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SPECIAL REPORT

Improving the Prevention and Treatment of Mucositis Preventing and Treating Oral Mucositis in the Primary Care Setting A ‘Fantastic Voyage’ Around the Mouth Nutrition, Microbes and Oral Mucositis (OM) The Mouth, Oral Mucositis, Dental Hygiene and Medical Treatment OM and Head and Neck Cancers Update Bone Marrow Transplant and Hematopoietic Stem Cell Transplantation, Immunotherapy and Cancer

Published by Global Business Media


CAPHOSOL® 1 box contains 30 doses treatment 1 dose treatment = 2 single-dose containers, each 15 ml, mixed together Pharmaceutical form: Mouth Rinse. Aqueous solution. Caphosol is a preparation comprising two separately packaged aqueous solutions, a phosphate solution (Caphosol A) and a calcium solution (Caphosol B) which, when both solutions are combined in equal volumes, forms a solution supersaturated with respect to both calcium and phosphate ions. Ingredients: Dibasic Sodium Phosphate 0.032, Monobasic Sodium Phosphate 0.009, Calcium Chloride 0.052, Sodium Chloride 0.569, Purified water qs (%w/w) Actions: Caphosol is an electrolyte solution designed to moisten, lubricate and clean the oral cavity including the mucosa of the mouth, tongue and oropharynx. Indications: Caphosol is indicated for dryness of the mouth and oropharynx (hyposalivation, xerostomia), regardless of the cause and regardless of whether the condition is temporary or permanent. Caphosol is also indicated as an adjunct to standard oral care in the prevention and treatment of the mucositis that may be caused by radiation or high dose chemotherapy. Relief of dryness of the oral mucosa in these conditions is associated with amelioration of pain. Directions for use: (1) Mix single-dose Caphosol A and 1 single dose Caphosol B in a clean glass. (2) Swish in the mouth thoroughly for 1 min with ½ of the solution and spit out. (3) Repeat with the remaining ½ of the solution and spit out. Use immediately after mixing the single-dose containers. Dosage: 4 to 10 times a day. Use for the duration of the treatment or as instructed by physician. Interactions with other treatments: There are no known interactions with medicinal or other products. Special precautions for use: Avoid eating or drinking for at least 15 minutes after use. Do not use if the seal of the single-dose container is broken or the single-dose container shows sign of leakage or damage. Contains sodium (71 mg per 30 ml dose treatment). Patients restricted to a low sodium diet should consult their physician before use. Keep out of the reach of children. Do not inject. Do not freeze. No adverse effects are anticipated, if Caphosol is swallowed accidentally. EUSA Pharma (UK) Limited Breakspear Park Breakspear Way Hemel Hempstead HP2 4TZ United-Kingdom medical@eusapharma.com

2015-06 IFU/CAP/UK/337/04


SPECIAL REPORT

Improving the Prevention and Treatment of Mucositis Preventing and Treating Oral Mucositis in the Primary Care Setting

Contents

A ‘Fantastic Voyage’ Around the Mouth Nutrition, Microbes and Oral Mucositis (OM) The Mouth, Oral Mucositis, Dental Hygiene and Medical Treatment OM and Head and Neck Cancers Update Bone Marrow Transplant and Hematopoietic Stem Cell Transplantation, Immunotherapy and Cancer

Foreword

3

Dr Charles Easmon, Editor

Preventing and Treating Oral Mucositis 4 in the Primary Care Setting

Published by Global Business Media

Published by Global Business Media Global Business Media Limited 62 The Street Ashtead Surrey KT21 1AT United Kingdom Switchboard: +44 (0)1737 850 939 Fax: +44 (0)1737 851 952 Email: info@globalbusinessmedia.org Website: www.globalbusinessmedia.org Publisher Kevin Bell Business Development Director Marie-Anne Brooks Editor Dr Charles Easmon Senior Project Manager Steve Banks Advertising Executives Michael McCarthy Abigail Coombes Production Manager Paul Davies For further information visit: www.globalbusinessmedia.org

What is Oral Mucositis? The Pathophysiology of Oral Mucositis Treatment Strategies for Preventing and Treating Oral Mucositis Preventing Oral Mucositis with Prophylactic Caphosol® Treatment Treating Active Oral Mucositis with Caphosol®: Reducing Pain and Other Symptoms of Oral Complications Summary

A ‘Fantastic Voyage’ Around the Mouth The Healthy Mouth Tour The Oral Mucositis Mouth Tour Post-Mouth Tour Evidence Review

Nutrition, Microbes and Oral Mucositis (OM)

Material in advertisements and promotional features may be considered to represent the views of the advertisers and promoters. The views and opinions expressed in this publication do not necessarily express the views of the Publishers or the Editor. While every care has been taken in the preparation of this publication, neither the Publishers nor the Editor are responsible for such opinions and views or for any inaccuracies in the articles. © 2016. The entire contents of this publication are protected by copyright. Full details are available from the Publishers. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical photocopying, recording or otherwise, without the prior permission of the copyright owner.

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Sophie Levingworth, Medical Correspondent

A Mass of Microbes Differential Diagnosis of OM and Why You as General Practitioners Should Participate in Managing OM Summary

The Mouth, Oral Mucositis, Dental Hygiene 14 and Medical Treatment Dr Charles Easmon MBBS MRCP MSc Public Health DTM&H DOccMed

Is OM a Common Problem Ignored By Doctors? Prevention and Treatment of OM

OM and Head and Neck Cancers Update The opinions and views expressed in the editorial content in this publication are those of the authors alone and do not necessarily represent the views of any organisation with which they may be associated.

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Dr Charles Easmon MBBS MRCP MSc Public Health DTM&H DOccMed, Editor

16

Sophie Levingworth, Medical Correspondent

Behavioural, Cultural Issues and Head and Neck Cancers Viruses and Head and Neck Cancers Strategies to Reduce Head and Neck Cancers and OM

Bone Marrow Transplant and Hematopoietic Stem Cell Transplantation, Immunotherapy and Cancer

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Dr Charles Easmon MBBS MRCP MSc Public Health DTM&H DOccMed

Using the Immune System to Fight Cancer Bone Marrow and Stem Cell Transplants Immunotherapy versus Bone Marrow/Stem Cell Transplant Risks of OM in Your Practice


IMPROVING THE PREVENTION AND TREATMENT OF MUCOSITIS

Foreword O

RAL MUCOSITIS (OM) is a distressing but

those having chemo and radiotherapy and bone

remedial side effect of treatment for life-

marrow/stem cell transplants, need to be aware of

threatening conditions such as head and neck

how common OM is and how severe the condition

cancer, general cancers and bone marrow/stem

can be. They also need to be aware that there are

cell transplantation amongst other conditions.

effective ways of treating and managing it.

The problem is caused by damage to mucous

The Native American Indians have an often quoted

membranes by chemo or radiotherapy. The

saying that you should never judge a man until you

mouth can be severely affected and, as such, this

have walked at least a mile in his moccasins. We use

may make eating difficult as well as speech.

this phrase to help us understand ‘empathy’ but in

Pain is a significant feature, dental hygiene

this series of articles we wish the clinician not just

deteriorates and teeth may be lost. Some have

to put him or herself in the other persons’ shoes to

referred to OM as the ‘collateral damage’ that

empathise, but put him or herself into their mouth.

occurs whilst treating serious health issues, but this

One of the key treatments available for OM can

damage may so affect a person’s quality of life that

be bought from a pharmacy directly or prescribed

they may prefer to have died. Nutrition is clearly

as a class 1 medical device. It is rich in calcium and

vital to survival and important after and during

phosphate ions and helps maintain the mouth’s

medical treatment but severe OM can lead to

normal neutral PH as well as moistening, lubricating

reduced eating habits and hence reduced nutrition.

and cleansing.

