Sage Journals: Discover world-class research

Abstract

Objective:

This scoping review aims to examine studies led or participated in by clinical pharmacists or nurses, investigating the work performed and roles played by clinical pharmacists and nurses in managing patients’ adverse reactions such as oral mucositis, summarizing the existing research foundation and evidence.

Methods:

This scoping review followed the methodology defined by the Joanna Briggs Institute, and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. Literature search was conducted in February 2024 across PubMed, Scopus, Cochrane, and Embase. Two independent researchers initially screened titles and abstracts in Covidence, followed by a full-text review. The extracted information and summaries were organized using Excel.

Results:

Twelve publications were included (randomized controls n = 8; retrospective descriptive studies n = 2; prospective cohort studies n = 2). Three publications studied clinical pharmacists providing pharmaceutical care to patients, while nine publications focused on nurses monitoring adverse reactions.

Conclusion:

In the chemoradiotherapy of head and neck cancers, the effective prevention and management of oral mucositis are crucial for improving patient prognosis. Clinical pharmacists and nurses, with their expertise and skills, play vital roles in the multidisciplinary treatment team, providing optimized treatment plans and comprehensive care support to patients. The direct care model implemented by pharmacists and nurses effectively alleviates symptoms and enhances the quality of life, thus fostering better treatment outcomes and patient satisfaction.

Keywords

Clinical pharmacists nurses oral mucositis clinical monitoring head and neck cancers

Introduction

Head and neck cancer (HNC) is the seventh most prevalent cancer worldwide. A significant proportion of HNC patients undergo radiation therapy (RT) as part of their treatment regimen. However, the oral and throat regions of these patients are often exposed to radiation, resulting in a high incidence of oral mucositis (OM). Research by Trotti et al.¹ reveals that approximately 80% of HNC patients receiving RT experience OM to varying degrees, with 34% of those undergoing conventional RT developing severe OM (grades 3–4).¹

The development of OM significantly increases pain levels in HNC patients and profoundly affects their quality of life (QoL).² Severe oral mucositis (SOM) is also closely associated with compromised nutritional status and weight loss.³ A decline in overall health can reduce patients’ tolerance to RT doses and may even necessitate the suspension of treatment, thereby affecting therapeutic outcomes.

Additionally, OM can lead to mouth ulcers and open wounds, increasing the risk of infection. SOM may cause bacterial, fungal, or viral infections,⁴ further exacerbating the patient’s condition.

Despite growing awareness, effective prevention and management of OM remain a persistent challenge in cancer care. Adequate prevention and treatment by healthcare professionals can potentially reduce the severity of radiation-induced OM, alleviate patients’ pain and discomfort, prevent malnutrition and infections, enhance treatment compliance, and thus improve patients’ QoL and treatment outcomes.

Guideline for the management of treatment-induced OM published by Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) recommend the use of mouthwashes or photobiomodulation to prevent OM in patients with HNC, with topical 0.2% morphine mouthwash to alleviate pain associated with OM.⁵ The 2020 guideline from the European Oral Care in Cancer Group emphasizes oral care as central to preventing and minimizing oral complications during and after treatment. The oral care team may vary by medical setting but typically includes dental professionals, dietitians, nurses, physicians, and pharmacists.⁶ The support provided by the team, along with good communication with patients, forms the core of all care plans, crucial for maintaining patients’ oral health. While the involvement of pharmacists and nurses is essential in managing treatment-related adverse reactions in oncology patients, research describing their specific roles in OM management remains limited. Studies as early as 2009 highlighted the significant contributions of clinical pharmacists in supportive care for oncology patients.⁷ Subsequent research has shown the effectiveness of pharmacists in managing OM caused by chemoradiotherapy (CRT) in HNC patients,^8–11 but there is a lack of specific measures and standardized workflows for pharmacist and nurse-led care for OM induced by RT and chemotherapy (CT) in HNC in real-world settings.

This scoping review aims to investigate the roles of clinical pharmacists and nurses in managing adverse reactions among HNC patients, particularly OM. It seeks to summarize existing research, highlight evidence-based practices, and explore opportunities for optimizing pharmacist- and nurse-led care for OM in clinical settings.

Methods

Study design

This review adheres to the JBI scoping review methodology updated in 2020¹² and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist,¹³ shown in Table 1.

Table1.

PRISMA-ScR checklist of this scoping review.

