口腔指南共识汇总

REVIEW ARTICLE

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Expert consensus on the prevention and treatment of

radiochemotherapy-induced oral mucositis

Juan Xia1, Xiaoan Tao1, Qinchao Hu1, Wei Luo2, Xiuzhen Tong3, Gang Zhou4, Hongmei Zhou5, Hong Hua6, Guoyao Tang7, Tong Wu

1,

Qianming Chen

5,8, Yuan Fan9, Xiaobing Guan10, Hongwei Liu6, Chaosu Hu11, Yongmei Zhou12, Xuemin Shen12, Lan Wu12, Xin Zeng5,

Qing Liu13, Renchuan Tao14, Yuan He15, Yang Cai16, Wenmei Wang17, Ying Zhang18, Yingfang Wu19, Minhai Nie20, Xin Jin21,

Xiufeng Wei22, Yongzhan Nie

23, Changqing Yuan24 and Bin Cheng1✉

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck

radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and

even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted

among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research

evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic

basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-

inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous

guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims

to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis,

and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of

patients.

International Journal of Oral Science (2025) 17:54

; https://doi.org/10.1038/s41368-025-00382-8

INTRODUCTION

Radiochemotherapy-induced

oral

mucositis

(OM)

refers

to

mucosal lesions characterized by congestion, erosion, ulcers

and atrophy that occur in the oral cavity of patients treated with

head and neck radiotherapy (RT), chemotherapy (CT), or

targeted drugs. Epidemiological data show that the incidence

of OM in patients undergoing radiochemotherapy for head and

neck tumors ranges from 59.4% to 100%.1 The incidence of OM

varies considerably in patients undergoing CT and is related to

the type and dose of chemotherapeutic agents. For example, the

incidence of OM in patients undergoing high-dose CT prior to

hematopoietic stem cell transplantation (HSCT) can be 70% or

more.1 OM can lead to pain, difficulty eating, dry mouth, and

taste disorders, which seriously affect the survival of patients

and even force the interruption of tumor treatment.1–3 There-

fore, effective prevention and intervention in OM development

are of great clinical importance. In recent years, oral mucositis

caused by molecular targeted therapy, immunotherapy and

other biological therapy strategies has gradually increased, and

the clinical treatment principles and significance of OM are the

Received: 18 October 2024 Revised: 30 May 2025 Accepted: 2 June 2025

1Department of Oral Medicine, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Stomatology,

Guangzhou, China; 2Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen

University Cancer Center, Guangzhou, China; 3Department of Hematology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; 4Department of Oral Medicine,

School and Hospital of Stomatology, Wuhan University, Wuhan, China; 5State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of

Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China; 6Department of Oral Medicine, Peking University School and Hospital of Stomatology,

Beijing, China; 7Department of Stomatology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 8Stomatology Hospital, School of Stomatology,

Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer

Center of Zhejiang University, Hangzhou, China; 9Department of Oral Medicine, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China; 10Beijing

Stomatological Hospital, Capital Medical University, Beijing, China; 11Department of Radiation Oncology, Fudan University Shanghai Cancer Centre, Department of Oncology,

Shanghai Medical College, Fudan University, Shanghai, China; 12Department of Oral Mucosal Diseases, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao

Tong University School of Medicine, Shanghai, China; 13The Third Affiliated Hospital of Air Force Medical University, Xi’an, China; 14Department of Periodontics and Oral Medicine,

College of Stomatology, Guangxi Medical University, Nanning, China; 15Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Department of Oral

Medicine, School of Stomatology, Tongji University, Shanghai, China; 16Hospital and School of Stomatology, Guizhou Medical University, Guiyang, China; 17Department of Oral

Medicine, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China; 18Department of Oral Emergency and Mucosal Diseases, School and Hospital of

Stomatology, China Medical University, Shenyang, China; 19Centre of Stomatology, Xiangya Hospital, Cental South University, Changsha, China; 20Department of Periodontics &

Oral Mucosal Diseases, The Affiliated Stomatology Hospital of Southwest Medical University, Luzhou, China; 21Chongqing Key Laboratory of Oral Diseases and Biomedical

Sciences, College of Stomatology, Chongqing Medical University, Chongqing, China; 22School of Stomatology, Jilin University, Changchun, China; 23State Key Laboratory of

Cancer Biology, Xijing Hospital, Fourth Military Medical University, Xi’an, China and 24Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao

University, Qingdao, China

Correspondence: Bin Cheng (chengbin@mail.sysu.edu.cn)

These authors contributed equally: Juan Xia, Xiaoan Tao, Qinchao Hu.

www.nature.com/ijos

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same. Thus, it is also included in tumor therapy-related oral

mucositis.

The first evidence-based clinical practice guidelines related to

OM were published in 2004 by the Multinational Association of

Supportive Care in Cancer and the International Society of Oral

Oncology (MASCC/ISOO).4–7 Subsequently, relevant guidelines

were published by the European Society for Medical Oncology

(ESMO) and the Cochrane Collaboration (UK).8,9 The China Society

for Radiation Oncology (CSTRO) in 2019 and the Antineoplastic

Agents Safety Management Committee of the Chinese Society of

Clinical Oncology (CSCO) in 2021 took the lead in publishing

relevant expert consensuses.10,11 However, to date, there has been

a

lack

of

in-depth

and

comprehensive

strategies

for

the

prevention, diagnosis, and treatment of this disease from the

perspective of oral specialty practices, a sufficient understanding

of the important role of oral health status in the prevention and

treatment of OM, and guidance for nondental specialists and

caregivers. Therefore, based on of evidence-based medicine as

well as existing clinical practice guidelines and expert consensus

worldwide, this expert consensus is formulated from the point of

view of stomatology. It combines experts and scholars from

stomatology, oncology, radiology and other disciplines to develop

an expert consensus on the clinical diagnosis and treatment of

OM that is clinically instructive and consistent with the national

conditions of China. Consensus among experts is reached using

the Delphi method. This consensus adds new content, including

auxiliary examination, diagnosis and differential diagnosis, and

efficacy indicators. New interventions, such as topical glucocorti-

coids,12,13 recombinant bovine basic fibroblast growth factor (rb-

bFGF),14–16 and elemental diets,17,18 are recommended in this

consensus. Some traditional Chinese medicines have also shown

good efficacy in the prevention and treatment of OM, such as

Shuanghua Baihe tablets19,20 and Kangfuxin liquid21–23; we also

discuss and recommend these new intervention strategies.

EPIDEMIOLOGICAL CHARACTERISTICS AND PATHOGENESIS

Risk factors

The risk factors for OM can be categorized into patient-related

factors and treatment-related factors (Fig. 1).

Patient-related factors.

These factors include previous onset of

OM after oncologic treatment, poor oral hygiene, decreased

salivary secretion function, poor oral habits, smoking, and poorly

controlled underlying systemic disease. The correlation between

patient age/sex and the occurrence of OM is controversial.1

Treatment-related factors.