The side effects of OM can be severe enough for the sufferer to wish to delay or stop therapy and it may lead to hospitalisation and parenteral feeding. General Practitioners, as part of a multi-disciplinary team managing people with head and neck cancers,

Dr Charles Easmon Editor

Dr Charles Easmon is a medical doctor with 30 years’ experience in the public and private sectors. After qualifying as a physician, he developed his interests in occupational medicine, public health and travel diseases.

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IMPROVING THE PREVENTION AND TREATMENT OF MUCOSITIS

Preventing and Treating Oral Mucositis in the Primary Care Setting

42% of HSCT patients rated Oral Mucositis as the single most debilitating aspect of their cancer treatment.7

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What is Oral Mucositis? It is estimated that in a General Practitioner’s (GP) population of around 10,000 patients, up to 275 people may be diagnosed with cancer within 5 years.1 Under the National Cancer Survivorship Initiative, there is recognition that more cancer patients will need to be supported in primary care.1 Currently, there is the Quality and Outcomes Framework indicator, which sets the target for all cancer patients to have a primary care cancer review within six months of their diagnosis.1 In conjunction, primary care healthcare professionals (HCPs) are being encouraged to become actively involved in the management of their cancer patients, including promoting the benefits of physical activity, supplying information that can help support patients, and helping them understand the effects and complications of cancer treatments and how to manage them.1 Oral mucositis (OM) is a debilitating and painful inflammatory complication of many common cancer treatments, such as chemotherapy and radiotherapy.2 Traditionally, the types of cancer patients who suffered from OM were treated in the hospital setting. As many as 97% of head and neck patients receiving radiotherapy and 70% of patients receiving haematopoietic stem cell transplantation (HSCT) have symptomatic OM.3-5 However, the increasing use of single-pill targeted therapies for the treatment of solid cancers, such as tyrosine kinase inhibitors (TKI) and mammalian target of rapamycin inhibitors (mTORi), means more and more cancer patients are receiving treatment in the community.4,6 Previously, around half of all patients undergoing chemotherapy for a solid tumour would experience adverse events affecting the oral cavity, but this group is likely to increase further with greater use of targeted therapies, which are commonly associated with oral complications.4-6 Patients receiving targeted

therapies in the community may be more likely to report to their GP practice first when adverse events occur. Insert Pull Quote against text on first page of the client’s article – “42% of HSCT patients rated Oral Mucositis as the single most debilitating aspect of their cancer treatment.”7 The pain and effect on quality of life associated with OM can be such that patients often rate it as the single most distressing aspect of their cancer treatment.7 Patients describe the pain and discomfort of OM, which may occur right the way through the alimentary canal, as like “having a ring around the Adam’s apple”. Others become unable to swallow, as in one patient’s experience “my mouth became ulcerated and I could not swallow my own saliva. Every day of treatment brought some new horrifying change to my body”.4,8 These patient experiences of OM relate to one of the most frustrating aspects of the condition: patients losing their ability to eat and drink. Symptoms such as dry cracked lips, a dry mouth, thick or absent saliva, pain and constriction of the throat, combine to make eating a prohibitively painful experience.8,9 Up to 90% of patients who experience difficulty swallowing relate it to the pain caused by the ulcerated mucosa.9 The pain can be so severe that maintaining function of the oral cavity is highly dependent on effective pain management.10 Feelings of isolation and loss of independence are compounded as OM commonly affects a patient’s ability to speak and communicate, meaning patients often cannot describe their experience to their nurses, friends or family.9 Thick saliva is commonly reported with respect to speech and eating, and it may also aggravate or stimulate vomiting in patients, who may already be experiencing nausea due to their treatment.10 Unsurprisingly, these symptoms mean patients with OM are at high risk of nutritional problems, which may result


IMPROVING THE PREVENTION AND TREATMENT OF MUCOSITIS

FIGURE 1. THE PATHOPHYSIOLOGICAL PROCESS LEADING TO THE DEVELOPMENT OF OM IN PATIENTS RECEIVING CANCER TREATMENT. ADAPTED FROM SONIS ST, ORAL ONCOL, 2009.12

“A gentleman presented two weeks into his radiation treatment with a lot of mucositis affecting his mouth. We gave him Caphosol® and he said within two days of starting Caphosol® his mouth felt just so much better!” - Health Promotion Advisor, Manchester Hospital

in undesirable weight loss, lack of energy and insufficient protection from infections.9 From a clinical perspective, OM can cause missed treatment cycles or dose reductions, resulting in less effective treatment of the cancer.11 The health burden of OM on the individual patient and the demands on healthcare resources can be greatly reduced by the correct care and treatment and there is an opportunity for primary care HCPs to make a profound difference to their patients who are receiving cancer treatment in the community.4

The Pathophysiology of Oral Mucositis Pathophysiology of OM is consistent regardless of the cancer therapy used in treatment.12 Damage occurs in the mucosa within seconds of radio- or chemotherapy treatment onset.12 At the molecular level, these treatments directly cause DNA strand breaks, and ultimately cause the death of the basal epithelial cells

of the mucosa.12 There is a lag between the initial damage to cells and the development of clinical manifestations of OM, during which time intracellular signalling pathways, such as NF-κB, are activated, resulting in the creation of many pro-inflammatory cytokines (Figure 1).12 The hallmark ulceration associated with OM develops by means of these processes.12 The ulcers associated with OM are deep and rapidly colonised by oral bacteria, presenting a risk for local and systemic infections.12,13 The prevention of OM ulceration can result in reduced pain experienced by the patient, reduced risk of infection, reduced use of feeding tubes and fewer hospitalisations.12 As understanding of the sequence of events that occur in the pathophysiology of OM has grown, it has presented new opportunities to improve treatments.12

Treatment Strategies for Preventing and Treating Oral Mucositis There is a substantial body of evidence to suggest that the burden of OM can be greatly reduced by the correct care and treatment of oral active complications.4 The foundation of any treatment programme to reduce the impact of OM should be appropriate oral hygiene.4 This is highlighted by the fact that pre-existing oral or dental disease is one of the most important risk factors associated with the development of OM.14 All patients should have a thorough oral examination by a dental professional and have any necessary corrective procedures conducted before treatment begins, as well as having a robust daily oral care regimen including brushing, flossing and rinsing with a saline solution.4,14 Beyond daily oral care, a WWW.PRIMARYCAREREPORTS.CO.UK | 5


IMPROVING THE PREVENTION AND TREATMENT OF MUCOSITIS

These studies highlight that Caphosol® treatment can reduce the incidence and severity of OM in patients receiving radiotherapy or high dose chemotherapy.

number of specially developed mouth rinses and barrier treatments are available for the treatment of OM. Caphosol® is a supersaturated calcium phosphate electrolyte solution that is recommended by the UK Oral Mucositis in Cancer Group (UKOMiC) guidelines, as part of a range of measures, for use in patients who are at moderate risk of oral cavity damage and/ or OM becoming more severe.4 Caphosol® is a mouth rinse licensed as a medical device for use as an adjunct to standard oral care which moistens, lubricates and cleanses the oral cavity.15 Caphosol® contains key minerals, such as calcium and phosphate, which play an important role in the maintenance of a normal healthy mucosa.15-17 The pH of the mouth is neutral and Caphosol® has a similar ionic composition and pH as saliva, meaning it may aid in the normal maintenance of pH in the oral cavity.16,18 It is delivered to the patient as two separate vials of solution, one blue and one clear, which are then mixed together. The patient then rinses the mouth with half of the combined solution for a total of one minute before spitting out. This is then repeated with the remaining solution for a further minute. Patients should repeat a minimum of four times a day up to ten times a day, depending on the degree of symptom relief required.15

