Photobiomodulation (low-level laser) therapy for immediate pain relief of persistent oral ulcers in chronic graft-versus-host disease

Abstract

Purpose

To determine the immediate pain-relieving effect of photobiomodulation therapy (PBMt) in patients with oral ulcers of chronic graft-versus-host disease (cGVHD) refractory to first line therapy with topical corticosteroids.

Methods

This retrospective study included all patients who underwent PBMt for pain relief of refractory oral cGVHD lesions. PBMt was applied using an intraoral approach to all sites with mucosal lesions, using a 940 nm InGaAsP diode laser device, with the following parameters: pulsed modulation (duty cycle of 50%), power 0.7 W, illuminated spot size 7.1 cm2, irradiance 98.6 mW/cm2, and irradiation time 90 s per point. Pain was self-assessed using a 0-to-10 scale immediately before and after PBMt.

Results

Data from eleven patients with a total of 56 PBMt sessions were analyzed. In 48 (85.7%) sessions, the patients reported less pain immediately after treatment, with a reduction of ≥ 50% of the initial pain level in 43 (76.8%) sessions. Mean pre- and post-treatment pain levels were 5.20 ±2.7 and 1.38 ±2.1, respectively (p < 0.001), i.e., a post-treatment reduction of 73.4% of the initial pain level. The benefits of the treatment remained for a mean of 6.50 ±5.4 days (range of 2 to 14 days). No adverse effects were reported.

Conclusions

PBMt seems to be a promising treatment modality for refractory oral cGVHD lesions as a rapid pain reliever with relatively long-lasting effects.

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Data availability

N/A (all the relevant data is provided in the article).

References

  1. 1.

    Elad S, Aljitawi O, Zadik Y (2020) Oral graft-versus-host disease: a pictorial review and a guide for dental practitioners. Int Dent J. In press. https://doi.org/10.1111/idj.12584

  2. 2.

    Elad S, Zadik Y, Caton JG, Epstein JB (2019) Oral mucosal changes associated with primary diseases in other body systems. Periodontol 2000 80(1):28–48. https://doi.org/10.1111/prd.12265

    Article  PubMed  Google Scholar 

  3. 3.

    Elad S, Zadik Y, Zeevi I, Miyazaki A, de Figueiredo MA, Or R (2010) Oral cancer in patients after hematopoietic stem-cell transplantation: long-term follow-up suggests an increased risk for recurrence. Transplantation. 90(11):1243–1244. https://doi.org/10.1097/TP.0b013e3181f9caaa

    Article  PubMed  Google Scholar 

  4. 4.

    Bar O, Elad S, Avni B, Abu-Tair J, Zaharia B, Hanut A, Zadik Y (2021) Oral verruciform xanthoma in chronic graft-versus-host disease patients. Support Care Cancer. 29(1):79–84. https://doi.org/10.1007/s00520-020-05681-w

    Article  PubMed  Google Scholar 

  5. 5.

    Kuten-Shorrer M, Woo SB, Treister NS (2014) Oral graft-versus-host disease. Dent Clin North Am. 58(2):351–368. https://doi.org/10.1016/j.cden.2013.12.007

    Article  PubMed  Google Scholar 

  6. 6.

    Zadik Y (2016) Restricted mouth opening in chronic graft-versus-host disease. Oral Surg Oral Med Oral Pathol Oral Radiol. 121(2):201–202. https://doi.org/10.1016/j.oooo.2015.07.041

    Article  PubMed  Google Scholar 

  7. 7.

    Elad S, Zadik Y, Yarom N (2017) Oral complications of nonsurgical cancer therapies. Atlas Oral Maxillofac Surg Clin North Am. 25(2):133–147. https://doi.org/10.1016/j.cxom.2017.04.006

    Article  PubMed  Google Scholar 

  8. 8.

    Elad S, Jensen SB, Raber-Durlacher JE, Mouradian N, Correa EMP, Schubert MM, Blijlevens NMA, Epstein JB, Saunders DP, Waltimo T, Yarom N, Zadik Y, Brennan MT (2015) Clinical approach in the management of oral chronic graft-versus-host disease (cGVHD) in a series of specialized medical centers. Support Care Cancer. 23(6):1615–1622. https://doi.org/10.1007/s00520-014-2503-x

    Article  PubMed  Google Scholar 

  9. 9.

