Advertisement

Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

A systematic review with meta-analysis of the effect of low-level laser therapy (LLLT) in cancer therapy-induced oral mucositis

Abstract

Purpose

The purpose of this study is to review the effects of low-level laser therapy (LLLT) in the prevention and treatment of cancer therapy-induced oral mucositis (OM).

Methods

A systematic review and meta-analysis of randomised placebo-controlled trials of LLLT performed during chemotherapy or radiation therapy in head and neck cancer patients.

Results

We found 11 randomised placebo-controlled trials with a total of 415 patients; methodological quality was acceptable at 4.10 (SD ± 0.74) on the 5-point Jadad scale. The relative risk (RR) for developing OM was significantly (p = 0.02) reduced after LLLT compared with placebo LLLT (RR = 2.03 (95% CI, 1.11 to 3.69)). This preventive effect of LLLT improved to RR = 2.72 (95% CI, 1.98 to 3.74) when only trials with adequate doses above 1 J were included. For treatment of OM ulcers, the number of days with OM grade 2 or worse was significantly reduced after LLLT to 4.38 (95% CI, 3.35 to 5.40) days less than placebo LLLT. Oral mucositis severity was also reduced after LLLT with a standardised mean difference of 1.33 (95% CI, 0.68 to 1.98) over placebo LLLT. All studies registered possible side-effects, but they were not significantly different from placebo LLLT.

Conclusions

There is consistent evidence from small high-quality studies that red and infrared LLLT can partly prevent development of cancer therapy-induced OM. LLLT also significantly reduced pain, severity and duration of symptoms in patients with cancer therapy-induced OM.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

References

  1. 1.

    Manas A, Palacios A, Contreras J, Sanchez-Magro I, Blanco P, Fernandez-Perez C (2009) Incidence of oral mucositis, its treatment and pain management in patients receiving cancer treatment at Radiation Oncology Departments in Spanish hospitals (MUCODOL Study). Clin Transl Oncol 11:669–676

  2. 2.

    Elting LS, Keefe DM, Sonis ST, Garden AS, Spijkervet FK, Barasch A et al (2008) Patient-reported measurements of oral mucositis in head and neck cancer patients treated with radiotherapy with or without chemotherapy: demonstration of increased frequency, severity, resistance to palliation, and impact on quality of life. Cancer 113:2704–2713

  3. 3.

    Elting LS, Cooksley C, Chambers M, Cantor SB, Manzullo E, Rubenstein EB (2003) The burdens of cancer therapy. Clinical and economic outcomes of chemotherapy-induced mucositis. Cancer 98:1531–1539

  4. 4.

    Nonzee NJ, Dandade NA, Patel U, Markossian T, Agulnik M, Argiris A et al (2008) Evaluating the supportive care costs of severe radiochemotherapy-induced mucositis and pharyngitis: results from a Northwestern University Costs of Cancer Program pilot study with head and neck and nonsmall cell lung cancer patients who received care at a county hospital, a Veterans Administration hospital, or a comprehensive cancer care center. Cancer 113:1446–1452

  5. 5.

    Keefe DM, Schubert MM, Elting LS, Sonis ST, Epstein JB, Raber-Durlacher JE et al (2007) Updated clinical practice guidelines for the prevention and treatment of mucositis. Cancer 109:820–831

  6. 6.

    Worthington HV, Clarkson JE, Eden OB (2007) Interventions for preventing oral mucositis for patients with cancer receiving treatment. Cochrane Database Syst Rev. CD000978

  7. 7.

    Lanzos I, Herrera D, Santos S, O’Connor A, Pena C, Lanzos E et al (2010) Mucositis in irradiated cancer patients: effects of an antiseptic mouthrinse. Med Oral Patol Oral Cir Bucal 15(5):e732–e738

  8. 8.

    Lilleby K, Garcia P, Gooley T, McDonnnell P, Taber R, Holmberg L et al (2006) A prospective, randomized study of cryotherapy during administration of high-dose melphalan to decrease the severity and duration of oral mucositis in patients with multiple myeloma undergoing autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 37:1031–1035

  9. 9.

    Lalla RV, Sonis ST, Peterson DE (2008) Management of oral mucositis in patients who have cancer. Dent Clin North Am 52:61–77, viii

  10. 10.