Preventing Oral Mucositis with Prophylactic Caphosol® Treatment A recent systematic review of the literature by Quinn et al. (2013) identified 17 OM studies, where 30 or more patients were recruited; 12 of these studies directly compared Caphosol® with a control treatment for the prevention of OM during cancer treatment. Nine of these reported that Caphosol ® prevented the development of OM or reduced the severity of OM. The other five studies were non-comparative, but reported a lower incidence or severity of OM with Caphosol® treatment than would be expected given the reported incidence of OM in the literature.2 The largest double-blind, prospective, randomised clinical trial to date of Caphosol® in the prevention and treatment of OM was conducted by Papas et al. (2003).16 They examined the severity and incidence of OM in 95 patients receiving high-dose chemotherapy as part of the conditioning regimen for HSCT. HSCT patients were randomised to receive either: pre-treatment topical fluoride treatment and Caphosol® rinses during the transplant, or pre-treatment topical placebo treatment and a fluoride mouth rinse during the transplant (control arm).16 Their study showed that Caphosol®-treated patients experienced fewer mean days of OM (3.72 vs. 7.20; p< 0.001) compared to controls. [Papas 2003, p4b] In addition, 40% of patients 6 | WWW.PRIMARYCAREREPORTS.CO.UK

in the Caphosol® arm had no OM compared with 19% in the control arm.16 In patients undergoing treatment for head and neck cancers, Miyamoto et al. (2012) conducted a retrospective matched-control study showing that a lower incidence of severe OM was reported among head and neck cancer patients treated with Caphosol® compared to historical controls.19 Similarly, Santos et al. (2010) conducted a single-centre observational study and showed that Caphosol® had a positive impact on the onset and severity of OM in 30 head and neck patients undergoing high-dose chemotherapy, radiotherapy or both.20 Considering a broader, more heterogeneous population of patients, Haas et al. (2008) investigated the prevalence of oral mucositis in 218 head and neck cancer patients retrospectively selected from an observational registry.21 These patients had all received Caphosol®4-10 times daily and were undergoing radiotherapy, chemotherapy or both for the treatment of cancer.21 This particular group were considered high-risk for developing OM, and of the 170 patients who completed follow-up after receiving treatment, 60% experienced no OM (grade 0), 20% had grade 1 OM, and 15% grade 2 OM. Grade 3 or 4 OM was seen in only 5% and 1% of these patients respectively.21 These studies highlight that Caphosol® treatment can reduce the incidence and severity of OM in patients receiving radiotherapy or high dose chemotherapy.

Treating Active Oral Mucositis with Caphosol®: Reducing Pain and Other Symptoms of Oral Complications To examine whether Caphosol® may be of benefit to patients experiencing oral complications as a result of treatment with targeted therapies, Boers-Doets et al. (2015) conducted a doubleblind randomised phase 3 study to compare patient reported outcomes among patients treated with Caphosol® or a salt water rinse treatment (NaCl).22 Patients included in their study were receiving targeted therapies, such as TKIs or mTORis, for the treatment of solid cancers.22 The study included 60 patients who were receiving either: everolimus (19), sunitinib (16), pazopanib (14), sorafenib (10) or temsirolimus (1).22 Overall, patients treated with Caphosol ® had significantly reduced symptoms of dry mouth and burning sensation versus NaCl (p=0.004 and p=0.017, respectively) (Figure 2), confirming the efficacy of Caphosol in treating the oral complications commonly suffered by patients receiving targeted therapies.22 A recently published study from the Christie NHS Foundation Trust, investigated the severity


IMPROVING THE PREVENTION AND TREATMENT OF MUCOSITIS

FIGURE 2. REDUCTION IN DRY MOUTH AND BURNING SENSATION IN PATIENTS USING A CAPHOSOL® RINSE WHO WERE RECEIVING CANCER TREATMENT FOR A SOLID TUMOUR WITH TKIS OR MTORIS. ADAPTED FROM BOERS-DOETS, 201522

“Oral mucositis can be one of the most distressing side effects of cancer treatment. Since using Caphosol® patients report a significant symptomatic benefit.” - Radiography Department, Nottingham University Hospitals and pain of OM among head and neck cancer patients receiving radiotherapy, with and without access to a health advisor (HA) and/ or Caphosol®.23 The local team conducted a retrospective audit of their current treatment protocol to identify gaps in practice (baseline period), before employing a HA responsible for the weekly review and initial assessment of patients receiving radiotherapy, using an improved protocol.23 In stage one of the assessment period patients received support from the HA as well as Caphosol® treatment; in stage two they received HA support only.23 During stage one of the study the most frequently reported grading of OM was ‘moderate’ which was reported by 47.5% of patients, with 42.5% of patients reporting ‘severe’ OM. In contrast in stage 2, when patients received standard HA support only, ‘severe’ OM was the most commonly reported OM grading by 55% of patients, with only 37.5% of patients reporting ‘moderate’ OM.23 Pain was also reduced in stage one of the study, with ‘moderate pain’ being the commonly reported rating (73%) when patients had access to Caphosol® and HA support, compared to

‘severe pain’ being the most commonly reported outcome in stage 2 and the baseline period (85% and 66%, respectively).23 The authors concluded that these findings “point to an improvement in patients’ wellbeing at a time of physical distress and as such increase motivation to successfully complete the [radiotherapy] regimen”.23 In a single-centre open label non-blinded study of patients receiving radiotherapy Kiprian et al. (2012), showed that patients treated with Caphosol reported reduced severity of discomfort and difficulty in swallowing and reduced experience of dry mouth.24 The patients also spent a reduced mean total number of days in hospital.24 Reduction in all of these symptoms/ outcomes suggests Caphosol® treatment may aid patients in maintaining their independence, as well as spending less time in the hospital setting. Similar results have been observed in HSCT patients, as was shown in the Papas et al. (2003) study. A significantly lower mean peak level of pain was reported for patients treated with Caphosol® compared to controls who received a fluoride rinse (19.80 vs. 50.33 on the Visual Analogue Scale (VAS); p< 0.0001).16 There was also a significant reduction in the doses of morphine required for pain management (34.54 mg vs. 122.78 mg; p=0.0001) and the length of time (days) for which morphine was required for analgesia (1.26 vs. 4.02; p=0.0003).16 These findings, along with the results in patients receiving radiotherapy, show that appropriate Caphosol® treatment not only reduces the pain and other symptoms experienced by patients, but may also lead to a reduction in utilisation of healthcare resources.16,24 WWW.PRIMARYCAREREPORTS.CO.UK | 7


IMPROVING THE PREVENTION AND TREATMENT OF MUCOSITIS

In a single-centre open label non-blinded study of patients receiving radiotherapy Kiprian et al. (2012), showed that patients treated with Caphosol reported reduced severity of discomfort and difficulty in swallowing and reduced experience of dry mouth

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Summary In the future there will be more cancer care and management within the primary care setting, as part of a more holistic approach to treatment.1 The overall incidence of oral complications of cancer treatment in primary care is only likely to grow as more patients receive cancer treatment and in particular the newer targeted therapies, which can lead to OM and specific oral complications such as dry mouth and pain.4-6 Although the debilitating nature of OM is well documented, with appropriate management and effective interventions the overall incidence and severity can be reduced.4 Caphosol® has been shown to reduce both the overall incidence of OM as well as the severity of pain, difficulty or discomfort swallowing and healthcare utilisation, such as reduced use of morphine and number of days spent in hospital.2,16,19-24 Recently published data also show that Caphosol® is efficacious in patients receiving targeted therapies, and can reduce the burning sensation and dry mouth associated with TKI or mTORi treatments.22 These data show that the inclusion of Caphosol® in OMprevention and treatment protocols warrants serious consideration.2 Primary care HCPs should be familiar with the current best practices in the management of OM to be able to provide appropriate care for patients presenting with this debilitating complication of cancer treatment.

