Skip to main content

Advertisement

SpringerLink
Log in

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

  • Review Article
  • Published:
Supportive Care in Cancer Aims and scope Submit manuscript

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.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Epstein JB, Thariat J, Bensadoun RJ, Barasch A, Murphy BA, Kolnick L, Popplewell L, Maghami E (2012) Oral complications of cancer and cancer therapy: from cancer treatment to survivorship. CA Cancer J Clin 62:400–422. doi:10.3322/caac.21157

    Article  PubMed  Google Scholar 

  2. Rosenthal DI, Lewin JS, Eisbruch A (2006) Prevention and treatment of dysphagia and aspiration after chemoradiation for head and neck cancer. J. Clin.Oncol. 24:2636–2643. doi:10.1200/JCO.2006.06.0079

    Article  PubMed  Google Scholar 

  3. van der Molen L, van Rossum MA, Burkhead LM, Smeele LE, Hilgers FJ (2009) Functional outcomes and rehabilitation strategies in patients treated with chemoradiotherapy for advanced head and neck cancer: a systematic review. Eur Arch Otorhinolaryngol 266:889–900. doi:10.1007/s00405-008-0817-3

    Article  PubMed  Google Scholar 

  4. Rapidis AD, Vermorken JB, Bourhis J (2008) Targeted therapies in head and neck cancer: past, present and future. Rev Recent Clin Trials 3:156–166

    Article  CAS  PubMed  Google Scholar 

  5. Watters AL, Epstein JB, Agulnik M (2011) Oral complications of targeted cancer therapies: a narrative literature review. Oral Oncol 47:441–448. doi:10.1016/j.oraloncology.2011.03.028

    Article  CAS  PubMed  Google Scholar 

  6. Lacouture ME, Anadkat MJ, Bensadoun RJ, Bryce J, Chan A, Epstein JB, Eaby-Sandy B, Murphy BA (2011) Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities. Support. Care Cancer 19:1079–1095. doi:10.1007/s00520-011-1197-6

    Article  PubMed  PubMed Central  Google Scholar 

  7. Vissink A, Jansma J, Spijkervet FK, Burlage FR, Coppes RP (2003) Oral sequelae of head and neck radiotherapy. Crit Rev Oral Biol Med 14:199–212

    Article  CAS  PubMed  Google Scholar 

  8. WALT/NAALT (September 9–12 2014) Photobiomodulation: mainstream medicine and beyond. WALT Biennial Congress and NAALT Annual Conference, Arlington Virginia USA

  9. Mester E, Spiry T, Szende B, Tota JG (1971) Effect of laser rays on wound healing. Am J Surg 122:532–535

    Article  CAS  PubMed  Google Scholar 

  10. Oron U, Yaakobi T, Oron A, Mordechovitz D, Shofti R, Hayam G, Dror U, Gepstein L, Wolf T, Haudenschild C, Haim SB (2001) Low-energy laser irradiation reduces formation of scar tissue after myocardial infarction in rats and dogs. Circulation 103:296–301

    Article  CAS  PubMed  Google Scholar 

  11. Rizzi CF, Mauriz JL, Freitas Correa DS, Moreira AJ, Zettler CG, Filippin LI, Marroni NP, Gonzalez-Gallego J (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. doi:10.1002/lsm.20371

    Article  PubMed  Google Scholar 

  12. Barolet D, Boucher A (2010) Prophylactic low-level light therapy for the treatment of hypertrophic scars and keloids: a case series. Lasers Surg Med 42:597–601. doi:10.1002/lsm.20952

    Article  PubMed  Google Scholar 

  13. Oliveira FA, Moraes AC, Paiva AP, Schinzel V, Correa-Costa M, Semedo P, Castoldi A, Cenedeze MA, Oliveira RS, Bastos MG, Camara NO, Sanders-Pinheiro H (2012) Low-level laser therapy decreases renal interstitial fibrosis. Photomed Laser Surg 30:705–713. doi:10.1089/pho.2012.3272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Meneguzzo DT, Lopes LA, Pallota R, Soares-Ferreira L, Lopes-Martins RA, Ribeiro MS (2013) Prevention and treatment of mice paw edema by near-infrared low-level laser therapy on lymph nodes. Lasers Med Sci 28:973–980. doi:10.1007/s10103-012-1163-7

