Efficacy of 5% methylene blue photodynamic therapy in the treatment of potentially malignant oral disorders: a randomized, double-blind, controlled trial
DOI:
https://doi.org/10.18203/2349-3259.ijct20242003Keywords:
PDT, Methylene blue, Treatment, Effectiveness, PMODAbstract
Background: Potentially malignant oral disorders (PMOD) play a vital role in the secondary prevention of oral cancer, especially considering the difficulty in identifying specific risk factors. Oral leukoplakia (OL), the most common PMOD, has a variable malignant transformation rate. Photodynamic therapy (PDT) emerges as a promising alternative in treating these conditions. This approach is particularly valuable for extensive lesions or patients with contraindications to conventional treatments. Despite promising results, the choice of photosensitizer agent still lacks consensus. The aim of this study is to evaluate the efficacy of PDT with 5% methylene blue compared to 20% aminolevulinic acid (ALA) in the treatment of OL.
Methods: This is a randomized, controlled, double-blind clinical trial with a non-inferiority testing approach. Patients will be allocated into two groups: leukoplakia experimental group (PDT with methylene blue) and leukoplakia control group (PDT with ALA). The analysis of results will be based on primary outcomes (clinical remission) and secondary outcomes (histological/cytological worsening, lesion appearance, symptoms, function, psychological impact, economic impact, treatment adherence, and adverse effects). Allocation will be performed in a randomized and stratified manner, ensuring equivalence between groups. Cost-effectiveness analysis will consider the direct costs of treatment from both professional and patient perspectives.
Conclusions: This study aims to contribute to the establishment of an effective, safe, and accessible treatment protocol for the most prevalent PMOD, filling an important gap in the scientific literature and providing guidelines for future clinical practices.
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References
Global Cancer Observatory (GLOBOCAN), 2020-International Agency for Research on Cancer (IARC). Available at: https://gco.iarc.fr/today/ data/factsheets/populations/900-world-fact-sheets.pdf. Accessed on 9 Mrch 2024.
Warnakulasuriya S, Kujan O, Aguirre-Urizar JM, Bagan JV, González-Moles MA, Kerr AR, et al. Oral potentially malignant disorders: A consensus report from an international seminar on nomenclature and classification, convened by the WHO Collaborating Centre for Oral Cancer. Oral Dis. 2021;27(8):1862-80.
Santos ES, Pérez-de-Oliveira ME, Normando AGC, Gueiros LAM, Rogatto SR, Vargas PA, et al. Systemic conditions associated with increased risk to develop oral squamous cell carcinoma: Systematic review and meta-analysis. Head Neck. 2022;44(12):2925-37.
Warnakulasuriya S, Johnson NW, Van der Waal I. Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol and Med. 2007;36(10):575-80.
Aguirre-Urizar JM, Lafuente-Ibáñez de Mendoza I, Warnakulasuriya S. Malignant transformation of oral leukoplakia: Systematic review and meta-analysis of the last 5 years. Oral Dis. 2021;27(8):1881-95.
Arduino PG, Surace A, Carbone M, Elia A, Massolini G, Gandolfo S, et al. Outcome of oral dysplasia: a retrospective hospital-based study of 207 patients with a long follow-up. J Oral Pathol Med. 2009;38(6):540-4.
Jin X, Jin X, Xu H, Deng J, Dan H, Ji P, et al. Photodynamic therapy for oral potentially malignant disorders. Photodiagnosis Photodyn Ther. 2019;28:146-52.
Gulzar MA, Gul N, Alvi FD, Khattak YR, Hasan US, Haneef MB, et al. Comparison of photodynamic therapy and corticosteroid therapy in management of oral lichen planus: A systematic review of randomized controlled trials. Photodiagnosis Photodyn Ther. 2023;44:103747.
Figueira JA, Veltrini VC. Photodynamic therapy in oral potentially malignant disorders-Critical literature review of existing protocols. Photodiagnosis Photodyn Ther. 2017;20:125-9.
Dolmans DE, Fukumura D, Jain RK. Photodynamic therapy for cancer. Nat Rev Cancer. 2003;3(5):380e7.