“Having worked in other cancer centres, where Caphosol® hasn’t been used, the difference it makes to patient’s swallow function is phenomenal. Without the use of Caphosol, I’ve seen patients present with severe grade 3 and above oral mucositis, which has compromised their oral intake severely. The ability to maintain oral intake, albeit a modified diet, is increased by using Caphosol.” - Macmillan Speech and Language Therapist, Sussex Cancer Centre


IMPROVING THE PREVENTION AND TREATMENT OF MUCOSITIS

References: 1. National cancer Survivorship Initiative. Living with and beyond cancer: taking action to improve outcomes, 2013. Available at: http://www.ncsi.org.uk/ [Accessed November 2015]

Quinn B. Efficacy of a supersaturated calcium phosphate oral rinse for the prevention and treatment of oral mucositis in patients receiving high-dose cancer therapy: a review of current data. Eur J Cancer Care (Engl), 2013; 22(5): 564–579 2.

3. Küstler WJ et al. Oral mucositis complicating chemotherapy and/or radiotherapy: options for prevention and treatment. CA Cancer J Clin, 2001; 51(5): 290–315 4. UK Oral Mucositis in Cancer Group. Mouth care guidance and support in cancer and palliative care, 2015. Available at: http://www.ukomic.co.uk/pdf/UK_OM_Guidelines.pdf [Accessed November 2015]

Sonis ST. Oral mucositis in cancer therapy, J Support Oncol, 2004; 2(6 Suppl 3): 3–8

5.

Al-Ansari S et al. Oral Mucositis induced by anticancer therapies, 2015; 2(4): 202–211

6.

Bellm LA et al. Patient reports of bone marrow transplantation, 2000; 8(1): 33–39

7.

Borbasi S et al. 5 themes described the experiences of patients with chemotherapy induced oral mucositis, Oncol Nurs Forum, 2002; 29: 1051–1057 8.

Chen HM. Patients’ experiences and perceptions of chemotherapy-induced oral mucositis in a day unit. Cancer Nurs, 2008; 31(5): 363–369

9.

Eilers J and Epstein JB. Assessment and measurement of oral mucositis. Semin Oncol Nurs, 2004; 20(1): 22–9

10.

Treister N and Sonis ST. Mucositis: biology and management. Curr Opin Otolaryngol Head Neck Surg, 2007; 15(2): 123–129

11.

Sonis ST. Mucositis: The impact, biology and therapeutic opportunities of oral mucositis. Oral Oncol. 2009; 45(12): 1015–1020

12.

13. Rubenstein EB et al. Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis. Cancer, 2004; 100(9 Suppl): 2026 – 2046

Brown CG and Wingard J. Clinical Consequences of Oral Mucositis. Semin Oncol Nurs, 2004; 20(1): 16–21

14.

15. Papas AS et al. A prospective, randomized trial for the prevention of mucositis in patients undergoing hematopoietic stem cell transplantation. Bone Marrow Transplant, 2003; 31(8): 705–712

EUSA Pharma. Caphosol® Product Information, 2015

16.

De Almeida PDV et al. Saliva Composition and Functions: A Comprehensive Review. J Contemp Dent Pract, 2008; 9(3): 72–80

17.

Aframian DJ et al. The distribution of oral mucosal pH values in healthy saliva secretors. Oral Dis, 2006; 12(4): 420–423

18.

19. Miyamoto CT et al. A retrospective match controlled study of supersaturated calcium phosphate oral rinse vs. supportive care for radiation induced oral Mucositis. J Cancer Therap, 2012; 3: 630–636

Santos T. et al. Advances in the control of oral mucositis during nurse visits. Spanish Oncology Nursing Society SEEO Congress, 2010

20.

 Haas M et al. Treatment of Oral Mucositis by Supersaturated Calcium Phosphate Oral Rinse in Patients Receiving Chemotherapy (CT) and Radiation (RT). Abstract presented at the 50th American Society for Radiation Oncology Conference, Boston, USA, 21st – 25th September, 2008.

21.

22. Boers-Doets CB et al. Supersaturdated calcium-phosphate rinse reduces dry mouth and burning sensation in cancer patients treated with TKI and mTORI – results of a double-blind, randomised phase III trial (NCT 01265810). Abstract presented at the European Cancer Congress, Vienna, Austria, 25th–29th September, 2015

Stringer J et al. Health advisor facilitated mouth care regime for patients with head and neck cancers undergoing intensity-modulated radiotherapy. J Radiother Pract, 2015; 14(4): 353–361

23.

Kiprian D et al. Evaluation of efficacy of Caphosol in prevention and alleviation of acute side effects in patients treated with radiotherapy for head and neck cancers. Poster presented at International Symposium on Supportive Care in Cancer, New York City, USA, 28th–30th June, 2012

24.

Disclaimer: This article was sponsored by EUSA Pharma. Medical writing assistance for the preparation of the article was provided by Rory Elsome of TVF Communications, London, UK and funded by EUSA Pharma.

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IMPROVING THE PREVENTION AND TREATMENT OF MUCOSITIS

A ‘Fantastic Voyage’ Around the Mouth Dr Charles Easmon MBBS MRCP MSc Public Health DTM&H DOccMed, Editor

The first shock is how Oral Mucositis will affect almost all of your head and neck cancer patients, your bone marrow/stem cell transplant patients and is a very high risk for all of your patients on chemo and/or radiotherapy

The Healthy Mouth Tour1 In the film the Fantastic Voyage2 Raquel Welch and other scientists become ‘miniaturised’ to be injected into the blood stream of a key scientist to remove a blood clot. We will imagine being shown around the mouth as a vast cavern with the opening at the lips. You encounter first, the teeth surrounded by the gums as outward projections from the jaw bone. Along the course of the tongue you come at the base to the oropharaynx and as you slide down, the hypopharynx is below you with the larynx in front and the nasopharynx3 above you. You crawl back up to the tongue to explore the cheeks, the soft palate, the tonsils and the uvula.

The Oral Mucositis Mouth Tour This will be unpleasant because the first thing you will notice is the smell and the dryness. All surfaces may be covered by different degrees of sores and ulceration. You will pass through cracked lips and have to dodge pools of stale saliva (it cannot be easily swallowed). The teeth may be heavily stained, fallen out or falling out. However, luckily, as a group of scientists, you have with you an oral treatment, a simple mouth rinse, that is rich in calcium and phosphate ions and you use this to moisten all surfaces 4-10 times every day, from day 1 of treatment and over time you start to see significant improvements. This oral treatment moistens, lubricates and cleanses the oral cavity as well as maintaining its neutral PH.

