title: Low level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 1: mechanisms of action, dosimetric, and safety considerations.
abstract: There is a large body of evidence supporting the efficacy of low level laser therapy (LLLT), more recently termed photobiomodulation (PBM), for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved, may expand the applications for PBM in the management of other complications associated with HNC treatment. This article (part 1) describes PBM mechanisms of action, dosimetry, and safety aspects and, in doing so, provides a basis for a companion paper (part 2) which describes the potential breadth of potential applications of PBM in the management of side-effects of (chemo)radiation therapy in patients being treated for HNC and proposes PBM parameters.
  
  
  
  This study is a narrative non-systematic review.
  
  
  
  We review PBM mechanisms of action and dosimetric considerations. Virtually, all conditions modulated by PBM (e.g., ulceration, inflammation, lymphedema, pain, fibrosis, neurological and muscular injury) are thought to be involved in the pathogenesis of (chemo)radiation therapy-induced complications in patients treated for HNC. The impact of PBM on tumor behavior and tumor response to treatment has been insufficiently studied. In vitro studies assessing the effect of PBM on tumor cells report conflicting results, perhaps attributable to inconsistencies of PBM power and dose. Nonetheless, the biological bases for the broad clinical activities ascribed to PBM have also been noted to be similar to those activities and pathways associated with negative tumor behaviors and impeded response to treatment. While there are no anecdotal descriptions of poor tumor outcomes in patients treated with PBM, confirming its neutrality with respect to cancer responsiveness is a critical priority.
  
  
  
  Based on its therapeutic effects, PBM may have utility in a broad range of oral, oropharyngeal, facial, and neck complications of HNC treatment. Although evidence suggests that PBM using LLLT is safe in HNC patients, more research is imperative and vigilance remains warranted to detect any potential adverse effects of PBM on cancer treatment outcomes and survival.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Judith A E M
authors.initials: JA
authors.lastname: Zecha
authors.affiliation: Department of Oral and Maxillofacial Surgery, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.|Department of Medical Dental Interaction and Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University, P.O. Box 22660, 1100 DD, Amsterdam, The Netherlands.
authors.forename: Judith E
authors.initials: JE
authors.lastname: Raber-Durlacher
authors.affiliation: Department of Haematology and Oncology/Cancer Services, Gold Coast University Hospital, Queensland Health, Gold Coast, QLD, Australia.
authors.forename: Raj G
authors.initials: RG
authors.lastname: Nair
authors.affiliation: Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.|Division of Otolaryngology and Head and Neck Surgery, City of Hope, Duarte, CA, 91010, USA.
authors.forename: Joel B
authors.initials: JB
authors.lastname: Epstein
authors.affiliation: Division of Oral Medicine, Brigham and Women's Hospital and the Dana-Farber Cancer Institute and Biomodels LLC, Boston, MA, 02115, USA.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Sonis
authors.affiliation: Division of Oral Medicine, Eastman Institute for Oral Health, and Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, 14620, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Elad
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, 02114, USA.|Department of Dermatology, Harvard Medical School, Boston, MA, 02115, USA.|Harvard-MIT Division of Health Science and Technology, Cambridge, MA, 02139, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hamblin
authors.affiliation: Weill Cornell Medical Center, Division of Oncology, New York, NY, USA.
authors.forename: Andrei
authors.initials: A
authors.lastname: Barasch
authors.affiliation: Department of Diagnostic Sciences and Oral Medicine, University of Tennessee Health Science Center, College of Dentistry, 875 Union Ave. Suite N231, Memphis, TN, 38163, USA.
authors.forename: Cesar A
authors.initials: CA
authors.lastname: Migliorati
authors.affiliation: Department of Oral and Maxillofacial Surgery, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Dan M J
authors.initials: DM
authors.lastname: Milstein
authors.affiliation: Laser Therapy Unit, Institut Jules Bordet, Centre des Tumeurs de l'Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Genot
authors.affiliation: Antoni van Leeuwenhoek Department of Head and Neck Oncology and Surgery, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Liset
authors.initials: L
authors.lastname: Lansaat
authors.affiliation: City of Hope, Duarte, CA, 91010, USA.
authors.forename: Ron
authors.initials: R
authors.lastname: van der Brink
authors.affiliation: Department of Oral Surgery, Faculty of Dentistry, University of Barcelona, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Arnabat-Dominguez
authors.affiliation: Antoni van Leeuwenhoek Department of Head and Neck Oncology and Surgery, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Lisette
authors.initials: L
authors.lastname: van der Molen
authors.affiliation: Antoni van Leeuwenhoek Department of Head and Neck Oncology and Surgery, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Irene
authors.initials: I
authors.lastname: Jacobi
authors.affiliation: Antoni van Leeuwenhoek Department Radiation Oncology Amsterdam, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Judi
authors.initials: J
authors.lastname: van Diessen
authors.affiliation: Department of Oral and Maxillofacial Surgery, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: de Lange
authors.affiliation: Department of Oral and Maxillofacial Surgery, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.|Antoni van Leeuwenhoek Department of Head and Neck Oncology and Surgery, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Ludi E
authors.initials: LE
authors.lastname: Smeele
authors.affiliation: Seattle Cancer Care Alliance (SCCA), 825 Eastlake Ave E Ste G6900, Seattle, WA, 98109, USA.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Schubert
authors.affiliation: World Association for Laser Therapy (WALT) Scientific Secretary, Centre de Haute Energie (CHE), 10 Bd Pasteur, 06000, Nice, France. renejean.bensadoun@che-nice.com.
authors.forename: René-Jean
authors.initials: RJ
authors.lastname: Bensadoun
mesh_terms: D059248:Chemoradiotherapy / Q000009:adverse effects*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology / Q000628:therapy*; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D028022:Low-Level Light Therapy / Q000009:adverse effects / Q000379:methods / Q000592:standards
keywords: Chemotherapy; Head and neck cancer; LLLT and PBM; Low level laser therapy; Low level light therapy; Mucositis; Orofacial complications; Photobiomodulation; Radiation therapy; Safety