    Zadik Y, Elad S, Shapira A, Shapira MY (2017) Treatment of oral mucosal manifestations of chronic graft-versus-host disease: dexamethasone vs. budesonide. Expert Opin Pharmacother. 18(3):235–242. https://doi.org/10.1080/14656566.2017.1282464

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Treister N, Duncan C, Cutler C, Lehmann L (2012) How we treat oral chronic graft-versus-host disease. Blood. 120(17):3407–3418. https://doi.org/10.1182/blood-2012-05-393389

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Hui RL, Lide W, Chan J, Schottinger J, Yoshinaga M, Millares M (2009) Association between exposure to topical tacrolimus or pimecrolimus and cancers. Ann Pharmacother. 43(12):1956–1963. https://doi.org/10.1345/aph.1M278

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Cai SC, Li W, Tian EA, Allen JC, Tey HL (2016) Topical calcineurin inhibitors in eczema and cancer association: a cohort study. J Dermatolog Treat. 27(6):531–537. https://doi.org/10.3109/09546634.2016.1163317

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Zadik Y (2020) Pharmacotherapy of oral mucosal manifestations of chronic graft-versus-host disease: when? what? and how? Expert Opin Pharmacother. 21(12):1389–1392. https://doi.org/10.1080/14656566.2020.1763307

    Article  PubMed  Google Scholar 

  14. 14.

    Epstein JB, Raber-Durlacher JE, Lill M, Linhares YPL, Chang J, Barasch A, Slief RIC, Geuke M, Zecha JAEM, Milstein DMJ, Tzachanis D (2017) Photobiomodulation therapy in the management of chronic oral graft-versus-host disease. Support Care Cancer. 25(2):357–364. https://doi.org/10.1007/s00520-016-3401-1

    Article  PubMed  Google Scholar 

  15. 15.

    Epstein JB, Raber-Durlacher JE, Epstein GL, Hazenberg MD, Tzachanis D, Spielberger RT (2020) Chronic oral graft-versus-host disease: induction and maintenance therapy with photobiomodulation therapy. Support Care Cancer. In press. https://doi.org/10.1007/s00520-020-05626-3

  16. 16.

    Arany PR (2016) Craniofacial wound healing with photobiomodulation therapy: new insights and current challenges. J Dent Res. 95(9):977–984. https://doi.org/10.1177/0022034516648939

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Gavish L, Houreld NN (2019) Therapeutic efficacy of home-use photobiomodulation devices: a systematic literature review. Photobiomodul Photomed Laser Surg. 37(1):4–16. https://doi.org/10.1089/photob.2018.4512

    Article  PubMed  Google Scholar 

  18. 18.

    Dillenburg CS, Martins MA, Munerato MC, Marques MM, Carrard VC, Sant'Ana Filho M, Castilho RM, Martins MD (2014) Efficacy of laser phototherapy in comparison to topical clobetasol for the treatment of oral lichen planus: a randomized controlled trial. J Biomed Opt. 19(6):068002. https://doi.org/10.1117/1.JBO.19.6.068002

    Article  PubMed  Google Scholar 

  19. 19.

    Jajarm HH, Falaki F, Mahdavi O (2011) A comparative pilot study of low intensity laser versus topical corticosteroids in the treatment of erosive-atrophic oral lichen planus. Photomed Laser Surg. 29(6):421–425. https://doi.org/10.1089/pho.2010.2876

    Article  PubMed  Google Scholar 

  20. 20.

    El Shenawy HM, Eldin AM (2015) A comparative evaluation of low-level laser and topical steroid therapies for the treatment of erosive-atrophic lichen planus. Open Access Maced J Med Sci. 3(3):462–466. https://doi.org/10.3889/oamjms.2015.072

    Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Al-Maweri SA, Kalakonda B, Al-Soneidar WA, Al-Shamiri HM, Alakhali MS, Alaizari N (2017) Efficacy of low-level laser therapy in management of symptomatic oral lichen planus: a systematic review. Lasers Med Sci. 32(6):1429–1437. https://doi.org/10.1007/s10103-017-2233-7

    Article  PubMed  Google Scholar 

  22. 22.

    Akram Z, Abduljabbar T, Vohra F, Javed F (2018) Efficacy of low-level laser therapy compared to steroid therapy in the treatment of oral lichen planus: a systematic review. J Oral Pathol Med. 47(1):11–17. https://doi.org/10.1111/jop.12619

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    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(6):365–381. https://doi.org/10.1089/pho.2010.2928

    Article  PubMed  Google Scholar 

  24. 24.