Post-Mouth Tour Evidence Review As many as 97% of head and neck patients receiving radiotherapy and 70% of patients receiving haematopoietic stem cell transplantation (HSCT) have symptomatic OM4,5,6. As miniaturised scientists you have visited just one healthy mouth and one unhealthy one 10 | WWW.PRIMARYCAREREPORTS.CO.UK

but now you and the team decide to review the data as to 1) how common is this problem? and 2) what evidence is there for the efficacy of your treatment? The first shock is how Oral Mucositis will affect almost all of your head and neck cancer patients, your bone marrow/stem cell transplant patients and is a very high risk for all of your patients on chemo and/or radiotherapy. With regard to the efficacy of your treatment you are directed to the following papers: 1) The systematic review of the literature by Quinn et al. (2013)7, which identified 17 OM studies. Of the 12 studies which directly compared your oral treatment with a control treatment for the prevention of OM during cancer treatment, 75% of these reported that your oral treatment prevented the development of OM or reduced the severity of OM. The other 25% were non-comparative, but reported a lower incidence or severity of OM with your oral treatment than would be expected given the reported incidence of OM in the literature. 2 ) A large double-blind, prospective, randomised clinical trial to date of your oral treatment in the prevention and treatment of OM conducted by Papas et al. (2003)8. In this, the severity and incidence of OM in 95 patients receiving high-dose chemotherapy was examined as part of the conditioning regimen for HSCT. HSCT patients were randomised to receive either: pre-treatment topical fluoride treatment and your oral treatment. This study showed that your oral treatment-treated patients experienced fewer mean days of OM (3.72 vs. 7.20; p< 0.001) compared to controls. In addition, 40% of patients in the your oral treatment arm had no OM compared with 19% in the control arm. 3) Miyamoto et al. (2012) conducted a retrospective matched-control study showing that a lower incidence of severe OM was reported among head and neck cancer patients


IMPROVING THE PREVENTION AND TREATMENT OF MUCOSITIS

treated with your oral treatment compared to historical controls. 4) Similarly, Santos et al. (2010)10 conducted a single-centre observational study and showed that your oral treatment had a positive impact on the onset and severity of OM in 30 head and neck patients undergoing high-dose chemotherapy, radiotherapy or both. 5) Considering a broader, more heterogeneous population of patients, Haas et al. (2008) investigated the prevalence of oral mucositis in 218 head and neck cancer patients

retrospectively selected from an observational registry. These patients had all received your oral treatment 4–10 times daily and were undergoing radiotherapy, chemotherapy or both for the treatment of cancer. This particular group were considered high-risk for developing OM, and of the 170 patients who completed follow-up after receiving treatment, 60% experienced no OM (grade 0), 20% had grade 1 OM, and 15% grade 2 OM. Grade 3 or 4 OM was seen in only 5% and 1% of these patients respectively. More recently, a study has shown the significant impact that this rinse can have on the oral complications caused by the newer targeted therapies. Ref: COMMT In your normal un-miniaturised state, you as GPs, Clinicians, oncologists and other members of the multi-displinary team determine never again to ignore the horrors of Oral Mucositis and to manage and treat it with the evidence that you now have in your hands.

References: http://www.medicalook.com/human_anatomy/organs/Mouth.html accessed 2/1/2016

1. 2.

http://www.imdb.com/title/tt0060397/?ref_=fn_al_tt_1

3.

http://www.headandneckcancerguide.org/adults/introduction-to-head-and-neck-cancer/throat-cancer/oropharyngeal-cancer/ accessed 2/1/2016

4.

Küstler WJ et al. Oral mucositis complicating chemotherapy and/or radiotherapy: options for prevention and treatment. CA Cancer J Clin, 2001; 51(5): 290–315

5.

UK Oral Mucositis in Cancer Group. Mouth care guidance and support in cancer and palliative care, 2015. Available at: http://www.ukomic.co.uk/pdf/UK_OM_Guidelines.pdf Accessed 2/1/2016

6.

Sonis ST. Oral mucositis in cancer therapy, J Support Oncol, 2004; 2(6 Suppl 3): 3–8

7.

Quinn B. Efficacy of a supersaturated calcium phosphate oral rinse for the prevention and treatment of oral mucositis in patients receiving high-dose cancer therapy: a review of current data. Eur J Cancer Care (Engl), 2013; 22(5): 564–579

8.

9.

10.

Papas AS et al. A prospective, randomized trial for the prevention of mucositis in patients undergoing hematopoietic stem cell transplantation. Bone Marrow Transplant, 2003; 31(8): 705–712 Miyamoto CT et al. A retrospective match controlled study of supersaturated calcium phosphate oral rinse vs. supportive care for radiation induced oral Mucositis. J Cancer Therap, 2012; 3: 630–636 Santos T. et al. Advances in the control of oral mucositis during nurse visits. Spanish Oncology Nursing Society SEEO Congress, 2010 Haas M et al. Treatment of Oral Mucositis by Supersaturated Calcium Phosphate Oral Rinse in Patients Receiving Chemotherapy (CT) and Radiation (RT). Abstract presented at the 50th American Society for Radiation Oncology Conference, Boston, USA, 21st – 25th September, 2008.

11. 

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Nutrition, Microbes and Oral Mucositis (OM) Sophie Levingworth, Medical Correspondent

Trying to fight cancer whilst malnourished does not make sense but sadly this is what many sufferers are forced to do because of the effects of OM.

When cells are damaged or recovering they need more of the relevant nutrients to affect this repair but if the sufferer finds eating painful or unpleasant then, obviously, recovery will be delayed

T

O BE force-fed or to have to feed by nasogastric tube are unpleasant alternatives to the normal process of putting food into your mouth. A normal person gets pleasure as well as nutrition from eating. OM is so unpleasant that it can stop sufferers eating, wanting to eat and affects their social lives2. The effect on nutrition at a time of treatment has the potential for synergistic problems. We need protein, fat, carbohydrates, trace elements and vitamins to survive. Some of these we digest and break down ourselves but some are broken down by microbes that have coevolved with us over the millennia. When cells are damaged or recovering they need more of the relevant nutrients to affect this repair but if the sufferer finds eating painful or unpleasant then, obviously, recovery will be delayed. When chemo or radiotherapy attack fast growing cells they affect all cells of all mucosas not just the mouth and so often associated with OM are other symptoms affecting the rest of the gastrointestinal wall and hence affecting absorption of food and vitamins.

A Mass of Microbes In recent years, increased interest had focused on the co-evolution of microbes alongside the human. It has been estimated that our body mass is 1-3% microbes, some of which have not even been scientifically classified yet. Our adult microbe mass is the weight of our brain (almost 1.5 kg) and comprises more than 100 trillion bacterial and fungal cells3. Biologist Alanna Collen famously reminds us that ’You are just 10% human’4 in that 90% of our cell mass is made up on non-human cells which weigh far less than human cells. In 1950s, microbial ecologist, Theodore Roseberry5, coined the term amphibiosis, to explain that some organisms can be both 12 | WWW.PRIMARYCAREREPORTS.CO.UK

harmful and beneficial within the same organism depending on balance and circumstances. This attempts to move us away from the concept of seeing all microbes as pathogens (diseasecausing microbes) and it is relevant to OM in several ways. The first is for the mouth itself which always has a collection of bacteria mostly living in a sort of balanced harmony but when OM occurs a previously harmless organism may show pathogenic features or the microbiome may be so affected that an outsider organism can flourish whereas previously it would not. Here the treatments for OM have a role in restoring a more neutral PH balance to the mouth and hence simulating a more normal environment or the healthier balance of microorganisms to prosper. The Human Microbiome Project6 (HMP) has extensively studied the mouth and every surface has a different population of microbes whether it be tongue, check, teeth, palate or the gingivial crevice (the gap between tooth and gum). The other area in which OM affects the microbiome is in the gut since the gut microbes need certain nutrients to maintain their balance and, once these are reduced or absent, another organism may become predominant that has less healthy effects on the host. Dr Martin Blaser estimates ‘that up to 15% of the calories present in your food are extracted by the guest bacteria in your colon and used to feed you’. The process of eating requires our brain to send signals and microbes and organs to release enzymes, hormones and liquids. This complex system is disturbed by OM in a negative fashion.

