Clinical evaluation of photodynamic therapy for oral leukoplakia: a retrospective study of 50 patients

Wang et al. BMC Oral Health (2024) 24:9 https://doi.org/10.1186/s12903-023-03791-5 BMC Oral Health Open Access RESEARCH Clinical evaluation of photodynamic therapy for oral leukoplakia: a retrospective study of 50 patients Yanting Wang1,2,3, Haonan Tang1,2,3, Keyi Wang1,2,3, Yuping Zhao1,2,3, Juanyong Xu1,2,3 and Yuan Fan1,2,3* Abstract Background Topical photodynamic therapy (PDT) has demonstrated encouraging results in the treatment of oral leukoplakia (OLK). However, data on the clinical efficacy of PDT in Chinese patients with OLK are still limited. Methods Fifty patients diagnosed with OLK were enrolled, including patients with various dysplastic tissues. All patients received topical PDT with 5-aminolevulinic acid (5-ALA) as a photosensitizer. Clinical efficacy was evaluated 4 weeks after treatment. Follow-up was performed every 3 months during the first year and every 6 months during the second year. Results The overall response rate was 68% (34/50): 12% (n = 6) complete and 56% (n = 28) partial responses. Aneuploidy was reduced in the patients with dysplastic lesions. Oral pain and local ulcers developed in 52% of the patients (n = 26). Patients with a long history of OLK including hyperplasia and dysplastic lesions, as well as those with non-homogenous lesions, were more likely to develop pain and ulcer. During follow-up, the recurrence rate of hyperplasia and dysplastic lesions was 32% (n = 16) and the malignant transformation rate of dysplastic lesions was 4% (n = 2). Lesions on the buccal mucosa were associated with recurrence (P = 0.044; OR: 0.108, 95% CI: 0.013–0.915). Conclusion Topical 5-ALA-mediated PDT is an effective treatment for OLK, particularly for homogenous leukoplakia, with few side effects. The buccal mucosa may be a protective factor that can reduce recurrence. Keywords Photodynamic therapy, 5-aminolevulinic acid, Oral leukoplakia, DNA ploidy analysis, Side effects, Recurrence *Correspondence: Yuan Fan 1 Department of Oral Mucosal Diseases, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China 2 Jiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China 3 Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China Introduction Owing to the increased risk of developing cancer in or near the lesion area, as well as in other parts of the oral cavity or head and neck region, oral leukoplakia (OLK) is listed as one of the oral potentially malignant disorders (OPMDs) [1]. A systemic review that included over 1,000 patients showed that the prevalence of OLK was between 1.49 and 4.27% [2]. Previous studies on leukoplakia indicated a wide range of malignant transformation rates (3–20%), and that this rate is increasing in the Chinese population [3, 4]. Although the main goal of OLK management is to prevent malignant transformation, the © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Wang et al. BMC Oral Health (2024) 24:9 reduction or elimination of lesions is also desired because of their biological and clinical features [1, 5]. Various therapeutic approaches have been used in the management of OLK, such as systemic medication (alpha tocopherol, isotretinoin, lycopene, etc.), topical medication (bleomycin, tretinoin, isotretinoin, etc.), and photodynamic therapy (PDT) [6]. Although these approaches have been applied to OLK management, there is no clear evidence for an effective therapy preventing recurrence and malignant transformation [7]. Routes of administration of 5-aminolevulinic acid (5-ALA) include topical, oral, intravenous, intravesical, inhalational, and sublingual routes. Topical 5-ALA application is most widely used for mucocutaneous lesion PDT because it can be applied repeatedly without cumulative toxicity or serious adverse effects [8]. Topical PDT is a nonsurgical therapy using photosensitizers that selectively accumulate in the target tissue prior to light delivery. It involves three components: a light source, a photosensitizer, and tissue oxygen. The interaction between the light source and the photosensitizer is activated in the presence of oxygen, generating reactive oxygen species (ROS). Intracellular cytotoxic ROS then cause oxidative damage to precancerous and malignant cells [9, 10]. Topical PDT has been used for over 10 years for treating oral leukoplakia, with promising results [11]. In the study by Chen H.M. et al., 24 OLK patients were treated by topical PDT, with a result of 8 patients showing complete response and 16 patients showing partial response [12]. OLK recurred during the follow-up period in two cases. Kübler A et al. reported 12 OLK lesions treated by topical PDT with complete response in 5, partial response in 4, and no response in 3 patients while no recurrence was revealed [13]. However, data on the efficacy of topical PDT in OLK treatment for Chinese OLK patients are limited. There remain many barriers that lead to a significant proportion of patients with oral leukoplakia being treated with topical PDT. In this study, we reviewed the outcomes of OLK patients treated with topical PDT and evaluated the treatment effect, side effects, recurrence, and related risk factors. These findings provide novel insights into benchmarks and standards in the clinical application of topical PDT. Materials and methods Patients Patients with OLK who received topical PDT in the Department of Oral Mucosal Diseases of the Affiliated Stomatological Hospital of Nanjing Medical University between January 2019 and October 2020 were recruited. Ethics committee approval was obtained prior to commencement of the study (PJ2019-115-001). Page 2 of 10 Fifty patients with untreated OLK were included in this study. The inclusion criteria were OLK patients clinically diagnosed and verified using histology (including hyperplasia and dysplasia), and aged 18–75 years [14, 15]. The exclusion criteria inclu (...truncated)