Low level laser therapy (LLLT) involves the use of a handheld infrared laser in an attempt to affect cells and physical symptoms often related to inflammation. This therapy has been approved by the U.S. Food and Drug Administration for treatment of post-mastectomy lymphedema. LLLT has also been evaluated for the prevention and treatment of mucositis in patients receiving stem cell transplantation conditioning or radiation therapy to the oral cavity area. For mucositis, LLLT is defined as a wavelength at 650 nm, power of 40 mW, and each square centimeter treated with sufficient time to deliver a tissue energy dose of 2 J/cm2.
Lalla, R.V., Bowen, J., Barasch, A., Elting, L, Epstein, J., Keefe, D.M., . . . Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology. (2014). MASCC/ISOO evidence based clinical practice guidelines for mucositis secondary to cancer therapy. Cancer, 120, 1453–1461. doi:10.1002/cncr.28592
Oberoi, S., Zamperlini-Netto, G., Beyene, J., Treister, N. S., & Sung, L. (2014). Effect of prophylactic low level laser therapy on oral mucositis: A systematic review and meta-analysis. PloS One, 9, e107418.
PHASE OF CARE: Active antitumor treatment
APPLICATIONS: Pediatrics, elder care
The primary outcome (overall severity of oral mucositis) of this analysis was that prophylactic LLLT reduced the overall risk of severe mucositis when compared to a placebo or no therapy (RR = .37, 95%, CI = .18–.67, p = .001). The absolute risk reduction was -.35 (95%, CI = -.48– -.2, p < .0001). Secondary outcomes included a decreased risk of severe mucositis at the time of expected worst severity with prophylactic LLLT (RR = .34, 95%, CI = .20–.59, p = .0001). Overall mean grade of mucositis: standardized mean difference = -1.49, 95%, CI = -2– -.95;=, p < .0001. Duration of severe (grade 3 or 4) mucositis: weighted mean difference = -5.32, 95%, CI = -9.45– -1.19, p = .01. Incidence of pain: RR = .89, 95%, CI = .76–1.04, p = .15. Incidence of severe pain: RR = .26, 95%, CI = .18–.37, p < .0001. Overall mean pain score: WMD = -2.46, 95%, CI = -4.4– -.77, p = .004. Number of patients needing opioid analgesia: RR = .47, 95%, CI = .37–.60, p < .0001. Unplanned interruption in radiation (from mucositis in patients with head and neck cancer): RR = .23, 95%, CI = .12–.44, p < .0001.
The overall risk of severe mucositis is decreased by the use of low-level laser therapy. The duration of mucositis, the risk of severe pain, the need for opioid analgesia, and radiation treatment interruption also is positively impacted by LLLT.
There is heterogeneity to the laser schedules, mucositis assessment scales, laser parameters, intervals, and time points for assessment and outcome reporting (per the authors). It is difficult to generalize this study to the pediatric population. The feasibility of using laser therapy continues to be an issue in nursing.
Prophylactic LLLT shows benefit in the prevention of oral mucositis. Additional research to delineate the feasibility of this intervention and define best practice is needed.
Antunes, H.S., Ferreira, E.M., de Matos, V.D., Pinheiro, C.T., & Ferreira, C.G. (2008). The impact of low power laser in the treatment of conditioning-induced oral mucositis: A report of 11 clinical cases and their review. Medicina Oral, Patología Oral y Cirugía Bucal, 13(3), 189–192.
Low-power laser therapy (LPLT) versus placebo
Only dentists knew the randomization.
Low level intensity laser: InGaAIP diode laser—660 nm, 46.7 mW
Oral care: Extrasoft toothbrushes; dental paste with a peroxidase system after meals, and alcohol-free chlorhexidine solution until neutrophil recovery TID
Evaluations were performed daily by one dentist (not blinded) and three nurses (blinded).
Crossover allowed for control group patients who developed grade 4 oral mucositis.
The sample was comprised of 38 patients with HSCT.
Adults M =36.5/36.8
Women = 7/8
Men = 12/11
Autologous HSCT = 5/5
Allogenic HSCT = 14/14
Centro de Transplante de Medula Ossea
January 2004-May 2005
Randomized, placebo-controlled, quantity and prospective clinical trial
All patients completed the study; none were lost to follow-up or excluded.