Differential Diagnosis of OM and Why You as General Practitioners Should Participate in Managing OM The good clinician always considers other diagnostic possibilities.


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The differentiation should consider apthous ulceration7, herpetic ulcers8, oral thrush9, denture/ oral trauma, gangrenous and acute necrotising stomatitis10 whilst noting that any may be secondary complications of OM. The end result of any of the above conditions is to reduce nutritional intake, fluid intake, delay recovery and in some cases it leads to the abandonment of therapy. When your patient is started on chemo or radiotherapy, anticipate the onset of OM or other oral complications and be prepared to advise early intervention, which will also increase the quality of life for your patient. Decide with your colleagues which oral grading system you are going to use to assess symptoms and signs and follow available guidelines that recommend evidence based early interventions. An industry group on OM was formed several years ago and in the absence of any current National Institute for Health and Care Excellence (NICE) this guidance can be

regarded as one of the best available resources in this area. This organisation The United Kingdom Oral Mucositis in Cancer Care Group (UKOMiC)11, describes itself as ‘a multiprofessional group of oral care experts working in cancer and palliative care’. The updated UKOMiC 2015 guidance12 advises good oral hygiene, cessation of smoking, fluoride toothpastes, plaque reduction and the early use of a topical oral agent13 with high concentrations of calcium and phosphate ions.

Summary The GP should think about their cancer patient, the side effects of their therapy, their nutrition and their microbes. OM is a common aspect of ‘collateral damage’ with chemo or radiotherapy but addressing oral hygiene and ensuring regular use if a topical oral agent can successfully reduce these negative effects. Your patients will be thankful for it, have better breath and may even blow you a kiss.

References: http://www.ucmp.berkeley.edu/alllife/threedomains.html accessed 2/1/2016

1. 2.

http://www.ncbi.nlm.nih.gov/pubmed/10650895 accessed 2/1/2016

3.

http://martinblaser.com/ accessed 2/1/2016

4.

http://www.amazon.com/10-Human-Microbes-Health-Happiness/dp/0062345982 accessed 2/1/2016

5.

https://en.wikipedia.org/wiki/Theodor_Rosebury#Works accessed 4/1/2016

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http://hmpdacc.org/ accessed 2/1/2016

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http://emedicine.medscape.com/article/867080-overview accessed 2/1/2016

8.

https://www.nlm.nih.gov/medlineplus/ency/article/001383.htm accessed 2/1/2016

9.

http://www.nhs.uk/Conditions/Oral-thrush---adults/Pages/Introduction.aspx accessed 2/1/2016

10.

http://www.slideshare.net/shabeelpn/acute-necrotising-ulcerative-gingivitis accessed 2/1/2016v

11.

http://www.ukomic.co.uk/ accessed 2/1/2016

12.

http://www.ukomic.co.uk/pdf/UK_OM_Guidelines.pdf accessed 2/1/2016

13.

http://tiny.cc/lfyc8x WWW.PRIMARYCAREREPORTS.CO.UK | 13


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The Mouth, Oral Mucositis, Dental Hygiene and Medical Treatment Dr Charles Easmon MBBS MRCP MSc Public Health DTM&H DOccMed

On a national level we should help people improve their oral hygiene but for precancer treatment this emphasis becomes even more important

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T

HE MOUTH is like a conductor of an orchestra of eating, kissing and talking. We often take it for granted. To chew on food and enjoy its tastes is pleasure. To drink, whether alcohol or non-alcohol has kept poets entertained since writing began. To be able to talk and respond to friends, colleagues and loved ones makes us feel more whole. Affection expressed through kissing is a key part of our lives. Imagine if none of this was easily possible and if each action was accompanied by pain or dryness then you can get closer to understanding the disease and deranged ‘conductor’ that is Oral Mucositis (OM). This condition has best been described by Rubinstein et al1 as: ‘Inflammation of the mucosal membrane, characterised by ulceration, which may result in pain, dysphagia and impairment of the ability to talk. Mucosal injury provides an opportunity for infection to flourish, placing the immunocompromised patient at risk of sepsis and septicaemia’. It is shockingly common in those undergoing cancer treatment and since mucosal cells are fast growing this should be no surprise. Rubinstein et al estimate that ‘oral and gastrointestinal (GI) mucositis can affect up to 100% of patients undergoing high-dose chemotherapy and hematopoietic stem cell transplantation, 80% of patients with malignancies of the head and neck receiving radiotherapy’. There are many ways to grade OM2 and these are listed below: 1) World Health Organization’s (WHO’s) Oral Toxicity Scale (OTS) GRADE 1 Soreness +/- erythema, no ulceration. GRADE 2 Erythema, ulcers. Patients can swallow solid diet. GRADE 3 Ulcers, extensive erythema. Patients

cannot swallow solid diet. GRADE 4 OM to the extent that alimentation is not possible. 2) National Cancer Institute’s Common Toxicity Criteria (NCI CTC) 3) Oral Assessment Guide 3 (OAG) 4) Oral Mucositis Index4,5 (OMI) 5) Oral Mucositis Assessment Scale6,7 (OMAS) 6) Nijmegen Nursing Mucositis Scoring System8 (NNMSS) 7) Visual Analogue Scale (VAS)9 Whichever scale is used at its most severe sufferers have expressed a desire for death rather than continuing with the suffering. From a patient’s point of view just imagine a dry, sore, painful mouth, a swollen cracked tongue, with teeth falling out that is cosmetically unattractive and that smells bad. There are many iatrogenic causes of OM. The Hippocratic Oath is based on ‘first do no harm’ but he did not have to deal with chemotherapy, radiotherapy and to a lesser extent immunotherapy. 1 in 2 people born after 1960 will be diagnosed with some form of cancer during their lifetime.10 Cancer is our modern enemy11. It will affect 1 in 3 of us over the age of 60 and we now know there are many preventable risk factors12. Chemotherapy is targeted poison and whilst it targets the cancer, we have always been aware of its ‘collateral damage’ to any fast growing cells13,14. The most visible side effect is hair loss but damage to the mucosa although less visible can be and is as devastating to the sufferer. Radiotherapy15, which is used in more than half of all cancers, does the same, which is very well illustrated by photographs of the hands of Marie Curie before she died . Fortunately immunotherapy17 does not cause as much OM.


IMPROVING THE PREVENTION AND TREATMENT OF MUCOSITIS

Prevention and Treatment of OM

Is OM a Common Problem Ignored By Doctors? The care of cancer patients should be holistic and involves a team approach. Doctors may focus on treatment rather than the side-effects of that treatment but this is something that few others, especially nurses can ignore. The aim of this article is to raise all doctorsâ&#x20AC;&#x2122; awareness of OM, its potential severity, the morbidity it causes and the fact that something can be done about it. Due to high-dose chemotherapy and/ or radiation preconditioning, it is particularly common in patients preparing for bone marrow/ stem cell transplantation and leads to significant numbers of patients requiring feeding tubes (up to 62%) and many are hospitalised for total parenteral nutrition, intravenous analgesia, and intravenous antibiotics18.