RT mainly includes the following:

transillumination site, irradiation dose, irradiation volume, fractio-

nated RT and radiation types.10,11,24–34 For example, more than

90% of patients treated with systemic RT experience OM, and at

least 33% of patients undergoing local RT for head and neck

cancer (HNC) developed oral mucositis.27–29 In addition, the mode

of radiation also affects OM occurrence. The lowest incidence of

OM is 16.9% in patients treated with intensity-modulated radio-

therapy (IMRT).30–32 The incidence of OM with proton beam

radiotherapy (PBRT) is comparable to that of conventional RT for

the head and neck region, which is 33.4%.32 However, the

incidence of OM in patients undergoing hyperfractionated RT and

accelerated fractionation treatment remains high, at approxi-

mately 94% and 71.4%–93.1%, respectively.28,29,33 It is generally

believed that when the oral cavity is exposed to high doses of RT

• Head and neck radical radiotherapy patients

• Treated with high-dose methotrexate and cytarabine

• Receiving high-dose radiochemotherapy before HSCT

• Concurrent radiochemotherapy

• Definitive radiotherapy or palliative radiotherapy

• Radiotherapy combined with targeted therapy

• Currently receiving systemic anti-cancer treatments

known to cause oral mucositis or other complications

• Not receiving systemic anti-cancer treatments

known to cause oral mucositis or other complications

Median

Low

• No previous oral complications

• Without systemic diseases, good oral hygiene

Risk scale of OM

High

• History of mild OM

• Poor oral hygiene and reduced salivary function;

or poor oral habits, smokers

• History of moderate to severe OM

• Poorly controlled underlying systemic diseases

Patient-related factors

Treatment-related factors

Fig. 1

Risk level assessment of radiochemotherapy-induced oral mucositis. Created using Figdraw

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International Journal of Oral Science (2025) 17:54

((58.8 ± 2.2) Gy), the incidence of severe mucositis of grade 3 or

above (mucosal patchy ulcers with significant bleeding and severe

pain, affecting eating, and even facing life-threatening risks

requiring urgent treatment) can reach 45.8%.34

CT mainly includes categories, dosages, regimens and other

factors;11,24 concurrent RT; high-dose CT or RT administered prior

to HSCT; and targeted therapy drugs in combination with

radiochemotherapy.11,35 The incidence of OM in individuals

receiving traditional TAC (docetaxel, adriamycin, cyclophospha-

mide) regimens can reach 60%, whereas dose-intensive regimens

reduce the incidence to 30%.24 The incidence of severe mucositis

at grade 3 or higher in chemoradiotherapy regimens is as high as

45%; however, this can be reduced to 26% by using IMRT.36 The

incidence of OM varies when targeted therapy is employed.

Specifically, mammalian target of rapamycin (mTOR) and human

epidermal growth factor receptor (HER) inhibitors, such as

everolimus and afatinib, are associated with occurrence rates

ranging from 24%–64% and 25%–72.1%, respectively.35,37,38 The

morbidity rate of epidermal growth factor receptor (EGFR)

inhibitors varies significantly, with dacomitinib reaching values

of 37%–41%.39,40 Cetuximab potentially reaches a maximum of

37%,41 whereas erlotinib has the lowest morbidity, which is

typically controlled within 1%.42 In comparison, angiogenesis

inhibitors, anaplastic lymphoma kinase (ALK) inhibitors, and

tyrosine

kinase

inhibitors

all

maintain

lower

OM

rates

of

approximately 29% and rates of severe mucositis of grade 3 or

higher of 4%.43–45 The incidence of OM with bevacizumab is only

4%, and there have been no reported cases of severe mucositis of

grade 3 or higher.46

Considering patients’ own factors and treatment-related factors,

clinicians can assess the risk of developing OM before tumor

treatment based on 3 risk classes: high, medium and low (Fig. 1).

Depending on different risk scales, various prevention and

treatment strategies can be employed.

Pathology and pathogenesis

OM can be divided into acute and chronic forms. The acute phase

manifests as tissue edema, capillary dilatation, necrosis and

rupture of epithelial cells, and exudation of fibrin and blood cells.

Sonis et al. summarized the developmental pathological process

of mucositis based on the following five stages: the initiation

stage, initial damage response stage, signal amplification stage,

ulceration stage, and repair stage.47

Initiation stage.

Mucosal tissues quickly enter the initial phase

after exposure to RT or CT. At this point, DNA damage is

commonly observed in epithelial basal cells and submucosal cells,

and DNA double-strand breaks are noted in endothelial cells.48

Non-DNA damage occurs simultaneously and often manifests as a

dramatic increase in the levels of reactive oxygen species (ROS)

associated with cellular damage, leading to oxidative stress within

cells.48,49 Lymphocyte activation is mediated by the innate

immune response of an organism. The initiation phase is the

basis for mucositis development, and effective interventions

targeting this phase can prevent further mucosal tissue damage.

Initial damage response stage.

Elevated ROS levels activate

transcription factors such as P53, Wnt and NF-κB50,51 and induce

changes in the expression of inflammatory mediators, such as

tumor necrosis factor (TNF-α), interleukins (ILs), cyclo-oxygenase 2

(COX-2), and cell adhesion molecule (CAMs).52,53 In addition, c-Jun

and c-Jun N-terminal kinase (JNK) expression is upregulated,54

activating other transcription factors, such as nuclear factor

erythroid 2-related factor 2 (NRF2). The accumulation of TNF-α,

IL-6 and IL-1β in the mucosal epithelium and connective tissues

leads to increased oxidative stress, basal cell death, and tissue

destruction. The Toll-like receptor (TLR) signaling pathway and

various kinase pathways, such as the mitogen-activated protein

kinase (MAPK) pathway, play a role in this process.55 Broken DNA

strands caused by radiochemotherapy can directly activate the

intracellular ceramide pathway, leading to apoptosis as well as

increased permeability of cell membranes.56 Moreover, elevated

ROS levels activate sphingomyelinase or ceramide synthetase,

which hydrolyses the cell membrane lipid sphingomyelin, leading

to increased intracellular ceramide levels. Fibroblasts secrete

matrix metalloproteinase (MMP) family proteins, such as MMP1

and MMP3, which disrupt the epithelial basement membrane,

hydrolyze the subepithelial collagenous matrix, and promote the

spread of inflammatory factors to deeper layers of mucosal tissue.

Signal amplification stage.

The persistent damage to mucosal

tissue caused by radiochemotherapy manifests as positive feed-

back regulation and creates a vicious cycle of inflammatory factors

affecting proinflammatory signaling pathways. This prompts entry

into the signal amplification phase of OM. For example, exposure

to cytotoxic rays or drugs leads to NF-κB signaling pathway

activation. The expression of the proinflammatory cytokines TNF-α

and IL-1β increases, and these factors are released extracellularly,

triggering NF-κB pathway activation in adjacent cells. This results

in

the

upregulation

of

MAPK,

COX2,

and

tyrosine

kinase

expression.

TNF-α

also

contributes

to

the

upregulation

of

ceramides through sphingomyelinase activation, leading to cell

apoptosis. Postapoptotic debris and pathogenic microorganisms

infiltrating loose intercellular adhesion channels activate the

immune system and further activate the NF-κB pathway.57,58

Patients at this pathological stage have not yet exhibited

significant clinical signs; however, in severe cases, mucosal

erythema may be observed.