    Article  PubMed  Google Scholar 

  15. Luo L, Sun Z, Zhang L, Li X, Dong Y, Liu TC (2013) Effects of low-level laser therapy on ROS homeostasis and expression of IGF-1 and TGF-beta1 in skeletal muscle during the repair process. Lasers Med Sci 28:725–734. doi:10.1007/s10103-012-1133-0

    Article  PubMed  Google Scholar 

  16. Bjordal JM, Couppe C, Chow RT, Tuner J, Ljunggren EA (2003) A systematic review of low level laser therapy with location-specific doses for pain from chronic joint disorders. Aust. J. Physiother. 49:107–116

    Article  PubMed  Google Scholar 

  17. Bjordal JM, Johnson MI, Iversen V, Aimbire F, Lopes-Martins RA (2006) Low-level laser therapy 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. doi:10.1089/pho.2006.24.158

    Article  CAS  PubMed  Google Scholar 

  18. 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. doi:10.1016/S0140-6736(09)61522-1

    Article  PubMed  Google Scholar 

  19. Chow R, Armati P, Laakso EL, Bjordal JM, Baxter GD (2011) Inhibitory effects of laser irradiation on peripheral mammalian nerves and relevance to analgesic effects: a systematic review. Photomed Laser Surg 29:365–381. doi:10.1089/pho.2010.2928

    Article  PubMed  Google Scholar 

  20. Clarkson JE, Worthington HV, Furness S, McCabe M, Khalid T and Meyer S (2010) Interventions for treating oral mucositis for patients with cancer receiving treatment. Cochrane. Database. Syst.Rev.:CD001973. doi:10.1002/14651858.CD001973.pub4

  21. Worthington HV, Clarkson JE, Bryan G, Furness S, Glenny AM, Littlewood A, McCabe MG, Meyer S and Khalid T (2011) Interventions for preventing oral mucositis for patients with cancer receiving treatment. Cochrane. Database. Syst.Rev.:CD000978. doi:10.1002/14651858.CD000978.pub5

  22. Bjordal JM, Bensadoun RJ, Tuner J, Frigo L, Gjerde K, Lopes-Martins RA (2011) 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. doi:10.1007/s00520-011-1202-0

    Article  PubMed  Google Scholar 

  23. Bensadoun RJ, Nair RG (2012) Low-level laser therapy in the prevention and treatment of cancer therapy-induced mucositis: 2012 state of the art based on literature review and meta-analysis. Curr Opin Oncol 24:363–370. doi:10.1097/CCO.0b013e328352eaa3

    Article  CAS  PubMed  Google Scholar 

  24. Migliorati C, Hewson I, Lalla RV, Antunes HS, Estilo CL, Hodgson B, Lopes NN, Schubert MM, Bowen J, Elad S (2013) Systematic review of laser and other light therapy for the management of oral mucositis in cancer patients. Support Care Cancer 21:333–341. doi:10.1007/s00520-012-1605-6

    Article  PubMed  Google Scholar 

  25. Oberoi S, Zamperlini-Netto G, Beyene J, Treister NS, Sung L (2014) Effect of prophylactic low level laser therapy on oral mucositis: a systematic review and meta-analysis. PLoS one 9:e107418. doi:10.1371/journal.pone.0107418

    Article  PubMed  PubMed Central  Google Scholar 

  26. Hodgson BD, Margolis DM, Salzman DE, Eastwood D, Tarima S, Williams LD, Sande JE, Vaughan WP, Whelan HT (2012) Amelioration of oral mucositis pain by NASA near-infrared light-emitting diodes in bone marrow transplant patients. Support Care Cancer 20:1405–1415. doi:10.1007/s00520-011-1223-8

    Article  PubMed  Google Scholar 

  27. Hudson DE, Hudson DO, Wininger JM, Richardson BD (2013) Penetration of laser light at 808 and 980 nm in bovine tissue samples. Photomed Laser Surg 31:163–168. doi:10.1089/pho.2012.3284

    Article  PubMed  PubMed Central  Google Scholar 

  28. Hashmi JT, Huang YY, Sharma SK, Kurup DB, De TL, Carroll JD, Hamblin MR (2010) Effect of pulsing in low-level light therapy. Lasers Surg Med 42:450–466. doi:10.1002/lsm.20950

    Article  PubMed  PubMed Central  Google Scholar 

  29. Hawkins D, Abrahamse H (2005) Biological effects of helium-neon laser irradiation on normal and wounded human skin fibroblasts. Photomed Laser Surg 23:251–259. doi:10.1089/pho.2005.23.251