Section/topic	Item	PRISMA-ScR checklist item	Reported on page number
Title			Page 1
Title	1	Identify the report as a scoping review	1
Abstract			Page 2
Structured summary	2	Provide a structured summary that includes (as applicable) background, objectives, eligibility criteria, sources of evidence, charting methods, results, and conclusions that relate to the review questions and objectives	2
Introduction			Page 6–8
Rationale	3	Describe the rationale for the review in the context of what is already known. Explain why the review	6
Objectives	4	Provide an explicit statement of the questions and objectives being addressed with reference to their key elements (e.g., population or participants, concepts, and context) or other relevant key elements used to conceptualize the review questions and/or objectives	Page 7–9
Methods			Page 9–13
Protocol and registration	5	Indicate whether a review protocol exists; state if and where it can be accessed (e.g., a Web address); and if available, provide registration information, including the registration number	9
Eligibility criteria	6	Specify characteristics of the sources of evidence used as eligibility criteria (e.g., years considered, language, and publication status), and provide a rationale	10
Information sources	7	Describe all information sources in the search (e.g., databases with dates of coverage and contact with authors to identify additional sources), as well as the date the most recent search was executed	9
Search	8	Present the full electronic search strategy for at least 1 database, including any limits used, such that it could be repeated	10
Selection of the sources of evidence	9	State the process for selecting sources of evidence (i.e., screening and eligibility) included in the scoping review	10
Data charting process	10	Describe the methods of charting data from the included sources of evidence (e.g., calibrated forms or forms that have been tested by the team before their use, and whether data charting was done independently or in duplicate) and any processes for obtaining and confirming data from investigators	11
Data items	11	List and define all variables for which data were sought and any assumptions and simplifications made	11
Critical appraisal of individual sources of evidence	12	If done, provide a rationale for conducting a critical appraisal of included sources of evidence; describe the methods used and how this information was used in any data synthesis (if appropriate)	11–12
Synthesis of results	13	Describe the methods of handling and summarizing the data that were charted	NA
Results			Page 14–26
Selection of sources of evidence	14	Give numbers of sources of evidence screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally using a flow diagram	14
Characteristics of sources of evidence	15	For each source of evidence, present characteristics for which data were charted and provide the citations	Appendix 1
Results of individual sources of evidence	16	For each included source of evidence, present the relevant data that were charted that relate to the review questions and objectives	15–26
Synthesis of results	17	Summarize and/or present the charting results as they relate to the review questions and objectives	Tables 4, 5
Discussion			Page 27–32
Summary of evidence	18	Summarize the main results (including an overview of concepts, themes, and types of evidence available), link to the review questions and objectives, and consider the relevance to key groups	29–31
Limitations	19	Discuss the limitations of the scoping review process	31–32
Conclusions	20	Provide a general interpretation of the results with respect to the review questions and objectives, as well as potential implications and/or	32
Funding
Funding	21	Describe sources of funding for the included sources of evidence, as well as sources of funding for the scoping review. Describe the role of the funders of the scoping review	NA

Search strategy

From February to March 2024, two independent researchers conducted searches of Scopus database, the Cochrane Library database, Embase database, and PubMed database. Use the following terms: (((((((Head and Neck Neoplasms[MeSH Major Topic]) OR (Upper Aerodigestive Tract NCancer[Title/Abstract])) OR (UADT Neoplasm[Title/Abstract])) OR (Otorhinolaryngeal Cancer[Title/Abstract])) OR (Tongue Neoplasm[Title/Abstract])) OR (Oral Cancer[Title/Abstract])) AND (((Stomatitis[MeSH Major Topic]) OR (Stomatitides[Title/Abstract])) OR (Oromucositi*[Title/Abstract]) OR (Oral Mucositi*[Title/Abstract])) OR (Aphthous[Title/Abstract])) AND ((((((((((((((Pharmacists[MeSH Major Topic]) OR (Nurses[MeSH Major Topic])) OR (Nursing[MeSH Major Topic])) OR (Pharmaceutical services[MeSH Major Topic])) OR (Practice patterns, Nurses’[MeSH Major Topic])) OR (Practice patterns, pharmacists’[MeSH Major Topic])) OR (pharmaceutical care[Title/Abstract])) OR (pharmaceutical service*[Title/Abstract])) OR (Nursing*[Title/Abstract])) OR (Nursing care[Title/Abstract])) OR (Oncology Nursing[Title/Abstract])) OR (clinical pharmacist*[Title/Abstract])) OR (Pharmacist*[Title/Abstract])) OR (Nurse*[Title/Abstract])). These search criteria were selected to capture the management by all study clinical pharmacists and nurses of patients with HNC who developed OM following CRT.

Inclusion and exclusion criteria

Covidence system was used for conducting this scoping review. The criteria for exclusion and inclusion adopted in this scoping review are delineated as follows:

Exclusion criteria:

(1) Reviews.

(2) Non-English publications.

(3) Publications without interventions on OM.

(4) Publications prior to 2009.

(5) Publications with inaccessible full texts.

(6) Studies involving patients under the age of 18.

(7) Patients without head and neck tumors.

Inclusion criteria:

(1) Studies on interventions for OM.

(2) Nurse or pharmacist-led clinical studies.

(3) Studies over the past 15 years.

(4) Studies with interventions targeting adults.

Upon importing the searched publications from the four databases into Covidence, the exclusion criteria were utilized for the screening process within the Covidence system. Table 2 shows the research findings obtained from the four databases.

Table 2.

Searched database outcomes and Covidence importation results.

Database	Searched result	Imported result
Pubmed	41	41
Scopus	41	41
Cochrane Library	78	78
Embase	89	89

Data extraction

Two independent researchers extracted data from the 12 included publications. Following extraction, the researchers cross-verified the data to ensure consistency and accuracy. Data were extracted using Microsoft Excel in a tabular format, including publication year, authors, country, study type, patient disease type, treatment methods, primary intervenors, main intervention contents, intervention content for the intervention group, numbers of participants in the intervention group, intervention content for the control group, numbers of participants in the control group, methods and content of intervention effect assessment, intervention outcomes, study results, and study limitations.

Quality assessment

The quality of the publications was assessed, since there is no unified assessment method or tool for scoping reviews, we referred to the evaluation methods from two review papers. The assessment methodology proposed by Hölbl et al.¹⁴ in their 2018 study involves assigning scores to the intrinsic quality of the included studies and their relevance to the research. González-García et al.¹⁵ in 2021 subsequently applied this evaluative approach within the context of scoping review research. The quality assessment method utilized in this scoping review is predicated upon these two aforementioned studies. These studies received scores based on the criteria listed in the table, scored as follows: No or almost none = 0; Moderate, with relevant content = 1; Adequately described the issue = 2. The criteria are illustrated in Table 3.