Sulewska M, Duraj E, Sobaniec S, Graczyk A, Milewski R, Wróblewska M, et al. A clinical evaluation of efficacy of photodynamic therapy in treatment of reticular oral lichen planus: a case series. Photodiagnosis Photodyn Ther. 2019;25:50-7.
Nagi R, Muthukrishnan A, Rakesh N. of photodynamic therapy (PDT) in the management of symptomatic oral lichen planus-A systematic review. J Oral Biol Craniofac Res. 2023;13(2):353-9.
He Y, Deng J, Zhao Y, Tao H, Dan H, Xu H, et al. Efficacy evaluation of photodynamic therapy for oral lichen planus: a systematic review and meta-analysis. BMC Oral Health. 2020;20(1):302.
Zhang R, Gao T, Wang D. Photodynamic therapy (PDT) for oral leukoplakia: a systematic review and meta-analysis of single-arm studies examining efficacy and subgroup analyses. BMC Oral Health. 2023;23(1):568.
Binnal A, Tadakamadla J, Rajesh G, Tadakamadla SK. Photodynamic therapy for oral potentially malignant disorders: A systematic review and meta-analysis. Photodiagnosis Photodyn Ther. 2022;37:102713.
Prasanna SW, Ingle E, Aruna PR, Pravada C, Koteeswaran D, Ganesan S. Photodynamic therapy of oral leukoplakia and oral lichen planus using methylene blue: A pilot study. J Innov Opt H Sci. 2015;1540005.
Dong B, Zhou G, Lu R. Effect of photodynamic therapy for oral potentially malignant disorders: How should we evaluate it? Photodiagnosis Photodyn Ther. 2023;42:103610.
Peralta-Mamani M, Silva BM, Honório HM, Rubira-Bullen IRF, Hanna R, Silva PSS. Clinical Efficacy of Photodynamic Therapy in Management of Oral Potentially Malignant Disorders: A Systematic Review and Meta-Analysis. J Evid Based Dent Pract. 2023;(2):101899.
Santos AF, Terra LF, Wailemann RA, Oliveira TC, Gomes VM, Mineiro MF, et al. Methylene blue photodynamic therapy induces selective and massive cell death in human breast cancer cells. BMC Cancer. 2017;17(1):194.
Mordon S. Treating hidradenitis suppurativa with photodynamic therapy. J Cosmet Laser Ther. 2018;20(4):223-8.
Jajarm HH, Falaki F, Sanatkhani M, Ahmadzadeh M, Ahrari F, Shafaee H. A comparative study of toluidine blue- mediated photodynamic therapy versus topical corticosteroids in the treatment of erosive-atrophic oral lichen planus: a randomized clinical controlled trial. Laser Med Sci. 2015;30(5):1475-80.
Muller S, Tilakaratne WM. Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Tumours of the Oral Cavity and Mobile Tongue. Head Neck Pathol. 2022;16(1):54-62.
Chen HM, Yu CH, Tsai T, Hsu YC, Kuo RC, Chiang CP. Topical 5-aminolevulinic acid-mediated photodynamic therapy for oral verrucous hyperplasia, oral leukoplakia and oral erythroleukoplakia. Photodiagnosis Photodyn Ther. 2007;4(1):44-52.
Tsai JC, Chiang CP, Chen HM, Huang SB, Wang CW, Lee MI, et al. Photodynamic Therapy of oral dysplasia with topical 5-aminolevulinic acid and light-emitting diode array. Lasers Surg Med. 2004;34(1):8-24.
Speight PM, Khurram SA, Kujan O. Oral potentially malignant disorders: Risk of progression to malignancy. Oral Surg Oral Med Oral Pathol Oral Radiol. 2018;125(6):612-27.
Delgado DA, Lambert BS, Boutris N, McCulloch PC, Robbins AB, Moreno MR, et al. Validation of Digital Visual Analog Scale Pain Scoring with a Traditional Paper-based Visual Analog Scale in Adults. J Am Acad Orthop Surg Glob Res Rev. 2018;23;2(3):e088.
López-Pintor RM, Diniz-Freitas M, Ramesh SSK, Valdéz JA, Bissonnette C, Dan H, et al. World Workshop on Oral Medicine VIII: Development of a core outcome set for oral lichen planus: a consensus study. Oral Surg Oral Med Oral Pathol Oral Radiol. 2023;135(6):792-803.
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