    Article  CAS  PubMed  Google Scholar 

  30. Karu TI (2010) Multiple roles of cytochrome c oxidase in mammalian cells under action of red and IR-A radiation. IUBMB.Life 62:607–610. doi:10.1002/iub.359

  31. Khakh BS, Burnstock G (2009) The double life of ATP. Sci.Am. 301(84–90):92

    Google Scholar 

  32. Murrell GA, Francis MJ, Bromley L (1990) Modulation of fibroblast proliferation by oxygen free radicals. Biochem.J. 265:659–665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Antunes F, Boveris A and Cadenas E (2004) On the mechanism and biology of cytochrome oxidase inhibition by nitric oxide. Proc.Natl.Acad.Sci.U.S.A 101:16774–16779. doi:10.1073/pnas.0405368101

  34. Chung H, Dai T, Sharma SK, Huang YY, Carroll JD, Hamblin MR (2012) The nuts and bolts of low-level laser (light) therapy. Ann.Biomed.Eng 40:516–533. doi:10.1007/s10439-011-0454-7

    Article  PubMed  PubMed Central  Google Scholar 

  35. Karu TI, Kolyakov SF (2005) Exact action spectra for cellular responses relevant to phototherapy. Photomed.Laser Surg. 23:355–361. doi:10.1089/pho.2005.23.355

    Article  CAS  PubMed  Google Scholar 

  36. Karu T (1989) Photobiology of low-power laser effects. Health Phys 56:691–704

    Article  CAS  PubMed  Google Scholar 

  37. Assis L, Moretti AI, Abrahao TB, Cury V, Souza HP, Hamblin MR, Parizotto NA (2012) Low-level laser therapy (808 nm) reduces inflammatory response and oxidative stress in rat tibialis anterior muscle after cryolesion. Lasers Surg.Med. 44:726–735. doi:10.1002/lsm.22077

    Article  PubMed  PubMed Central  Google Scholar 

  38. Karu TI, Pyatibrat LV, Kalendo GS (2004) Photobiological modulation of cell attachment via cytochrome c oxidase. Photochem.Photobiol.Sci. 3:211–216. doi:10.1039/b306126d

    Article  CAS  PubMed  Google Scholar 

  39. Fujimaki Y, Shimoyama T, Liu Q, Umeda T, Nakaji S, Sugawara K (2003) Low-level laser irradiation attenuates production of reactive oxygen species by human neutrophils. J.Clin.Laser Med.Surg. 21:165–170. doi:10.1089/104454703321895635

    Article  PubMed  Google Scholar 

  40. Silveira PC, da Silva LA, Pinho CA, De Souza PS, Ronsani MM, Scheffer DL, Pinho RA (2013) Effects of low-level laser therapy (GaAs) in an animal model of muscular damage induced by trauma. Lasers Med.Sci. 28:431–436. doi:10.1007/s10103-012-1075-6

    Article  PubMed  Google Scholar 

  41. de Lima FM, Villaverde AB, Albertini R, Correa JC, Carvalho RL, Munin E, Araujo T, Silva JA, Aimbire F (2011) Dual effect of low-level laser therapy (LLLT) on the acute lung inflammation induced by intestinal ischemia and reperfusion: action on anti- and pro-inflammatory cytokines. Lasers Surg.Med. 43:410–420. doi:10.1002/lsm.21053

    Article  PubMed  Google Scholar 

  42. Lohr NL, Keszler A, Pratt P, Bienengraber M, Warltier DC, Hogg N (2009) Enhancement of nitric oxide release from nitrosyl hemoglobin and nitrosyl myoglobin by red/near infrared radiation: potential role in cardioprotection. J.Mol.Cell Cardiol. 47:256–263. doi:10.1016/j.yjmcc.2009.03.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Lopes NN, Plapler H, Chavantes MC, Lalla RV, Yoshimura EM, Alves MT (2009) Cyclooxygenase-2 and vascular endothelial growth factor expression in 5-fluorouracil-induced oral mucositis in hamsters: evaluation of two low-intensity laser protocols. Support Care Cancer 17:1409–1415. doi:10.1007/s00520-009-0603-9