Table 3.

Quality assessment questions and scoring criteria for included studies.

Questions	Score (0–2)
Question 1: Involvement of pharmacists or nurses in treatment	No – moderate – yes
Question 2: Specific measures in place for managing OM in patients	No – moderate – yes
Question 3: Emphasis on the importance of pharmacists’ or nurses’ work	No – moderate – yes
Question 4: Effectiveness and scalability of clinical care by pharmacists or nurses	No – moderate – yes

Result

Search results

All identified records were imported into the Covidence.¹⁶ Of the 226 publications, duplicates were automatically identified and removed by the platform, leaving 168 publications. These records were independently screened by two researchers. During the initial screening, titles and abstracts were reviewed, and publications that did not meet the inclusion criteria were excluded, resulting in 117 exclusions. The full texts of the remaining 63 publications were then evaluated, and a second screening was conducted based on predefined full-text exclusion criteria. Ultimately, 12 publications met the inclusion criteria and were included in this scoping review. The detailed process of the literature search is illustrated in Figure 1.

Figure 1.

Literature search flowchart.

Quality assessment

The quality assessment was independently conducted by two researchers simultaneously, with the final results being consolidated and any discrepancies resolved. The quality scores of the included studies ranged from 5 to 8. Specifically, four studies scored 5, one scored 6, five scored 7, and two scored 8. The average scores for the assessment questions were as follows: Question 1 had an average score of 2 ± 0; Question 2 had an average score of 1.33 ± 0.49; Question 3 had an average score of 1.42 ± 0.79; and Question 4 had an average score of 1.67 ± 0.49. The overall average quality score of the 12 studies was 6.42 ± 1.16, indicating generally high methodological quality.

Data extraction results

The national backgrounds of the 12 studies were extracted, representing five countries: China, Turkey, Japan, Sweden, and the USA. The 12 included publications focused on the prevention or treatment of OM in patients with HNC. Of these, eight publications were randomized controlled trials, two were retrospective studies, and two were cohort studies. The basic information of the 12 extracted publications, as filtered and shown in Excel, is presented in appendix document, the document summarizes the study methods, participants, interventions, indicators, and outcomes.

Summary of research indicators

The extracted indicators included QoL (n = 6), Pain Index (n = 7), Incidence of OM (n = 7), OM Score (n = 2), Xerostomia Score (n = 1), Nutritional Status Score (n = 2), and Incidence of Esophagitis (n = 1). Studies consistently showed that interventions aimed at improving QoL and reducing pain index scores were effective. All six studies indicated that clinical interventions by pharmacists and nurses had a positive impact on the patients’ QoL. This underscores the indispensable roles of pharmacists and nurses in the clinical management of OM in patients undergoing radiotherapy and CT.

Seven evaluation metrics utilized 12 different scoring tools: five categories of tools were used to assess QoL, two were used for the Pain Index, two for OM scoring, one for assessing Xerostomia, two for evaluating Nutritional Status, and additionally, two studies employed the “Oral Assessment Guide” developed by Eilers et al. to evaluate the overall oral health of patients, it includes eight categories: voice, swallowing, lips, tongue, saliva, mucosa, gums, and teeth or dentures. The results are shown in Table 4.

Table 4.

Statistics of scoring tools used in included studies.

Studies (durations)	Evaluation metrics	Assessment tools
Yüce and Yurtsever¹⁷ 21 days (during chemotherapy)	1. QoL2. Oral Assessment Guide (OAG)3. Incidence of OM	1. EORTC QLQ-C30 Version 3.0 QoL questionnaire for cancer patients, developed by the European Organisation for Research and Treatment of Cancer (EORTC)
Hu et al.¹⁸ 2016.3–2017.12	1. QoL2. Pain Index	1. WHO QoL Scale (WHO QOL-100) to evaluate QoL2. Numeric Rating Scale (NRS) for pain
Sun et al.¹⁹ 2020.12–2021.12	1. QoL2. Pain Index	1. Karnofsky Performance Status Scale by the International Union Against Cancer to evaluate QoL2. Pre- and post-treatment comparison using the Visual Analogue Scale (VAS) to assess analgesic effectiveness
Fujii et al.²⁰ 2017.9–2020.7	1. QoL2. Incidence of OM	1. EuroQol 5 dimension 5 level (EQ-5D-5L) for assessing health-related QoL in outpatient cancer CT patients
Yoshida et al.²¹ 2019.9–2022.8	1. Numeric pain score2. Status of OM (severity and onset time)	1. Numeric Rating Scale (NRS) for pain scoring2. Common terminology criteria for adverse events version 5.0 for assessing the occurrence and severity of OM
Ling and Larsson²² 2006–2008 (each patient lasted 3 weeks)	1. QoL evaluation2. Pain score3. OM score	1. EORTC QLQ-H&N35, QoL questionnaire for head and neck cancer patients developed by the EORTC2. Visual Analogue Scale (VAS)3. Revised WHO scale for assessing OM grade
Liao et al.²³ 2018.7–2020.6 (each patient lasted 6 months)	1. Oral health status	Assessment according to the Oral Assessment Guide by Eilers et al. Scoring ranges from 1 (normal) to 3 (severe). The total score of the Oral Assessment Guide, where 8 represents good oral health and 24 indicates poor oral health
Xu et al.²⁴ 2011.12–2012.12	1. OM score2. Dry mouth scoring3. Pain scoring	1. WHO classification of radiogenic OM injuries2. Visual Analogue Scale (VAS) for assessing dryness and oropharyngeal pain levels
Yoshida et al.²⁵ 2017.2–2019.1	OM score	Assessment of the presence and severity of OM using the radiologic criteria based on the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
Duzova and Can²⁶ 2018.11–2020.3 (each patient lasted 7 weeks)	1. Patient identification table2. OM scoring3. QoL	1. A questionnaire compiled by researchers based on a literature review, consisting of 26 questions including 17 open-ended and 9 closed questions, used to assess sociodemographic characteristics, disease-related features, and treatment features of HNC patients2. CTCAE v5.0 toxicity criteria: Using the National Cancer Institute’s (NCI) Common Toxicity Criteria (CTC) grading scale3. (1) EORTC QLQ C-30 questionnaire to evaluate patient QoL. (2) EORTC QLQ-HN35 module, specifically for assessing the QoL of head and neck cancer patients
Kara et al.²⁷ 2020.9–2021.2 (each patient lasted 6 weeks)	1. Incidence of OM2. Nutritional risk assessment3. Incidence of esophagitis	1. Follow-up table for OM and related factors: OM grading, factors influencing OM (e.g., weight, CT in the past 15 days), complications of mucositis (e.g., difficulty speaking, pain, taste changes, esophagitis), and mucositis-related factors (e.g., stress levels)2. NRS: Nutritional Risk Screening score
Kartin et al.²⁸ 20 months (each patient lasted 7 weeks)	1. Oral assessment guide2. OM score3. Pain score4. Nutritional status5. QoL evaluation	1. Oral Assessment Guide developed by Eilers et al., showcasing changes in voice, swallowing, lips, tongue, saliva, mucous membrane, gums, and dentures2. WHO Oral Toxicity Scale3. Visual Analogue Scale (VAS) to assess pain intensity4. SGA Index (Subjective Global Assessment) for overall evaluation5. EORTC QLQ-C30, a core QoL questionnaire (EORTC QLQ-C30) used to evaluate patient QoL

