To assess the impact of saline mouth rinse regimen and education program on radiation-induced OM symptoms and QOL in patients with oral cavity cancer receiving RT or CCRT.

Ninety‐one OCC patients were randomly divided into a group that received saline mouth rinses and an education program and a control group that received standard care. OM symptoms and QOL were assessed with the WHO Oral Toxicity Scale, MSS‐moo, and UW‐QOL. Data were collected at the first postoperative visit to the radiation department (T0) and at 4 weeks and 8 weeks after beginning RT or CCRT.

• N: 91   
• AGE: 20 years or older
• MALES: 93.8%  
• FEMALES: 6.2%
• CURRENT TREATMENT: Radiation, combination radiation and chemotherapy  
• KEY DISEASE CHARACTERISTICS: Diagnosed with oral cavity cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Undergoing postoperative adjuvant RT or CCRT

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Cancer center in northern Taiwan

• PHASE OF CARE: Active anti-tumor treatment
• APPLICATIONS: Elder care

Double-blind RCT one control and two intervention groups.

OM symptoms and QOL were assessed with the WHO Oral Toxicity Scale, MSS‐moo, and UW‐QOL. Data were collected at the first postoperative visit to the radiation department (T0) and at 4 weeks and 8 weeks after beginning RT or CCRT.

Patients in both groups had significantly higher levels of physical and social‐emotional QOL at 8 weeks after beginning RT or CCRT compared to the first visit. Patients in the saline rinse group had significantly better physical and social‐emotional QOL as compared to the standard care group at 8 weeks. Radiation‐induced OM symptoms and overall QOL were not different between the groups.

The authors concluded that the saline rinse and education program promote better physical and social‐emotional QOL in OCC patients receiving RT/CCRT. The results of this study indicated that saline mouth rinses with an education program were effective in increasing physical and social‐emotional QOL by improving the radiation‐induced OM symptoms and promoting oral comfort in patients receiving RT/CCRT for HNC, as compared to standard care. However, no improvement in radiation‐induced OM symptoms and overall QOL was found.

• Small sample (< 100)
• Other limitations/explanation: Small study with limitations in descriptive measurement.

It might be helpful to provide and teach saline mouth rinses to patients

To evaluate the efficacy and route of administration of omega-3 fatty acids for the prevention and treatment of oral mucositis.

Patients were randomized to omega-3 (two capsules daily with meals, each capsule contained 2,000 mg of fish oil plus EPA/DHA). The placebo contained corn oil with EPA/DHA.

• N = 30 control group, 30 in the omega 3-fatty acid intervention group  
• AGE: 22-63 years old
• MALES: 23 (38%)  
• FEMALES: 37 (62%)
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Leukemia or breast cancer diagnosis 
• OTHER KEY SAMPLE CHARACTERISTICS: Patients were actively undergoing chemotherapy treatments with WHO grade I mucositis and were not to be treated with chemical agents.

• SITE: Single site   
• SETTING TYPE: Not specified    
• LOCATION: Kerman, Iran

• PHASE OF CARE: Active anti-tumor treatment
• APPLICATIONS: Elder care, palliative care

Double-blinded random control study

Mucositis was evaluated based on the WHO, Oral Mucositis Weekly Questionnaire (OMPQ), and Western Consortium for Cancer Nursing Research (WCCNR) criteria.

At 1 and 2 weeks, the severity of mucositis was lower in the omega-3 group compared with the control group and, after 2 weeks, there was no evidence of mucositis in the patients taking omega-3. Patients taking omega-3 compared with the placebo exhibited a better ability to eat, and the difference between the two groups was statistically significant (p = 0.002). The average duration of mucositis in the omega-3 group was 5.5 days and in the placebo groups, 10-12 in the placebo group. The mean pain intensity scores during the first 24 hours were 5 ± 5.4 and 8 ± 6.4 in the omega-3 and placebo groups, respectively. The maximum and minimum values of pain severity scores in the omega-3 group were 6 and 0 in the placebo group. The patients’ quality of life in both groups showed a statistically significant difference in weeks 2 and 3 (p = 0.01).