Ulceration stage.

Continuous secretion of inflammatory factors

leads to severe mucosal tissue damage, loss of epithelial integrity,

and ulcer formation. Owing to the presence of exposed nerve

endings, patients experience significant pain, which results in a

decreased

ability

for

self-oral

hygiene

management.

Many

pathogenic microorganisms colonize the ulcer surface, and their

toxic factors, such as cell wall components, penetrate into deeper

submucosal tissues through the ulcer surface. This prompts

lymphocytes, macrophages, and neutrophils to infiltrate and

aggregate in this area, where they continuously secrete large

amounts of proinflammatory and proapoptotic factors, leading to

more extensive cell apoptosis and tissue disintegration.59 In severe

cases, it can lead to systemic infection.

Repair stage.

At the end of radiochemotherapy, damaged

mucosal tissue has the potential to promote wound healing and

self-repair. Epithelial cell proliferation and migration led by the

submucosal

matrix

and

mesenchymal-related

signals

repair

mucosal epithelium continuity, maintain redox balance, and

remodel the oral microbial ecology. This process is related to

the regimen, use of concurrent CT, dosage and duration of

radiochemotherapy. However, the genome of the newly produced

mucosal epithelium differs from that of the original mucosal

epithelium, perhaps resulting in a lower tissue tolerance threshold

to radiochemotherapy.

CLINICAL MANIFESTATIONS

When patients with radiotherapy-induced oral mucositis (RIOM)

receive a cumulative dose of 10 Gy, they often experience a

burning sensation and eating irritation. When the cumulative dose

reaches 30 Gy, they may suffer from severe pain, xerostomia,

halitosis, and difficulty eating. In severe cases, they may endure

dysgeusia and restricted opening of the mouth. A few patients

may experience alopecia, pigmentation and fibrosis in the

irradiated field. In the acute stage, congestion, edema, erosion,

ulceration, and pseudomembrane formation may occur in the oral

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International Journal of Oral Science (2025) 17:54

mucosa of patients with RIOM, and the lesions gradually subside

and heal when RT ends (Fig. 2). In severe cases, these signs and

symptoms may last up to 2 or 5–7 weeks after RT ends.1 Chronic

RIOM may also develop up to two years after the completion of

radiotherapy and is characterized by secondary damage resulting

from extensive atrophy of the salivary glands. Primary clinical

manifestations include xerostomia and dysgeusia, with cardinal

physical signs presenting as widespread atrophy, thinning, and

congestion of the oral mucosa. Chronic RIOM is frequently

complicated by concurrent Candida infections. Patients typically

exhibit dermatological alterations in irradiated skin areas, includ-

ing dryness, desquamation, hyperpigmentation, and subcuta-

neous fibrosis.

Chemotherapy-induced oral mucositis (CIOM) usually begins

with a sense of local burning or stinging in the mucosa

approximately 4 to 5 days after the initiation of CT, with pain

symptoms worsening after 7 to 10 days and culminating

approximately 2 weeks later.11 The signs are similar to those in

the acute phase of RIOM, which mainly manifests as erosion,

ulceration, pseudomembranes, or crust (Fig. 3). If the lesion is not

infected, it normally resolves within three weeks following

treatment. When accompanied by a secondary infection, the oral

mucosa shows clinical symptoms of diseases such as Candida

albicans infection and herpes simplex virus infection.

The clinical manifestations of OM induced by molecular

targeted drugs are related to the drug category. For example,

mucosal ulceration occurs 10 days after mTOR inhibitor dosing but

generally

resolves

within

1

week.35,60

EGFR

inhibitors

are

associated with the development of ulcers 2–3 weeks after

dosing, and some patients may experience pain, dysphagia, and

dysgeusia.35,61 Vascular endothelial growth factor (VEGF) inhibitors

cause

diffuse

oral

mucosal

sensory

abnormalities,

mucosal

congestion, or ulceration within the first week of dosing.62,63 In

the context of PD-1/PD-L1 immune checkpoint inhibitors such as

navulizumab, OM typically occurs 3 months after the initiation of

treatment and is characterized by a mossy lesion with symme-

trically distributed white reticulation, which may be accompanied

by mild erythema and/or ulceration.64–66

OM is graded according to the signs and symptoms of patients.

Currently, the commonly used grading criteria for OM include the

World

Health

Organization

(WHO)

Oral

Toxicity

Scale,

the

Radiation Therapy Oncology Group (RTOG) scoring criteria for

acute

RIOM,

and

the

National

Cancer

Institute’s

Common

Terminology Criteria for Adverse Events (NCI-CTCAE) (Fig. 4). The

WHO grading standard focuses more on the assessment of eating

conditions, whereas the RTOG and NCI-CTCAE criteria emphasize

the evaluation of oral pathological and physiological conditions.

RTOG classifies toxicity into acute (within 1–3 months) and late

(after 3 months) phases, which are generally used for patients

undergoing RT alone. NCI-CTCAE is generally used for patients

undergoing

comprehensive

treatments

such

as

concurrent

chemoradiotherapy. Although only the WHO and RTOG criteria

have been formally adopted through expert voting, the NCI-

CTCAE criteria remain included in this consensus according to the

recommendations of oncology and radiology experts owing to

their critical importance in clinical application. These three criteria

are collectively presented to serve as a comprehensive reference

framework for guiding clinical practice and research implementa-

tion. To date, no evidence is available to suggest which grading

criteria are superior. Multiple grading standards are recommended

for comprehensive assessment.

DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS

The diagnostic criteria for OM include a history of radio-

chemotherapy, a history of targeted drug therapy or radiation

exposure, an association between the onset timing of oral

mucosal damage and radiochemotherapy regimens, and typical

clinical signs and symptoms of oral mucosal damage. Differ-

ential diagnosis is required mainly for acute episodes of erosive

ulcerative lesions, especially those that may appear widely

distributed, such as herpetiform recurrent aphthous ulcers,

primary herpetic gingivostomatitis, allergic stomatitis, erythema

multiforme, oral lichen planus (erosive type), and coccigenic

stomatitis. The early erythematous phase of OM should be

differentiated from oral candidiasis.1,67,68

Notably, patients receiving RT often experience a decline in

immune function. When OM presents with erosions, ulcers, and

other lesions, it is often associated with microbial infections. If

necessary, a complete blood count and cultures for bacteria, fungi,

and other pathogens can be performed to identify the type of

infection and administer targeted medication, thereby improving

a

d

c

b

Fig. 2

Radiotherapy-induced oral mucositis. Female, 3 months after surgery and radiotherapy for the breast tumor. Painful oral erosions

appeared during radiotherapy and persisted for a long time, accompanied by dry mouth. Large areas of congestion and scattered erosions

were observed in the cheeks, with fine white lines around the cheeks. White lines with a few scales were observed on the lips. a Left cheek;

b upper right cheek; c lower right cheek; d lips

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International Journal of Oral Science (2025) 17:54

clinical efficacy.1,11 However, owing to differences in economic

levels and medical technical levels among institutions in different

regions, performing bacterial/fungal cultures and antibiotic sus-

ceptibility tests as necessary prerequisites for the use of anti-

microbial drugs to treat OM would significantly increase the cost of

medical treatment and the complexity of clinical diagnosis and

treatment for patients. Therefore, for those who experience poor

anti-infective effects according to empirical routines, antibiotic

susceptibility tests should be performed in a timely manner to guide

the clinical use of drugs. For example, in the case of IMRT for

nasopharyngeal carcinoma, in which the incidence of RIOM is 100%

and accompanied infections are common, performing a throat

swab culture for bacteria can guide the selection of antibiotics, and

the infection control effect is superior to that of empirical

medication.69 The necessity of viral testing is controversial, and it

is not the first choice for auxiliary diagnostic methods.