LPLT less intense oral mucositis
Grade 0 = 1, 63.2%, 12 of 19 versus 10.5%, 2 of 19 (p < 0.001)
6 LPLT, 31.5% WHO Grade 2
94.7% WHO 0–2
Control group was the opposite (data not provided) (p < 0.001).
Mucositis-free survival hazard ration grade 2, 3, and 4 was 0.41 (p = 0.002); the hazard ration grade for grade 3 and 4 was 0.07.
OMAS = 84.2% (16) patients receiving laser treatment stayed on a weighted average zone of 0–2.9 versus 26.3% (5) (p = 0.007).
Patients receiving laser treatment presented with small extension of ulcerous area (p = 0.003).
Control group showed mucositis earlier (D + 5) than laser group (D + 6) (p = 0.67, NS).
Longer duration 6 versus 9 (p = 0.13, NS)
Longer to heal (p = 0.15)
No differences in presence and intensity of pain
No differences in blood cultures
The level of agreement among evaluators was 81.7%.
Implies difference when p value is not significant
Narrative frequently does not match p values.
Cruz, L.B., Ribeiro, A.S., Rech, A., Rosa, L.G., Castro, C.G., & Brunetto, A.L. (2007). Influence of low-energy laser in the prevention of oral mucositis in children with cancer receiving chemotherapy. Pediatric Blood and Cancer, 48(4), 435–440.
780 nm 60 mW 4 J/cm2 was applied uniformly to five areas of the oral cavity for five consecutive days from initiation of chemotherapy.
The sample was pediatric patients (some with HSCT) receiving a variety of chemotherapies.
Laser group: n = 29
Control group: n = 31
The study ran from May 2003-February 2005.
RCT was the study design.
Nutritional Status Assessment
Day 8 results: 13 patients in the laser group and 7 patients in the control group with mucositis; median grade of mucositis was 2 for the laser group and 1 for the control group (p = 0.234)
Day 15 results: 13 patients in the laser group and 11 patients in the control group with mucositis; median grade of mucositis was 1 in both groups; prevalence and severity were similar (p = 0.208)
Almost identical prevalence of mucositis and other findings; no evidence to support laser for prevention
Rigorous oral care may have masked results.
Optimal timing of laser treatment is unknown.
Jaguar, G.C., Prado, J.D., Nishimoto, I.N., Pinheiro, M.C., deCastro, D.O., Jr., da Cruz Perez, D.E., et al. (2007). Low-energy laser therapy for prevention of oral mucositis in hematopoietic stem cell transplantation. Oral Diseases, 13(6), 538–543.
Prophylactic laser treatment was administered daily from beginning of conditioning regimen to two days after stem cell transplantation.
Patients received gallium aluminum arsenate diode laser therapy on four anatomic sites of the oral mucosa.
660 nm 10 mW 2.5 J/cm2 was administered. Each anatomic site was illuminated for 10 seconds per point.
Patients with HSCT from Brazil aged 17-62 years
Historical control group (1999–2000): n = 25
Laser group: n = 24
The study occurred from January 2003-September 2004.
Administration of morphine
Time of parenteral nutrition
Incidence of mucositis was the same in both groups.
Percentage of grade 2, 3, and 4 mucositis was less in laser group, not SS (p = 0.12). The laser group took longer to develop grade 1 (4.36 versus 6.12 days [p = 0.01], had fewer days of pain (5.64 versus 2.45 [p = 0.04], and had fewer patients who required morphine (10 versus 4 [p = 0.07].
Limited sample size and methodology
Number of patients with grade 3–4 may have been SS with larger sample.
Khouri, V.Y., Stracieri, A.B., Rodrigues, M.C., Moraes, D.A., Pieroni, F., Simoes, B.P., & Voltarelli, J.C. (2009). Use of therapeutic laser for prevention and treatment of oral mucositis. Brazilian Dental Journal, 20(3), 215–220.
To evaluate the frequency and evolution of oral mucositis (OM) among stem cell transplant recipients subjected to therapeutic laser versus mucositis formula
Patients (n = 22) were randomly assigned to control or low level laser therapy (LLLT) daily. The treatment phase for both groups began with the initial clinical manifestations of mucositis with follow up until day +15 after transplant. Two types of laser were used on alternate days, one indicated for tissue repair and the other for analgesia.
This was a single-site conducted in the bone marrow transplant unit (BMTU) of the University Hospital School of Medicine of Ribeirao Preto (UHSMRP) at the University of São Paulo in Brazil.
The study was a randomized controlled trial.
