Low-level laser therapy (LLLT) involves the use of a hand-held infrared laser in an attempt to affect cells and physical symptoms often related to inflammation. The therapy has been approved by the Food and Drug Administration for treatment of post-mastectomy lymphedema. LLLT has also been evaluated for prevention and treatment of mucositis.
Clarkson, J.E., Worthington, H.V., Furness, S., McCabe, M., Khalid, T., & Meyer, S. (2010). Interventions for treating oral mucositis for patients with cancer receiving treatment. Cochrane Database of Systematic Reviews, 8, CD001973.
To assess the effectiveness of interventions for treatment of oral mucositis or its associated pain for patients receiving chemotherapy or radiation therapy
Databases searched were MEDLINE, CancerLIT, EMBASE, CINAHL, LILACS (Latin American and Caribbean Health Sciences Literature), Cochrane Oral Health Group and PaPaS Trials Registers, Cochrane Central Register of Controlled Trials (CENTRAL), OpenSIGLE, and Current Controlled Trials. Handsearching carried out by the Cochrane Collaboration was included. Reference lists from relevant articles were searched and the authors of eligible trials were contacted to identify trials and obtain additional information.
Search keywords were (neoplasm* OR leukemia OR leukaemia OR lymphoma* OR plasmacytoma OR “histiocytosis malignant” OR reticuloendotherliosis OR “sarcoma mast cell” OR “LettererSiwe disease” OR “immunoproliferative small intestine disease” OR “Hodkin disease” OR “bone marrow transplant*” OR cancer* OR tumor* OR malignan* OR netropeni* OR carino* or Adenocarcinoma* OR radioth* OR radiat* OR radiochemo* OR irradiat* OR chemo*) AND (stomatitis OR “Stevnes Johnson syndrome” OR “candidiasis oral” OR mucositis OR (oral AND (cand* OR mucos* OR fung*)) OR mycosis OR mycotic OR thrush. Extensive appendices are provided with specific search strategies used for each database.
Studies were included in the review if they
The final assessment incorporated 32 studies. Out of an initial 95 eligible studies, 64 were excluded because of study design issues, protocol violations, lack of useable data, or no relevant outcomes.
Treatment of mucositis
Summary of data from single trials showed the following interventions to demonstrate statistically significant benefit (p < 0.05).
Other interventions for treatment of mucositis evaluated included chlorhexadine versus salt and soda, Gelclair verus sucralfate and mucaine,”Magic” mouthwash versus salt and soda, sucralfate versus placebo and versus salt and soda, and tetrachlorodecaoxide.
Management of pain with mucositis
The following interventions demonstrated statistically significant benefit in managing pain (p < 0.05).
The lack of independent duplication of studies investigating the same intervention limits the strength of evidence and ability to generalize results.
Most studies reviewed had small sample sizes and may have been underpowered to demonstrate significant differences in outcomes.
Different scoring systems for mucositis were used, and, in some studies, the method of scoring was not defined.
The need for further well-designed trials to evaluate the effectiveness of interventions continues.
Adoption of standard clinical outcome measures should be considered, including patient-based measures and inclusion of the cost of interventions.
Fekrazad, R., & Chiniforush, N. (2014). Oral mucositis prevention and management by therapeutic laser in head and neck cancers. Journal of Lasers in Medical Sciences, 5, 1–7.
STUDY PURPOSE: To assess the effect of low level laser therapy (LLLT) for oral mucositis
TYPE OF STUDY: Systematic review
PHASE OF CARE: Active antitumor treatment
Most evidence showed a positive effect of LLLT on oral mucositis in delayed time of onset, lower peak severity, and shortened duration. One study in children showed no benefit of LLLT when optimal dental and oral care were provided.
LLLT is beneficial for the management of oral mucositis; however, ideal wavelengths, timing, and frequency of treatment are unclear.