    Article  PubMed  Google Scholar 

  44. Lopes NN, Plapler H, Lalla RV, Chavantes MC, Yoshimura EM, da Silva MA, Alves MT (2010) Effects of low-level laser therapy on collagen expression and neutrophil infiltrate in 5-fluorouracil-induced oral mucositis in hamsters. Lasers Surg.Med. 42:546–552. doi:10.1002/lsm.20920

    Article  PubMed  Google Scholar 

  45. Mendenhall WM, Parsons JT, Buatti JM, Stringer SP, Million RR, Cassisi NJ (1995) Advances in radiotherapy for head and neck cancer. Semin.Surg.Oncol. 11:256–264

    Article  CAS  PubMed  Google Scholar 

  46. Mancini ML, Sonis ST (2014) Mechanisms of cellular fibrosis associated with cancer regimen-related toxicities. Front Pharmacol 5:51. doi:10.3389/fphar.2014.00051

    Article  PubMed  PubMed Central  Google Scholar 

  47. Fillipin LI, Mauriz JL, Vedovelli K, Moreira AJ, Zettler CG, Lech O, Marroni NP, Gonzalez-Gallego J (2005) Low-level laser therapy (LLLT) prevents oxidative stress and reduces fibrosis in rat traumatized Achilles tendon. Lasers Surg Med 37:293–300. doi:10.1002/lsm.20225

    Article  PubMed  Google Scholar 

  48. Lev-Tov H, Brody N, Siegel D, Jagdeo J (2013) Inhibition of fibroblast proliferation in vitro using low-level infrared light-emitting diodes. Dermatol.Surg. 39:422–425. doi:10.1111/dsu.12087

    Article  CAS  PubMed  Google Scholar 

  49. Huang YY, Chen AC, Carroll JD, Hamblin MR (2009) Biphasic dose response in low level light therapy. Dose.Response 7:358–383. doi:10.2203/dose-response.09-027.Hamblin

    Article  PubMed  PubMed Central  Google Scholar 

  50. Huang YY, Sharma SK, Carroll J, Hamblin MR (2011) Biphasic dose response in low level light therapy—an update. Dose.Response 9:602–618. doi:10.2203/dose-response.11-009.Hamblin

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Sommer AP, Pinheiro AL, Mester AR, Franke RP, Whelan HT (2001) Biostimulatory windows in low-intensity laser activation: lasers, scanners, and NASA’s light-emitting diode array system. J.Clin.Laser Med.Surg. 19:29–33. doi:10.1089/104454701750066910

    Article  CAS  PubMed  Google Scholar 

  52. (WALT) WAfLT www.waltza.co.za.

  53. Bjordal JM (2012) Low level laser therapy (LLLT) and World Association for Laser Therapy (WALT) dosage recommendations. Photomed Laser Surg 30:61–62. doi:10.1089/pho.2012.9893

    Article  PubMed  Google Scholar 

  54. Jenkins PA, Carroll JD (2011) How to report low-level laser therapy (LLLT)/photomedicine dose and beam parameters in clinical and laboratory studies. Photomed.Laser Surg. 29:785–787. doi:10.1089/pho.2011.9895

    Article  PubMed  Google Scholar 

  55. Guirro RR, Weis LC (2009) Radiant power determination of low-level laser therapy equipment and characterization of its clinical use procedures. Photomed.Laser Surg. 27:633–639. doi:10.1089/pho.2008.2361

    Article  PubMed  Google Scholar 

  56. Gomes Henriques AC, Ginani F, Oliveira RM, Keesen TS, Galvao Barboza CA, Oliveira Rocha HA, de Castro JF, Della Coletta R, de Almeida FR (2014) Low-level laser therapy promotes proliferation and invasion of oral squamous cell carcinoma cells. Lasers Med Sci 29:1385–1395. doi:10.1007/s10103-014-1535-2

    PubMed  Google Scholar 

  57. Simpson DR, Mell LK, Cohen EE (2015) Targeting the PI3K/AKT/mTOR pathway in squamous cell carcinoma of the head and neck. Oral Oncol 51:291–298. doi:10.1016/j.oraloncology.2014.11.012

    Article  CAS  PubMed  Google Scholar 

  58. Chang L, Graham PH, Hao J, Ni J, Bucci J, Cozzi PJ, Kearsley JH, Li Y (2013) Acquisition of epithelial-mesenchymal transition and cancer stem cell phenotypes is associated with activation of the PI3K/Akt/mTOR pathway in prostate cancer radioresistance. Cell Death Dis 4:e875. doi:10.1038/cddis.2013.407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Nagata Y, Takahashi A, Ohnishi K, Ota I, Ohnishi T, Tojo T, Taniguchi S (2010) Effect of rapamycin, an mTOR inhibitor, on radiation sensitivity of lung cancer cells having different p53 gene status. Int J Oncol 37:1001–1010