Basic oral hygiene is important and so Pretreatment dental checks are advised for anyone undergoing chemo or radiotherapy. In the 1970s and 1980s one of the glaring differences between a British film star and an American one was their teeth. In general the Americans dazzled as they showed a pristine set of perfect teeth whilst the Brit would have been at home is Dickenâ&#x20AC;&#x2122;s time. The British actors are now (mostly) catching up but sadly not the British Public. Our National dental hygiene and welfare is poor. It has been estimated that around 33% of adults in England have tooth decay and that 25% of five-year-old children have some degree of tooth decay19. On a national level we should help people improve their oral hygiene but for pre-cancer treatment this emphasis becomes even more important. Excellent free advice is available for General Practitioner from the charity The Mouth Cancer Foundation20, The British Dental Health Foundation21 and the industry funded The UK Oral Mucositis in Cancer Group22. Once treatment has started, the consequences of OM are self-evident if the doctor alongside the rest of the holistic team thinks about it. Various guidelines now advise that beyond the 1st stage of OM treatment should be given and one such over the counter treatment is an oral substance rich in calcium and phosphate ions (given 4-10 times a day).

References: http://www.ncbi.nlm.nih.gov/pubmed/15108223 accessed 31/12/2015

1. 2.

https://www.ebmt.org/Contents/Resources/Library/Slidebank/Documents/EBMT%202010%20SC%20Slide%20Bank/N1063a%20Fliedner.pdf accessed 31/12/2015

3.

https://www.starship.org.nz/media/172991/oral.pdf accessed 31/12/2015

4.

http://www.ncbi.nlm.nih.gov/pubmed/12449720 accessed 31/12/2015

5.

http://www.meducator3.net/algorithms/content/oral-mucositis-index-omi-schubert-et-al accessed 31/12/2015

6.

https://www.cibmtr.org/meetings/materials/crpdmc/documents/2007/february/cutlerc_mucositisasb.pdf accessed 31/12/2015

7.

http://www.nccn.org/JNCCN/PDF/mucositis_2008.pdf accessed 31/12/2015

8.

http://www.ncbi.nlm.nih.gov/pubmed/16882117 accessed 31/12/2015

9.

http://www.physio-pedia.com/Visual_Analogue_Scale accessed 31/12/2015

10. 11. 12. 13.

http://www.cancerresearchuk.org/content/cancer-statistics-for-the-uk#heading-Three accessed 31/12/2015 http://www.pbs.org/show/story-cancer-emperor-all-maladies/ accessed 31/12/2015 http://www.the-scientist.com/?articles.view/articleNo/44872/title/Cancer-Not-Just--Bad-Luck-/ accessed 31/12/2015 http://www.cancer.org/treatment/treatmentsandsideeffects/treatmenttypes/chemotherapy/whatitishowithelps/chemo-what-it-is-chemo-side-effects accessed 31/12/2015

14.

http://www.webmd.com/cancer/questions-answers-chemotherapy#0 accessed 31/12/2015

15.

http://www.cancer.org/treatment/treatmentsandsideeffects/treatmenttypes/radiation/index accessed 31/12/2015

16.

https://www.pinterest.com/pin/339458890633702001/ accessed 2/1/2016

17.

http://www.cancer.org/treatment/treatmentsandsideeffects/treatmenttypes/immunotherapy/immunotherapy-what-is-immunotherapy accessed 31/12/2015

18.

http://tiny.cc/s6yc8x accessed 31/12/2015

19.

http://www.nhs.uk/conditions/Dental-decay/Pages/Introduction.aspx accessed 31/12/2015

20.

http://www.mouthcancerfoundation.org/ accessed 2/1/2016

21.

https://www.dentalhealth.org/ accessed 2/1/2016

22.

http://www.ukomic.co.uk/new-om-guidelines.html accessed 2/1/2016 WWW.PRIMARYCAREREPORTS.CO.UK | 15


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OM and Head and Neck Cancers1 Update Sophie Levingworth, Medical Correspondent

The carcinogenic potential of viruses now seems obvious and plausible since viruses use cellular DNA to replicate themselves and it seems logical that this might contribute to tumorgenesis

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T

HESE ARE tumours of squamous cells that line moist mucosa and, as expected, treatment whether by chemo or radiotherapy gives a very high risk of Oral Mucositis (OM). So all patients with Head and Neck Cancer should be assumed to be a high risk of OM and preventative and treatment measures should be put in place as soon as possible by the General Practitioner (GP) and the multidisciplinary team.

Behavioural, Cultural Issues and Head and Neck Cancers In Georgian England, the habit of taking snuff (fine-ground tobacco) was rife amongst the upper classes. The habit required a ’pinch’ of snuff to be placed in each nostril and then to be sniffed. Positioning the snuff in the nostril required a nasal posture based on gravity that led to the term ’’toffee nosed”2. Snuff taking could lead to head and neck cancers but, fortunately, it is not now a common habit, but smoking, although declining, is. Chewing tobacco was common in the American West and led to many a joke about ‘spittoons’. It is still popular in some parts of the USA, despite its obvious carcinogenic potential. In many countries, indoor3 (and presumably outdoor) air pollution is a risk factor for head and neck cancers based on airborne carcinogens. In some cultures, chewing betel nuts (South East Asia) is common but has predictable risks. Other cultural habits have been linked to head and neck cancers such as consuming a tea-like beverage in South America and preserved or salted foods during childhood. The incidence of oropharyngeal cancer is particularly high in parts of South East Asia. Alcohol remains one of our national vices but is a separate risk factor for head and neck cancers and combined with smoking has a cumulative effect.

Viruses and Head and Neck Cancers Viruses have now been linked to around 15% of all cancers4. The carcinogenic potential of viruses now seems obvious and plausible since viruses use cellular DNA to replicate themselves and it seems logical that this might contribute to tumorgenesis. In addition, we now know that virus DNA or RNA can be inserted into our own DNA and, in fact, in some areas have become part of our ‘normal’ transmissible DNA (possibly contributing up to 8-9% of our DNA5,6,7. Denis Burkitt8,9 was a pioneering, evangelical and missionary doctor who spent long periods preaching, teaching and researching in Africa. He discovered Burkitt’s Lymphoma and is credited with linking this (via epidemiological maps) to previous exposure to a then unidentified infectious disease and it was subsequently found to be linked to the Epstein-Barr Virus. This link of viruses to cancer has led to much subsequent research and we now know that HPV10 infection can increase the risk of oropharyngeal cancer. The good news is that HPV related cancers have a better prognosis than those without and now that there is a vaccine against HPV infection we expect, over time, to see a decrease in cancers caused by it.

Strategies to Reduce Head and Neck Cancers and OM As a General Practitioner, you can encourage your patients not to smoke, drink excessively and avoid casual sexual relationships. You have tools to help you through the National Health Service (NHS)11 and the National Institute for Health and Care Excellence (NICE)12. If you are aware of any cultural risk factors such as betel nut chewing you can advise on this. In your practice, you can support and encourage parents to ensure that their girls take up the provided HPV vaccine and, on


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a private basis, should you wish to, you can vaccinate boys or older women, or at least point them to suitable providers.