Omega-3 fatty acids show promise in reducing the severity and duration of mucositis as well as the associated pain intensity.

• Small sample (< 100)
• Other limitations/explanation: Only two types of diagnosis breast cancer and leukemia were included.

These results show promise for treating patients with oral mucositis with omega-3 fatty acid.

To compare between LLLT and placebo for overall disease-free survival (DFS) and progression-free survival (PFS) of patients with head and neck cancer who received chemoradiation therapy. Randomized double-blinded placebo controlled phase III trial

Patients received low-level laser therapy or placebo; LLLT with an InGaAIP diod (660 nm to 100 mW-1 J-4J/cmsq, and a spot size of 0.24 cm² five days a week before radiotherapy. contact with the mucosa on nine points per region for 10 seconds per point, totaling 12 minutes per patient for LLLT.

• N: 94; laser group = 47, placebo group = 47    
• AGE: Mean age of LG = 53.5, PG = 55.7; non-significant
• MALES: LG male, 89.4%; PG male, 85.1%    
• FEMALES: LG female, 10.6 %; PG female, 14.9%
• CURRENT TREATMENT: Combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Head and neck cancer (nasopharynx, oropharynx, and hypopharynx cancer)

• SITE: Not stated/unknown Instituto Nacional de Câncer (INCA)
• SETTING TYPE: Not specified    
• LOCATION: Rio de Janeiro Brazil

PHASE OF CARE: Active anti-tumor treatment

Randomized phase III trial of patients with head and neck cancer. Details of randomization not provided.  

Both group received treatments of chemotherapy (cisplatin 100 mg/m² at day 1, 22, and 43) and radiotherapy according to tumor localization, using megavoltage radiotherapy with 2D and 3D techniques. A total dose of 70.2 Gy daily in 39 fractions, five days a week, using a cobalt-60 and a linear accelerator unit.

The adverse effects were evaluated daily, according to the Common Toxicity Criteria, version 3.0, from the National Cancer Institute (NCI-CTC) [16]. Oral mucositis was evaluated every day during the treatment period, according to the OMS and OMAS scales. The modified visual analog scale was used to evaluate pain. Body weight (body mass index) was measured every week. Patients were evaluated by a complete physical examination, oroscopy, nasopharyngoscopy, hematologic and biochemical profiles, chest radiography, and CT/MRI performed every four months for the first two years, every six months from the third to the fifth year, and then annually according to the RECIST criteria.

• Overall survival: LG 57.4% versus PG 40.4%; p = 0.9 NS; HR = 1.64; 95% CI [0.92, 2.91]
• DFS: PG 65.9% versus 58.6%; p = 0.659 NS; HR = 1.19; 95% CI [0.55, 2.57]
• PFS*: 61.7% versus 40.4%; p = 0.03; HR = 1.93; 95% CI [1.07, 3.5] 
• OM stage 3-4*: LG 6.3% versus PG 48% (p < 0.001)
• Gastrostomies*: LG 14.9% versus PG 38.3%; RRR = 0.39 (95% CI [0.18, 0.84]), p = 0.01
• Complete chemotherapy interruption: LG 12.8% versus PG 19.1%
• Chemotherapy dose reduction: LG 2.1% versus PG 6.4%
• Opioid use*: LG = 31.9% versus PG = 85.1; RRR = 0.38 (95% CI [0.24, 0.58]; p < 0.001
• Temporary radiotherapy interruption due to radiodermatitis: LG 14.9% versus PG 8.5%

* statistically significant findings.

Laser group had better progression-free survival and complete response, however this did not carry over to overall survival significance. Oral mucositis severity was statistically significantly lower in LLLT group.