The laser treatment group had lower frequency of oral mucositis (p = 0.02) and a lower mean grade of mucositis (p < 0.01).
The inclusion of LLLT was effective in lowering the frequency and treating oral mucositis in patients being treated with high dose myeloablative chemotherapy in preparation for stem cell transplant.
Laser therapy is effective in the treatment of mucositis, but it is very high tech and requires special equipment and highly trained personnel.
Kuhn, A., Porto, F.A., Miraglia, P., & Brunetto, A.L. (2009). Low-level infrared laser therapy in chemotherapy-induced oral mucositis: A randomized placebo-controlled trial in children. Journal of Pediatric Hematology/Oncology, 31, 33–37.
To evaluate the efficacy of low level laser therapy (LLLT) for the treatment of chemotherapy-induced oral mucositis (OM) in pediatric patients undergoing chemotherapy or stem cell transplant
Children and adolescents with cancer receiving chemotherapy or hematopoietic stem cell transplantation (HSCT) who developed grade II OM were included. OM was scored daily by the same investigator. In the experimental group, the treatment was applied to each OM lesion for five consecutive days. The control group received sham treatments to each OM lesion for five consecutive days also.
This was a single site, inpatient study conducted in the Pediatric Oncology Unit of the Hospital de Clinicas de Porto Alegre at Federal University of Rio Grande do Sul, Brazil.
The study was a randomized, placebo-controlled trial.
No differences were found in grades of mucositis as a function of the LLLT protocol. Mucositis was diagnosed 5.0 to 7.5 days postchemotherapy. On the seventh day after the diagnosis of mucositis, 1 out of 9 patients in the laser group and 9 out of 12 patients in the sham group had grade II or greater OM (p = 0.029). The mean OM duration in the laser group as compared to the sham group was 3.1 days less (p = 0.004).
LLLT can significantly reduce the duration of chemotherapy-induced OM in children.
Laser therapy is effective in treatment of mucositis, but it is very high tech and requires special equipment and highly trained personnel.
Schubert, M.M., Eduardo, F.P., Guthrie, K.A., Franquin, J., Bensadoun, R.J., Migliorati, C.A., et al. (2007). A phase III randomized double-blind placebo-controlled clinical trial to determine the efficacy of low level laser therapy for the prevention of oral mucositis in patients undergoing hematopoietic cell transplantation. Supportive Care in Cancer, 15(10), 1145–1154.
Low level laser therapy (LLLT) using two different low level GaAIAs diode lasers was administered 650 nm to group I and 780 nm to group II compared to sham treatment in the placebo group (group III) beginning on the first day of conditioning and continuing through two days after HCT.
Assessors and patients were blinded; only the laser therapist knew the treatment type.
Powered for 22 subjects per group
70 patients were treated on protocol.
Group 1: n = 23
Group 2: n = 24
Group 3: n = 24
The median age was 44–48 years (range = 18–69 years).
Autologous versus allogeneic was 17% versus 82% in group I, 9% versus 90% in group 2, and 8% versus 92% in group III.
Randomized, double-blind, placebo-controlled study of patients with HCT
Oral mucositis index OMI and VAS for pain
0, 4, 7, 11, 14, 18, 21
State mean OMI scores varied most at day 11. Scores approached significance (p = 0.06 not significant) when adjusted. Patient-specific average OMI scores for TBI were p = 0.03 (group I) and p = 0.23 (group II).
Two patients died with severe mucositis.
Patients in the placebo group appeared to have suffered more pain than patients in the laser treatment group, particularly group I.
The study demonstrated a tendency for LLLT to reduce severity of mucositis during the second week.
Pain data were incomplete; some patients were too ill to do VAS.
Although randomly assigned, TBI and busulfan/cytoxan were not equally distributed.
Small sample size
Set up as a prevention trial, so treatment only occurred through day 2.
Weissheimer, C., Curra, M., Gregianin, L.J., Daudt, L.E., Wagner, V.P., Martins, M.A.T., & Martins, M.D. (2017). New photobiomodulation protocol prevents oral mucositis in hematopoietic stem cell transplantation recipients--A retrospective study. Lasers in Medical Science, 32, 2013–2021.
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
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.
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.
Lalla, R.V., Bowen, J., Barasch, A., Elting, L., Epstein, J., Keefe, D.M., ... Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO). (2014). MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer, 120, 1453–1461.
