Judith A E M Zecha1, Judith E Raber-Durlacher1,2, Raj G Nair3, Joel B Epstein4,5, Stephen T Sonis6, Sharon Elad7, Michael R Hamblin8,9,10, Andrei Barasch11, Cesar A Migliorati12, Dan M J Milstein1, Marie-Thérèse Genot13, Liset Lansaat14, Ron van der Brink15, Josep Arnabat-Dominguez16, Lisette van der Molen14, Irene Jacobi14, Judi van Diessen17, Jan de Lange1, Ludi E Smeele1,14, Mark M Schubert18, René-Jean Bensadoun19. 1. Department of Oral and Maxillofacial Surgery, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. 2. 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. 3. Department of Haematology and Oncology/Cancer Services, Gold Coast University Hospital, Queensland Health, Gold Coast, QLD, Australia. 4. Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA. 5. Division of Otolaryngology and Head and Neck Surgery, City of Hope, Duarte, CA, 91010, USA. 6. Division of Oral Medicine, Brigham and Women's Hospital and the Dana-Farber Cancer Institute and Biomodels LLC, Boston, MA, 02115, USA. 7. Division of Oral Medicine, Eastman Institute for Oral Health, and Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, 14620, USA. 8. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, 02114, USA. 9. Department of Dermatology, Harvard Medical School, Boston, MA, 02115, USA. 10. Harvard-MIT Division of Health Science and Technology, Cambridge, MA, 02139, USA. 11. Weill Cornell Medical Center, Division of Oncology, New York, NY, USA. 12. 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. 13. Laser Therapy Unit, Institut Jules Bordet, Centre des Tumeurs de l'Université Libre de Bruxelles, Brussels, Belgium. 14. Antoni van Leeuwenhoek Department of Head and Neck Oncology and Surgery, Netherlands Cancer Institute, Amsterdam, The Netherlands. 15. City of Hope, Duarte, CA, 91010, USA. 16. Department of Oral Surgery, Faculty of Dentistry, University of Barcelona, Barcelona, Spain. 17. Antoni van Leeuwenhoek Department Radiation Oncology Amsterdam, Netherlands Cancer Institute, Amsterdam, The Netherlands. 18. Seattle Cancer Care Alliance (SCCA), 825 Eastlake Ave E Ste G6900, Seattle, WA, 98109, USA. 19. World Association for Laser Therapy (WALT) Scientific Secretary, Centre de Haute Energie (CHE), 10 Bd Pasteur, 06000, Nice, France. renejean.bensadoun@che-nice.com.
Abstract
PURPOSE: 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. METHODS: This study is a narrative non-systematic review. RESULTS: 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. CONCLUSION: 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.
PURPOSE: 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. METHODS: This study is a narrative non-systematic review. RESULTS: 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. CONCLUSION: 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.
Entities:
Keywords:
Chemotherapy; Head and neck cancer; LLLT and PBM; Low level laser therapy; Low level light therapy; Mucositis; Orofacial complications; Photobiomodulation; Radiation therapy; Safety
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