    Zecha JA, Raber-Durlacher JE, Nair RG, Epstein JB, Sonis ST, Elad S, Hamblin MR, Barasch A, Migliorati CA, Milstein DM, Genot MT, Lansaat L, van der Brink R, Arnabat-Dominguez J, van der Molen L, Jacobi I, van Diessen J, de Lange J, Smeele LE, Schubert MM, Bensadoun RJ (2016) 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(6):2781–2792. https://doi.org/10.1007/s00520-016-3152-z

    Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Zadik Y (2019) Photobiomodulation for the palliation of oral mucositis in cancer patients: the future is here. Future Oncol. 15(32):3647–3649. https://doi.org/10.2217/fon-2019-0461

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Treister NS, London WB, Guo D, Malsch M, Verrill K, Brewer J, Margossian S, Duncan C (2016) A feasibility study evaluating extraoral photobiomodulation therapy for prevention of mucositis in pediatric hematopoietic cell transplantation. Photomed Laser Surg. 34(4):178–184. https://doi.org/10.1089/pho.2015.4021

    Article  PubMed  Google Scholar 

  27. 27.

    Zadik Y, Arany PR, Fregnani ER et al (2019) Systematic review of photobiomodulation for the management of oral mucositis in cancer patients and clinical practice guidelines. Support Care Cancer. 27(10):3969–3983. https://doi.org/10.1007/s00520-019-04890-2

    Article  PubMed  Google Scholar 

  28. 28.

    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(6):1747–1757. https://doi.org/10.1016/j.ajpath.2013.09.003

    Article  PubMed  Google Scholar 

  29. 29.

    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. https://doi.org/10.1016/j.oraloncology.2016.01.005

    Article  PubMed  Google Scholar 

  30. 30.

    Antunes HS, Herchenhorn D, Small IA, Araújo CMM, Viégas 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. 71:11–15. https://doi.org/10.1016/j.oraloncology.2017.05.018

    Article  PubMed  Google Scholar 

  31. 31.

    Brandão 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(7):2417–2423. https://doi.org/10.1007/s00520-018-4046-z

    Article  PubMed  Google Scholar 

  32. 32.

    Zecha JA, Raber-Durlacher JE, Nair RG et al (2016) Low-level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 2: proposed applications and treatment protocols. Support Care Cancer. 24(6):2793–2805. https://doi.org/10.1007/s00520-016-3153-y

    Article  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Heiskanen V, Zadik Y, Elad S (2020) Photobiomodulation therapy for cancer treatment-related salivary gland dysfunction: a systematic review. Photobiomodul Photomed Laser Surg. 38(6):340–347. https://doi.org/10.1089/photob.2019.4767

    Article  PubMed  Google Scholar 

  34. 34.

    Elad S, Cheng KKF, Lalla RV, Yarom N, Hong C, Logan RM, Bowen J, Gibson R, Saunders DP, Zadik Y, Ariyawardana A, Correa ME, Ranna V (2020) Bossi P; Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO). MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 126(19):4423–4431. https://doi.org/10.1002/cncr.33100

    Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Miranda-Silva W, Gomes-Silva W, Zadik Y, Yarom N, Al-Azri AR, Hong CHL, Ariyawardana A, Saunders DP, Correa ME, Arany PR, Bowen J, Cheng KKF, Tissing WJE, Bossi P, Elad S (2020) MASCC/ISOO clinical practice guidelines for the management of mucositis: sub-analysis of current interventions for the management of oral mucositis in pediatric cancer patients. Support Care Cancer. In press. https://doi.org/10.1007/s00520-020-05803-4

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Affiliations

Authors

Contributions

Conceptualization, Y.Z., O.F., B.A., S.G., and O.R.; methodology, Y.Z., O.F., B.A., S.G., and O.R.; data acquisition, O.F.; data analysis, Y.Z.; data interpretation, Y.Z., O.F., B.A., S.G., Y.H., C.N., and O.R.; writing—original draft preparation, Y.Z.; writing—review and editing, O.F., B.A., S.G., Y.H., C.N., and O.R.; supervision, Y.Z.; project administration, Y.Z.; all authors have read and agreed to the final version of the article.

Corresponding author

Correspondence to Yehuda Zadik.

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The study protocol was approved by the Institutional Review Board (HMO-20-0330).

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The Institutional Review Board determined of exemption from informed consent (because of the retrospective design of the study).

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Finfter, O., Avni, B., Grisariu, S. et al. Photobiomodulation (low-level laser) therapy for immediate pain relief of persistent oral ulcers in chronic graft-versus-host disease. Support Care Cancer (2021). https://doi.org/10.1007/s00520-021-05997-1

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Keywords

  • Allogeneic hematopoietic stem cell transplantation
  • Chronic graft-versus-host disease
  • Hematopoietic stem cell transplantation
  • Low-level laser
  • Oral complications
  • Oral medicine
  • Pain
  • Photobiomodulation