A systematic review and meta-analysis of the effect of low-level laser therapy (LLLT) on chemotherapy-induced oral mucositis in pediatric and young patients
Oral mucositis is one of the most frequent complications after chemotherapy, occurring in approximately 52 to 80% of children receiving treatment for cancer. Recently, it has been suggested that the use of low-energy laser could reduce the grade of oral mucositis and alleviate the symptoms. In 2014, Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology has recommended low-level laser therapy in prevention of mucositis for hematopoietic stem cell transplantation patients because of its beneficial effects in majority of recent studies. However, the recommendation was made for adult patients, not pediatric patients. Data about the effect of low-level laser therapy in pediatric patients is limited. This study aims to synthesize the available clinical evidences on the effects of low-level laser therapy (LLLT) in the prevention and treatment of chemotherapy-induced oral mucositis (OM). A meta-analysis was performed using trials identified through the Cochrane Central Register of Controlled Trials, Embase, MEDLINE, Web of Science, China Biology Medicine (CBM), Wanfang Database, and China National Knowledge Infrastructure (CNKI). Data on occurrence, duration, and severity of oral mucositis were collected. All randomized controlled studies and clinical controlled studies comparing LLLT to routine qualified prevention or treatment during or after chemotherapy were critically appraised and analyzed. We found 8 qualified clinical trials with a total of 373 pediatric patients; the methodological quality was acceptable. After prophylactic LLLT, the odds ratio for developing OM was significantly lower compared with placebo(OR = 0.50, 95% CI 0.29 to 0.87, P = 0.01), the odds ratio for developing grade III OM or worse was statistically significantly lower compared with placebo (OR = 0.30, 95% CI (0.10, 0.90), P = 0.03), and the OM severity was statistically significantly lower compared with placebo (SMD = − 0.56, 95% CI (− 0.98, − 0.14), P = 0.009). For therapeutic LLLT, the OM severity was significantly reduced compared to routine care (SMD = − 1.18, 95% CI (− 1.52, − 0.84), P < 0.00001). Oral pain was also reduced after LLLT over routine care (MD = − 0.73, 95% CI (− 1.36, − 0.11), P = 0.02).
What is known:
• Low-level laser therapy (LLLT) was recommended by Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology; however, evidences about LLLT on oral mucositis in pediatric and young patients were insufficient and lack supportive synthesized data.
• Recently, there have been several new RCTs or CCTs for pediatric patients or young adults.
What is new:
• Prophylactic LLLT reduces the occurrence of mucositis and severe mucositis and decreases the average severity of oral mucositis in pediatric and young patients.
• Therapeutic LLLT reduces the average severity of oral mucositis and oral pain.
KeywordsLow-level laser therapy Oral mucositis Chemotherapy Pediatric patients
Hematopoietic stem cell transplantation
International Society of Oral Oncology
Low-level laser therapy
Multinational Association of Supportive Care in Cancer
Pediatric Oncology Group of Ontario
He Mengxue contributed to conception and design, acquisition, analysis, and interpretation, drafted manuscript, critically revised manuscript, gave final approval and agrees to be accountable for all aspects of work ensuring itegrity and accuracy.
Zhang Binghua contributed to conception and design, interpretation, drafted manuscript, critically revised manuscript, gave final approval, and agrees to be accountable for all aspects of work ensuring itegrity and accuracy.
Shen Nanping contributed to conception and design, and critically revised manuscript.
Wu Na contributed to acquisition,analysis, and critically revised manuscript.
Sun Jiwen contributed to acquisition, analysis, and critically revised manuscript.
This study was academically funded by the Shanghai Municipal Education Commission Gaoyuan Nursing Grant Support (hlgy16014kyx) and the Shanghai Supporting and Training Funds for Young Teachers in University (Shanghai Gaoxiao Qingnian Jiaoshi Peiyang Zizhu Jihua) (ZZjdyx13142).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants performed by any of the authors. For this type of study, no formal consent is required.
- 2.Ahmed KM, Hussein SA, Noori AJ, Abdulateef SN, Abdulla BK (2015) Evaluation of low level laser therapy in the management of chemotherapy-induced oral mucositis in pediatric and young cancer patients: a randomized clinical trial. Eur Sci J 11:209–222Google Scholar
- 5.Basso FG, Soares DG, Pansani TN, Cardoso LM, Scheffel DL (2016) Proliferation, migration and experssion of oral-mucosal-healing-related genes by oral fibroblasts receiving low-level laser therapy after inflammatory cytokines challenge. Lasers Surg Med 48(10):1006–1014. https://doi.org/10.1002/lsm.22553
- 16.Hozo SP, Djulbegovic B, Hozo I (2005) Estimating the mean and variance from the median, range and the size of a sample. BMC Med Res Methodol 5:13. https://doi.org/10.1186/1471-2288-5-13
- 27.Smoot B, Chiavola-Larson L, Lee J, Manibusan H, Allen DD (2015) Effect of low-level laser therapy on pain and swelling in women with breast cancer-related lymphedema: a systematic review and meta-analysis. J Cancer Surviv 9(2):287–304. https://doi.org/10.1007/s11764-014-0411-1 CrossRefPubMedGoogle Scholar
- 28.Soto M, Lalla RV, Gouveia RV, Zecchin VG (2015) Pilot study on the effecacy of combined intraoral and extraoral low-level laser therapy for prevention of oral mucositis in pediatric patients undergoing hematopoietic stem cell transplantation. Photomed Laser Surg 33(11):540–546. https://doi.org/10.1089/pho.2015.3954 CrossRefPubMedGoogle Scholar
- 29.Sung L, Robinson P, Treister N, Baggott T (2015) Guideline for the prevention of oral and oropharyngeal mucositis in children receiving treatment for cancer or undergoing haematopoietic stem cell transplantation. BMJ Support Palliat Care 7(1):7–16. https://doi.org/10.1136/bmjspcare-2014-000804
- 31.Vitale MC, Modaffari C, Decembrino N, Zhou FX, Zecca M (2017) Preliminary study in a new protocol for the treatment of oral mucositis in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT) and chemotherapy (CT). Lasers Med Sci 32(6):1423–1428. 10.1007/s10103-017-2266-y