• Small sample (< 100)
• Unintended interventions or applicable interventions not described that would influence results
• Subject withdrawals ≥ 10%
• Other limitations/explanation: Limited information in article regarding original study, so do not have many details that would be helpful

LLLT was beneficial to reduce oral mucositis. No statistically significant results for overall survival is likely affected by type II error (small sample size), and larger sample size study is needed. This study found statistically significant improvement for progression-free survival and LLLT may improve not only mucositis occurrence/severity but also patients’ survival.

To evaluate if Shaunghaubaihe tablets can prevent oral mucositis for patients with locally advanced nasopharyngeal carcinoma undergoing chemoradiotherapy.

Multi-site, randomized, double blind study of Shuanghuabaihe tablets versus placebo (four tablets, three times a day) started at the initiation of chemoradiotherapy and lasting seven weeks. Patients could stop taking the tablets if grade 3 mucositis developed.

• N = 240   
• AGE: 18-70 years old 
• MALES: 70% (intervention) and 63.03% (placebo)  
• FEMALES: 30% (intervention) and 36.97% (placebo)
• CURRENT TREATMENT: Combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Nasopharyngeal carcinoma

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: China

PHASE OF CARE: Active anti-tumor treatment

RCT. Patients age 18-70 years with locally advanced nasopharygeal carcinoma randomly assigned to receive Shaunghaubaihe tablets or a placebo, starting at the initiation of chemoradiation.

The incidence of different stages of mucositis was compared using Fisher’s exact test and the 95% confidence intervals. The Kaplan-Meier method was used to estimate the median time of the occurrence of OM (latency). To compare latency, the Cox proportional hazard model was used for hazard ratio (HR) and 95% CI values. One-way ANOVA and Fisher’s exact were used to compare toxicities and secondary efficacy endpoints. All data was analyzed using SAS, version 9.2, software.

Shaunghaubaihe tablets significantly reduced the incidence, latency, and severity of oral mucositis in patients with nasopharyngeal cancer.

Two patients from placebo and eight from treatment arm did not complete the entire course of radiation therapy. This is an initial study and further clinical study is needed to evaluate and verify therapeutic effects.

Therapeutic agents that prevent oral mucositis are needed because systemic oral care alone is insufficient.

To estimate the efficacy of traditional Chinese medicine (Chining decoction, CHIN) for radiation-induced oral mucositis in patients with head and neck cancer.

70 consecutive patients were randomly assigned to receive CHIN (treatment group) or recombinant human epidermal growth factor (rhEGF) spray (control group) at a 1:1 ratio in the period between May 2014 to December 2015. CHIN was administered to treatment group from the first day of radiotherapy until the completion of radiotherapy. Simultaneously, the rhEGF spray was administered to control group on the oral mucosa of the irradiated area. The clinical benefit was determined by gradation of mucositis (Common Terminology Criteria for Adverse Events, version 4.0), oral pain, and xerostomia (visual analysis scale) for each week during radiotherapy. Body mass index was evaluated before and after radiotherapy.

• N = 70   
• AGE: 17-76
• MALES: 76%  
• FEMALES: 24%
• CURRENT TREATMENT: Radiation
• KEY DISEASE CHARACTERISTICS: Head and neck cancer
• OTHER KEY SAMPLE CHARACTERISTICS: No history of oral ulcer and salivary gland diseases, No history of anti-tumor therapies.

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: China

PHASE OF CARE: Active anti-tumor treatment

Prospective control randomized trial

• The National Cancer Institute Common Toxicity Criteria Oral Mucositis Scale.
• Oral pain and xerostomia were assessed by the patients with the visual analysis scale (VAS).
• Body mass index (BMI) was used to assess the nutritional status of patients before and after treatment.

• Patients in the treatment group had prominent remission of oral pain and grade of mucositis on each observing point compared with those in control group (p < 0.01).
• Xerostomia was decreased notably in treatment group compared with control group (p < 0.01).
• The degrees of OM in the treatment group were 1.57 (SD = 0.51) versus 2.49 (SD = 0.7) in the control group (p < 0.01).

CHIN presented an obvious advantage in preventing radiation-induced oral mucositis compared with rhEGF spray.

