Systematic review of photobiomodulation for the management of oral mucositis in cancer patients and clinical practice guidelines
To systematically review the literature and update the evidence-based clinical practice guidelines for the use of photobiomodulation (PBM), such as laser and other light therapies, for the prevention and/or treatment of oral mucositis (OM).
A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO) using PubMed and Web of Science. We followed the MASCC methods for systematic review and guidelines development. The rigorously evaluated evidence for each intervention, in each cancer treatment setting, was assigned a level-of-evidence (LoE). Based on the LoE, one of the following guidelines was determined: Recommendation, Suggestion, or No Guideline Possible.
Recommendations are made for the prevention of OM and related pain with PBM therapy in cancer patients treated with one of the following modalities: hematopoietic stem cell transplantation, head and neck (H&N) radiotherapy (without chemotherapy), and H&N radiotherapy with chemotherapy. For each of these modalities, we recommend 1–2 clinically effective protocols; the clinician should adhere to all parameters of the protocol selected. Due to inadequate evidence, currently, No Guideline Possible for treatment of established OM or for management of chemotherapy-related OM. The reported clinical settings were extremely variable, limiting data integration.
The evidence supports the use of specific settings of PBM therapy for the prevention of OM in specific patient populations. Under these circumstances, PBM is recommended for the prevention of OM. The guidelines are subject to continuous update based on new published data.
KeywordsCancer Chemotherapy Laser therapy LED LLLT Low-level laser therapy Prevention Treatment Oral complications of cancer therapy Oral mucositis Pain Photobiomodulation Photobiostimulation Radiotherapy Stomatitis Evidence-based Guidelines
Head and neck
Hematopoietic stem cell transplantation
Low-level laser therapy
Level of evidence
Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology
Photobiomodulation therapy parameters
Randomized controlled trial
The authors would like to thank the medical librarians, Lorraine Porcello, MSLIS, MSIM, from the Bibby Dental Library, Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY, USA, and to Daniel A. Castillo, MLIS from the Edward G. Miner Library, University of Rochester Medical Center, Rochester, NY, USA, for their valuable assistance during the literature search phase.
Compliance with ethical standards
Conflict of interest
Per the MASCC Guidelines policy, employees of commercial entities were not eligible to serve on this MASCC Guidelines Panel. The following authors disclose no conflict of interest: YZ, ERF, HSA, RJB, LAG, AM, RGN, VR, WJET, AV, RL, CAM, KKFC and SE. The following authors disclose a potential conflict of interest as detailed in the ICMJE form for disclosure of potential conflicts of interest: PRA, PB and RVL.
PRA has received grants and personal fees from Lumitex and NIDCR/NIH , personal fees from NeomedLight, grants from NST Consulting, grants from Phillips Research, grants from American Society of Lasers in Surgery and Medicine, grants from American Dental Education Association, non-financial support from Thor Photomedicine, non-financial support from Weber Medical; In addition, PRA has a patent Laser systems for dental therapy issued and serve in the honorary positions of President of World Association for Photobiomodulation Therapy,
Immediate Past-President of North American Association for Photobiomodulation Therapy, Chair of Society for Photonics and Engineers, Mechanisms for Photobiomodulation Therapy, Technical Group member of Photobiomodulation therapy, Optical Society of America, Program Chair of Society for Advanced Wound Care, Wound Healing Society.
PB has served an advisory role for AstraZeneca, Helsinn, and Kyowa Kyrin and received grants from Merck, Kyowa Kyrin, and Roche.
RVL has served as a consultant for Colgate Oral Pharmaceuticals, Galera Therapeutics, Ingalfarma SA, Monopar Therapeutics, Mundipharma, and Sucampo Pharma; has received research support to his institution from Galera Therapeutics, Novartis, Oragenics, and Sucampo Pharma; and has received stock in Logic Biosciences.