Nursing interventions for OM in included studies

Eight studies reported nursing interventions for OM, which included pharmacological treatments and patient education. Nursing interventions incorporated seven basic care medications, eight medications for managing oral pain, and three nebulized treatments. Four studies provided three types of patient education: how to prevent and manage OM, medication education, and psychological care to alleviate anxiety and other emotions, as shown in Table 5.

Table 5.

Interventions in included studies.

Category	Main participants	Interventions
Oral care: Yüce and Yurtsever,¹⁷ Hu et al.,¹⁸ Sun et al.,¹⁸ Yoshida et al.,²¹ Liao et al.,²³ Xu et al.,²⁴ Yoshida et al.,²⁵ Kartin et al.²⁸	Pharmacists and nurses	1. Use of bismuth-containing antibacterial mouthwash, topical spray of recombinant human epidermal growth factor, and vitamin B122. Mouthwash with azulene sulfonate sodium hydrate, and a moisturizing ointment with dimethyl isopropylene. Use at least six times daily: upon waking, after breakfast, after lunch, around 3 p.m., after dinner, and before bed3. Guidance on the Bass brushing method, brushing with a soft, small-headed toothbrush for 5 min at least twice daily. After each brushing, rinse with 100 ml of green tea solution for 60 s (5% green tea mouthwash: dissolve 5 g (1 teaspoon) of green tea powder in 100 ml of water to make the solution)4. For dry mouth, chew sugar-free mints or suck on ice chips. Avoid alcohol, lemon, and glycerin products
Patient education: Yüce and Yurtsever,¹⁷ Hu et al.,¹⁸ Sun et al.,¹⁹ Kara et al.²⁷	Pharmacists and nurses	1. Inform patients about the potential occurrence of OM during radiotherapy through videos and oral presentations, and provide nutritional advice2. Educate patients about pain, explain drug-related adverse reactions, and help them understand pain and actively treat side effects3. Provide psychological care to help patients alleviate tension and anxiety caused by pain
Pain management: Hu et al.,¹⁸ Sun et al.,¹⁹ Ling and Larsson²²	Nurses	1. Assess patient pain four times within 24 h. After pain control, assess once every 24 h. Record pain scores, radiation sessions, and OxyContin doses. Establish a pain care chart documenting pain characteristics, location, timing, medication, and nursing interventions. Patients take 10 mg OxyContin orally, adjusting the dose according to pain relief until significant alleviation. Provide standardized pain management intervention with analgesics2. Within 1 week, conduct pain assessment, individualized medication selection, treatment evaluation, and adjustment. Apply combinations of acetaminophen, non-steroidal anti-inflammatory drugs, and opioids in a stepwise manner. For neuropathic pain: use amitriptyline, gabapentin, or pregabalin. For patients with irradiated oral areas, use lidocaine and benzydamine
Oxygen and ultrasonic nebulization: Xu et al.²⁴	Nurses	1. Undergo daily oxygen or ultrasonic nebulization after radiotherapy. The medications used are 10 ml saline, 240,000 U gentamicin, 4000 U trypsin, 5 mg dexamethasone, with an oxygen flow rate of 8 L/min for 20 min each session until the end of radiotherapy

