Courtney Lacey is a third year BSc Oral Health Science student at the University of the Highlands and Islands (UHI). She carried out this literature review as part of her final year assessment, and chose the topic based on her own experience of chemotherapy-induced oral mucositis.

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Abstract

Introduction This review aims to answer the clinical question: ‘Does chemotherapy-induced oral mucositis affect quality of life in adult oncology patients?'

Methodology The methodology included searching on electronic databases such as Web of Science and Google Scholar to answer a PEO question. Boolean operators and truncation were utilised whilst considering inclusion and exclusion criteria.

Results Seven papers were critically appraised and included: one randomised-controlled trial, three cross-sectional studies, and three cohort studies. The studies concluded that oral mucositis can lead to a reduced quality of life for various reasons.

Discussion The findings of this review indicate that oral mucositis can cause negative psychological effects, dysphagia and pain, leading to a decreased quality of life, which can be compounded by other complications of chemotherapy (and lifestyle factors).

Conclusion Educating patients on basic oral care, nutrition and advising early prophylactic treatment before chemotherapy commences can reduce the incidence and severity of oral mucositis, leading to a less profound decrease in quality of life.

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©Olga Pankova/Moment/Getty Images Plus

Introduction

Chemotherapy is an anti-neoplastic, systemic treatment using intravenous and/or oral cytotoxic agents, aiming to destroy cells, and cytostatic agents, to inhibit cell proliferation.1 Chemotherapeutic agents aren't tissue selective so healthy cells are affected too. Their mechanism of action generally determines the side effects.2 Common side effects include: nausea, bone marrow suppression and various oral manifestations.3 Oral mucositis (OM) (Fig. 1) is an iatrogenic complication of many chemotherapy regimens which affects the oral mucosa. OM can present up to ten days after each infusion, resulting in: ulceration, erythema, oedema and pain, often managed by prescribed opioids.4

Fig. 1
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Oral mucositis affecting the attached gingiva during cycle 3, after infusion 4, of Escalated BEACOPDac regimen in a 25-year-old female with Stage IV Hodgkin's lymphoma. (a) Three days after infusion. (b) Four days after infusion. (c) Five days after infusion. (d) Six days after infusion

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Chemotherapy patients (CP) are prone to neutropoenia and more susceptible to infections and OM due to immunosuppression.5 Consequently, maintaining a high standard of oral hygiene (OH) throughout treatment is imperative.4 Neutropoenic patients are often prescribed G-CSF to be injected subcutaneously, encouraging bone marrow to produce neutrophils to reduce the risk of infection.6

Cambridge Dictionary7 defines quality of life (QoL) as ‘the level of enjoyment, comfort, and health in someone's life'. I was driven to research the effects of OM on QoL in adults after developing OM myself. I aim to raise awareness of OM amongst healthcare professionals and oncology patients, whilst implementing changes to help reduce the incidence/severity of these oral lesions.

Background: Clinical presentation and risk factors

OM clinically appears as an erythematous lesion with ill-defined borders. Ulceration develops and a pseudomembraneous slough forms (Fig. 2) which normally subside within three weeks.3 Risk factors include: age, impaired liver and kidney functions, inadequate OH, poor systemic health and periodontitis; Porphyromonas gingivalis inhibits wound healing.8

Fig. 2
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Oral mucositis affecting the attached gingiva during cycle 4, after infusion 4 of Escalated BEACOPDac regimen in a 25-year-old female with Stage IV Hodgkin's lymphoma. (a) Six days after infusion. (b) Seven days after infusion. (c) Eight days after infusion. (d) Ten days after infusion

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Methodology

A ‘SMART' question was formulated using the PEO format. Google Scholar and Web of Science were used to conduct the initial searches in September-October 2023, alongside forward and backward reference searching. Specific search terms include: ‘chemotherapy', ‘adult' and ‘oral mucositis'. Boolean operators and truncation were utilised to find niche literature that meets the inclusion criteria. Included papers were published between 2013-2023 to avoid outdated research. Duplicates and extraneous papers were excluded - they did not meet the question parameters. Seven papers were included after being critically appraised. Randomised-controlled trials (RCT), cross-sectional (CS), observational and cohort study designs are included.

Results

A six-month cohort study by Martinez et al.9 investigated the incidence and management of OM in 30 CP. Forty percent were female and 60% were male (median age of 53.5 years). Different haematological malignancies were compared with the number of OM episodes, graded using the World Health Organisation (WHO) toxicity scale. ‘Nursing Interventions Classification' (2010) and MASCC/ICOO guidance was used. Oral Mucositis Daily Questionnaires (OMDQ) were completed by patients, collecting subjective data.

Results showed OM can cause pain, dysphagia and poor nutrition, negatively impacting QoL. Participants were followed-up within 5-35 days. 21.9% developed grade 1-2 OM, 4.1% developed grade 3-4 OM. Authors concluded that patients who started early prophylaxis delayed OM, this was statistically significant (SS). Prophylaxis should be introduced to patients, upon identifying those with more risk factors, to potentially prevent OM.

