Systematic review of photobiomodulation for the management of oral mucositis in cancer patients and clinical practice guidelines

  • Yehuda ZadikEmail author
  • Praveen R. AranyEmail author
  • Eduardo Rodrigues Fregnani
  • Paolo Bossi
  • Héliton Spindola Antunes
  • René-Jean Bensadoun
  • Luiz Alcino Gueiros
  • Alessandra Majorana
  • Raj G. Nair
  • Vinisha Ranna
  • Wim J. E. Tissing
  • Anusha Vaddi
  • Rachel Lubart
  • Cesar Augusto Migliorati
  • Rajesh V. Lalla
  • Karis Kin Fong Cheng
  • Sharon Elad
  • On behalf of The Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO)
Special Article



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.


Cancer 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






Light-emitting diode


Low-level laser therapy


Level of evidence


Oral mucositis


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.

Supplementary material

520_2019_4890_MOESM1_ESM.docx (78 kb)
ESM 1 (PDF 80 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Yehuda Zadik
    • 1
    • 2
    Email author
  • Praveen R. Arany
    • 3
    Email author
  • Eduardo Rodrigues Fregnani
    • 4
  • Paolo Bossi
    • 5
  • Héliton Spindola Antunes
    • 6
  • René-Jean Bensadoun
    • 7
  • Luiz Alcino Gueiros
    • 8
  • Alessandra Majorana
    • 9
  • Raj G. Nair
    • 10
  • Vinisha Ranna
    • 11
  • Wim J. E. Tissing
    • 12
  • Anusha Vaddi
    • 13
  • Rachel Lubart
    • 14
  • Cesar Augusto Migliorati
    • 15
  • Rajesh V. Lalla
    • 16
  • Karis Kin Fong Cheng
    • 17
  • Sharon Elad
    • 13
  • On behalf of The Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO)
  1. 1.Department of Oral MedicineOral and Maxillofacial Center, Medical Corps, Israel Defense ForcesTel-HashomerIsrael
  2. 2.Department of Oral MedicineSedation and Maxillofacial Imaging, Hebrew University-Hadassah School of Dental MedicineJerusalemIsrael
  3. 3.Department of Oral Biology and Biomedical Engineering, School of Dental Medicine, Engineering and Applied SciencesUniversity at BuffaloBuffaloUSA
  4. 4.Oral Medicine ServiceHospital Sírio-Libanês São PauloSão PauloBrazil
  5. 5.Department of Medical and Surgical Specialties, Radiological Sciences and Public Health - Medical Oncology, ASST-Spedali CiviliUniversity of BresciaBresciaItaly
  6. 6.Clinical Research DivisionNational Cancer Institute of Brazil (INCA)Rio de JaneiroBrazil
  7. 7.Gérant, Responsable de ServiceCentre de Haute EnergieNiceFrance
  8. 8.Departamento de Clínica e Odontologia PreventivaUniversidade Federal de PernambucoRecifeBrazil
  9. 9.University of BresciamDepartment of Medical and Surgical Specialties, Radiological Sciences and Public Health, Dental Clinic Oral MedicineBresciaItaly
  10. 10.Griffith University and Gold Coast University HospitalSouthportAustralia
  11. 11.Department of Oral and Maxillofacial SurgeryThe Mount Sinai HospitalNew YorkUSA
  12. 12.Division of Pediatric Oncology/Hematology/Immunology, Beatrix Childrens HospitalUniversity Medical Center GroningenGroningenThe Netherlands
  13. 13.Oral Medicine, Eastman Institute for Oral HealthUniversity of Rochester Medical CenterRochesterUSA
  14. 14.Departments of Physics and ChemistryBar-Ilan UniversityRamat-GanIsrael
  15. 15.College of DentistryUniversity of FloridaGainesvilleUSA
  16. 16.Section of Oral MedicineUniversity of Connecticut HealthFarmingtonUSA
  17. 17.Yong Loo Lin School of Medicine, Clinical Research CentreNational University of SingaporeSingaporeSingapore

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