Classification of results based on study objectives

Eight studies implemented preventive measures for OM. The results of two studies demonstrated that these preventive measures significantly reduced the severity of OM in the experimental group, as well as improved medication adherence and QoL in these patients.^17,25 One study found that early intervention in patients reduced the pain and swallowing difficulties associated with OM compared to a control group that received later intervention.²² Yoshida et al.²⁵ in their 2021 study highlighted that early monitoring by a multidisciplinary team can significantly decrease hospital stay lengths and weight loss in patients, reduce the frequency of analgesic use, significantly enhance patients’ QoL, and increase the cost-effectiveness of disease treatment.¹⁷

Three studies focused on symptomatic interventions. Results from one of these studies showed a notable improvement in the QoL of the experimental group patients. Research by Fujii and others demonstrated that post-intervention, the incidence of Grade 2 or higher OM significantly decreased, and there was a significant improvement in patients’ QoL.²¹

OM interventions led by clinical pharmacists

Three studies were primarily led by clinical pharmacists. In a retrospective study conducted in 2022 by Fujii et al.,²⁰ comprehensive pharmaceutical services were provided to patients undergoing CT. The involvement of clinical pharmacists reduced the incidence of adverse reactions in the experimental group and also improved the patients’ QoL Yoshida et al.’s²⁵ study in 2021 provided patients with regular medication guidance and education, showing that the experimental group had a significant reduction in the use of local anesthetics and opioids, a notable decrease in hospital stay durations, and improved weight loss outcomes. In a study by Yoshida et al.,²¹ only medication guidance was performed, which showed that the incidence of Grade 2 OM was lower in the patient group guided by clinical pharmacists compared to the control group, with a reduction in steroid usage and improved medication adherence. This demonstrates that professional pharmaceutical care by clinical pharmacists has positive outcomes on patients’ oncological treatments, not only reducing the incidence of OM but also enhancing patients’ QoL and overall benefits.

Clinical care led by nurses

In nine studies where nurses were the principal investigators, the nurses provided patient education prior to the commencement of oncologic treatments, implemented standardized pain management interventions, assessed nursing outcomes after completing supportive care, and conducted follow-ups. The results of a randomized controlled trial conducted by Hu et al.¹⁸ in 2018 indicated that early pain intervention could effectively improve patients’ QoL. The nursing outcomes from Duzova et al.’s²⁶ Nurse Navigation Program demonstrated effective prevention of weight loss, reduced incidence of OM, decreased xerostomia, swallowing difficulties, patient pain, and fatigue, and improved QoL. Kartin et al.’s²⁸ study showed that through nurse-led oral care and nutritional programs, patients’ nutritional statuses could be improved. Yüce and Yurtsever¹⁷ focused solely on patient education in the intervention group, and the results indicated not only a reduction in the incidence of OM but also maintained stable QoL. This illustrates that nurses play pivotal roles in the care of oncology patients, providing clear insights into patients’ living habits and accurately delivering personalized patient education. They can respond promptly to adverse reactions, playing crucial roles throughout the treatment process.

Discussion

During the treatment of HNC, the incidence rate of OM ranges from 59.4% to 100%. In addition to the damage to normal cells caused by conventional RCT, other risk factors contribute to a higher incidence rate of OM in HNC patients compared to other types of cancer. These factors include tumor location, cumulative radiation dose, radiation field, radiation technique, and concurrent CT, all of which influence the incidence of OM.²⁹ This scoping review aims to investigate the roles of clinical pharmacists and nurses in managing adverse reactions among HNC patients, particularly OM. Our analysis of the 12 retrieved studies was summarized across 8 key aspects. The evaluation of study indicators revealed that the majority of studies focused on QoL scores, pain scores, and the incidence of OM. However, conditions such as xerostomia, nutritional risks, and esophagitis-related infections were less frequently investigated, and the assessment tools used were not standardized. These clinical symptoms in OM patients warrant attention from both nurses and pharmacists, highlighting the need to refine patient care protocols. Regarding OM intervention strategies, most studies emphasized basic oral care and pain management. In studies involving pharmacists, patient education and psychological care were incorporated, providing long-term support that significantly improved patients’ QoL. This suggests that when pharmacists join oncology treatment teams, their role extends beyond medication guidance; they can also enhance treatment adherence through patient education. Furthermore, we summarized nurse-led OM interventions, which demonstrated a broader scope compared to pharmacist-led interventions. These studies addressed not only quality of QoL but also xerostomia, dysphagia, and nutritional status, offering comprehensive patient care. This underscores the indispensable role of nurses in managing cancer patients, as they provide precise and timely care for adverse reactions at the clinical forefront, playing a crucial role in optimizing patient outcomes.

An assessment of the current management status of OM as an adverse reaction in cancer patients reveals a high incidence rate, yet the management protocols remain incomplete. Existing practice guidelines are updated infrequently and contain numerous recommendations, which may complicate the standardization of care. Generally speaking, OM interventions are conducted by specialist doctors, nurses, and stomatologists. MASCC/ISOO guideline recommends the implementation of a multi-drug combined oral care program for HNC patients receiving radiotherapy to prevent OM. Patients receiving moderate-dose radiotherapy (<50 Gy) and concurrent radiotherapy with CT are advised to use Benzydamine mouthwash (a non-steroidal anti-inflammatory drug type mouthwash) to prevent OM. For patients undergoing radiotherapy alone, low-level laser therapy is recommended. Additionally, the guideline suggests using 0.2% topical morphine mouthwash for managing pain related to OM. Alongside mouthwash for pain relief, the guideline recommends the use of two natural substances to prevent OM inflammation in patients with HNC.