• Small sample (< 100)
• Risk of bias (no control group)

To test the effectiveness of four natural compounds (propolis, aloe vera, calendula, and chamomile) in the prevention of acute mucositis during chemoradiotherapy for head and neck cancer.

The patients were randomized to receive a mixture of the natural ingredients or placebo. All patients received dental and nutritional evaluations and were allowed to use standard supportive care such as baking soda mouth rinses, NSAIDs, opioids, and IV hydration. The placebo had the same volume, color, flavor, and density as the experimental solution. The pharmacist who dispensed the study drugs managed the randomization list. Patients were instructed to rinse with 7 ml four times per day (before each meal and RT) during weekdays and before each meal (three times per day) on weekends. Weekly interviews were conducted along with a physical examination, including visual inspection of the oral cavity and the oropharynx, by a nurse and a radiation oncologist. Body weight, objective mucositis, pain control, and dysphagia were assessed during these visits.

• N = 104   
• AGE: median = 57 years
• MALES (%): 86.45  
• FEMALES (%): 13.55
• CURRENT TREATMENT: Combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Head and neck
• OTHER KEY SAMPLE CHARACTERISTICS: Squamous cell carcinoma of the oral cavity, pharynx, or larynx. Squamous cell carcinoma in the neck of unknown primary. Previously untreated with chemotherapy or radiation therapy for head and neck cancer, good oral intake with no feeding tubes (NG or PEG) at study entry, and ECOG 0-1.

• SITE: Single site   
• SETTING TYPE: Not specified    
• LOCATION: Regina Elena National Cancer Institute, Rome, Italy

PHASE OF CARE: Active anti-tumor treatment

Phase III double-blind randomized placebo controlled; 1:1 experimental versus control

CTCAE, version 3.0, was used for grading mucositis. The Verbal Descriptor Scale was used for assessing pain. Locoregional control and OS were computed with the Kaplan-Meier method from the last day of treatment and comparison was done with the log-rank test (These were included in the secondary endpoints of the study).

No difference was noted between arms.

The prophylactic use of the natural agent combination, propolis, aloe vera, calendula, and chamomile, did not show a benefit versus placebo in the prevention of oral mucositis for patients with head and neck cancer receiving chemoradiotherapy.

This was a well-conducted single-site clinical trial.

Use of natural ingredients for supportive care in oncology is usually preferable to more expensive, hard to access pharmacologic interventions. However, if the evidence does not support their use, even natural ingredients should not be used due to potential increase costs and untoward effects. Nurses play an important role in patient and HCP education about evidence-based interventions.

To evaluate the effect and toleration of transmucosal opioid for painful mucositis affecting swallowing.

Retrospective medical chart review was done for data collection for individuals who had opioid maintenance and received fentanyl pectin nasal spray for incidental mucositis pain. Results in patients were compared at different time points when they did and did not use fentanyl pectin nasal spray for incidental breakthrough pain.

• N: 40   
• AGE: Mean age = 64.08 years, range = 36-80
• MALES: 70%  
• FEMALES: 30%
• CURRENT TREATMENT: Radiation, combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Head and neck cancer, orophyarynx most common site

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Spain

PHASE OF CARE: Active anti-tumor treatment

Retrospective observational

• Oral intake
• Prevalence of breakthrough pain
• Numeric rating scale for pain intensity

After implementation of transmucosal opioid for incidental pain, oral intake improved (p = 0.000). With use of fentanyl pectin nasal spray, intensity of breakthrough pain episodes went from 5.73 (SD = 1.54) to 2.25 (SD = 2.45).

Transmucosal opioids may be helpful in managing incidental pain associated with mucositis, and may facilitate oral nutritional intake.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement/methods not well described

Due to rapid onset, transmucosal opioid use for incidental pain that interferes with swallowing and oral intake in patients with head and neck cancer may be of benefit. Further well-designed research in this area is warranted.

To compare the efficacy of benzydamine HCl with sodium bicarbonate in the prevention of concurrent chemo rt-induced OM in patients with head and neck cancer.