570 articles were included in this literature review. Literature contained prevention and/or treatment methods for mucositis. Interventions for treatment of mucositis were given, recommendations against an intervention were provided, suggestions in favor of an intervention were supplied, and suggestions against an intervention were given.
Recommendations included a combination of teeth brushing, flossing, mouth rinsing, and use of growth factors and cytokines in treatment of mucositis. The use of anti-inflammatory agents was also recommended. Low level laser therapy was recommended in prevention of mucositis with specific types of cancer treatment. Cryotherapy was also recommended for patients receiving chemotherapy. A list of natural and miscellaneous agents was recommended for treatment and prevention of mucositis.
Limitations of this study include clinical situations that were not seen in the literature review or that are rare in clinical settings. These limitations occur because of conflicting evidence or not enough evidence provided.
Nurses should be assessing patients' pain control, nutritional support, ability to eat, and oral hygiene practices, and should be teaching on the use of oral care products that are essential for prevention.
Migliorati, C., Hewson, I., Lalla, R. V., Antunes, H.S., Estilo, C.L., Hodgson, B., … Elad, S. (2013). Systematic review of laser and other light therapy for the management of oral mucositis in cancer patients. Supportive Care in Cancer, 21(1), 333–341.
To review available literature to develop guidelines for the use of laser and other light therapies in patients with cancer
A total of 692 papers initially were identified, and 24 clinical trials were included in the final review.
Guidelines support use of LLLT for the prevention of oral mucositis in patients undergoing HCT and in patients with head and neck cancer receiving radiotherapy. The research in this area involves a variety of laser devices, protocols, and dosage, making it difficult to identify a specific protocol for clinical application. The most effective wavelengths and dosages are not yet clear. Most protocols examined have involved daily and long treatment times. Based on accumulating evidence, LLLT or other forms of light therapy have the potential to become part of routine treatment.
Peterson, D.E., Bensadoun, R.J., Roila, F., & ESMO Guidelines Working Group. (2010). Management of oral and gastrointestinal mucositis: ESMO Clinical Practice Guidelines. Annals of Oncology, 21(Suppl. 5), v261–v265.
To summarize the evidence around the use of radiotherapy, standard-dose chemotherapy, and high-dose chemotherapy with or without total body irradiation plus hematopoietic stem cell transplantation (HSCT) for the management of mucositis
The primary author was the principal investigator on the National Institutes of Health (NIH) R13 Conference Grant that provided partial support for the symposium “Oral Complications of Emerging Cancer Therapies,” 14-15 April 2009, Bethesda, MD, USA. Production of a Journal of the National Cancer Institute (JNCI) Monograph for conference publications was supported by an unrestricted educational grant form Biovirum, which owned palifermin at the time of the publication. Peterson also is a member of the Scientific Advisory Board and a paid consultant for the GI Co., Inc, which is responsible for the development of recombinant intestinal trefoil factor, for which the phase II study is cited in the references.
The mucositis guidelines reported contain few changes from the previous two versions of the ESMO Clinical Practice Guidelines. With the 2009 MASCC/ISCO Mucositis Study Group in June 2009, it was decided that no new guidelines were warranted based on the current published literature. Progress has been made in the understanding of molecular basis of mucositis. Evidence-based, cancer-specific identification of risk factors and management of mucositis depend on clinical research so that approval of new drugs and devices will be possible.
Sung, L., Robinson, P., Treister, N., Baggott, T., Gibson, P., Tissing, W., . . . Dupuis, L.L. (2015). Guideline for the prevention of oral and oropharyngeal mucositis in children receiving treatment for cancer or undergoing haematopoietic stem cell transplantation. BMJ Supportive and Palliative Care. Advance online publication.
PHASE OF CARE: Active antitumor treatment
Cryotherapy or low-level laser therapy may be offered to cooperative children receiving chemotherapy or HSCT conditioning with regimens associated with a high rate of mucositis. Keratinocyte growth factor (KGF) may be offered to children receiving HSCT conditioning with regimens associated with a high rate of severe mucositis. However, KGF use merits caution as there was a lack of efficacy and significant toxicity data as well as a lack of long-term follow-up data in pediatric cancers. No other interventions were recommended for oral mucositis prevention in children.
No keywords, inclusion criteria, or exclusion criteria were stated in the article.
Although some information was missing in this study, the decision making process and results of the evidence review were well-described. The inclusion of a description of research gaps, summarized in a table, showed the comprehensiveness of this review.