The MASCC/ISOO Guidelines for the Management of OM offer a comprehensive synthesis of existing research.⁵ However, several clinical symptoms related to OM have not been addressed for intervention measures. Dry mouth, nutritional status, and incidence of esophagitis, which are mentioned in the 12 studies included, are clinically relevant issues associated with secondary infections and nutritional support. These aspects still require further study. Additionally, a comprehensive clinical nursing framework for managing OM in patients with HNC has not yet been established.

The guidelines recommend various treatment methods that require the involvement of professional clinical pharmacists to address patient medication issues. However, the role of pharmacists in this area is rarely emphasized. In the three pharmacist-led studies examined in this scoping review, pharmacists provided patients with nutritional counseling, delivered pain education, elucidated adverse drug reactions, facilitated patients’ understanding of pain, actively managed side effects, and alleviated tension and anxiety related to pain through the use of promotional videos and verbal presentations. However, these studies failed to address key areas such as comprehensive pharmaceutical monitoring by clinical pharmacists, personalized pharmaceutical care, and routine medication education for patients. Additionally, there appears to be a lack of clarity regarding the delineation of responsibilities between pharmacists and nurses in clinical settings, with nurses often assuming roles in medication education and personalized pharmaceutical services. Therefore, it is imperative for clinical pharmacists to clearly define and formalize their roles within the clinical process and diligently execute their clinical tasks accordingly.

Studies have shown that when pharmacists provide medication advice, even if the types of medications do not change, pharmacist-guided medication significantly benefits rational drug use and can impact health outcomes.³⁰ Furthermore, collaboration between nurses and pharmacists in medication coordination can prevent potential harm.³¹ Optimizing pharmacist–nurse interventions for OM, clarifying their responsibilities, and highlighting their roles are crucial for ensuring long-term patient treatment and clinical benefits.

This study is the first to conduct a scoping review summarizing the prevention and targeted care of OM in patients undergoing CRT for HNC over the past 15 years. It emphasizes that supportive care provided by pharmacists and nurses in clinical practice benefits patients. Currently, OM remains an underestimated side effect of cancer treatment. The data regarding OM induced by RCT are predominantly derived from adverse event reports in cancer treatment-related studies, with a paucity of large-scale study data. The data utilized in this study are largely estimated frequencies based on the outcomes of relevant research. Furthermore, a multicenter randomized controlled trial conducted in 2019 compared the severity assessment scores of RCT-induced OM across different regions, revealing significant differences in incidence rates.³² The subjective judgments of the assessors were found to be relevant to the trial results. Clinically, our researchers have also observed that OM is typically documented only when it reaches a more severe stage. Additionally, the absence of a standardized scale for severity assessment poses challenges in OM evaluation.³⁰ A limited number of interventions supported by high level evidence may not be universally applicable to all types of OM patients, leading to considerable variability in treatment protocols across different medical centers. SOM can result in premature termination or readjustment of treatment, increased hospitalization days, heightened public health costs, and a diminished QoL for patients. There is an urgent need for collaborative efforts from basic, translational, and clinical workers to improve the QoL of cancer patients and reduce management costs.

MASCC/ISOO established a mucositis research section in 1998 to address this important issue. Clinical practice guidelines published in 2004 recommended oral care protocols, including patient education, to mitigate the severity of mucositis caused by CT or radiotherapy.³³ In the 2014 clinical practice guideline, the group recommended oral care protocols as a preventive measure for cancer treatment-induced OM.³⁴ Subsequent studies have demonstrated the beneficial effects of basic oral care in preventing OM. According to the 2020 clinical practice guidelines, basic oral care remains the best method for oral care in cancer patients, and educating patients about its benefits is still appropriate.⁵

In the 12 studies we analyzed, several studies involved pharmacists and nurses providing basic oral care to patients in the intervention group. These interventions resulted in reduced pain, lower OM grades, improved QoL, reduced incidence of OM, lower xerostomia scores, improved nutritional status scores, and reduced incidence of esophagitis. Although this study did not include large sample trials or standardized scoring tools, it preliminarily indicates that multidisciplinary team oral basic care involving pharmacists and nurses can help cancer patients achieve optimal treatment experiences and outcomes.

From the research results, it is evident that SOM during cancer treatment significantly disrupts treatment progression. In the study by Yüce and Yurtsever,¹⁷ nine patients in the non-education group developed grade 3 or higher OM by the third week, whereas none did in the education group. Additionally, the non-education group experienced significantly more cases of xerostomia, swallowing obstruction, and taste deterioration, with lower QoL at the end of treatment compared to the education group. Yoshida et al.’s²⁵ study revealed differences in albumin levels, WBC counts, and neutrophil counts among OM patients receiving pharmacist intervention, with the control group showing more severe opioid use and weight loss. Hava Cara’s 2023 study demonstrated that nurse-provided oral care training and counseling helped maintain stable stress indices during treatment. These findings indicate that providing care counseling and patient education when patients experience such adverse reactions can effectively prevent OM and improve patients’ understanding of the disease, thereby enhancing medication adherence and reducing psychological burdens. With the assistance of pharmacists, medication cost-effectiveness and patients’ QoL can be improved. This highlights the importance of the services provided by clinical pharmacists and nurses.

