Efficacy of low-level laser therapy (LLLT) in the prevention and treatment of radiation-induced oral mucositis
Level of evidence: B
Low-level laser therapy probably reduces incidence and severity of radiation induced mucositis. It may also alleviate mucositis related pain.
A meta-analysis of 14 randomized trials (869 patients) found that low-level laser therapy (LLLT) given during head and neck (chemo)radiotherapy significantly reduced the incidence, severity, and pain of oral mucositis, although standardized protocols are still needed «Shen B, Zhou Y, Wu D, ym. Efficacy of photobiomodulation therapy in the management of oral mucositis in patients with head and neck cancer: A systematic review and meta-analysis of randomized controll»1.
Evidence from Western countries is limited. A small double-blind RCT from Spain showed significantly less mucositis with LLLT compared with controls, without increased side effects «Marín-Conde F, Castellanos-Cosano L, Pachón-Ibañez J, ym. Photobiomodulation with low-level laser therapy reduces oral mucositis caused by head and neck radio-chemotherapy: prospective randomized cont»2. In contrast, the UK-based Phase III LiTEFORM trial did not demonstrate clear benefit, largely due to under-recruitment and limited statistical power «Nugent M, Bryant V, Butcher C, ym. Photobiomodulation in the management of oral mucositis for adult head and neck cancer patients receiving irradiation: the LiTEFORM RCT. Health Technol Assess 2022;26»3.
MASCC/ISOO guidelines (2020) recommend LLLT for preventing oral mucositis in head and neck patients receiving radiotherapy or chemoradiotherapy «Elad S, Cheng KKF, Lalla RV, ym. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer 2020;126(19):4423-4431 »4. Benefits have also been observed in patients receiving other antineoplastic treatments «Cruz AR, Minicucci EM, Betini M, ym. Efficacy of photobiomodulation in the treatment of oral mucositis in patients undergoing antineoplastic therapy: systematic review and meta-analysis. Support Care »5.
The evidence comes from systematic reviews and meta-analysis of RCT studies and single RCT studies, the level of evidence is downgraded one level due to study limitations (small studies and varying treatment protocols) and imprecision.
| Reference | Study type | Population | Intervention and comparison | Outcomes | Risk of bias «Additional comments for included studies»2 |
|---|---|---|---|---|---|
| «Shen B, Zhou Y, Wu D, ym. Efficacy of photobiomodulation therapy in the management of oral mucositis in patients with head and neck cancer: A systematic review and meta-analysis of randomized controll»1 | SR/MA | Patients with head and neck cancer, aged ≥18yrs, scheduled for (chemo)radiotherapy | Low level laser therapy (Wavelength range 632.8-940 nm, power range 10-100 mW) 3-5 sessions/week (3/week, 2 studies; 5/week, 11 studies; NS/1 study) for 2-10 weeks (2 weeks, 1 study; 5 weeks, 1 study; 6 weeks, 4 studies; 6.5 weeks; 2 studies; 7 weeks, 1 study; 45 days, 1 study; mean 45.7 days, 1 study; 10 weeks, 1 study; NS, 2 studies)vs. standard oral care, including mouthwash, analgesics +/- sham | 1.Incidence of OM (according to RTOG, CTCAE, WHO) 2. Incidence of severe (Grade ≥3) OM 3. OM-related pain (VAS) | Low |
| «Marín-Conde F, Castellanos-Cosano L, Pachón-Ibañez J, ym. Photobiomodulation with low-level laser therapy reduces oral mucositis caused by head and neck radio-chemotherapy: prospective randomized cont»2 | RCT | Patients with oral/oropharyngeal SCC scheduled for chemoradiotherapy | Low level laser therapy (940 nm, 500 mW) vs. sham | Grade, appearance, and remission of mucositis | High |
| «Nugent M, Bryant V, Butcher C, ym. Photobiomodulation in the management of oral mucositis for adult head and neck cancer patients receiving irradiation: the LiTEFORM RCT. Health Technol Assess 2022;26»3 | RCT | Patients aged ≥18yrs scheduled for H&N radiotherapy with ≥60Gy | Low level laser therapy (660 nm, 50mW) vs. sham | The mean Oral Mucositis Weekly Questionnaire-Head and Neck Cancer score at 6 weeks. | High |
RCT=randomized controlled trial; SR=systematic review; MA=meta-analysis, OM=oral mucositis
| Reference | Comments |
|---|---|