    Article  CAS  PubMed  Google Scholar 

  60. Pellicioli AC, Martins MD, Dillenburg CS, Marques MM, Squarize CH, Castilho RM (2014) Laser phototherapy accelerates oral keratinocyte migration through the modulation of the mammalian target of rapamycin signaling pathway. J Biomed Opt 19:028002. doi:10.1117/1.jbo.19.2.028002

    Article  PubMed  Google Scholar 

  61. Sperandio FF, Giudice FS, Correa L, Pinto DS Jr, Hamblin MR, de Sousa SC (2013) Low-level laser therapy can produce increased aggressiveness of dysplastic and oral cancer cell lines by modulation of Akt/mTOR signaling pathway. J.Biophotonics. doi:10.1002/jbio.201300015

  62. Pardali K, Moustakas A (2007) Actions of TGF-beta as tumor suppressor and pro-metastatic factor in human cancer. Biochim Biophys Acta 1775:21–62. doi:10.1016/j.bbcan.2006.06.004

    CAS  PubMed  Google Scholar 

  63. Siegel PM, Massague J (2003) Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer. Nat Rev Cancer 3:807–821. doi:10.1038/nrc1208

    Article  CAS  PubMed  Google Scholar 

  64. Prime SS, Davies M, Pring M, Paterson IC (2004) The role of TGF-beta in epithelial malignancy and its relevance to the pathogenesis of oral cancer (part II). Crit Rev Oral Biol Med 15:337–347

    Article  CAS  PubMed  Google Scholar 

  65. Hwang YS, Park KK, Chung WY (2014) Stromal transforming growth factor-beta 1 is crucial for reinforcing the invasive potential of low invasive cancer. Arch Oral Biol 59:687–694. doi:10.1016/j.archoralbio.2014.03.017

    Article  CAS  PubMed  Google Scholar 

  66. Dang Y, Liu B, Liu L, Ye X, Bi X, Zhang Y, Gu J (2011) The 800-nm diode laser irradiation induces skin Collagen synthesis by stimulating TGF-beta/smad signaling pathway. Lasers Med Sci 26:837–843. doi:10.1007/s10103-011-0985-z

    Article  PubMed  Google Scholar 

  67. Chen YK, Huang AH, Cheng PH, Yang SH, Lin LM (2013) Overexpression of smad proteins, especially Smad7, in oral epithelial dysplasias. Clin Oral Investig 17:921–932. doi:10.1007/s00784-012-0756-7

    Article  PubMed  Google Scholar 

  68. Dhillon AS, Hagan S, Rath O, Kolch W (2007) MAP kinase signalling pathways in cancer. Oncogene 26:3279–3290. doi:10.1038/sj.onc.1210421

    Article  CAS  PubMed  Google Scholar 

  69. Cui X, Li S, Li T, Pang X, Zhang S, Jin J, Hu J, Liu C, Yang L, Peng H, Jiang J, Liang W, Suo J, Li F, Chen Y (2014) Significance of elevated ERK expression and its positive correlation with EGFR in Kazakh patients with esophageal squamous cell carcinoma. Int J Clin Exp Pathol 7:2382–2391

    PubMed  PubMed Central  Google Scholar 

  70. Feng J, Zhang Y, Xing D (2012) Low-power laser irradiation (LPLI) promotes VEGF expression and vascular endothelial cell proliferation through the activation of ERK/Sp1 pathway. Cell Signal 24:1116–1125. doi:10.1016/j.cellsig.2012.01.013

    Article  CAS  PubMed  Google Scholar 

  71. Kawano Y, Utsunomiya-Kai Y, Kai K, Miyakawa I, Ohshiro T, Narahara H (2012) The production of VEGF involving MAP kinase activation by low level laser therapy in human granulosa cells. Laser Ther 21:269–274. doi:10.5978/islsm.12-OR-15

    Article  PubMed  PubMed Central  Google Scholar 

  72. Gupta A, Keshri GK, Yadav A, Gola S, Chauhan S, Salhan AK, Bala Singh S (2014) Superpulsed (Ga-As, 904 nm) low-level laser therapy (LLLT) attenuates inflammatory response and enhances healing of burn wounds. J Biophotonics 9999. doi:10.1002/jbio.201400058