Several emerging technologies, including molecular diagnostics

and artificial intelligence, play significant roles in the diagnosis

and prediction

of

OM. For

example,

various

inflammatory

biomarkers, such as TNF-α, IL-1β, and IL-6, are significantly

elevated in the saliva of patients undergoing chemoradiotherapy

and are positively correlated with OM severity. These biomarkers

can serve as auxiliary diagnostic tools or facilitate early identifica-

tion

of high-risk

patients.70

Furthermore,

machine

learning

methods have demonstrated effectiveness in predicting OM

occurrence among patients receiving radiotherapy,71,72 che-

motherapy73 and hematopoietic stem cell transplantation.74

DISEASE MANAGEMENT MEASURES

Disease prevention plan

Effective prevention measures can reduce the incidence and

severity of OM, delay lesion onset, alleviate pain, and significantly

improve patients’ quality of life. Clinicians can assess the risk level

of patients about to undergo radiochemotherapy on the basis of

the OM risk assessment (Fig. 1), categorize patients into high-risk,

medium-risk, and low-risk groups, and then formulate and

implement different preventive measures accordingly.

Oral health promotion and management.

Patients who were well

versed in oral health care and understood the adverse effects of

RT and CT had a lower incidence, severity, and duration of OM

following their initial treatment. This finding could be attributed to

patients’ conscious efforts to keep their oral mucosa moist,

maintain oral health and hygiene, and effectively control their oral

flora.75,76 When OM progresses to a severe stage, patients may

encounter a range of biopsychosocial issues, including difficulty

eating,

nutritional

imbalances,

social

barriers,

and

painful

discomfort, all of which contribute to a loss in an individual’s

quality of life. Good oral hygiene education and patient

management can significantly reduce the adverse effects and

complications of OM, such as reduced salivation, dysphagia, and

dysgeusia, and improve quality of life scores (QoLSs).77 As OM

causes symptoms such as pain, bleeding and limited mouth

opening, it can lead to a reduction in patients’ ability to take

care of their own oral health. Oral health education enables

patients to be aware of the importance of oral health and

hygiene care in relieving OM symptoms and improving patients’

self-oral management ability and adherence.78 The content of

oral

health

education

may

include

nutritional

advice

for

preventing OM, suggestions for preventing and improving dry

mouth, advice on issues such as taste and smell changes,

techniques for using toothbrushes and dental floss, and daily

self-assessment of their oral mucosa.

Patients who actively and continuously manage their oral

health before, during, and after radiochemotherapy and control

oral pathogen infections can effectively delay the onset of OM

and prevent OM progression to severe stages. Kartin et al.

proposed comprehensive self-oral care measures and nutritional

plans for patients undergoing radiochemotherapy, which can

effectively reduce the severity of OM pain, improve patient

malnutrition, and enhance their QoLS.79 Brushing teeth, rinsing

the mouth, using dental floss and interdental brushes, keeping

the oral mucosa moist, and maintaining a low temperature are

all measures used to strengthen self-oral management.80

For patients who are about to undergo radiochemotherapy, the

timing of implementing self-oral management is equally impor-

tant. Basic oral management measures, including tooth brushing

and water rinsing, should begin one week before the start of

radiochemotherapy. This can effectively delay OM onset in

nasopharyngeal cancer patients undergoing radiochemotherapy,

reduce its severity, and result in higher oral health assessment

a

d

c

b

Fig. 3

Chemotherapy-induced oral mucositis. Male, postoperative liver cancer and were taking chemotherapy drugs for 9 months, large

erosions and ulcers were observed on both the cheeks and the back of the tongue, and thicker blood crusts were observed on the lower lip.

a Left cheek; b right cheek; c dorsum of the tongue; d lips

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International Journal of Oral Science (2025) 17:54

scores. Implementing oral health management measures only the

day before starting radiochemotherapy is unlikely to have a

significant effect on alleviating oral mucositis.81 The frequency of

daily oral care (such as the number of rinses) and the selection of

products/medications for patients should be adjusted to the

various OM grading stages.75,79

Before patients undergo radiochemotherapy, a comprehensive

and professional oral health examination and assessment by

dentists to preemptively identify and eliminate potential risk

factors for OM could facilitate the smooth progression of

radiochemotherapy and effectively control hematogenous infec-

tions.82 OM risk can be effectively reduced by weekly professional

oral examinations and treatments, including scaling and brushing,

nutritional intake counseling, and lifestyle guidance, in breast

cancer patients undergoing CT.83 A randomized controlled phase

III trial revealed that regular professional oral care, such as teeth

cleaning, reduces the incidence and severity of OM in breast

cancer patients treated with everolimus and exemestane while

also improving patients’ tolerance and compliance in managing

CT-induced complications.84 Professional oral assessment and

treatment should include the following six aspects:85,86 (1)

comprehensive assessment of OM susceptibility factors (oral

hygiene, caries, metal restorative materials, and dentures); (2)

controlling the susceptibility factors that can cause mucosal or

periodontal infections and prevent the development of localized

infections and systemic spread of infection (periodontal scaling,

removal of residual roots/crowns/affected teeth, conversion of

metal to nonmetal fillings, removal of poorly restored restorations,

maintenance of oral hygiene); (3) reducing oral discomfort and

pain; (4) maintaining basic oral function to support nutritional

intake and speech function; (5) managing oral complications from

RT and drug-targeted therapies; and (6) enhancing individual

quality of life.

Topical drug prevention.

Despite available evidence that patients

receiving professional oral management practices can help

prevent OM, approximately 75% of patients still present with

adverse signs on the oral mucosa following RT.84 For low- and

median-risk patients, a combination of oral specialty prophylaxis,

such as anti-inflammatory and analgesic agents, healing promo-

tion and coinfection control, is needed.