However, this scoping review has several limitations, such as the small sample size (551 patients in the experimental group and 395 in the control group) and regional constraints, including China, Turkey, Japan, Sweden, and the United States. Representation from these countries is insufficient, making it challenging to accurately reflect the clinical practices of pharmacists and nurses more. The norms and responsibilities of pharmacists vary significantly among these countries. Moreover, the study did not account for several confounding factors, including the impact of patients’ dietary habits, as immune responses play a crucial role in the OM development following radiation-induced cell damage. High consumption of pro-inflammatory foods (such as saturated fatty acids, fried foods, and added sugars) can induce chronic inflammation, while low intake of fruits and vegetables increases the risk of DNA damage in cells.²⁹ The severity of OM is also influenced by various treatment factors, such as total radiation dose, daily radiation dose, and volume of irradiated mucosa.³⁵ A cumulative dose of 20–30 Gy in the oral cavity has been shown to induce OM.³⁶ Compared with RT alone, concurrent CRT is associated with an increased risk of radiation-induced mucositis, resulting in a higher incidence and prolonged duration of OM.³⁷ Tobacco consumption is also associated with increased Radiation-Induced Mucositis incidence and severity.^35,38,39 Pre-CRT inflammatory periodontal disease and poor dental health are additional environmental risk factors for RT and CT-induced OM.⁴⁰ This scoping review further identified that discrepancies in guidance provided by nurses and clinical pharmacists may engender patient distrust in their therapeutic process, thereby potentially compromising treatment outcomes. This underscores the presence of communication voids and an ambiguous delineation of responsibilities within clinical practice, highlighting the necessity for further research to address these critical issues.

Conclusion

In the management of HNC, effective prevention and management of OM during CRT are crucial for enhancing patient outcomes. Clinical pharmacists and nurses play indispensable roles within the multidisciplinary treatment team by leveraging their expertise and skills to provide optimized therapeutic strategies and comprehensive care support for patients. The direct care model employed by pharmacists and nurses significantly alleviates symptoms and enhances the QoL for patients, thereby fostering improved treatment efficacy and patient satisfaction.

Supplemental Material

sj-docx-1-smo-10.1177_20503121251339581 – Supplemental material for Clinical pharmacists and nurses in the management of oral mucositis in head and neck cancer patients during antineoplastic therapy: A scoping review

Supplemental material, sj-docx-1-smo-10.1177_20503121251339581 for Clinical pharmacists and nurses in the management of oral mucositis in head and neck cancer patients during antineoplastic therapy: A scoping review by Palizhati Kaisha, Xinxin Li, Yiqun Tang and Yufen Zheng in SAGE Open Medicine

Footnotes

Acknowledgements

We appreciate the support of China Pharmaceutical University and Jiangsu Cancer Hospital for their support in the completion of this article.

ORCID iD

Yufen Zheng

Ethical considerations

Not applicable.

Author contributions

Palizhati Kaisha: The author participated in the conception and design of this study, data search and analysis, and manuscript writing of this study. Participated in every revision during the manuscript correction phase. Xinxin Li: This author participated in the design, data analysis, and manuscript writing of this study and also contributed to the manuscript writing. Participated in every revision during the manuscript correction phase. Yufen Zheng: This author helped with acquisition, analysis, and interpretation of data; and revising the article. Guided every revision during the manuscript correction phase. Yiqun Tang: This author helped with design and supervision of the study, data interpretation, literature search, critical review, and final approval of the manuscript. Guided every revision during the manuscript correction phase.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Supplemental material

Supplemental material for this article is available online.

References

Trotti

Bellm

Epstein

, et al. Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review. Radiother Oncol 2003; 66(3): 253–262.

Elting

Keefe

Sonis

, et al. Patient-reported measurements of oral mucositis in head and neck cancer patients treated with radiotherapy with or without chemotherapy: demonstrating the need for further clinical research. Support Care Cancer 2008; 16(5): 525–538.

Sonis

ST.

A biological approach to mucositis. J Support Oncol 2004; 2(1): 21–36.

Peterson

Bensadoun

Roila

, et al. Management of oral and gastrointestinal mucositis: ESMO Clinical Practice Guidelines. Ann Oncol 2011; 22(Suppl 6): vi78–vi84.

Elad

Cheng

KKF

Lalla

, et al. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer 2020; 126(19): 4423–4431.

European Oral Care in Cancer Group. Oral care guidance and support. 1st ed. European Oral Care in Cancer Group, 2017, p. 7.

Scarpace

Brodzik

Mehdi

, et al. Treatment of head and neck cancers: issues for clinical pharmacists. Pharmacotherapy 2009; 29(5): 578–592.

Khadela

Vyas

Bhikadiya

, et al. Impact of clinical pharmacist services on quality adjusted life years in head and neck cancer patients. Int J Clin Pharm 2021; 43(5): 1208–1217.

Suzuki

Kobayashi

Okayasu

, et al. Pharmacotherapy for adverse events reduces the length of hospital stay in patients admitted to otolaryngology ward: a single arm intervention study. PLoS One 2014; 9(12): e115879.

10.

Lau

Saunders

Sacco

, et al. Evaluation of pharmacist interventions in a head and neck medical oncology clinic. J Oncol Pharm Pract 2020; 26(6): 1390–1396.

11.

Zheng

Ding

, et al. Pharmacist-led management improves treatment adherence and quality of life in opioid-tolerant patients with cancer pain: a randomized controlled trial. Pain Ther 2022; 11(1): 241–252.

12.

Aromataris

Lockwood

Porritt

, et al. JBl manual for evidence synthesis. Adelaide: JBl, 2020.

13.

Tricco

Lillie

Zarin

, et al. PRISMA Extension for Scoping Reviews (PRISMA-ScR): checklist and explanation. Ann Intern Med 2018; 169(7): 467–473.

14.