A cohort study by Mercadente et al.10 investigated the prevalence and characteristics of oral lesions in a sample of 669 advanced oncology patients over six months from three different care settings, 192 of whom had chemotherapy within the past month. 51.12% were male, 48.88% were female (mean age of 72.1 years ± 12.3). The WHO-Toxicity scale and Terminology Criteria for Adverse Events version 4.0 was utilised to describe OM. One hundred and forty-nine participants experienced OM and at least 40% consequently experienced eating and drinking impairments. Six percent of participants with OM were unable to eat or drink fluids, whereas 38.9% were able to eat and drink as normal. Sixteen percent of participants experienced OM induced pain (average 5.5/10) and OM is said to be more prevalent in those with current infections, defected oral mucosa and/or poor OH. Less than 33% of participants recall having information about possible oral complications following chemotherapy, nor were they offered contact with dental professionals for assistance. In conclusion, the impact of oral complications can have negative effects physically and psychologically and any symptoms should be addressed promptly.

A CS study by Chaitanya et al.11 included 121 CP (48.76% males, 51.24% females, 20-80 years old) from four oncology centres in Hyderabad assessing anxiety and depression in patients with OM. Confounding factors which could have influenced their mental health include: socio-economic factors, financial situation, lifestyle, stage of cancer, pain and education. Participants mostly presented with mild-moderate OM with borderline anxiety and established depression. Mental health generally worsened in line with the severity of OM. A non-pharmaceutical approach is advised, when possible, as opposed to the prescription of selective serotonin reuptake inhibitors (SSRIs) which can induce oral side effects, exacerbating anxiety/depression.

Yüce and Yurtsever12 conducted a RCT with 60 male and female CP, over 18-years-old, with similar baseline characteristics from three hospital settings. They aimed to investigate how OM affected QoL in those receiving additional oral care advice (education group with 66.7% females, aged 55.4 years ± 15.2) compared to those receiving standard information (control group with 50% females, aged 58.1 ± 14.1). Thirty participants were in each group, all with similar risk factors. Overall, less incidences of OM presented in the education group. Furthermore, participants in the control group had a higher average symptom score. Providing extra oral care education was effective. The severity of OM showed a SS difference on days: 5, 10, 15 and 21. The overall health of patients in the education group was better than the control group.

Frowen, Hughes and Skeat13 performed a CS study to investigate the prevalence of oral manifestations in patients with non-head-and-neck cancers, and their link to 14 types of malignancies. Two hundred and thirty-nine CP (49% males, 51% females with a median age of 59 years) from a Specialist Cancer Centre in Melbourne participated. Data were obtained from patients on one occasion using ‘Vanderbilt Head and Neck Cancer Symptom Survey - version 2.0' and a ‘Likert Scale'. The study concludes that OM and xerostomia link to long-term dysphagia, making them more susceptible to aspiration pneumonia, malnutrition and reduced QoL in patients with different cancer diagnoses.

Lee et al.14 recruited 37 CP (48.65% males, 51.35% females) with acute leukaemia, aged 52.38 years ± 12.48, to participate in a cohort study investigating the clinical signs and symptoms of OM. Baseline characteristics were identified as chemotherapy commenced, ensuring the absence of oral manifestations, and their recall examination took place during week 2. Participants completed an OMDQ on day 14, rating discomfort when eating, swallowing, drinking, soreness, talking and sleeping out of 10. 8 participants presented with OM which was graded using the WHO-Toxicity Scale, with experienced dentists blinded to patients' records to reduce bias. Spearman's correlation analysis was utilised to identify links between the WHO score, number of OM lesions and discomfort from the self-reported questionnaire. An increased WHO-Toxicity grade showed a positive correlation with eating difficulties.

Jena et al.15 conducted a CS study in a tertiary oncology setting in Odisha. One hundred and thirty-eight CP with 14 different malignancies participated (45.6% males, 54.3% females, age 25-75 years). Socio-demographic variables (education, OH and socio-economic status) were considered. Sixty percent presented with oral manifestations and 10.14% with OM. An increased age, socio-economic status and poor OH led to more OM incidences. An altered oral microflora following chemotherapy can affect the prevalence and severity of OM, further research is advised.

Discussion

In the papers discussed, the WHO-toxicity scale is commonly used when grading OM (0-4) based on the clinical picture, ability to eat/swallow and pain - this provides high interobserver reproducibility. Self-report questionnaires (eg OMDQ) and scales (eg Likert) are regularly used to collect information. They are reproducible, cost-effective ways of collecting qualitative and quantitative data. Answers can be subjective, skewing the results.