- 1.Elad S, Zadik Y, Yarom N (2017) Oral complications of nonsurgical cancer therapies. Atlas Oral Maxillofac Surg Clin North Am 25:133–147Google Scholar
- 3.Sonis ST, Oster G, Fuchs H, Bellm L, Bradford WZ, Edelsberg J, Hayden V, Eilers J, Epstein JB, LeVeque FG, Miller C, Peterson DE, Schubert MM, Spijkervet FK, Horowitz M (2001) Oral mucositis and the clinical and economic outcomes of hematopoietic stem-cell transplantation. J Clin Oncol 19:2201–2205CrossRefGoogle Scholar
- 4.Mester E, Korenyi-Both A, Spiry T, Scher A, Tisza S (1973) Stimulation of wound healing by means of laser rays. (clinical and electron microscopical study). Acta Chir Acad Sci Hung 14:347–356Google Scholar
- 7.de Freitas LF, Hamblin MR (2016) Proposed mechanisms of photobiomodulation or low-level light therapy IEEE journal of selected topics in quantum electronics: a publication of the IEEE Lasers and Electro-optics Society 22Google Scholar
- 10.Lalla RV, Bowen J, Barasch A, Elting L, Epstein J, Keefe DM, McGuire DB, Migliorati C, Nicolatou-Galitis O, Peterson DE, Raber-Durlacher JE, Sonis ST, Elad S, Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in CCancer and, International Society of Oral Oncology (MASCC/ISOO). (2014) MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer 120:1453–1461Google Scholar
- 11.Migliorati C, Hewson I, Lalla RV, Antunes HS, Estilo CL, Hodgson B, Lopes NN, Schubert MM, Bowen J, Elad S, Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). (2013) Systematic review of laser and other light therapy for the management of oral mucositis in cancer patients. Support Care Cancer 21:333–341Google Scholar
- 12.Ranna V, Cheng K, Castillo D, Porcello L, Vaddi A, Lalla R, Bossi P, Elad S (2019) Development of the MASCC/ISOO Clinical Practice Guidelines for Mucositis: an overview of the methods. Support Care Cancer. https://doi.org/10.1007/s00520-019-04891-1
- 14.Somerfield MPJ, Pfister D, Bennett C, Recht A, Smith T, Weeks J, Winn R, Duraant J (2000) ASCO clinical practice guidelines: process, progress, pitfalls, and prospects classic papers and current comments, vol 4, pp 881–886Google Scholar
- 15.Schubert MM, Eduardo FP, Guthrie KA, Franquin JC, Bensadoun RJ, Migliorati CA, Lloid CM, Eduardo CP, Walter NF, Marques MM, Hamdi M (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 15:1145–1154CrossRefGoogle Scholar
- 17.Antunes HS, Herchenhorn D, Small IA, Araujo CM, Viegas CM, Cabral E, Rampini MP, Rodrigues PC, Silva TG, Ferreira EM, Dias FL, Ferreira CG (2013) Phase III trial of low-level laser therapy to prevent oral mucositis in head and neck cancer patients treated with concurrent chemoradiation. Radiother Oncol 109:297–302CrossRefGoogle Scholar
- 18.Oton-Leite AF, Silva GB, Morais MO, Silva TA, Leles CR, Valadares MC, Pinezi JC, Batista AC, Mendonca EF (2015) Effect of low-level laser therapy on chemoradiotherapy-induced oral mucositis and salivary inflammatory mediators in head and neck cancer patients. Lasers Surg Med 47:296–305CrossRefGoogle Scholar
- 20.Bezinelli LM, de Paula Eduardo F, da Graca Lopes RM, Biazevic MG, de Paula Eduardo C, Correa L, Hamerschlak N, Michel-Crosato E (2014) Cost-effectiveness of the introduction of specialized oral care with laser therapy in hematopoietic stem cell transplantation. Hematol Oncol 32:31–39CrossRefGoogle Scholar
- 21.de Paula Eduardo F, Bezinelli LM, da Graca Lopes RM, Nascimento Sobrinho JJ, Hamerschlak N, Correa L (2015) Efficacy of cryotherapy associated with laser therapy for decreasing severity of melphalan-induced oral mucositis during hematological stem-cell transplantation: a prospective clinical study. Hematol Oncol 33:152–158CrossRefGoogle Scholar