  73. Kushibiki T, Hirasawa T, Okawa S, Ishihara M (2013) Regulation of miRNA expression by low-level laser therapy (LLLT) and photodynamic therapy (PDT). Int J Mol Sci 14:13542–13558. doi:10.3390/ijms140713542

    Article  PubMed  PubMed Central  Google Scholar 

  74. Png KJ, Halberg N, Yoshida M, Tavazoie SF (2012) A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells. Nature 481:190–194. doi:10.1038/nature10661

    Article  CAS  Google Scholar 

  75. Song S, Zhou F, Chen WR (2012) Low-level laser therapy regulates microglial function through Src-mediated signaling pathways: implications for neurodegenerative diseases. J.Neuroinflammation. 9:219. doi:10.1186/1742-2094-9-219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Shabbir M, Ryten M, Thompson C, Mikhailidis D and Burnstock G (2008) Purinergic receptor-mediated effects of ATP in high-grade bladder cancer. BJU.Int. 101:106–112. doi:10.1111/j.1464-410X.2007.07286.x

  77. Marchesini R, Dasdia T, Melloni E, Rocca E (1989) Effect of low-energy laser irradiation on colony formation capability in different human tumor cells in vitro. Lasers Surg.Med. 9:59–62

    Article  CAS  PubMed  Google Scholar 

  78. Kreisler M, Christoffers AB, Willershausen B, d'Hoedt B (2003) Low-level 809 nm GaAlAs laser irradiation increases the proliferation rate of human laryngeal carcinoma cells in vitro. Lasers Med.Sci. 18:100–103. doi:10.1007/s10103-003-0265-7

    Article  CAS  PubMed  Google Scholar 

  79. de Castro JL, Pinheiro AL, Werneck CE, Soares CP (2005) The effect of laser therapy on the proliferation of oral KB carcinoma cells: an in vitro study. Photomed.Laser Surg. 23:586–589. doi:10.1089/pho.2005.23.586

    Article  PubMed  Google Scholar 

  80. Schaffer M, Sroka R, Fuchs C, Schrader-Reichardt U, Schaffer PM, Busch M and Duhmke E (1997) Biomodulative effects induced by 805 nm laser light irradiation of normal and tumor cells. J.Photochem.Photobiol.B 40:253–257.

  81. Pinheiro AL, Carneiro NS, Vieira AL, Brugnera A Jr, Zanin FA, Barros RA, Silva PS (2002) Effects of low-level laser therapy on malignant cells: in vitro study. J.Clin.Laser Med.Surg. 20:23–26. doi:10.1089/104454702753474977

  82. Werneck CE, Pinheiro AL, Pacheco MT, Soares CP, de Castro JL (2005) Laser light is capable of inducing proliferation of carcinoma cells in culture: a spectroscopic in vitro study. Photomed.Laser Surg. 23:300–303. doi:10.1089/pho.2005.23.300

    Article  PubMed  Google Scholar 

  83. Renno AC, McDonnell PA, Parizotto NA, Laakso EL (2007) The effects of laser irradiation on osteoblast and osteosarcoma cell proliferation and differentiation in vitro. Photomed.Laser Surg. 25:275–280. doi:10.1089/pho.2007.2055

    Article  CAS  PubMed  Google Scholar 

  84. Powell K, Low P, McDonnell PA, Laakso EL, Ralph SJ (2010) The effect of laser irradiation on proliferation of human breast carcinoma, melanoma, and immortalized mammary epithelial cells. Photomed.Laser Surg. 28:115–123. doi:10.1089/pho.2008.2445

    Article  PubMed  Google Scholar 

  85. Coombe AR, Ho CT, Darendeliler MA, Hunter N, Philips JR, Chapple CC, Yum LW (2001) The effects of low level laser irradiation on osteoblastic cells. Clin.Orthod.Res. 4:3–14

    Article  PubMed  Google Scholar 

  86. Liu YH, Cheng CC, Ho CC, Pei RJ, Lee KY, Yeh KT, Chan Y, Lai YS (2004) Effects of diode 808 nm GaAlAs low-power laser irradiation on inhibition of the proliferation of human hepatoma cells in vitro and their possible mechanism. Res Commun Mol Pathol Pharmacol 115-116:185–201