LLLT has been shown to be effective in reducing the symptoms of oral mucositis in patients undergoing transplantation and those receiving treatment for head and neck cancer. The specifics for optimal LLLT timing, duration, and so forth have not been determined. Further research on these aspects is needed.
Qutob, A.F., Gue, S., Revesz, T., Logan, R.M., & Keefe, D. (2013). Prevention of oral mucositis in children receiving cancer therapy: A systematic review and evidence-based analysis. Oral Oncology, 49, 102–107.
To investigate, critically appraise, and rate the evidence regarding agents used for the prevention of mucositis in children
Databases searched included CINAHL, Cochrane library, Ovid MEDLINE, PubMed, BioMed Central, and other internet-based sources. A total of 19 databases were searched.
Search keywords were mucositis, stomatitis, oral inflammation, mouth mucosal inflammation, prophylaxis, management, and prevent; in addition to keywords to identify children and all types of cancer therapy.
Studies were included in the search if they
Studies were excluded if they
The authors concluded that oral care protocols should be used; oral sucralfate suspension, prostaglandin E2, and GM-CSF mouthwash should not be considered based on current evidence; and chlorhexidine (without use as part of an oral care protocol), laser therapy, and glutamine should not be considered because of conflicting evidence.
Findings provide further support for use of oral care protocols. Results provided no other useful recommendations for preventive therapies but identified the need for further research in this area.
Worthington, H.V., Clarkson, J.E., Bryan, G., Furness, S., Glenny, A.M., Littlewood, A., … Khalid, T. (2011). Interventions for preventing oral mucositis for patients with cancer receiving treatment. Cochrane Database of Systematic Reviews (Online), 4(4), CD000978.
To evaluate the evidence for prophylactic agents in management of oral mucositis in patients with cancer receiving treatment
Databases searched were MEDLINE, CANCERLIT, Embase, CINAHL, Latin American and Caribbean Health Sciences Literature (LILACS), System for Information on Grey Literature in Europe (SIGLE), and the Cochrane Database.
An extensive list of search terms and strategies used per database was provided in the article.
Studies were included in the review if they
A total of 383 references were retrieved. Risk of bias was evaluated according to the Cochrane Handbook for Systematic Reviews of Interventions. Studies were categorized as low, unclear, or high risk of bias. Studies were labeled using the GRADES system for evaluating quality of evidence.
Findings support the benefits of cryotherapy and keratinocyte growth factor. The low quality of evidence in most of the other interventions points to the need for ongoing, well-designed research in this area. The presentation of findings in many publications made meta-analysis impossible.
The rationale for the authors' summaries of findings was not entirely clear. Similar RR ratio results with similar evidence quality levels were identified differently in terms of potential benefit. Although the review was inclusive and extensive, interpretation of results was inconsistent. High heterogeneity existed in most interventions, and most studies were either at high or unclear risk of bias with low GRADES scoring. Studies did not always differentiate between mucositis and candidiasis, which would affect recommendations.
This article suggests strong support for use of cryotherapy and keratinocyte growth factor for mucositis prevention. It suggests possible benefit from aloe vera, amifostine, IV glutamine, G-CSF, honey, laser, and antibiotic lozenges. Sucralfate may reduce the severity of mucositis. These findings should be interpreted with caution, given the relatively low quality of overall evidence and high heterogeneity across studies included in meta-analysis, as well as the fact that treatments and sample characteristics were highly varied.
Amadori, F., Bardellini, E., Conti, G., Pedrini, N., Schumacher, R.F., & Majorana, A. (2016). Low-level laser therapy for treatment of chemotherapy-induced oral mucositis in childhood: A randomized double-blind controlled study. Lasers in Medical Science, 31, 1231–1236.
To evaluate the efficacy of low-level laser therapy (LLLT) to reduce the severity of chemotherapy-related oral mucositis in children
Patients were randomized to receive LLLT or sham control interventions. Therapy began on day 1 of diagnosis of oral mucositis and was continued daily for the next three days. Study assessments were done immediately before beginning laser therapy, on day 4 after completion of laser therapy, and on day 7. Individuals who applied the laser treatment were not involved in mucositis data collection.