- 22.Antunes HS, de Azevedo AM, da Silva Bouzas LF, Adao CA, Pinheiro CT, Mayhe R, Pinheiro LH, Azevedo R, D’Aiuto de Matos V, Rodrigues PC, Small IA, Zangaro RA, Ferreira CG (2007) Low-power laser in the prevention of induced oral mucositis in bone marrow transplantation patients: a randomized trial. Blood 109:2250–2255CrossRefGoogle Scholar
- 25.Silva LC, Sacono NT, Freire Mdo C, Costa LR, Batista AC, Silva GB (2015) The impact of low-level laser therapy on oral mucositis and quality of life in patients undergoing hematopoietic stem cell transplantation using the oral health impact profile and the functional assessment of cancer therapy-bone marrow transplantation questionnaires. Photomed Laser Surg 33:357–363CrossRefGoogle Scholar
- 29.Ottaviani G, Gobbo M, Sturnega M, Martinelli V, Mano M, Zanconati F, Bussani R, Perinetti G, Long CS, Di Lenarda R, Giacca M, Biasotto M, Zacchigna S (2013) Effect of class IV laser therapy on chemotherapy-induced oral mucositis: a clinical and experimental study. Am J Pathol 183:1747–1757CrossRefGoogle Scholar
- 32.Chermetz M, Gobbo M, Ronfani L, Ottaviani G, Zanazzo GA, Verzegnassi F, Treister NS, Di Lenarda R, Biasotto M, Zacchigna S (2014) Class IV laser therapy as treatment for chemotherapy-induced oral mucositis in onco-haematological paediatric patients: a prospective study. Int J Paediatr Dent 24:441–449CrossRefGoogle Scholar
- 34.Bensadoun RJ, Franquin JC, Ciais G, Darcourt V, Schubert MM, Viot M, Dejou J, Tardieu C, Benezery K, Nguyen TD, Laudoyer Y, Dassonville O, Poissonnet G, Vallicioni J, Thyss A, Hamdi M, Chauvel P, Demard F (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 7:244–252CrossRefGoogle Scholar
- 35.Arora H, Pai KM, Maiya A, Vidyasagar MS, Rajeev A (2008) Efficacy of He-Ne laser in the prevention and treatment of radiotherapy-induced oral mucositis in oral cancer patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 105:180–186, 186.e1Google Scholar
- 36.Gouvea de Lima A, Villar RC, de Castro G Jr, Antequera R, Gil E, Rosalmeida MC, Federico MH, Snitcovsky IM (2012) Oral mucositis prevention by low-level laser therapy in head-and-neck cancer patients undergoing concurrent chemoradiotherapy: a phase III randomized study. Int J Radiat Oncol Biol Phys 82:270–275CrossRefGoogle Scholar
- 37.Gautam AP, Fernandes DJ, Vidyasagar MS, Maiya AG, Nigudgi S (2013) Effect of low-level laser therapy on patient reported measures of oral mucositis and quality of life in head and neck cancer patients receiving chemoradiotherapy--a randomized controlled trial. Support Care Cancer 21:1421–1428CrossRefGoogle Scholar
- 40.Gobbo M, Ottaviani G, Perinetti G, Ciriello F, Beorchia A, Giacca M, Di Lenarda R, Rupel K, Tirelli G, Zacchigna S, Biasotto M (2014) Evaluation of nutritional status in head and neck radio-treated patients affected by oral mucositis: efficacy of class IV laser therapy. Support Care Cancer 22:1851–1856CrossRefGoogle Scholar
- 44.Cowen D, Tardieu C, Schubert M, Peterson D, Resbeut M, Faucher C, Franquin JC (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 38:697–703CrossRefGoogle Scholar
- 46.Huang YY, Sharma SK, Carroll J, Hamblin MR (2011) Biphasic dose response in low level light therapy - an update. Dose Response 9:602–618Google Scholar
- 49.(2006) Standards for the design and conduct of systematic reviews with low-level laser therapy for musculoskeletal pain and disorders. Photomed Laser Surg 24:759–760Google Scholar
- 52.Antunes HS, Herchenhorn D, Small IA, Araujo CMM, Viegas CMP, de Assis Ramos G, Dias FL, Ferreira CG (2017) Long-term survival of a randomized phase III trial of head and neck cancer patients receiving concurrent chemoradiation therapy with or without low-level laser therapy (LLLT) to prevent oral mucositis. Oral Oncol 71:11–15CrossRefGoogle Scholar
- 53.Brandao TB, Morais-Faria K, Ribeiro ACP, Rivera C, Salvajoli JV, Lopes MA, Epstein JB, Arany PR, de Castro G Jr, Migliorati CA, Santos-Silva AR (2018) Locally advanced oral squamous cell carcinoma patients treated with photobiomodulation for prevention of oral mucositis: retrospective outcomes and safety analyses. Support Care Cancer 26:2417–2423CrossRefGoogle Scholar