Anti-infective drugs:

Chlorhexidine rinses have been shown to

play a significant role in antimicrobial therapy for periodontal

tissues, as these drugs inhibit bacterial, fungal and viral coloniza-

tion. As a risk factor for OM, intraoral microbial colonization of

pathogenic organisms in combination with cytotoxic therapy

plays a significant role in contributing to OM development. Meta-

analysis has shown that local application of chlorhexidine rinses

effectively prevent CIOM.87,88 However, chlorhexidine does not

have significant preventive effects on RIOM. Patients in the CT

group receiving 0.12% chlorhexidine gargle solution three times a

day at 15 mL/dose presented a decreased incidence, faster

remission, and reduced severity of OM, whereas those in the RT

group had no significant preventive effect. Intraoral microflora

colonization was reduced in both groups.89 Two additional

randomized controlled trials further validated that local applica-

tion of chlorhexidine does not effectively prevent RIOM90 and may

even cause more severe OM, as well as more noticeable adverse

effects (taste alternation and tooth staining).91 Therefore, the local

application of chlorhexidine rinses is only recommended for the

prevention or mitigation of CIOM, not RIOM.

Sodium bicarbonate removes detached cellular debris from the

surface of the oral mucosa, increases the pH, and inhibits

acidophilic bacteria. Sodium bicarbonate mouthwash has prophy-

lactic effects against OM and postpones the onset of CIOM in

patients undergoing CT for acute leukemia.92 However, it is less

effective than oral rinsing with benzydamine in preventing

RIOM.93 It is recommended that 10 g of sodium bicarbonate

powder be dissolved in 1 L of sterile water or physiological saline

and used at 15 mL/2 min/4 times/day, starting from the day before

RT and continuing for two weeks after treatment is completed.

Pro-healing drugs:

Granulocyte-macrophage colony-stimulating

factor (GM-CSF) promotes the aggregation of lymphocytes and

myeloid cells, such as macrophages and Langerhans cells,

inducing local tissue inflammatory responses and stimulating

macrophages to secrete pro-healing molecules. Additionally, GM-

CSF stimulates the growth of keratinocytes and fibroblasts,

promoting ulcer surface repair and wound healing.94 The use of

GM-CSF for oral administration or gargling has a definite effect on

preventing RIOM, effectively delaying the progression of RIOM to

severe stages.95–97 A GM-CSF oral rinse (150 g GM-CSF in 100 mL

Ulcer

Increased pain

Semi-solid diet

Asymptomatic/

mild symptoms

No treatment

needed

Erythema

Mild pain

Discontinuous

patchy

erythema(<1.5 cm)

Moderate pain

Tolerable, analgesics

can be used

Notable ulcer pain

Only able to

consume liquid diet

Patch fusion

(>1.5 cm)

Severe pain

Requires strong

analgesics

Severe pain

Interferes with

oral intake

Patchy ulcers

Severe pain

Inability to eat

Ulcer formation

Bleeding

Severe pain

Life-threatening

risk

Requires

emergency

treatment

Moderate pain

Requires liquid diet

Mucosal erythema

Mild pain

No analgesics

needed

WHO

RTOG

NCI·

CTCAE

Grade 5

Grade 0

Grade 1

Grade 2

Grade 4

Grade 3

No findings

No findings

—

—

—

Death

Fig. 4

Criteria and Illustrations for the Clinical Grade of Oral Mucositis. WHO World Health Organization, RTOG Radiation Therapy Oncology

Group, NCI National Cancer Institute, CTCAE Common Terminology Criteria for Adverse Events

Expert consensus on the prevention and treatment of. . .

Xia et al.

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International Journal of Oral Science (2025) 17:54

of 0.9% NaCl solution) was prepared and gargled 4 times a day

from the pretreatment date (25 mL per wash >3 min) and

swallowed

in

small

amounts

after

gargling.

However,

the

effectiveness of subcutaneous GM-CSF injections in preventing

RIOM is controversial.98–102

Topical application of Kangfuxin liquid significantly reduces the

incidence and severity of RIOM.22 Kangfuxin liquid can increase

the function and quantity of neutrophils in wounds while

promoting the secretion and deposition of the extracellular

matrix, expediting the healing process. Starting from the day of

RT, 10 mL Kangfuxin liquid is gargled for 3 minutes, and the

mixture is then swallowed slowly, three times a day, until the end

of RT. When needed, Kangfuxin liquid ice cubes can be used for

buccal administration.23

Anti-inflammatory and analgesic drugs:

As nonsteroidal anti-

inflammatory drugs, benzydamine inhibits the secretion of TNF-α

and IL-1 from local mucosal tissues, acting as anti-inflammatory,

antibacterial and local analgesic agents.103,104 For head and neck

squamous cell carcinoma (HNSCC) patients receiving moderate

doses of RT (a total radiation dose of up to 50 Gy, with a daily

radiation dose less than 2.2 Gy), the use of benzydamine oral

rinses could reduce the incidence of erythema and ulcers by

approximately 30%, relieve patients’ pain, and prevent RIOM

effectively and safely.105,106 For patients receiving concurrent

chemoradiotherapy, a benzydamine oral rinse is also useful for

preventing OM and controlling oral mucosal infections.93,107,108

The recommended usage is as follows. For patients receiving

moderate radiation doses (<50 Gy) or CT, a 0.15% benzydamine

oral rinse (15 mL/2 min/dose) should be used 4-8 times per day

starting on the day of treatment. The oral rinse can be diluted

proportionally if the solution is too thick.

Rebamipide inhibits the production of reactive oxygen species

by inflammatory cells and scavenges hydroxyl radicals.109,110 The

use of oral rinses with rebamipide may prolong the onset and

reduce the severity of OM in RT patients.111 The recommended

concentration for patients receiving radiation for HNC is 4%.112 It

can be started three days before radiochemotherapy, with a

dosage of 5 mL for 30 s per rinse, six times a day. The rinse should

be continued for three months.

Systemic drug prevention.

For high-risk patients with tumors

prone to OM, in addition to necessary oral hygiene management

and local treatment, systemic pro-healing and anti-inflammatory

agents are recommended to prevent the occurrence of moderate

or severe OM.

Intravenous keratinocyte growth factor-1 (KGF-1) is effective in

preventing OM. However, its outpatient application is limited, and

it is mostly used in hospitalized patients. Intravenous injection of

KGF-1 can reduce the incidence of moderate to severe OM in

patients receiving head and neck radiochemotherapy, prevent the

occurrence of OM, and delay the onset of severe OM.113,114 For

acute leukemia patients who require CT, KGF-1 can also play a role

in preventing the exacerbation of OM.115 Currently, a consensus

on the dosage and frequency of KGF-1 usage is not available.