| «Shen B, Zhou Y, Wu D, ym. Efficacy of photobiomodulation therapy in the management of oral mucositis in patients with head and neck cancer: A systematic review and meta-analysis of randomized controll»1 | Seven randomized controlled trials from Brazil, four from India, one each from UK, Spain, and Egypt. Seven double-blind trials, one triple-blind trial, two phase III trials. High heterogeneity in mucositis incidence, high variation of PBMT parameters among studies, inconsistency in outcome measures used across studies. |
| «Marín-Conde F, Castellanos-Cosano L, Pachón-Ibañez J, ym. Photobiomodulation with low-level laser therapy reduces oral mucositis caused by head and neck radio-chemotherapy: prospective randomized cont»2 | Small sample size. Data analyzed only for 26 of the initially recruited 36 patients due to discontinuation of the follow-up. Unbalanced patient characteristics across the treatment arms. |
| «Nugent M, Bryant V, Butcher C, ym. Photobiomodulation in the management of oral mucositis for adult head and neck cancer patients receiving irradiation: the LiTEFORM RCT. Health Technol Assess 2022;26»3 | Recruitment target not met: Lack of statistical power |
Results
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to study limitations, imprecision. | |||||
| «Shen B, Zhou Y, Wu D, ym. Efficacy of photobiomodulation therapy in the management of oral mucositis in patients with head and neck cancer: A systematic review and meta-analysis of randomized controll»1 | 11 studies 778 pts (392 /386) | 7 weeks | N/A | N/A | -Incidence of mucositis during (chemo)radiotherapy RR=0.49(0.25-0.97) -Occurrence of severe mucositis until the completion of the treatment RR=0.45(0.24-0.85) |
| «Marín-Conde F, Castellanos-Cosano L, Pachón-Ibañez J, ym. Photobiomodulation with low-level laser therapy reduces oral mucositis caused by head and neck radio-chemotherapy: prospective randomized cont»2 | 26 pts (11/15) | 5 weeks | No mucositis in 72.7% vs. 20%; 40% of controls had mucositis grade 2 (p<0.01) -No differences in medication use or side effects (p>0.05) | ||
| «Nugent M, Bryant V, Butcher C, ym. Photobiomodulation in the management of oral mucositis for adult head and neck cancer patients receiving irradiation: the LiTEFORM RCT. Health Technol Assess 2022;26»3 | 87 pts (44/43) | 6 weeks | Mean mucositis scores 33.2 (SD 10) in the LLLT group vs. 27.4 (SD 13.8) in the sham group | ||
I=intervention; C=comparison; CI=confidence interval
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: high The quality of evidence is downgraded due to study limitations. | |||||
| «Cruz AR, Minicucci EM, Betini M, ym. Efficacy of photobiomodulation in the treatment of oral mucositis in patients undergoing antineoplastic therapy: systematic review and meta-analysis. Support Care »5 | 5 studies 117/118 pts Control=sham+oral care (105 pts), oral care (13 pts) | N/A | N/A | -Alleviation of OM-related pain WMD –1,09 [-1.38- -0.880], p<0.00001 | |
I=intervention; C=comparison; CI=confidence interval, WMD=weighted mean difference
References
- Shen B, Zhou Y, Wu D, ym. Efficacy of photobiomodulation therapy in the management of oral mucositis in patients with head and neck cancer: A systematic review and meta-analysis of randomized controlled trials. Head Neck 2024;46(4):936-950 «PMID: 38265122»PubMed
- Marín-Conde F, Castellanos-Cosano L, Pachón-Ibañez J, ym. Photobiomodulation with low-level laser therapy reduces oral mucositis caused by head and neck radio-chemotherapy: prospective randomized controlled trial. Int J Oral Maxillofac Surg 2019;48(7):917-923 «PMID: 30591391»PubMed
- Nugent M, Bryant V, Butcher C, ym. Photobiomodulation in the management of oral mucositis for adult head and neck cancer patients receiving irradiation: the LiTEFORM RCT. Health Technol Assess 2022;26(46):1-172 «PMID: 36484364»PubMed
- Elad S, Cheng KKF, Lalla RV, ym. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer 2020;126(19):4423-4431 «PMID: 32786044»PubMed
- Cruz AR, Minicucci EM, Betini M, ym. Efficacy of photobiomodulation in the treatment of oral mucositis in patients undergoing antineoplastic therapy: systematic review and meta-analysis. Support Care Cancer 2023;31(12):645 «PMID: 37853254»PubMed