Sixty locally advanced patients with head and neck cancer treated with high-dose RT concurrently with platinum-based chemotherapy were randomly assigned to receive either benzydamine HCl or sodium bicarbonate from the first day of treatment to two weeks after completion of treatment.

• N: 60   
• AGE: 18-70 years
• MALES (%): 24 and 23  
• FEMALES (%): 6 and 7
• CURRENT TREATMENT: Radiation 
• KEY DISEASE CHARACTERISTICS: Patients with locally advanced head and neck cancer with high-dose radiotherapy and platinum-based chemotherapy 
• OTHER KEY SAMPLE CHARACTERISTICS: Starting similar chemRT regimens; matched

• SITE: Multi-site   
• SETTING TYPE: Outpatient    
• LOCATION: Chiang Mai UH (CMUH), King Chulalongkom Memorial H (KCMH), Siriraj H (SH) and Udonthani Cancer H (UCH)

• PHASE OF CARE: Active anti-tumor treatment
• APPLICATIONS:  Elder care, palliative care

RCT with two intervention groups

Patients were evaluated by the radiation oncologists at baseline before CCRT, weekly during CCRT, at the end of CCRT, and at four weeks after CCRT. The Oral Mucositis Assessment Scale (OMAS) was used to assess severity of mucositis. Ulceration score was 0 for no lesion, 1 for lesion less than 1 cm², 2 for lesion 1–3 cm², and 3 for lesion more than 3 cm². Erythema score was 0 for no lesion, 1 for mild to moderate erythema, and 3 for severe erythema. Pain score (0–10), all prescribed medications including analgesic, artificial saliva supplement, and anti-infection medications, the need for hospitalization, treatment interruption, and the addition of nutritional support or feeding tube were also recorded. Oral candidiasis assessment was based on the physical examination of pseudomembranous lesions or angular cheilitis in centers except at CMUH center where confirmation by microscopic identification of Candida was used.

Prophylaxis rinsing with benzydamine HCl can be more effective in reducing severity of OM induced by CCRT, when compared to basic care with sodium bicarbonate mouthwash. Median of OMAS scores at weekly assessment during CCRT was lower in benzydamine HCl group compared to control. In both groups, maximum of third quartile of OMAS scores around fifth to seventh week of CCRT. Scores decreased at four weeks after CCRT. Statistically, median for OMAS scores was significantly lower in study group at every week between second and eighth week of CCRT. The corresponding p values for those weeks in chronological order were 0.003, < 0.001, < 0.001, < 0.001, < 0.001, 0.01, and 0.04. Maximum of third quartile of OMAS scores to be around fifth to sixth week in both groups. Maximum OMAS score across whole period of CCRT in benzydamine HCl group was 25, lower than maximum of 37 in sodium bicarbonate group. No significant difference in median of pain scores between two groups during CCRT and at follow-up. Corresponding p values from second to eighth week were 0.88, 0.59, 0.96, 0.73, 0.63, 0.92, and 0.15 and p value at follow-up after CCRT was 0.8. Maximum of third quartile of pain scores at seventh week of CCRT in study group and eighth week in control group. Maximum pain score across period of CCRT was 10 in both groups. Four weeks after CCRT, median of pain score decreased to 2 in both groups. Poor compliance was defined as patients in postoperative CCRT group and in definitive CCRT group who received weekly chemotherapy less than 3 cycles and 4 cycles, respectively. More patients with poor compliance in control group than in study group (i.e., 13 patients versus 10 patients). No differences were found between the two groups. Most patients in both groups need analgesic drugs; 89% in control group and 90% in study group, p value = 1. The most common analgesic drugs used were opioids (syrup morphine/morphine sulfate tablet; MST/morphine sulfate sustain released; kapanol^®), prescribed usage rates were 48% in control group and 33% in study group. For antifungal agents, none in benzydamine HCl group needed them, whereas 19% of patients in sodium bicarbonate group required nystatin oral suspension or clotrimazole tablet. Rate of feeding tube placement was same in both groups during CCRT (i.e., 24 and 22% in the study group and the control group, respectively). Oral retention and compliance for mouthwash products were better in sodium bicarbonate arm than in benzydamine HCl arm. Four patients (6.75%) in study arm could not tolerate full dose of benzydamine HCl due to burning and stinging sensation. For these patients, mouthwash was diluted at 1:1 with water.