Baseline characteristics were obtained by Martinez et al.9 including sex, smoking status, dental prostheses, chemotherapy regimen and blood test results at the commencement of chemotherapy and on the day that OM presented. Yüce and Yurtsever12 recorded baseline characteristics and patients were fairly allocated to the control and education groups. Frowen, Hughes and Skeat13 recorded data about age, sex, type of malignancy and treatment. Lee et al.14 recorded clinical signs prior to chemotherapy and on day 14. Each study that included participants with similar baseline characteristics provided findings with more validity and confidence that the different outcomes are due to the intervention (chemotherapy) rather than confounding variables.9,12,13,14

Yüce and Yurtsever12 addressed risk factors such as age, gender, chemotherapy regimen, smoking status, alcohol consumption, neutrophil levels, OH and malignancy type. Chemotherapy regimens with 5-fluoracil, methotrexate or etoposide increase the risk of OM development.16

Food and fluid ingestion is vital in patients undergoing chemotherapy to boost energy and strength, ‘flush out' toxins, reduce susceptibility to infection and aid recovery.17 Most studies mention dysphagia due to OM, resulting in dehydration and malnutrition. These can hinder treatment outcomes as the chemotherapeutic agents have a more toxic effect making patients more prone to infections, potentially causing death.18 Education about the prevention and management of oral sequalae following chemotherapy seems effective, reducing the prevalence and intensity of OM. Therefore, it should routinely be provided to every patient prior to the commencement of chemotherapy.12 A literature review by Bezerra et al.19 concluded that patients with excellent OH are significantly less susceptible to OM. Patients should be encouraged to report symptoms immediately as OM can be life-threatening. This would be beneficial as delaying chemotherapy to recuperate from OM could impact the cancer prognosis, increasing morbidity and mortality.

The aforementioned studies suggest that pain caused by OM negatively impacts QoL. If OM develops, opioids such as morphine and codeine are commonly prescribed analgesics to manage pain, ameliorating QoL. Opioids are contraindicated in individuals with respiratory depression or previous opioid misuse due to the addictive effect. Common side effects include nausea and xerostomia, exacerbating oral discomfort.20 Non-opioids should be offered alternatively when possible, such as benzydamine or amitriptyline.21 Cryotherapy can help to treat OM as the vasoconstrictive properties prevent the toxic drugs from injuring the oral mucosa; sometimes, it's contraindicated.3

Some papers discussed the psychological effects of OM. Yüce and Yurtsever12 stated self-esteem and body image can be affected, whilst Mercadente et al.10 also discussed the social impact of ulceration. Other causes for poor psychological effects such as anxiety/depression could be due to confounding variables eg stage of cancer, finances, lifestyle etc.11

Jena et al.15 suggested that more oral manifestations developed with a longer duration of chemotherapy rather than due to the number of cycles. Santilal and Graça22 and Chaitanya et al. produced the same findings.

Chaitanya et al.11 did not provide follow-up appointments to review anxiety/depression levels. Similarly, Frowen, Hughes and Skeat13 collected data once without follow-ups. Oral manifestations may present after the point of data collection so some incidences potentially weren't accounted for. Yüce and Yurtsever12 followed-up multiple times to investigate the severity of OM with time.

Education about optimising OH before chemotherapy, providing diet advice and advising prophylaxis can help to reduce the prevalence and severity of these lesions, decreasing morbidity and mortality rates

Chemotherapeutic agents can cause many other complications (Table 1). The oral sequalae, systemic and psychological effects of chemotherapy could have a cumulative effect on the decreased QoL.

Table 1 Common oral and systemic manifestations following chemotherapy9,10,11,12,13,14,15
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Conclusion

Studies suggest that OM negatively impacts QoL in adult oncology patients for various reasons: pain, psychological effects and dysphagia (which can lead to dehydration/malnutrition). OM can be debilitating and potentially life-threatening; symptoms should be reported immediately. Education about optimising OH before chemotherapy, providing diet advice and advising prophylaxis can help to reduce the prevalence and severity of these lesions, decreasing morbidity and mortality rates. Analgesics can be used to manage the pain, reducing the use of opioids when possible due to the adverse effects and contraindications. Non-pharmacological help is preferable over SSRIs (which can cause further adverse effects). Other oral, systemic, social and psychological effects of chemotherapy can also decrease QoL. Confounding factors which may exacerbate QoL weren't always considered in the aforementioned studies, indicating the need for further research.

Oncology and dental professionals should work as a multi-disciplinary team to improve patient outcomes.

Clinical recommendations

Educating patients on OH advice, nutrition and prophylaxis before commencing chemotherapy effectively reduces the prevalence and severity of OM. Oncology staff should provide this information verbally and written for patients to read at home. Printing leaflets has financial implications, so patients should be emailed when possible. Patients experiencing poor mental health may benefit from a non-pharmacological approach as SSRIs can induce adverse side effects, exacerbating oral discomfort and QoL. Oncology and dental professionals should work as a multi-disciplinary team to improve patient outcomes.

Recommendations for future research

Further international RCTs from different settings investigating the impact of OM on QoL in adult CP should be carried out and collated in the form of a meta-analysis to support this literature review and to provide further advice on prevention and management of OM. The research can provide evidence-based guidelines to support oncology patients with OM.

Ethical considerations

Consent was obtained allowing the images within this review to be included.