However, a common dose used in clinical trials is 360 μg/kg, and

the number of intravenous injections is often six. It can be

administered once daily from 3 days before to 3 days after

radiochemotherapy initiation or once a week starting one week

before radiochemotherapy and continuing weekly thereafter.9

Glutamine can alleviate the oxidative damage caused by

ionizing radiation by inhibiting the secretion of proinflammatory

factors. It activates collagen synthesis, provides the necessary

energy for cell proliferation, and promotes mucosal wound

healing.116 For patients with HNC undergoing RT, oral glutamine

(10 g/1 000 mL, taken 2 h before RT) can effectively prevent and

remedy RIOM, significantly alleviate the severity of OM, reduce

opioid analgesic use and decrease the likelihood of nasogastric

tube feeding and treatment interruptions.117,118 In patients with

solid tumors during CT, treatment with an oral glutamine

suspension has also been shown to be effective in relieving

moderate to severe OM and reducing patient pain (2 g/M2, twice a

day).119,120

Pilocarpine has effects similar to those of acetylcholine,

stimulating the secretion of saliva and sweat and preventing

xerostomia caused by RIOM. Studies have shown that oral

administration of pilocarpine significantly reduces the incidence

of severe RIOM (grade ≥3) in HNC patients.13,121 However,

pilocarpine does not have significant effects on patients with oral

squamous cell carcinoma receiving concurrent chemoradiother-

apy.13 Pilocarpine can significantly reduce the severity of OM in

patients with solid tumors and acute leukemia undergoing

chemotherapy,122 but it does not provide benefits for patients

undergoing pretransplant conditioning for HSCT.123 It can be

administered orally at 5 mg/dose 3 times/day prior to treatment

and reduced to 2.5 mg/dose 4 times/day if the patient sweats

significantly.

As traditional Chinese medicines, Shuanghua Baihe tablets

contain berberine as a Coptis Rhizoma component and have been

proven to have antibacterial, antifungal, antioxidant, and anti-

inflammatory properties. For patients undergoing RT in the head

and neck region, Shuanghua Baihe tablets can be used to reduce

the incidence of OM, alleviate the degree of pain, and shorten the

healing time.19,20 The tablets can be taken orally from the first day

of treatment (4 tablets/dose, 3 times/day).

Photobiotherapy prevention.

Low-level laser therapy (LLLT) can

directly act on cellular mitochondria, maintain cellular home-

ostasis, promote cell proliferation and collagen synthesis, increase

cellular metabolism, accelerate wound healing and tissue repair,

induce angiogenesis, enhance leucocyte activity, reduce damage

caused by radiochemotherapy to tissues, and have analgesic

effects.124 For pediatric patients undergoing HSCT, high-dose

radiochemotherapy or radiochemotherapy for head and neck

tumors, a low-level laser (620–750 nm) is beneficial for preventing

and controlling severe OM (grade ≥3).125–127 For patients with

head and neck tumors undergoing chemoradiotherapy, LLLT has

also been proposed to have a role in preventing OM.128 Owing to

the lack of well-designed and large-scale clinical trials, the

parameters for LLLT mostly depend on the experience of clinical

physicians. For patients with HNC undergoing chemoradiotherapy,

the parameters for preventing OM in multiple clinical trials of LLLT

include a wavelength ranging from 632.8 to 660 nm, an energy

density ranging from 2.5 to 4 J/cm2, and power ranging from 10 to

100 mW.129 Notably, individual studies reported that LTTT was not

effective in preventing radiochemotherapy-induced OM,130 but

most studies support its effectiveness. In addition, some experi-

mental studies suggest that photobiomodulation has a carcino-

genic effect,131–133 but current clinical evidence shows that

photobiomodulation has good safety.134,135 Nonetheless, clin-

icians should inform patients of the potential risks of photo-

biomodulation therapy before its use.

Additionally, the use of cryotherapy136 and standard oral

care137,138 in conjunction with LLLT are advisable for OM

prevention.

Others.

Saline solution can serve as a mild mouthwash, helping

patients maintain oral health and hygiene, as well as improving

their comfort level.139 It has been suggested that topical

application of sucralfate mouthwash or oral administration of

sucralfate in patients can be effective in preventing OM;140–143

however, some studies report the opposite conclusion.144,145

Cryotherapy refers to chewing ice chips before and after CT to

reduce the temperature of the oral mucosa. This can constrict

mucosal blood vessels and decrease blood flow, thereby reducing

the effects of CT drugs on the oral mucosa and preventing OM

Expert consensus on the prevention and treatment of. . .

Xia et al.

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International Journal of Oral Science (2025) 17:54

occurrence.146–150 However, although cryotherapy has the advan-

tages of low cost and ease of implementation, its preventative

efficacy is limited by the drug’s half-life, and it cannot replace the

important role of patient oral care education and monitoring in

the prevention of OM. Additionally, patients with nasopharyngeal

carcinoma who undergo RT can wear personalized oral stents to

reduce the radiation dose received by the oral mucosa; this can

help to preserve healthy oral mucosa and potentially avoid

RIOM.151

Disease control plan

Oral health management.

On the basis of sufficient evidence

available,83,84,152,153 professional oral management by dental

specialists during RT for tumors is conducive to monitoring the

health condition of the oral mucosa, relieving symptoms and

promoting healing. Specific measures include (1) conducting a

comprehensive oral examination weekly during the treatment

period to closely monitor oral conditions, with particular attention

given to the second week after CT, which is a high-incidence

period for OM; (2) taking appropriate management measures

based on oral assessment, such as periodontal scaling, crown

surface polishing, tongue microbiome control, and the use of

antimicrobial mouthwashes or corticosteroid ointments; and (3)

instructing and checking the patient’s tooth brushing method by a

doctor or nurse, advising patients to brush their teeth gently once

in the morning and once before bed, brushing gently and

avoiding abrasing soft tissues. In addition, if patients have a

tendency for severe gum or mucosal bleeding, using cotton swabs

to remove deposits from the surface of teeth and mucosa.

For special populations such as pediatric patients, owing to

their weaker ability to control their own oral hygiene, it is more

important to emphasize the role of guardians in helping children

achieve self-oral hygiene management. Additionally, to closely

monitor any oral complications that arise in children receiving CT/

RT and facilitate antitumor treatment, a variety of oral manage-

ment strategies should be used.154,155 Specific measures include

(1) long-term professional oral management by dental specialists;

(2) oral health education for patients and their guardians; (3) daily

assessment of oral hygiene in hospitalized patients; and (4) the

use of various oral management measures, such as compound

mouthwashes (antimicrobial + analgesic + glucocorticoid +

vitamin B + fluoride-containing), in conjunction with photobio-

modulation therapy.

Medication

Anti-inflammatory drugs, analgesics and antidepressants:

Burn-

ing, irritation, and pain are common clinical symptoms in patients

with OM, resulting in eating, swallowing, and speech disorders, as

well as a lower quality of life. Topical applications of doxepin,

lidocaine, and tetracaine can effectively alleviate pain symptoms

associated with OM.

Doxepin is a tricyclic antidepressant that works by blocking

sodium ion channels156 and preventing stimulus conduction in

cutaneous and mucosal nociceptors. It has sedative and analgesic

effects when used topically. Several studies have shown that using

doxepin oral rinses can provide rapid analgesia when radio-

chemotherapy

patients

experience

mucosal

pain,

and

the

analgesic effect can last for more than 2 hours.157–160 The drug

may have side effects such as taste disturbances and drowsiness

after use, and patients can use it as a sleep aid. Doxepin oral rinse

(5 mg/mL) can be used for 1 min; this should be followed by

coughing and spitting it out 3–6 times/day.