Progressive decline in mucositis severity occurred in both groups, and no significant difference in grading existed between groups. Pain scores were lower in those treated with laser therapy (p < 0.05), and those getting LLLT required less analgesia.
The findings suggested that LLLT may help the management of pain from oral mucositis among children receiving chemotherapy.
The findings did not show the efficacy of LLLT among children to reduce the severity of oral mucositis. Further well-designed research is needed to determine if a role exists for LLLT in children receiving chemotherapy.
Arbabi-Kalati, F., Arbabi-Kalati, F., & Moridi, T. (2013). Evaluation of the effect of low level laser on prevention of chemotherapy-induced mucositis. Acta Medica Iranica, 51, 157–162.
To evaluate the efficacy of low-level laser therapy for prevention of chemotherapy-induced mucositis and xerostomia
Patients were randomized to receive the laser or sham procedure. The laser group had laser therapy prior to each episode of chemotherapy with a 630-nm laser with a dose of 5 J/cm2. Patients in the sham control group underwent procedures with the laser unit turned off. All patients received the same instruction for ongoing oral care and underwent mucous and salivary health assessment by an oral medicine specialist prior to beginning chemotherapy, after two weeks, and then every two weeks until the end of chemotherapy treatment. Severity of pain, mucositis, and xerostomia was assessed at these times, and observers were blinded to patients’ study group assignments. Data were collected for 14 weeks.
This was a single-site, outpatient study conducted in Iran.
Patients were undergoing the active antitumor treatment phase of care.
This was a randomized, double-blind, sham-controlled study.
In the laser group, over the course of the study, 8.3% of patients experienced grade 2 mucositis and none experienced a higher grade of mucositis, compared to 91.6% of patients in the control group who developed grade 2 or higher mucositis (p = 0.001). By week two, xerostomia intensity was significantly lower in the laser group than the control group (p < 0.005). Across all time points, pain intensity in the laser group was significantly lower (p = 0.001). Difference in pain was substantial, with a mean of 0.7 in the laser group compared to 6.8 in the control group at week 2. The magnitude of these differences in pain intensity was large at all study assessment times.
Findings showed that provision of low-level laser treatment was effective in preventing chemotherapy-induced mucositis, xerostomia, and associated pain.
The results here support the effectiveness of low-level laser treatment for prevention of chemotherapy-induced mucositis. The actual number of laser treatments given was not clear. One of the difficulties in evaluating laser evidence for prevention of mucositis is the different treatment schedules and doses used in the research. Further research to identify the most effective laser dosages and schedules would be helpful to facilitate clinical translation of this evidence.
Cauwels, R.G., & Martens, L.C. (2011). Low level laser therapy in oral mucositis: A pilot study. European Archives of Paediatric Dentistry, 12, 118–123.
To study the capacity of pain relief and wound healing of low-level laser therapy (LLLT) in chemotherapy-induced oral mucositis in a pediatric population
Children were treated using a GaAIAs diode laser with 830 nm continuous wavelength an output of 150 mW. Laser was applied every 48 hours until complete healing of the lesion occurred.
The study was conducted at a single site in Belgium.
The study used a convenience sample.
Fifty episodes of oral mucositis were included. Pain scores improved after each session with only one exception.
The LLLT appeared to be effective for pain relief in this population.
de Castro, J.F., Abreu, E.G., Correia, A.V., Brasil, C.D., da Cruz Perez, D.E., & Pedrosa, F.D. (2013). Low-level laser in prevention and treatment of oral mucositis in pediatric patients with acute lymphoblastic leukemia. Photomedicine and Laser Surgery, 31, 613–618.