    Elting LS, Shih YC, Stiff PJ, Bensinger W, Cantor SB, Cooksley C (2007) Economic impact of palifermin on the costs of hospitalization for autologous hematopoietic stem-cell transplant: analysis of phase 3 trial results. Biol Blood Marrow Transplant 13(7):806–813

  11. 11.

    Hwang WY, Koh LP, Ng HJ, Tan PH, Chuah CT, Fook SC et al (2004) A randomized trial of amifostine as a cytoprotectant for patients receiving myeloablative therapy for allogeneic hematopoietic stem cell transplantation. Bone Marrow Transpl 34:51–56

  12. 12.

    Lubart R, Eichler M, Lavi R, Friedman H, Shainberg A (2005) Low-energy laser irradiation promotes cellular redox activity. Photomed Laser Surg 23:3–9

  13. 13.

    Rizzi CF, Mauriz JL, Freitas Correa DS, Moreira AJ, Zettler CG, Filippin LI et al (2006) Effects of low-level laser therapy (LLLT) on the nuclear factor (NF)-kappaB signaling pathway in traumatized muscle. Lasers Surg Med 38:704–713

  14. 14.

    Lopes-Martins RA, Marcos RL, Leonardo PS, Prianti AC Jr, Muscara MN, Aimbire F et al (2006) Effect of low-level laser (Ga-Al-As 655 nm) on skeletal muscle fatigue induced by electrical stimulation in rats. J Appl Physiol 101:283–288

  15. 15.

    Leal Junior EC, Lopes-Martins RA, Frigo L, De Marchi T, Rossi RP, de Godoi V et al (2010) Effects of Low-level laser therapy (LLLT) in the development of exercise-induced skeletal muscle fatigue and changes in biochemical markers related to post-exercise recovery. J Orthop Sports Phys Ther 40(8):524–532

  16. 16.

    Bjordal JM, Johnson MI, Iversen V, Aimbire F, Lopes-Martins RA (2006) Photoradiation in acute pain: a systematic review of possible mechanisms of action and clinical effects in randomized placebo-controlled trials. Photomed Laser Surg 24:158–168

  17. 17.

    Bjordal JM, Johnson MI, Lopes-Martins RA, Bogen B, Chow R, Ljunggren AE (2007) Short-term efficacy of physical interventions in osteoarthritic knee pain. A systematic review and meta-analysis of randomised placebo-controlled trials. BMC Musculoskelet Disord 8:51

  18. 18.

    Bjordal JM, Lopes-Martins RA, Joensen J, Ljunggren AE, Couppe C, Stergioulas A et al (2008) A systematic review with procedural assessments and meta-analysis of low level laser therapy in lateral elbow tendinopathy (tennis elbow). BMC Musculoskelet Disord 9:75

  19. 19.

    Chow RT, Johnson MI, Lopes-Martins RA, Bjordal JM (2009) Efficacy of low-level laser therapy in the management of neck pain: a systematic review and meta-analysis of randomised placebo or active-treatment controlled trials. Lancet 374:1897–1908

  20. 20.

    Dickersin K, Scherer R, Lefebvre C (1994) Identifying relevant studies for systematic reviews. BMJ 309:1286–1291, 12 November 1994

  21. 21.

    Cohen J (1977) Statistical power analysis for behavioural sciences. Academic, New York

  22. 22.

    Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJM, Gavaghan DJ et al (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Controlled Clin Trials 17:1–12

  23. 23.

    Kjaergard LL, Als-Nielsen B (2002) Association between competing interests and authors’ conclusions: epidemiological study of randomised clinical trials published in the BMJ. BMJ 325:249

  24. 24.

    Simoes A, Eduardo FP, Luiz AC, Campos L, Sa PH, Cristofaro M et al (2009) Laser phototherapy as topical prophylaxis against head and neck cancer radiotherapy-induced oral mucositis: comparison between low and high/low power lasers. Lasers Surg Med 41:264–270

  25. 25.

    Shea B, Moher D, Graham I, Pham B, Tugwell P (2002) A comparison of the quality of Cochrane reviews and systematic reviews published in paper-based journals. Eval Health Prof 25:116–129

  26. 26.