Lidocaine can also be used to alleviate OM-related pain, which is

characterized by rapid onset. In contrast, the analgesic effect lasts for

a shorter duration than doxepin (approximately 30 min to 1 h),

which may lead to an increased frequency of drug administra-

tion.157,161 Patients can rinse with a lidocaine solution and then spit

it out or apply viscous lidocaine + 1% cocaine directly to painful

mucosal areas.162

A clinical trial proposed that the use of 1.5% tetracaine gel can

safely and effectively reduce RIOM-related pain in a significant

proportion of HNC patients.163 However, larger randomized

controlled trials are needed to investigate the effects of tetracaine

compared with those of other topical analgesics.

Topical glucocorticoids are often applied clinically to relieve

RIOM symptoms. It has been reported that topical dexamethasone

ointment reduces the incidence of severe OM in patients treated

with RT for OSCC; however, no substantial efficacy has been

observed in patients treated with concurrent chemoradiother-

apy.13 Triamcinolone acetonide mucoadhesive films have also

been shown to be effective in reducing pain in RIOM patients.12

When

stimulated

by

radiochemotherapy,

mucosal

tissues

release large amounts of inflammatory factors, free radicals, and

oxidative stress, leading to rapid destruction of epithelial tissue. A

oral rinse containing 0.2% vitamin E (antioxidant), 0.1% triamci-

nolone acetonide (anti-inflammatory agent) and 0.2% hyaluronic

acid (topical reductant to reduce stimulation of reactive oxygen on

mucosal tissues) can achieve good therapeutic effects on OM.164

The usage was gargling 2 mL/min, 3 times/day, and not eating or

drinking for 15 min afterward.

Protective oral gel is a bioadhesive material that can adhere to

mucosal ulcers, quickly forming a protective barrier that provides

wound protection and analgesia. Several clinical trials have

demonstrated that protective oral gel can adhere to red, swollen

and ulcerated oral mucosa of head and neck CT/HSCT patients

and provide analgesic effects for a long period of time (6–8 h),

effectively relieving regional pain.165–167

Antimicrobials:

Mucosal tissues of patients undergoing radio-

chemotherapy are prone to damage and disintegration, providing

channels for oral bacteria and fungi to invade deeper tissues.

Patients often suffer from pain and other antitumor therapy

complications, resulting in poor self-cleaning. This can cause

residual food debris in the oral cavity, providing sustenance for

pathogenic

microorganisms.

The cell

wall and

other

toxic

substances can cause more severe cellular phagocytosis and

tissue inflammatory responses. Using chlorhexidine and sodium

bicarbonate oral rinses, miconazole mucoadhesive buccal tablets

to control the number and activity of bacteria and fungi in the oral

cavity can be effective in relieving OM symptoms.

Studies

have

shown

that

0.12%

or

0.2%

chlorhexidine

mouthwash can reduce the duration and severity of OM in

patients undergoing chemotherapy.89,168 Five percent sodium

bicarbonate mouthwash can effectively treat and alleviate OM

severity, accelerate lesion healing, and subsequently improve the

QoL of cancer patients during CT.169,170 Miconazole has strong

inhibitory activity against most strains of Candida, especially

fluconazole-resistant strains.171 Miconazole mucoadhesive buccal

tablets have been used for oropharyngeal candidiasis in HIV

patients172 and in patients with HNC undergoing CT.173 It is also

an effective alternative to oral amphotericin B suspension in

patients undergoing high-dose therapy/autologous stem cell

transplantation (HDT/ASCT), reducing complications caused by

excessively high levels of antifungal agents in blood.174

Pro-healing drugs:

IL-11 promotes peripheral platelet production,

stimulates hematopoietic stem cell proliferation, and facilitates ulcer

healing. It regulates macrophage function, promotes the secretion of

epidermal growth factor, shortens the cell growth cycle, and

accelerates tissue repair. IL-11 oral rinses can effectively reduce OM

clinical grade, shorten healing tim,175,176 and promote a decrease in

serum C-reactive protein levels, alleviating pain.177 The use of an IL-

11 oral rinse (1.5 mg/100 mL) after brushing and rinsing is

recommended, and 10 mL should be gargled for 10 min per wash,

4 times/day.

Expert consensus on the prevention and treatment of. . .

Xia et al.

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International Journal of Oral Science (2025) 17:54

Recombinant bovine basic fibroblast growth factor (rb-bFGF) is

effective in reducing the healing time of RIOM lesions.16 When

used in combination with Kouyanqing granules14 or sodium

bicarbonate mouthwash,15 it has a good therapeutic effect on

RIOM in patients undergoing RT for HNC. Notably, given the cell

growth-promoting effects of rb-bFGF, clinicians should consider its

advantages and disadvantages and make comprehensive deci-

sions regarding its use in patients with oral malignant tumors

receiving radiochemotherapy.

Kangfuxin liquids and Shuanghua Baihe tablets are potentially

effective in both the prevention and treatment of OM. In patients

receiving RT in the head and neck region, Kangfuxin liquid has

been shown to significantly reduce OM duration and severity.21,22

A randomized controlled trial with a larger sample size also

revealed that oral administration of Shuanghua Baihe tablets

effectively relieves OM.19,20 The usage is consistent with that

previously described.

On

the

basis

of

the

overwhelming

evidence

avail-

able,117,119,178,179 oral glutamine is effective in prevention and

treatment of OM. The use of 10 g/dose oral glutamine suspension

3 times/day for patients receiving RT and 2.5 g/5 mL/dose

glutamine suspension 3 times/day for patients with solid tumors

receiving CT can effectively reduce moderate to severe OM.

Diet and nutrition.

An elemental diet is a chemically refined meal

that contains all the easily digestible and absorbable nutrients

needed by the body, including amino acids, carbohydrates,

vitamins, inorganic salts, trace minerals, and minimal fats. This

diet can effectively aid in the early recovery and symptom relief of

OM. Oral administration of an elemental diet (containing 79.3%

carbohydrates, 17.6% amino acids, 0.6% soybean oil, 2.0%

minerals, and 0.5% vitamins) may promote early recovery from

OM damage induced by pretreatment of HSCT patients, thereby

reducing hospital stays.18 Elemental diets can also effectively

improve OM in OSCC patients and increase the radiochemother-

apy completion rate.17

Photobiotherapy.

LLLT is not only significantly effective in

preventing OM but also widely recognized for its ability to relieve

OM symptoms. Despite the evident benefits of LLLT, different

parameter settings may lead to varying treatment outcomes and

poor reproducibility.7,180 A systematic review and meta-analysis181

reported that LLLT (wavelength of 632.8–685 nm, energy density

of 1.3–6.2 J/cm2, and power of 5–100 mW) has good clinical

outcomes for HNC patients undergoing radiochemotherapy,

reducing patient pain and the risk of developing severe OM.

Another meta-analysis suggested that182 the most commonly

used laser parameters for OM treatment include a wavelength of

660 nm, an energy density of 4 J/cm2, a power density of 1 W/cm2,

an energy of 0.16 J, a power of 40 mW, and a spot size of 0.04 cm2.

Currently, most clinical trials of LLLT are conducted using

intraoral irradiation. Some scholars have proposed that extraoral

LLLT can be equivalent to intraoral transillumination in reducing

OM clinical grade and pain levels and accelerating the healing

time of mucosal damage.183 In addition, extraoral LLLT has the

benefits of shortening the treatment period (approximately 4 min),

improving the cooperation of pediatric patients,184 and demon-

strating efficacy in the treatment of mucositis of the lips and

esophagus.