To evaluate the influence of low-level laser therapy (LLLT) on the prevention and treatment of oral mucositis (OM)
Patients were distributed by convenience sampling into two groups (A and B) based on the order in which they were hospitalized. Group A was composed of patients who received preventive laser (red or infrared subgroups A1 [n = 10] and A2 [n = 10], respectively) for five days, beginning on the first day of chemotherapy. Group B was composed of patients who did not receive any preventive intervention, and those who developed post-chemotherapy mucositis were subjected to therapeutic laser (red or infrared subgroups B1 [n = 10] and B2 [n = 10]) until full remission of the lesions.
The patients were distributed by convenience sampling into two groups (A and B) based on the order in which they were hospitalized. Group A received preventive laser, and Group B received therapeutic laser.
Evaluations were done by daily use of the World Health Organization (WHO) scale grade 0–IV, and patient self-assessed pain was measured by means of the visual analog scale (VAS) (0–10). This assessment was made before each LLLT session.
The overall incidence of OM was 57.5% up to the age of 8 years; the degree of mucositis was significantly higher than that observed among patients older than 8 years. Generally in group A, 40% of patients developed OM, and in Group B, 75% of patients developed OM. In subgroup A1, 30% had mucositis, and in subgroup A2, 50% had mucositis. In subgroup B1, 70% had mucositis, and in subgroup B2, 80% had mucositis. In both groups, 75% did not develop pain symptoms. The Mann-Whitney test showed that there were statistically significant differences between the type of laser with the number of days with pain and severity of mucositis.
This study validates that there are positive results with the use of LLLT in reducing the incidence and severity of OM in patients undergoing anticancer treatment. The study confirmed that there is a reduction in the average duration of OM that occurred in both groups.
Among the pediatric population receiving consolidation chemotherapy with methoexate, the study showed that prophylactic laser (with red laser 660nm) produced a better outcome than when patients did not receive any preventive intervention for OM. For nursing, this is another option to help reduce the severity and duration of OM. It is likely that nurses would need to work in a multidisciplinary setting to provide the patient population with this intervention. The study does not provide information about the professional who is trained and able to provide the LLLT.
Freitas, A.C., Campos, L., Brandao, T.B., Cristofaro, M., Eduardo Fde, P., Luiz, A.C., ... Simoes, A. (2014). Chemotherapy-induced oral mucositis: Effect of LED and laser phototherapy treatment protocols. Photomedicine and Laser Surgery, 32, 81–87.
A prospective study to compare the effect of an established laser therapy protocol with a potential therapy utilizing LED (light-emitting diode) on chemotherapy-induced oral mucositis
Both therapies analyzed in this study were efficient in preventing breaks in treatment.
LED phototherapy may be a viable alternative to traditional laser therapy to treat oral mucositis. This study, however, is small and has several flaws. Nurses should educate patients on proper oral hygiene to be used in combination with LED and laser therapy to promote optimal healing.
Genot-Klastersky, M.T., Klastersky, J., Awada, F., Awada, A., Crombez, P., Martinez, M.D., et al. (2008). The use of low-energy laser (LEL) for the prevention of chemotherapy- and/or radiotherapy-induced oral mucositis in cancer patients: Results from two prospective studies. Supportive Care and Cancer, 16(12), 1381–1387.
100 mW laser was delivered to tissues with a 1.2 mm spot size. Treatment areas included inferior and superior lips, right and left cheeks, right and left tongue, palate and velum palate, right and left gums, and tongue frenulum.
Average energy was 2 J/cm2 on all sites, with a calculated mean duration of 33 seconds per site; each treatment lasted six minutes.
(1) Patients with various solid tumors treated with chemotherapy; previous oral mucositis of 2 or higher
26 patients for 90% power
Patients with concomitant RT and those \"expected to be poor compliers to the treatment schedule\" were excluded.
Mean age 51 was years (range = 32–73 years).