You can encourage general dental hygiene using some of the tools provided by the charity the Mouth Cancer Foundation13, The British Dental Health Foundation14 and the industry funded The UK Oral Mucositis in Cancer Group15. In your patients with cancer, especially those who are to have bone marrow transplants, stem cell transplants or chemo or radiotherapy for head and neck cancer, you can advise about early prevention of OM and ensure that no part of the multi-disciplinary team neglects to introduce a suitable oral treatment as soon as possible.

References:

http://www.cancer.gov/types/head-and-neck/head-neck-fact-sheet accessed 2/1/2016

1.

2.

http://www.amazon.co.uk/Beau-Brummell-The-Ultimate-Style/dp/1416584587 accessed 2/1/2016

3.

http://apps.who.int/iris/bitstream/10665/51744/1/WHSQ_1990_43_n3_127-138.pdf?ua=1 accessed 2/1/2016

4.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1994798/ accessed 2/1/2016 http://phenomena.nationalgeographic.com/2015/02/01/our-inner-viruses-forty-million-years-in-the-making/ accessed 2/1/2016

5.

6.

http://phenomena.nationalgeographic.com/2013/05/10/the-lurker-how-a-virus-hid-in-our-genome-for-six-million-years/ accessed 2/1/2016

7.

https://www.newscientist.com/article/dn27384-virus-hiding-in-our-genome-protects-early-human-embryos/ accessed 2/1/2016

8.

http://www.nytimes.com/1993/04/16/obituaries/dr-denis-burkitt-is-dead-at-82-thesis-changed-diets-of-millions.html accessed 2/1/2016

9.

https://www.drmcdougall.com/misc/2013nl/jan/burkitt.htm accessed 2/1/2016

10.

11.

12.

13.

14.

15.

http://www.mouthcancerfoundation.org/sites/mcfdev/files/body/PDFs/hpv-mouth-cancer%20%282%29%20Revised%20LoRes.pdf accessed 2/1/2016

http://www.nhs.uk/Change4Life/Pages/drink-less-alcohol.aspx accessed 2/1/2016 http://pathways.nice.org.uk/pathways/smoking/smoking-prevention-and-cessation-overview 2/1/2016 http://www.mouthcancerfoundation.org/ accessed 2/1/2016 https://www.dentalhealth.org/ accessed 2/1/2016 http://www.ukomic.co.uk/new-om-guidelines.html accessed 2/1/2016

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Bone Marrow Transplant1 and Hematopoietic Stem Cell Transplantation2, Immunotherapy3 and Cancer Dr Charles Easmon MBBS MRCP MSc Public Health DTM&H DOccMed

The mouth provides a reflection of general health and may reveal some of the toxicities of cancer treatments4

Cancer cells can cause T cell exhaustion by affecting cell surface molecules that regulate the immune responses and this allows them to escape immune surveillance and leads to unchecked tumour growth

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Using the Immune System to Fight Cancer In the Pulitzer Prize winning book ‘The Emperor of All Maladies: A Biography of Cancer’ by Siddhartha Mukherjee5, the author describes a ‘biography’ of cancer from the earliest recorded case to modern times. It has been a long battle and we are winning some wars but cancer remains as the emperor of all maladies. A key problem is that normal growth and regeneration are about cell proliferation, which is the same (although modified) means of cancer growth. The next problem is that to kill cancer cells you often kill non-cancerous cells and this ‘collateral damage’ can itself be devastating as witnessed in Oral Mucositis (OM). The battle against cancers has left many hostages to fortune. We sadly accept that many of our tools are not ideal. Chemotherapy causes significant side-effects, as does radiotherapy. Immunotherapy may provide a kinder solution to treating some cancers and is of interest because it causes less OM. The more common side-effects with Immunotherapy are ‘dermatitis (pruritus, rash), enterocolitis, endocrinopathies (hypophysitis, thyroiditis), liver enzyme abnormalities, and uveitis’6. Cancer cells can cause T cell exhaustion by affecting cell surface molecules that regulate the immune responses and this allows them to escape immune surveillance and leads to unchecked tumour growth. Immunotherapy has

started with monoclonal antibodies that target immune checkpoints in 2 key ways 1) they down regulate the immune response that would allow tumour cells to grow and 2) they up regulate the immune response that would allow tumour cells to be killed. The first successful treatments have been in malignant melanoma and since then success has been achieved in both renal cell carcinoma (RCC) and non-small cell lung cancer NSCLC.

Bone Marrow and Stem Cell Transplants Replacing solid organs is conceptually ‘tangible’. A kidney from donor A goes to recipient B. Replacing liquids does not intuitively seem like an ‘organ’ transplant but that effectively is what a bone marrow/stem cell transplant is in that it replaces a faulty cell line with an effective one. For a bone marrow/stem cell transplant to work, either chemo or radiotherapy is required to secure a lack of growth of the faulty line and/or suppression of any adverse immune response to the new material. This aggressive chemo or radiotherapy almost inevitably and predictably leads to OM. Stem cells, as their name suggests, are the precursors of many other cells and they can be sourced in 3 key ways 1) your own cells are stored and frozen before the treatment and then put back into you after the treatment 2) a donor provides suitable cells or 3) the cells come from a baby’s umbilical cord. Any of these procedures


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can be called a bone marrow/stem cell transplant even though the new cells are not put into the marrow or necessarily sourced directly from it in the donor. The range of conditions treatable by bone marrow /stem cell transplant is wide and includes: Liquid cancers like myeloma, leukemias, Myeloproliferative disorders Solid tumours like lymphomas, Neuroblastomas, Germ cell tumors Autoimmune disorders (systemic lupus erythematosus [SLE], systemic sclerosis) Many anaemias, inborn errors of metabolism, immune deficiency disorders & Amyloidosis Immunotherapy versus Bone Marrow/Stem Cell Transplant Risks of OM in Your Practice

Immunotherapy versus Bone Marrow/Stem Cell Transplant Risks of OM in Your Practice Immunotherapy is relatively new but set to expand with rapid advances in gene sequencing science. It probably has a limited future in Head and Neck Cancer because the body has what we call ‘protected sites’ and these sites are difficult for immunotherapy to access. Sadly, many cancer sites within the head and neck would fit into this category. So for Head and Neck Cancer patients, be on the alert for OM. For the limited number of your patients who can benefit from immunotherapy the relative risk of OM is low unless they have additional chemo and/or radiotherapy. For your bone marrow/stem cell transplant patients the risk of OM is very high and common sense indicates early action. Quinn et al and The UK Oral Mucositis in Cancer Group7 provide guidance for the General Practitioner and the multi-disciplinary team looking after a cancer or bone marrow/stem cell transplant patient.

References: https://www.nlm.nih.gov/medlineplus/ency/article/003009.htm accessed 2/1/2016

1.

2.

3.

http://emedicine.medscape.com/article/208954-overview accessed 2/1/2016 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264429/#bib21 2/1/2016

4.

https://www.ons.org/sites/default/files/publication_pdfs/00%20MOECT_Front.pdf accessed 2/1/2016

5.

http://www.amazon.co.uk/The-Emperor-All-Maladies-Biography/dp/0007250924 accessed 31/12/2015

6.

Page DB, Postow MA, Callahan MK, Allison JP, Wolchok JD. Immune modulation in cancer with antibodies. Annu Rev Immunol. 2014;65:185–202.

[PubMed] accessed 2/1/2016

7.

http://www.ukomic.co.uk/new-om-guidelines.html accessed 2/1/2016

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Notes:

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