Others.

Topical morphine oral rinse is beneficial in relieving OM

pain,185–187 but its use has limitations. Moreover, studies have

shown that morphine can lead to a reduction in cell migration,

which in turn inhibits wound healing.188,189

Honey and propolis are considered natural antioxidants that

effectively block the production of free radicals and act as anti-

inflammatory and pro-healing agents. Some studies have sug-

gested that honey/propolis may reduce the progression of OM to

severe OM and have abirritation and weight maintenance effects

for patients,190–192 whereas some clinical trials have reported that

the therapeutic effect of honey/propolis does not differ from that

of placebo group.193–195

In summary, clinicians can conduct risk assessments for patients

undergoing oncological treatment and choose from the above

OM control measures according to the patient’s actual situation

based on comprehensive consideration. The clinical guidelines for

the prevention and treatment of OM are shown in Fig. 5. If the

therapeutic effect is good and recovery is satisfactory, standard

treatment and visitation procedures should be followed without

the need for additional follow-ups or interventions. If the effect is

poor and the patient’s condition worsens, the patient should

communicate with an attending physician to consider discontinu-

ing or reducing the intensity of antitumor treatment. After the OM

has

subsided,

the

plan

should

be

adjusted

to

complete

subsequent antitumor therapy. Importantly, from the pretreat-

ment phase of radiochemotherapy until one month after antic-

ancer treatment completion, dental specialists should provide

continuous oral care for patients and educate patients on self-

examination and self-management once every 1–2 weeks. Indivi-

duals who have had RT to the head and neck region should be

monitored throughout a patient’s life to prevent and treat the

occurrence and development of chronic OM over time.

Follow-up

Continue oral care

and self-monitoring

once per 1-2 weeks

until one month after

radiochemotherapy

completion (patients

undergone RT in head

and neck area should

be monitored for life

to prevent chronic

OM in time)

Poor effect,

worsening

condition

Good effect

and recovery

 Grade 4

< Grade 4

Efficacy evaluation

Median

High

Low

Grade assessment

of OM condition

Conduct risk assessment

based on risk factors

Communicate with

attending physician to

consider discontinuing

or reducing intensity of

anti-tumor treatment

Non-drug

treatment

· Oral care

· Nutritional

support

· Disease

monitoring

· LLLT

Drug treatment

(analgesia,

antidepressants,

pro-healing

agents)

Treatment and visit according

to predetermined standard

procedures

· Systemic drug adminis-

tration

Treatment

Prevention

Oncology

patients

· Oral hygiene education,

self-management, and

preventive oral specialty

treatment

· Topical drug application:

(antimicrobials, pro-

healing, analgesia)

· LLLT

Fig. 5

Guidelines for the clinical prevention and management of radiochemotherapy-induced oral mucositis

Expert consensus on the prevention and treatment of. . .

Xia et al.

9

International Journal of Oral Science (2025) 17:54

Indicators of efficacy

The effectiveness of OM clinical preventive and therapeutic

measures can be assessed in terms of OM lesion severity and

degree of oral pain; additionally, assessments can be supplemen-

ted by examining the incidence, duration and safety evaluation of

severe oral mucositis (grade 3 or higher).106,196,197 The severity of

OM lesions can be determined according to clinical grading

criteria such as the WHO, RTOG or NCI-CTCAE; the degree of oral

pain can be assessed using the visual analog scale (VAS) (0–10),

and the pain affect faces scale (PAFS) (0–10). Safety assessments

mainly include records of adverse reactions and adverse events.

CONCLUSION AND EXPECTATION

Oral

mucositis

is

one

of

the

most

common

and

severe

complications induced by antitumor therapy and can cause

redness, swelling and pain in the oral mucosa of patients, leading

to speech and eating difficulties and reducing the quality of life of

individuals. In severe cases, it can force interruption of radio-

chemotherapy plans, interfere with antitumor treatment progres-

sion, and extend a patient’s hospital stay. Therefore, clinicians

should pay attention to patients with tumors and HSCT who are

susceptible to the risk of OM, monitor and manage their oral

hygiene and health, provide oral health information and educa-

tion to them and their families to prevent the occurrence of OM,

prevent and control coinfections, alleviate pain, control symptom

deterioration and promote the healing process through pharma-

cological and nonpharmacological means.

This consensus acknowledges several inherent limitations. First, the

evidence selection process may carry potential biases due to the

possible subjectivity in prioritizing certain research. Second, expert

opinions, although valuable, might reflect individual specialty back-

grounds or clinical experiences that could influence recommendation

alignment. Third, significant knowledge gaps persist in specific clinical

areas, potentially limiting the generalizability of recommendations

across diverse health care systems. Finally, the incorporation of

recommendations

involving

traditional

Chinese

medicine

into

international practice currently faces implementation challenges.

Notably, current clinical research on OM intervention strategies

predominantly presents a low evidence hierarchy, underscoring

the imperative need for future high-quality randomized controlled

trials to establish robust guidance for the clinical management of

OM. Furthermore, the implementation of preventive and ther-

apeutic measures should be judiciously tailored to regional

economic disparities and variations in health care infrastructure

across medical institutions. This adaptive approach ensures

optimal patient benefit through context-sensitive application of

medical interventions while maintaining rigorous adherence to

evidence-based practice standards.

ACKNOWLEDGEMENTS

This study was supported by the National Natural Science Foundation of China

(U23A20445)

and

the

Science

and

Technology

Program

of

Guangzhou

(202206080009). The authors are grateful to the other experts in the specialist

group and evidence-based medicine group for their contributions in the develop-

ment of this consensus and their names are listed as follows. Fangchun Chen,

Ruiyang Chen, Hongxia Dan, Gefei Du, Huabing Ge, Ying Han, Yun Hong, Lu Jiang,

Mei Lin, Rui Lu, Xiaobo Luo, Xingchen Peng, Xiangmin Qi, Jing Shi, Hongying Sun, Yan

Sun, Zheng Sun, Yaqin Tan, Yaling Tang, Hui Wang, Wanchun Wang, Xiaoping Wang,

Yufeng Wang, Zhi Wang, Fanglong Wu, Zhimin Yan, Jing Zhang, Yuxing Zhang,

Zengtong Zhou, Yu Zhou, Guopei Zhu. The authors also thank Weiyu Li for her

assistance in preparing the consensus.

AUTHOR CONTRIBUTIONS

Conceptualization & Investigation, B.C.; Supervision, B.C.; Original draft, J.X., X.T., and

Q.H.; Review & Editing, W.L., X.T., G.Z., H.Z., H.H., G.T., T.W., Q.C., Y.F., X.G., H.L., C.H., Y.Z.,

X.S., L.W., X.Z., Q.L., R.T., Y.H., Y.C., W.W., Y.Z., Y.W., M.N., X.J., X.W., Y.N., and C.Y.

ADDITIONAL INFORMATION

Competing interests: The authors declare no competing interests.

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