20 women; 6 men
(2) Randomized trial for patients with hematologic malignancies who developed mucositis receiving radiochemotherapy prior to HSCT. Therapy started 24 hours after diagnosis of mucositis. Sham laser control was used.
20 patients were needed in each arm for 90% power.
n = 36 (18 patients in each arm)
Grade of mucositis using EORTC scale
Grading was performed by a nurse prior to each treatment session and afterward once a week by an independent blinded professional observer.
All treated areas were examined.
1. 21 of 26 patients were considered to have prevented mucositis (81%, 95% CI = 61%–93%); 4 with no mucositis, and 17 with grade I. Five patients had grade 2 or higher; median duration was 10 days (range = 8–14 days).
2. Grade 3 mucositis was observed in 16 patients in the sham group and in 3 LEL treated patients (p = 0.001). Overall success rate was 15 of 18 (83%, 95% CI = 59%–96%) and 2 of 18 in the control group (11%, 95% CI = 1–35).Time to grade 3 mucositis was calculated (p < 0.0001).
Of 16 patients in the control arm who developed grade 3–4, eight later received laser treatment; regression to grade 1 mucositis was three days in this group and four days in those who did not receive LEL.
Limited sample size, although the prevention trial (1) achieved 90% power.
The heterogeneous population in the prevention trial makes the results difficult to generalize. Oral care and other factors were not reported.
Nes, A.G., & Posso, M.B. (2005). Patients with moderate chemotherapy-induced mucositis: Pain therapy using low intensity lasers. International Nursing Review, 52(1), 68–72.
Laser energy 35 J/cm2 once a day for five days after the development of chemotherapy-induced \"moderate\" mucositis.
Laser has an 830 nm wavelength with a potency of 250 mW.
Each patient was informed of the oral hygiene protocol:
Avoid spicy food acid fruits, alcohol, and food and drinks with high temperature.
Use a soft toothbrush and avoid dental floss.
Only use mouth solution provided by health personnel (3% bicarbonate).
Do not smoke.
The study was conducted March-August 2002.
Thirteen individuals were treated. Convenience sample for chemo-induced mucositis-related pain.
Mucositis was determined using the Brown methodology. Patients determined to have moderate mucositis (score 13-18) were included in the study.
VAS pain scale
Brown methodology for classification of mucositis.
Significantly lower pain (p = 0.007) after each treatment. Average pain reduction was 67%. Pain reduction across the five days of treatment was also significant (p = 0.000).
Authors note that after five days, pain is usually reduced to such an extent not to require further treatment.
Limited sample size, short study – no control
Other factors may have contributed to pain reduction, including normal healing and placebo effect.
Optimal energy level is not determined.
Cost is high, and treatment is not available at most centers.
Main focus of study was on pain .
Oton-Leite, A.F., Silva, G.B., Morais, M.O., Silva, T.A., Leles, C.R., Valadares, M.C., . . . Mendonca, E.F. (2015). Effect of low-level laser therapy on chemoradiotherapy-induced oral mucositis and salivary inflammatory mediators in head and neck cancer patients. Lasers in Surgery and Medicine, 47, 296–305.
To evaluate the effect of low-level laser therapy (LLLT) on the severity of oral mucositis (OM) and the release of salivary molecules (TNF~a, IL-1b, IL6, IL10, TGF-b, EGF< FGF< VEGF< MMP2/TIMP2, and MMP9/TIMP2) during chemoradiation in patients with head and neck cancer
Randomized, double-blinded, placebo-controlled clinical trial
LLLT reduced OM in the experimental group when compared to the control group. This study added to the growing body of literature demonstrating that LLLT is an effective intervention for OM in patients receiving treatment for cancer.
Reducing OM can have a distinct impact on patients' quality of life, pain control, and ability to complete chemoradiation in a timely manner. Nurses have daily interactions with patients to assist them through the completion of therapy. This study contributed to the growing body of literature demonstrating that LLLT is an effective intervention for OM.