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 photobiomodu...»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...»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. Photobiomodulat...»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 clinic...»4. Benefits have also been observed in patients receiving other antineoplastic treatments «Cruz AR, Minicucci EM, Betini M, ym. Efficacy of p...»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 photobiomodu...»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...»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. Photobiomodulat...»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 photobiomodu...»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...»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. Photobiomodulat...»3 | Recruitment target not met: Lack of statistical power |
| 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 photobiomodu...»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...»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. Photobiomodulat...»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 p...»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