    CAS  PubMed  Google Scholar 

  87. Sroka R, Schaffer M, Fuchs C, Pongratz T, Schrader-Reichard U, Busch M, Schaffer PM, Duhmke E, Baumgartner R (1999) Effects on the mitosis of normal and tumor cells induced by light treatment of different wavelengths. Lasers Surg.Med. 25:263–271. doi:10.1002/(SICI)1096-9101(1999)25:3<263::AID-LSM11>3.0.CO;2-T

    Article  CAS  PubMed  Google Scholar 

  88. Murayama H, Sadakane K, Yamanoha B, Kogure S (2012) Low-power 808-nm laser irradiation inhibits cell proliferation of a human-derived glioblastoma cell line in vitro. Lasers Med Sci 27:87–93. doi:10.1007/s10103-011-0924-z

    Article  PubMed  Google Scholar 

  89. Al-Watban FA, Andres BL (2012) Laser biomodulation of normal and neoplastic cells. Lasers Med Sci 27:1039–1043. doi:10.1007/s10103-011-1040-9

    Article  PubMed  Google Scholar 

  90. Crous AM, Abrahamse H (2013) Lung cancer stem cells and low-intensity laser irradiation: a potential future therapy? Stem Cell Res Ther 4:129. doi:10.1186/scrt340

    Article  PubMed  PubMed Central  Google Scholar 

  91. Schartinger VH, Galvan O, Riechelmann H, Dudas J (2012) Differential responses of fibroblasts, non-neoplastic epithelial cells, and oral carcinoma cells to low-level laser therapy. Support. Care Cancer 20:523–529. doi:10.1007/s00520-011-1113-0

    Article  PubMed  Google Scholar 

  92. Tsai SR, Yin R, Huang YY, Sheu BC, Lee SC, Hamblin MR (2015) Low-level light therapy potentiates NPe6-mediated photodynamic therapy in a human osteosarcoma cell line via increased ATP. Photodiagn Photodyn Ther 12:123–130. doi:10.1016/j.pdpdt.2014.10.009

    Article  CAS  Google Scholar 

  93. Barasch A, Raber-Durlacher J, Epstein JB, Carroll J (2015) Effects of pre-radiation exposure to LLLT of normal and malignant cells. Support Care Cancer. doi:10.1007/s00520-015-3051-8

    PubMed  Google Scholar 

  94. Mester E, Szende B, Gartner P (1968) The effect of laser beams on the growth of hair in mice. RadiobiolRadiother(Berl) 9:621–626

    CAS  Google Scholar 

  95. de CMJ, Pinheiro AN, de Oliveira SC, Aciole GT, Sousa JA, Canguss MC and Dos Santos JN (2011) Influence of laser phototherapy (lambda 660 nm) on the outcome of oral chemical carcinogenesis on the hamster cheek pouch model: histological study. Photomed.Laser Surg. 29:741–745. doi:10.1089/pho.2010.2896

  96. Frigo L, Luppi JS, Favero GM, Maria DA, Penna SC, Bjordal JM, Bensadoun RJ, Lopes-Martins RA (2009) The effect of low-level laser irradiation (In-Ga-Al-AsP—660 nm) on melanoma in vitro and in vivo. BMC.Cancer 9:404. doi:10.1186/1471-2407-9-404

    Article  PubMed  PubMed Central  Google Scholar 

  97. Myakishev-Rempel M, Stadler I, Brondon P, Axe DR, Friedman M, Nardia FB, Lanzafame R (2012) A preliminary study of the safety of red light phototherapy of tissues harboring cancer. Photomed.Laser Surg. 30:551–558. doi:10.1089/pho.2011.3186

    Article  PubMed  PubMed Central  Google Scholar 

  98. Schaffer M, Bonel H, Sroka R, Schaffer PM, Busch M, Reiser M, Duhmke E (2000) Effects of 780 nm diode laser irradiation on blood microcirculation: preliminary findings on time-dependent T1-weighted contrast-enhanced magnetic resonance imaging (MRI). J Photochem Photobiol B 54:55–60

    Article  CAS  PubMed  Google Scholar 

  99. 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 109:297–302. doi:10.1016/j.radonc.2013.08.010

    Article  PubMed  Google Scholar 

  100. Liu TC, Zhang J, Li XE (2013) The balance between normal and tumor tissues in phototherapy of tissues harboring cancer. Photomed Laser Surg 31:93–94. doi:10.1089/pho.2012.3355