    Antunes HS, Ferreira EM, de Matos VD, Pinheiro CT, Ferreira CG (2008) The Impact of low power laser in the treatment of conditioning-induced oral mucositis: a report of 11 clinical cases and their review. Med Oral Patol Oral Cir Bucal 13:E189–E192

  27. 27.

    Arun Maiya G, Sagar MS, Fernandes D (2006) Effect of low level helium-neon (He–Ne) laser therapy in the prevention & treatment of radiation induced mucositis in head and neck cancer patients. Indian J Med Res 124:399–402

  28. 28.

    Abramoff MM, Lopes NN, Lopes LA, Dib LL, Guilherme A, Caran EM et al (2008) Low-level laser therapy in the prevention and treatment of chemotherapy-induced oral mucositis in young patients. Photomed Laser Surg 26:393–400

  29. 29.

    Bensadoun RJ, Franquin JC, Ciais G, Darcourt V, Schubert MM, Viot M et al (1999) Low-energy He/Ne laser in the prevention of radiation-induced mucositis. A multicenter phase III randomized study in patients with head and neck cancer. Support Care Cancer 7:244–252

  30. 30.

    Cowen D, Tardieu C, Schubert M, Peterson D, Resbeut M, Faucher C et al (1997) Low energy helium–neon laser in the prevention of oral mucositis in patients undergoing bone marrow transplant: results of a double blind randomized trial. Int J Radiat Oncol Biol Phys 38:697–703

  31. 31.

    Genot-Klastersky MT, Klastersky J, Awada F, Awada A, Crombez P, Martinez MD 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. Support Care Cancer 16:1381–1387

  32. 32.

    Cruz LB, Ribeiro AS, Rech A, Rosa LG, Castro CGJ, Brunetto AL (2007) Influence of low-energy laser in the prevention of oral mucositis in children with cancer receiving chemotherapy. Pediatr Blood Cancer 48:435–440

  33. 33.

    Kuhn A, Porto FA, Miraglia P, Brunetto AL (2009) Low-level infrared laser therapy in chemotherapy-induced oral mucositis: a randomized placebo-controlled trial in children. J Pediatr Hematol Oncol 31:33–37

  34. 34.

    Schubert MM, Eduardo FP, Guthrie KA, Franquin JC, Bensadoun RJ, Migliorati CA 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. Support Care Cancer 15:1145–1154

  35. 35.

    Kuhn A, Vacaro G, Almeida D, Machado A, Braghini PB, Shilling MA et al (2007) Low-level infrared laser therapy for chemo- or radiation-induced oral mucositis: a randomized placebo-controlled study. J Oral Laser Applications 7:175–181

  36. 36.

    Chor A, Torres SR, Maiolino A, Nucci M (2010) Low-power laser to prevent oral mucositis in autologous hematopoietic stem cell transplantation. Eur J Haematol 4:78–79

  37. 37.

    Clarkson JE, Worthington HV, Furness S, McCabe M, Khalid T, Meyer S (2010) Interventions for treating oral mucositis for patients with cancer receiving treatment. Cochrane Database Syst Rev 8:CD001973.

  38. 38.

    Albertini R, Villaverde AB, Aimbire F, Salgado MA, Bjordal JM, Alves LP (2007) Anti-inflammatory effects of low-level laser therapy (LLLT) with two different red wavelengths (660 nm and 684 nm) in carrageenan-induced rat paw edema. J Photochem Photobiol B 89(1):50–55

  39. 39.

    Brosseau L, Robinson V, Wells G, Debie R, Gam A, Harman K et al. (2005) Low level laser therapy (classes I, II and III) for treating rheumatoid arthritis. Cochrane Database Syst Rev CD002049.

Download references

Acknowledgements

Post-mortem to professor Anne Elisabeth Ljunggren for her encouragement and contribution to the early work on this manuscript. Unfortunately, she was unable to see its completion.

Conflicts of interest

None

Author information

Correspondence to Jan Magnus Bjordal.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Bjordal, J.M., Bensadoun, R., Tunèr, J. et al. A systematic review with meta-analysis of the effect of low-level laser therapy (LLLT) in cancer therapy-induced oral mucositis. Support Care Cancer 19, 1069–1077 (2011). https://doi.org/10.1007/s00520-011-1202-0

Download citation

Keywords

  • Low-level laser therapy
  • Oral mucositis
  • Cancer
  • Chemotherapy
  • Radiation therapy