorder characterised by frequent and watery NCI-CTCAE version 4.03 26.National Cancer Institute CTCAE; http://evs.nci.nih.gov/ftp1/CTCAE/About.html (9 April 2015, date last accessed).Google 1 = of stools over mild in with 2 = of stools over moderate in with 3 = of stools over severe in with limiting of 4 = life-threatening consequences; urgent intervention indicatedGrade 5 = death There is no definition for targeted therapy-associated stomatitis defined in the NCI-CTCAE version 4.03 [26.National Cancer Institute CTCAE; http://evs.nci.nih.gov/ftp1/CTCAE/About.html (9 April 2015, date last accessed).Google Scholar. AEs can be within the system organ class 'Gastrointestinal disorders–Other, with the of 1 = asymptomatic or mild symptoms; clinical or intervention not indicatedGrade 2 = or intervention limiting 3 = severe or significant but not or of limiting 4 = life-threatening consequences; urgent intervention indicatedGrade 5 = death of clinical assessment that are primarily by may and that assessment should include and Lalla have thus proposed a with a pain and an objective of lesions 28.Boers-Doets C.B. Lalla R.V. The mIAS scale: a scale to measure mTOR inhibitor-associated stomatitis.Support Care Cancer. 2013; 21: S140Google Scholar. It is that dose be only when both and objective are lesions with significant pain use of care interventions and of mIAS this scale is designed to dose intensity of the treatment of the underlying resulting in 0 = no pain to 1 = pain to with pain the last reported as 2 or less on a 2 = pain to with pain the last reported as 5 or less on a 3 = pain to with pain the last reported as 6 or more on a scale 0 = no mIAS no erythema and no to in the 1 = oral and/or pharyngeal erythema, to but no 2 = oral and/or pharyngeal to of 3 = oral and/or pharyngeal to with at one for 7 of developing mucositis has been associated with and of of the cancer therapy. therapy (e.g. head and neck radiation with concurrent may the of oral mucositis. in and xerostomia when are et intensity conventional radiotherapy in head and neck cancer a 3 Oncol. 2011; Full Text Full Text PDF PubMed Scopus Google Scholar], incidence and of mucosal toxicity have not generally been significantly by of state-of-the-science radiation technologies (e.g. this modelling continues to be there to be risk factors (e.g. in some that for a degree of clinical study of these more defined factors the in relation to clinical expression of toxicity. risk factors, (e.g. can contribute important patients should be for nutritional risk and early enteral nutrition in the event In addition, patients develop clinically significant due to or other drugs during cancer treatment may from oral mucositis. are important in the of of (e.g. and should be and such as and and or should be oral is it is important that patients be about oral complications treatment. should also be to have in order to have the oral cavity and that they should the care at first signs and symptoms of oral complications 4.Boers-Doets C.B. Raber-Durlacher J.E. Treister N.S. et al.Mammalian target of rapamycin inhibitor-associated stomatitis.Future Oncol. 2013; 9: 1883-1892Crossref PubMed Scopus (59) Google Scholar. oral care is key in and oral the oral is thus important. A comprehensive Oral Care is in et al. due to and/or no guidelines for the prevention or treatment of oral mucositis were possible for the interventions of normal in patients receiving chemotherapy or haematopoietic stem cell or J. et review of oral care for the management of oral mucositis in cancer Care Cancer. 2013; 21: PubMed Scopus Google Scholar]. on this no in of normal is can be this is typically well by patients and may to mouth care of a Oral Care key strategies for of oral mucosal injury and during treatment of optimal nutritional support throughout the entire