Prophylaxis oral rinsing with benzydamine HCl for patients undergoing high-dose radiotherapy concurrently with platinum-based chemotherapy was superior to sodium bicarbonate mouthwash in terms of alleviating the severity of oral mucositis and encouraging trend for reducing the need of oral antifungal agents use.

• Small sample (< 100)
• Other limitations/explanation: Small study with limitations in descriptive measurement.

Review prophylaxis and acute treatment protocol practices.

The aim of this study was to evaluate the effect of photobiomodulation (PBM) in reducing the incidence and severity of OM in patients undergoing HSCT, comparing two protocols that differ only in session frequency, either daily or three times a week.

PBM applied three times per week versus seven times per week in patients undergoing HSCT

• Patients received three PBM sessions weekly (on Monday, Wednesday, and Friday). PBM was applied using a continuous-wave diode laser (0.24 J total radiant energy per point, 33 points)
• Patients received daily PBM sessions. PBM was applied using the same continuous-wave diode laser at the same settings used for group I (0.24J total radiant energy per point, 33 points)
• There is a slight difference in the power outage of each intervention as well as exposure time.

• N = 99
• AGE: 13 to 71 years
• MALES: 51.5%
• FEMALES: 48.5%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: OM
• OTHER KEY SAMPLE CHARACTERISTICS: Allogeneic HSCT, autologous HSCT

• SITE: Single site    
• SETTING TYPE: Inpatient  (not specifically  identified)
• LOCATION: Porto Alegre Clinical Hospital

• PHASE OF CARE: Active anti-tumor treatment
• APPLICATIONS:  Pediatrics, elder care, palliative care

A retrospective study was to evaluate the preventive effect of PBM applied three times per week versus seven times per week in patients undergoing HSCT.

Differences between groups were evaluated using the chi-square test or Fischer’s exact test for qualitative data and the Mann-Whitney test for quantitative data. Receiver operating characteristic (ROC) curves were constructed to analyze the sensitivity and specificity of quantitative risk factors in predicting the presence or absence of OM. The area under the curve is a measure of test accuracy. The SPSS for Windows software package, version 18.0, was used to perform these statistical analyses. Two-way analysis of variance (ANOVA) was used to compare OM average between groups, and the t test was used to compare the average OM at each point.

PBM was effective in preventing OM in patients undergoing HSCT even when it was applied three times a week. Both PBM protocols were equally efficient in preventing OM (p = 0.34, ANOVA). 

Independent of the PBM protocol used, patients who received allogeneic transplant (p < 0.01, Fischer’s exact test), total body irradiation (TBI, 12 Gy) (p = 0.01, chi-square test), busulfan plus cyclophosphamide (p < 0.01, chi-square test), or methotrexate-containing regimens (p < 0.01, Fischer’s exact test) demonstrated higher OM incidence and severity. Myelosuppression (p < 0.01, Mann-Whitney test) and impaired renal function (p = 0.02, Mann-Whitney test) were also considered risk factors for OM.

The study indicates that PBM is effective in preventing OM in patients undergoing HSCT even when administered three times a week.

• Small sample (< 100)
• Intervention expensive, impractical, or training needs (The cost of bringing in a professional or asking the patient to go to a dental office was a hindrance.)
• Other limitations/explanation: Retrospective nature of the study. Allo versus auto transplant regimens are different treatment paths especially the chemotherapy regimens that could influence toxicities.

OM is frequently seen side effect of patients receiving HSCT, these lesions impact patient quality of life, controlling this condition is extremely important, and developing effective interventions is a high priority in protocol support among patients with cancer.