    Article  PubMed  Google Scholar 

  101. Sonis ST, Hashemi S, Epstein JB, Nair RG, Raber-Durlacher JE (2016) Could the biological robustness of low level laser therapy (Photobiomodulation) impact its use in the management of mucositis in head and neck cancer patients. Oral Oncol.54:7–14. doi::10.1016/j.oraloncology.2016.01.005

Download references

Author information

Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    Judith A. E. M. Zecha, Judith E. Raber-Durlacher, Dan M. J. Milstein, Jan de Lange & Ludi E. Smeele

  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

    Judith E. Raber-Durlacher

  3. Department of Haematology and Oncology/Cancer Services, Gold Coast University Hospital, Queensland Health, Gold Coast, QLD, Australia

    Raj G. Nair

  4. Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA

    Joel B. Epstein

  5. Division of Otolaryngology and Head and Neck Surgery, City of Hope, Duarte, CA, 91010, USA

    Joel B. Epstein

  6. Division of Oral Medicine, Brigham and Women’s Hospital and the Dana-Farber Cancer Institute and Biomodels LLC, Boston, MA, 02115, USA

    Stephen T. Sonis

  7. Division of Oral Medicine, Eastman Institute for Oral Health, and Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, 14620, USA

    Sharon Elad

  8. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, 02114, USA

    Michael R. Hamblin

  9. Department of Dermatology, Harvard Medical School, Boston, MA, 02115, USA

    Michael R. Hamblin

  10. Harvard-MIT Division of Health Science and Technology, Cambridge, MA, 02139, USA

    Michael R. Hamblin

  11. Weill Cornell Medical Center, Division of Oncology, New York, NY, USA

    Andrei Barasch

  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

    Cesar A. Migliorati

  13. Laser Therapy Unit, Institut Jules Bordet, Centre des Tumeurs de l’Université Libre de Bruxelles, Brussels, Belgium

    Marie-Thérèse Genot

  14. Antoni van Leeuwenhoek Department of Head and Neck Oncology and Surgery, Netherlands Cancer Institute, Amsterdam, The Netherlands

    Liset Lansaat, Lisette van der Molen, Irene Jacobi & Ludi E. Smeele

  15. City of Hope, Duarte, CA, 91010, USA

    Ron van der Brink

  16. Department of Oral Surgery, Faculty of Dentistry, University of Barcelona, Barcelona, Spain

    Josep Arnabat-Dominguez

  17. Antoni van Leeuwenhoek Department Radiation Oncology Amsterdam, Netherlands Cancer Institute, Amsterdam, The Netherlands

    Judi van Diessen

  18. Seattle Cancer Care Alliance (SCCA), 825 Eastlake Ave E Ste G6900, Seattle, WA, 98109, USA

    Mark M. Schubert

  19. World Association for Laser Therapy (WALT) Scientific Secretary, Centre de Haute Energie (CHE), 10 Bd Pasteur, 06000, Nice, France

    René-Jean Bensadoun

Authors
  1. Judith A. E. M. Zecha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Judith E. Raber-Durlacher
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Raj G. Nair
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joel B. Epstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Stephen T. Sonis
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sharon Elad
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Michael R. Hamblin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Andrei Barasch
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Cesar A. Migliorati
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Dan M. J. Milstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Marie-Thérèse Genot
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Liset Lansaat
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Ron van der Brink
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Josep Arnabat-Dominguez
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Lisette van der Molen
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Irene Jacobi
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Judi van Diessen
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Jan de Lange
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Ludi E. Smeele
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Mark M. Schubert
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. René-Jean Bensadoun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to René-Jean Bensadoun.

Ethics declarations

Judith E. Raber-Durlacher, Raj G. Nair, Joel B. Epstein, Ron van der Brink, Josep Arnabat Dominguez, and Rene-Jean Bensadoun have received travel expenses and hotel accommodation from THOR Photomedicine Ltd. UK. Raj Nair has received an honorarium from THOR, UK. Michael R Hamblin was supported by US NIH grant R01AI050875. All the other authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zecha, J.A.E.M., Raber-Durlacher, J.E., Nair, R.G. et al. 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. Support Care Cancer 24, 2781–2792 (2016). https://doi.org/10.1007/s00520-016-3152-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00520-016-3152-z

Keywords

Search

Navigation