- 56.Soares RG, Farias LC, da Silva Menezes AS, de Oliveira ESCS, Tabosa ATL, Chagas PVF, Santiago L, Santos SHS, de Paula AMB, Guimaraes ALS (2018) Treatment of mucositis with combined 660- and 808-nm-wavelength low-level laser therapy reduced mucositis grade, pain, and use of analgesics: a parallel, single-blind, two-arm controlled study. Lasers Med Sci 33:1813–1819CrossRefGoogle Scholar
- 57.Marín-Conde F, Castellanos-Cosano L, Pachón-Ibañez J, Serrera-Figallo MA, Gutiérrez-Pérez JL, Torres-Lagares D (2018) 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, in pressGoogle Scholar
- 59.Vitale MC, Modaffari C, Decembrino N, Zhou FX, Zecca M, Defabianis P (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 32:1423–1428CrossRefGoogle Scholar
- 60.Gobbo M, Verzegnassi F, Ronfani L, Zanon D, Melchionda F, Bagattoni S, Majorana A, Bardellini E, Mura R, Piras A, Petris MG, Mariuzzi ML, Barone A, Merigo E, Decembrino N, Vitale MC, Berger M, Defabianis P, Biasotto M, Ottaviani G, Zanazzo GA (2018) Multicenter randomized, double-blind controlled trial to evaluate the efficacy of laser therapy for the treatment of severe oral mucositis induced by chemotherapy in children: laMPO RCT. Pediatr Blood Cancer 65:e27098CrossRefGoogle Scholar
- 62.Leite Cavalcanti A, Jose de Macedo D, Suely Barros Dantas F, Dos Santos Menezes K, Filipe Bezerra Silva D, Alves de Melo Junior W, Fabia Cabral Cavalcanti A (2018) Evaluation of oral mucositis occurrence in oncologic patients under antineoplastic therapy submitted to the low-level laser. Coadjuvant Ther J Clin Med 7Google Scholar
- 63.Bezinelli LM, Eduardo FP, Neves VD, Correa L, Lopes RM, Michel-Crosato E, Hamerschlak N, Biazevic MG (2016) Quality of life related to oral mucositis of patients undergoing haematopoietic stem cell transplantation and receiving specialised oral care with low-level laser therapy: a prospective observational study. Eur J Cancer Care (Engl) 25:668–674CrossRefGoogle Scholar
- 66.Eduardo Fde P, Bezinelli LM, Orsi MC, Rodrigues M, Ribeiro MS, Hamerschlak N, Correa L (2011) The influence of dental care associated with laser therapy on oral mucositis during allogeneic hematopoietic cell transplant: retrospective study Einstein (Sao Paulo, Brazil) 9: 201–206Google Scholar
- 67.Eduardo Fde P, Bezinelli LM, de Carvalho DL, Lopes RM, Fernandes JF, Brumatti M, Vince CS, de Azambuja AM, Vogel C, Hamerschlak N, Correa L (2015) Oral mucositis in pediatric patients undergoing hematopoietic stem cell transplantation: clinical outcomes in a context of specialized oral care using low-level laser therapy. Pediatr Transplant 19:316–325CrossRefGoogle Scholar
- 68.Arbabi-Kalati F, Arbabi-Kalati F, Moridi T (2013) Evaluation of the effect of low level laser on prevention of chemotherapy-induced mucositis. Acta Med Iran 51:157–162Google Scholar
- 76.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–E192Google Scholar
- 77.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 & neck cancer patients Indian. J Med Res 124:399–402Google Scholar
- 80.Kelner NCJ (2007) Low energy laser in prevention of oral mucositis in patients receiving radiotherapy and/or chemotherapy in Pernambuco cancer hospital. Appl Cancer Res 27:182–187Google Scholar
- 83.Genot-Klastersky MT, Klastersky J, Awada F, Awada A, Crombez P, Martinez MD, Jaivenois MF, Delmelle M, Vogt G, Meuleman N, Paesmans M (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 16:1381–1387CrossRefGoogle Scholar
- 85.Soto M, Lalla RV, Gouveia RV, Zecchin VG, Seber A, Lopes NN (2015) Pilot study on the efficacy 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 33:540–546CrossRefGoogle Scholar