Hölbl

Kompara

Kamišalić

, et al. A systematic review of the use of blockchain in healthcare. Symmetry 2018; 10(10): 470.

15.

González-García

Pinto-Carral

Pérez-González

, et al. Nurse managers’ competencies: a scoping review. J Nurs Manag 2021; 29(6): 1410–1419.

16.

Covidence. Covidence, https://www.covidence.org/ (accessed 27 February 2024).

17.

Yüce

UÖ

Yurtsever

. Effect of education about oral mucositis given to the cancer patients having chemotherapy on life quality. J Cancer Educ 2019; 34(1): 35–40.

18.

Chen

Wang

, et al. Standardized nursing and therapeutic effect of oxycontin on oral mucosal pain in nasopharyngeal carcinoma patients. J Cancer Res Ther 2018; 14(7): 1594–1599.

19.

Sun

Nie

Standardized nursing and clinical efficacy of OxyContin in reducing oral mucosal pain in patients with nasopharyngeal carcinoma: a randomized, double-blind, placebo-controlled study protocol. Medicine (Baltimore) 2020; 99(49): e23205.

20.

Fujii

Ueda

Hirose

, et al. Pharmaceutical intervention for adverse events improves quality of life in patients with cancer undergoing outpatient chemotherapy. J Pharm Health Care Sci 2022; 8(1): 8.

21.

Yoshida

Watanabe

Hoshino

, et al. Hospital pharmacist interventions for the management of oral mucositis in patients with head and neck cancer receiving chemoradiotherapy: a multicenter, prospective cohort study. Support Care Cancer 2023; 31(5): 316.

22.

Ling

Larsson

Individualized pharmacological treatment of oral mucositis pain in patients with head and neck cancer receiving radiotherapy. Support Care Cancer 2011; 19(9): 1343–1350.

23.

Liao

Hsu

Hsieh

, et al. Effectiveness of green tea mouthwash for improving oral health status in oral cancer patients: a single-blind randomized controlled trial. Int J Nurs Stud 2021; 121: 103985.

24.

Juan

Rong

Zhuo

P-Y

, et al. Effectiveness of oxygen nebulization at preventing radiotherapy-induced mucositis in patients with nasopharyngeal cancer. Int J Nurs Sci 2014; 1(2): 176–179.

25.

Yoshida

Kodama

Tanaka

, et al. Pharmacist involved education program in a multidisciplinary team for oral mucositis: its impact in head-and-neck cancer patients. PLoS One 2021; 16(11): e0260026.

26.

Duzova

Can

The effect of navigation programme on the management of symptoms related to head and neck radiotherapy. Transpl Immunol 2021; 69: 101488.

27.

Kara

Arikan

Kartoz

, et al. A prospective study of nurse-led oral mucositis management: impact on health outcomes of patients receiving radiotherapy for head and neck cancer and lung cancer. Semin Oncol Nurs 2023; 39(4): 151440.

28.

Kartin

Tasci

Soyuer

, et al. Effect of an oral mucositis protocol on quality of life of patients with head and neck cancer treated with radiation therapy. Clin J Oncol Nurs 2014; 18(6): E118–E125.

29.

Hansen

Bertelsen

Zukauskaite

, et al. Prediction of radiation-induced mucositis of H&N cancer patients based on a large patient cohort. Radiother Oncol 2020; 147: 15–21.

30.

Pulito

Cristaudo

Porta

, et al. Oral mucositis: the hidden side of cancer therapy. J Exp Clin Cancer Res 2020; 39(1): 210.

31.

Rubenstein

Peterson

Schubert

, 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.

32.

Ueno

Zenda

Konishi

, et al. The post hoc analysis comparing the severity grades of chemoradiotherapy-induced oral mucositis scored between the central and local assessors in a multicenter, randomized controlled trial of rebamipide for head and neck cancer. Int J Clin Oncol 2019; 24: 241–247.

33.

Lalla

Bowen

Barasch

, et al. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer 2014; 120(10): 1453–1461.

34.

Hua

Liang

Yang

Meta-analysis of the association between dietary inflammatory index (DII) and upper aerodigestive tract cancer risk. Medicine (Baltimore) 2020; 99(17): e19879.

35.

Sanguineti

Gunn

Parker

, et al. Weekly dose-volume parameters of mucosa and constrictor muscles predict the use of percutaneous endoscopic gastrostomy during exclusive intensity-modulated radiotherapy for oropharyngeal cancer. Int J Radiat Oncol Biol Phys 2011; 79(1): 52–59.

36.

Forastiere

Goepfert

Maor

, et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 2003; 349(22): 2091–2098.

37.

Chen

Lai

Huang

, et al. Changes and predictors of radiation-induced oral mucositis in patients with oral cavity cancer during active treatment. Eur J Oncol Nurs 2015; 19(3): 214–219.

38.

Wardill

Sonis

Blijlevens

NMA

, et al. Prediction of mucositis risk secondary to cancer therapy: a systematic review of current evidence and call to action. Support Care Cancer 2020; 28(11): 5059–5073.

39.

Haubek

The highly leukotoxic JP2 clone of Aggregatibacter actinomycetemcomitans: evolutionary aspects, epidemiology and etiological role in aggressive periodontitis. APMIS Suppl 2010; (130): 1–53.

40.

Nishii

Soutome

Kawakita

, et al. Factors associated with severe oral mucositis and candidiasis in patients undergoing radiotherapy for oral and oropharyngeal carcinomas: a retrospective multicenter study of 326 patients. Support Care Cancer 2020; 28(3): 1069–1075.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.02 MB